Abstract:
A new synthetic method of forming free radical polymerizable end terminal functionalized poloxamers and poloxamines in commercial scale batches which uses a binary system of inhibitors to eliminate the formation of high molecular weight impurities. It has also been surprisingly discovered that the inorganic impurities formed during the commercial scale synthetic process are removed by the use of resin materials.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    Poloxamer F127 block copolymers are known compounds and are generally available under the trademark PLURONIC. These block copolymers consist of hydrophilic poly(ethylene oxide) (PEO) and hydrophobic poly(propylene oxide) (PPO) blocks arranged in A-B-A tri-block structure: PEO-PPO-PEO with end terminal hydroxyl groups. In some instances, unmodified Poloxamer can be used in medical devices such as ophthalmic lenses. 
         [0002]    Poloxamers have the following general formula: 
         [0000]      HO(C 2 H 4 O) a (C 3 H 6 O) b (C 2 H 4 O) a H 
         [0000]    Reverse poloxamers are also known block copolymers and have the following general formula: 
         [0000]      HO(C 3 H 6 O) b (C 2 H 4 O) a (C 3 H 6 O) b H 
         [0000]    wherein a and b may be the same or different and are of varying lengths. 
         [0003]    Poloxamers and reverse poloxamers have end terminal hydroxyl groups that can be functionalized to be free radical polymerizable ethylenically unsaturated end groups. An example of a free radical polymerizable ethylenically unsaturated end terminal functionalized poloxamer is poloxamer dimethacrylate (e.g., PLURONIC F-127 dimethacrylate) as disclosed in US Patent Publication No. 2003/0044468 to Cellesi et al. U.S. Pat. No. 6,517,933 discloses glycidyl-terminated copolymers of polyethylene glycol and polypropylene glycol. U.S. Pat. No. 8,377,464 discloses polymerizable surfactants and a method of making same. 
         [0004]    Poloxamers and reverse poloxamers are surfactants with varying HLB values based upon the varying values of a and b, a representing the number of hydrophilic poly(ethylene oxide) units (PEO) being present in the molecule and b representing the number of hydrophobic poly(propylene oxide) units (PPO) being present in the molecule. While poloxamers and reverse poloxamers are considered to be difunctional molecules (based on the terminal hydroxyl groups) they are also available in a tetrafunctional form known as poloxamines, trade name TETRONIC. For poloxamines, the molecules are tetrafunctional block copolymers terminating in primary hydroxyl groups and linked by a central diamine. Poloxamines have the following general structure: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    Reverse poloxamines are also known and have varying HLB values based upon the relative ratios of a to b wherein a and b are as defined above. 
         [0005]    Polyethers, such as poloxamers and poloxamines block copolymers, that are present at the surface of substrates have long been known to inhibit bacterial adhesion and to reduce the amount of lipid and protein deposition (non-fouling surface). In the present invention, we provide an improved synthesis of free radical polymerizable ethylenically unsaturated end terminal functionalized poloxamer and/or poloxamine block copolymers (BASF Corp.). The improved synthesis of free radical polymerizable ethylenically unsaturated end terminal functionalized poloxamer and/or poloxamine block copolymers provides improved overall device performance when the block copolymers prepared according to the invention described herein are included in ophthalmic device forming formulations. 
         [0006]    It is known the terminal hydroxyl groups of PLURONIC F-127 can be functionalized to provide the desired reactivity/purpose as part of the total monomer mix, before/after polymerization. Most of the materials described in the literature that respond to external stimuli are acrylic group containing molecules. So, for example, acrylated PLURONIC F-127 is of importance in some lens formulation. 
         [0007]    Whether to acrylate the terminal hydroxyl groups in poloxamers can be determined by the functional group of the other reactive molecules in the monomer mixture. The acrylation can be achieved by the reaction of (unmodified) poloxamers and poloxamines such as PLURONIC F-127 with methacryloyl chloride or methacryloyl anhydride in the presence of a suitable base. Since PLURONIC F-127 is an EO-PO block copolymer, it is known to be susceptible to possible degradation upon coming into contact with free radicals; thus yielding undesired reaction byproducts such as high molecular weight impurities when produced under commercial manufacturing conditions. In addition, residual reaction solvent(s), inhibitors, inorganic salts and methacrylic acid (MAA) may also remain in the free radical polymerizable ethylenically unsaturated end terminal functionalized poloxamers and reverse poloxamers. An example of a free radical polymerizable ethylenically unsaturated end terminal functionalized poloxamer is poloxamer dimethacrylate (e.g., PLURONIC F-127 dimethacrylate). PLURONIC F-127 DM, (DM meaning dimethacrylate), made by previously known commercial scale synthetic methods resulted in a grade of material which was routinely outside of the manufacturing specifications for use in forming certain medical devices. This is important because these byproducts may be injurious to the desired polymerization of PLURONIC F-127 DM, particularly when they are being used in a monomer mix for contact lens production. Any undesired and/or high molecular weight impurity can greatly interfere with lens processing, as well as properties and/or performance of the commercialized contact lens. Therefore, it is desirable that functionalized block copolymers such as PLURONIC F-127 DM prepared in commercial scale amounts be free of any high molecular weight impurities which are beyond the limits set in the manufacturing specifications. 
         [0008]    In the commercial scale synthesis of PLURONIC F-127 DM, 2,6-ditert-butyl-4-methyl phenol (BHT) is added as a free radical inhibitor to minimize the formation of these undesired byproducts. However, this synthesis is still unable to prevent the formation of high molecular weight impurities and inorganic salts. These impurities pose a manufacturing risk during the filtration of a monomer mix for making hydrophilic contact lenses containing same by slowing down the filtering process considerably; and, as a result, premature curing, i.e., polymerization, of the monomer mix commences before the monomer mix is introduced to the mold. 
         [0009]    Premature curing (polymerization) of monomer materials is undesirable as it renders the monomer mix unsuitable for preparing the desired final product, e.g. contact lenses, and can cause clogging of machines used to make such products. In particular, when the monomer mix starts to polymerize prematurely it slowly forms a gel, typically from the bottom of the vessel upwards. Some monomer mixtures, however, auto-accelerate and can react quite violently. 
         [0010]    Therefore, there is still a need for an improved commercial scale synthetic process for providing a high purity functionalized block copolymers, such as PLURONIC F-127 DM. 
       SUMMARY OF THE INVENTION 
       [0011]    This invention describes a new synthetic method of forming free radical polymerizable end terminal functionalized poloxamers and poloxamines in commercial scale batches which uses a binary system of inhibitors to eliminate the formation of high molecular weight impurities. It has also been surprisingly discovered that the inorganic impurities formed during the commercial scale synthetic process are removed by the use of resin materials. 
         [0012]    To minimize the high molecular weight impurities previously formed during the commercial scale synthesis of poloxamer 407 DM and to develop different binary systems of inhibitors to avoid these high molecular impurities during the synthesis of poloxamer 407 DM, a novel commercial scale synthetic process is disclosed herein. 
         [0013]    Disclosed herein is a method comprising reacting a poloxamer or poloxamine compound with a first methacrylating agent in the presence of a solvent stabilized with a first free radical inhibitor to form a first reaction product, and further reacting the first reaction product with an organic base and a second methacrylating agent stabilized with a second free radical inhibitor to form a second reaction product, wherein the first free radical inhibitor is a different compound than the second free radical inhibitor. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0014]      FIG. 1  is the NMR Spectrum of the product of Example 1; 
           [0015]      FIG. 2  to  FIG. 9  are HPLC chromatograms showing the calculations of the product of Example 1; 
           [0016]      FIG. 10  to  FIG. 13  are GC chromatograms showing the calculations of the product of Example 1; 
           [0017]      FIG. 14  is the HPLC chromatogram showing the high molecular weight component identification of the product of Example 1; 
           [0018]      FIG. 15  is the GPC chromatogram of the product of Example 1; 
           [0019]      FIG. 16  is the NMR Spectrum of the product of Comparative Example 1 when the reaction is performed without using any inhibitor; 
           [0020]      FIG. 17  to  FIG. 24  are HPLC chromatograms showing the calculations of the product of Comparative Example 1 when the reaction is performed without using any inhibitor; 
           [0021]      FIG. 25  to  FIG. 29  are GC chromatograms showing the calculations of the product of Comparative Example 1 when the reaction is performed without using any inhibitor; 
           [0022]      FIG. 30  is the HPLC chromatogram showing the high molecular weight component identification of the product of Comparative Example 1 when the reaction is performed without using any inhibitor; 
           [0023]      FIG. 31  is the GPC chromatogram of the product of Comparative Example 1 when the reaction is performed without using any inhibitor; 
           [0024]      FIG. 32  is the NMR Spectrum of the batch FS-09903-070 when the reaction is performed using BHT and MEHQ as inhibitors for the optimized improved large scale synthesis of Poloxamer 407DM of Example 3; 
           [0025]      FIG. 33  to  FIG. 39  are HPLC chromatograms showing the calculations of the batch FS-09903-070 when the reaction is performed using BHT and MEHQ as inhibitors for the optimized improved large scale synthesis of Poloxamer 407DM of Example 3; 
           [0026]      FIG. 40  is GC chromatogram of the batch FS-09903-070 when the reaction is performed using BHT and MEHQ as inhibitors for the optimized improved large scale synthesis of Poloxamer 407DM of Example 3. There are no detectable solvent residue, MAA, BHT and MEHQ in the final product. 
           [0027]      FIG. 41  is the HPLC chromatogram showing the high molecular weight component identification of the batch FS-09903-070 when the reaction is performed using BHT and MEHQ as inhibitors for the optimized improved large scale synthesis of Poloxamer 407DM of Example 3; 
           [0028]      FIG. 42  and  FIG. 43  are GPC chromatograms of the batch FS-09903-070 when the reaction is performed using BHT and MEHQ as inhibitors for the optimized improved large scale synthesis of Poloxamer 407DM of Example 3. There is no detectable high molecular weight impurity. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0029]    A poloxamer or poloxamine compound is reacted with a first methacrylating agent in the presence of a solvent stabilized with a first free radical inhibitor to form a first reaction product, and the first reaction product is further reacted with an organic base and a second methacrylating agent stabilized with a second free radical inhibitor to form a second reaction product, wherein the first free radical inhibitor is a different compound than the second free radical inhibitor. In various embodiments of the inventions, the first and second methacrylating agents may be the same, or may be different. In a specific embodiment, the first and second methacrylating agent is methacryloyl chloride. In embodiments wherein the poloxamer or poloxamine compound is a poloxamer compound, the first reaction product may be a monomethacrylated poloxamer compound, and the second reaction product may be a dimethacrylated poloxamer compound. In embodiments wherein the poloxamer or poloxamine compound is a poloxamine compound, the first reaction product may be a monomethacrylated poloxamine compound, and the second reaction product may be a polymethacrylated (e.g., di-, tri-, or tetra-methacrylated) poloxamine compound. The poloxamer or poloxamine compound may be reacted with the first methacrylating agent in the presence of the organic base, or the organic base may be added to the first reaction product after reaction thereof. 
         [0030]    PEO- and PPO-containing block copolymers are presently preferred. One such copolymer that can be used with the method of the invention, is PLURONIC® F127, a block copolymer having the structure [(polyethylene oxide) 99 -(polypropylene oxide) 66 -(polyethylene oxide) 99 ]. The terminal hydroxyl groups of the copolymer are functionalized with free radical polymerizable ethylenically unsaturated end groups to allow for the reaction of the PEO- and PPO-containing block copolymer with other device forming monomers. 
         [0031]    A poloxamer compound such as PLURONIC F 127 is reacted with a methacrylating agent such as methacryloyl chloride while blanketed with nitrogen gas in the presence of a solvent such as anhydrous tetrahydrofuran (THF) stabilized with a free radical inhibitor such as 2,6 di tert-butyl-4-methyl phenol (BHT). After this portion of the synthesis has reacted, an organic base such as triethylamine (TEA) is added to the above solution with continued mixing. Alternatively, the organic base may be present during the first methacrylation reaction. To this reaction mixture is then added methacryloyl chloride which was stabilized with Hydroquinone monomethyl ether (MEHQ) with continued stirring under nitrogen gas. After the immediately above reaction has gone to completion the reaction mass is allowed to cool to room temperature (RT) and worked up to give the functionalized desired product as shown in the Reaction Scheme-1. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0032]    Turbidity measurements of PLURONIC F-127DM both in water and tetrahydrofuran were determined to be indicative of the presence of inorganic salts and any high molecular weight impurities. For the purpose of collecting the analytical data and to determine the desired product purity, dimethacrylation % conversion was checked by NMR &amp; HPLC; GPC was used to determine the Mw and Mn molecular weights and GC was used to determine the residual solvents and methacrylic acid. 
         [0033]    It is believed the formation of High Molecular Weight impurities in PLURONIC F-127DM is due to the inadvertent cross linking caused by the presence of undesirable radicals. The radicals formed in PLURONIC F-127DM chains can further react to form gel or High Molecular Weight impurities. This can be avoided by adding BHT as a free radical inhibitor. Any undesirable radical formed will react with BHT and result in a stabilized radical unable to react further thus avoiding gel formation. The two electron donating groups (t-butyl) in BHT also serve to activate the end terminal hydroxyl groups of the PEO-PPO containing block copolymer resulting in an increase of the efficiency of the inventive reaction. 
         [0034]    Although not entirely certain, the inventors believe the efficacy of BHT is limited to suppression of radicals formed at only the propylene oxide repeating units of Poloxamer block copolymer. The reason for this limitation could be due to the sterically hindered stabilized radicals formed from BHT. It has surprisingly been discovered that the usage of a combination of MEHQ with BHT in the synthetic scheme of the invention herein can effectively stabilize the radicals formed at both the ethylene oxide and propylene oxide units of the poloxamer block copolymer. 
         [0035]    Further, the radicals which are generated in the reaction medium due to use of highly polar solvents like THF at large scale reaction conditions are effectively stabilized by use of these two inhibitors. 
         [0036]    Mechanism (Action of Inhibitor): Usage of BHT 
         [0000]    
       
                 
         
             
             
         
       
       
                 
         
             
             
         
       
     
         [0037]    Effective oxidation of BHT gives rise to mixture of compound which are called quinoid compounds. 3,5,3′,5′-tetratert-butylstilbiene-4,4′-quinone and 2,6-ditert-butyl-1,4-benzoquinone. 
       EXAMPLES 
     Example 1 
     Modified Process for Manufacturing of Poloxamer 407 DM (FS09458-036): with Single Inhibitor System (BHT as an Inhibitor) 
       [0038]    Observations: When 2,6 ditert-butyl 4 methyl phenol (BHT) was used as an inhibitor, the High Molecular Weight component was minimized and the Turbidity of the product in THF and Water was very much reduced. 
         [0039]    Typical Procedure: 500 g of PLURONIC F-127 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 3500 mL) stabilized with 5250 mg of 2,6 ditert-butyl-4-methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 68 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 47.5 mL of freshly distilled methacryloyl chloride at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0040]    Work Up: The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 250 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 250 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 1165 mL of THF to get 2335 mL of mass. The mass was precipitated into 16000 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
         [0041]    Analytical Characterization 
         [0042]    % Conversion by  1 H-NMR: 
         [0043]    1H-NMR spectrum of FS09458-036 was recorded in DMSO-d6 on a Bruker Avance 400 MHz. The conversion was 82.3% ( FIG. 1 ) 
         [0044]    Calculation: 
         [0045]    No. of protons at 6.1 ppm 1.63+No. of protons at 5.6 ppm 1.67/4=3.3/4×100=82.3% 
         [0046]    Conversion by HPLC: Determination of Poloxamer 407 Dimethacrylate 
         [0047]    (FS09458-036): The HPLC analysis was performed Agilent 1200 series HPLC system with SHODEX KB-804(300×8) mm column a using SODIUM ACETATE BUFFER as Mobile Phase. 
         [0048]    Calculation: % Conversion by HPLC ( FIG. 2  to  FIG. 9 ) 
         [0000]    
       
         
               
               
             
               
               
               
               
             
               
             
               
               
               
               
             
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                   
                 Product: Poloxamer 407 Dimethacrylate 
               
               
                   
                 Study: % Conversion (By HPLC) 
               
               
                   
                 B. No.: FS09458-036 
               
               
                   
                 AR No.: A529453 
               
               
                   
                 Check standard weight (mg) = 203.4 
               
               
                   
                 Standard weight (mg) = 198.0 
               
               
                   
                 % Conversion for standard = 84.7 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                   
                   
                 Total peak 
               
               
                   
                 Peak-1 
                 Peak-2 
                 area 
               
               
                   
               
               
                 Check 
                 2350798 
                 1555236 
                 3906034 
               
               
                 standard 
                   
                   
                   
               
               
                 Standard 
                 2226408 
                 1329009 
                 3555417 
               
               
                   
                 % Agreement 
                   
                 106.94 
               
               
                   
               
             
          
           
               
                 System precision: 
               
             
          
           
               
                   
                   
                   
                 Total peak 
               
               
                 S. No. 
                 Peak-1 
                 Peak-2 
                 area 
               
               
                   
               
               
                 1 
                 2226408 
                 1329009 
                 3555417 
               
               
                 2 
                 2329288 
                 1391799 
                 3721087 
               
               
                 3 
                 2329679 
                 1444988 
                 3774667 
               
               
                 4 
                 2315375 
                 1467507 
                 3782882 
               
               
                 5 
                 2286721 
                 1361211 
                 3647932 
               
               
                 6 
                 2297159 
                 1503218 
                 3800377 
               
               
                 Average 
                 2297438.3 
                 1416288.7 
                 3713727.0 
               
               
                 Std. Dev 
                 38822.245 
                 66715.38316 
                 95340.99627 
               
               
                 % RSD 
                 1.69 
                 4.71 
                 2.57 
               
               
                   
               
             
          
           
               
                 % Conversion 
               
             
          
           
               
                   
                 Sample 
                   
                   
                   
                 % 
               
               
                   
                 weight 
                   
                   
                 Total peak 
                 Con- 
               
               
                 S. No. 
                 (g) 
                 Peak-1 
                 Peak-2 
                 area 
                 version 
               
               
                   
               
               
                 1 
                 198.9 
                 2593651 
                 1595599 
                 4189250.0 
                 95.11 
               
               
                 2 
                 199.0 
                 2614811 
                 1693300 
                 4308111.0 
                 97.76 
               
               
                 Average 
                   
                 2604231.00 
                 1644449.50 
                 4248680.50 
                 96.44 
               
               
                 Std.Dev 
                   
                 14962.38 
                 69085.04 
                 84047.42 
                 1.87 
               
               
                 % RSD 
                   
                 0.57 
                 4.2 
                 1.98 
                 1.94 
               
               
                   
               
               
                 
                   
                     
                       
                         
                           % 
                            
                           
                               
                           
                            
                           Conversion 
                         
                         = 
                         
                           
                             
                               
                                 
                                   Total 
                                    
                                   
                                       
                                   
                                    
                                   sample 
                                    
                                   
                                       
                                   
                                    
                                   area 
                                    
                                   
                                       
                                   
                                   × 
                                   standard 
                                    
                                   
                                       
                                   
                                    
                                   weight 
                                    
                                   
                                       
                                   
                                    
                                   
                                     ( 
                                     mg 
                                     ) 
                                   
                                   × 
                                 
                               
                             
                             
                               
                                 
                                   % 
                                    
                                   
                                       
                                   
                                    
                                   Conversion 
                                    
                                   
                                       
                                   
                                    
                                   of 
                                    
                                   
                                       
                                   
                                    
                                   the 
                                    
                                   
                                       
                                   
                                    
                                   standard 
                                 
                               
                             
                           
                           
                             
                               
                                 
                                   Average 
                                    
                                   
                                       
                                   
                                    
                                   total 
                                    
                                   
                                       
                                   
                                    
                                   standard 
                                    
                                   
                                       
                                   
                                    
                                   area 
                                   × 
                                 
                               
                             
                             
                               
                                 
                                   Sample 
                                    
                                   
                                       
                                   
                                    
                                   weight 
                                    
                                   
                                       
                                   
                                    
                                   
                                     ( 
                                     mg 
                                     ) 
                                   
                                 
                               
                             
                           
                         
                       
                     
                   
                 
               
             
          
         
       
     
         [0049]    GC analysis was performed using Agilent GC 6890N series equipped with G188 Head space Auto sampler. Nitrogen was the carrier gas with flame ionized detector. 
         [0050]    GC Calculation ( FIG. 10  to  FIG. 13 ): 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
               
               
             
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
               
                   
               
               
                 RESIDUAL MONOMER REPORT 
               
               
                 Product: Poloxamer 
               
               
                 Batch No.: FS09458-036 
               
               
                 A.R. No.: A529453 
               
               
                   
               
             
             
               
                 System suitability: 
               
             
          
           
               
                 S. No. 
                 Monomer 
                 Wt. 
               
               
                   
               
               
                 1 
                 THF 
                 0.0923 
               
               
                 2 
                 IPA 
                 0.102 
               
               
                 3 
                 MAA 
                 0.2198 
               
               
                 4 
                 BHT 
                 0.092 
               
               
                   
               
             
          
           
               
                   
                 THF 
                 IPA 
                 MAA 
                 BHT 
               
               
                   
               
               
                 STD-1 
                 78.607 
                 81.421 
                 168.016 
                 134.286 
               
               
                 STD-2 
                 79.75 
                 80.485 
                 164.034 
                 133.905 
               
               
                 STD-3 
                 77.716 
                 77.771 
                 172.812 
                 127.356 
               
               
                 Average 
                 78.691 
                 79.89233333 
                 168.2873333 
                 131.849 
               
               
                 Std. Dev 
                 1.02 
                 1.90 
                 4.40 
                 3.90 
               
               
                 % RSD 
                 1.30 
                 2.37 
                 2.61 
                 2.95 
               
               
                   
               
             
          
           
               
                   
                 Area of 
                 % Residual 
                   
               
             
          
           
               
                 Mono- 
                 Test 
                 Test 
                 Test 
                 Test 
                 Total 
               
               
                 mer 
                 sample-1 
                 sample-2 
                 sample-1 
                 sample-2 
                 Residual 
               
               
                   
               
               
                 THF 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
               
               
                 IPA 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
               
               
                 MAA 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
               
               
                 BHT 
                 71.403 
                 73.102 
                 0.271365585 
                 0.277822599 
                 0.274594 
               
               
                   
               
               
                 Sample weight (g) = 0.0918 
               
             
          
         
       
     
         [0051]    High Molecular Component was identified using HPLC System: Chromatogram is given below. It is found that HMW component is 0.35% was present in this sample ( FIG. 14 ). 
         [0052]    GPC: 
         [0053]    GPC of FS-09458-036 was performed using Agilent 1200 Series with Addon GPC software. PEG-PPg was used as the GPC standards ( FIG. 15 ). 
         [0054]    Turbidity measurement of the Poloxamer 407 DM was measured in NTU units using HF Scientific Turbidity meter (Make): Model-Micro 100 Turbid meter. Solution was prepared in 10% water and THF. The turbidity was measured in water (3 NTU) and in THF (6 NTU). 
         [0055]    Methacrylic acid content: Titration method was followed. 
       Comparative Example 1 
     Old Process for Manufacturing of Poloxamer 407 DM: without any Inhibitor 
       [0056]    Observations: High Molecular Weight component was observed and the Turbidity of the product in THF and Water was very much high. 
         [0057]    Typical Procedure: 
         [0058]    500 g of PLURONIC F-127 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 3500 mL was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 68 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 47.5 mL of methacryloyl chloride which at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0059]    Work Up: 
         [0060]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 250 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was concentrated to remove 1165 mL of THF to get 2335 mL of mass. The mass was precipitated into 16000 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
         [0061]    Analytical Characterization 
         [0062]    % Conversion by  1 H-NMR: 
         [0063]    1H-NMR spectrum of FS-09458-037 was recorded in DMSO-d6 on a Bruker Avance 400 MHz. The conversion was 87.7%. Calculation: No. of protons at 6.1 ppm 1.75+No. of protons at 5.6 ppm 1.76=3.51/4×100=87.7 ( FIG. 16 ) 
         [0064]    % Conversion by HPLC: Determination of Poloxamer 407 Dimethacrylate: 
         [0065]    The HPLC analysis of FS-09458-037 was performed using Agilent 1200 series HPLC system with SHODEX KB-804(300×8) mm column a using SODIUM ACETATE BUFFER as Mobile Phase. 
         [0066]    Calculation: % Conversion by HPLC ( FIG. 17  to  FIG. 24 ) 
         [0000]    
       
         
               
               
             
               
               
               
               
             
               
             
               
               
               
               
             
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
               
                   
               
               
                   
                 Product: Poloxamer 407 Dimethacrylate 
               
               
                   
                 Study: % Conversion (By HPLC) 
               
               
                   
                 B. No.: FS09458-037 
               
               
                   
                 AR No.: A532877 
               
               
                   
                 Check standard weight (mg) = 202.1 
               
               
                   
                 Standard weight (mg) = 199.2 
               
               
                   
                 % Conversion for standard = 84.7 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                   
                   
                 Total peak 
               
               
                   
                 Peak-1 
                 Peak-2 
                 area 
               
               
                   
               
               
                 Check 
                 2243804 
                 1652655 
                 3896459 
               
               
                 standard 
                   
                   
                   
               
               
                 Standard 
                 2242333 
                 1744509 
                 3986842 
               
               
                   
                 % Agreement 
                   
                 96.33 
               
               
                   
               
             
          
           
               
                 System precision: 
               
             
          
           
               
                   
                   
                   
                 Total peak 
               
               
                 S. No. 
                 Peak-1 
                 Peak-2 
                 area 
               
               
                   
               
               
                 1 
                 2242333 
                 1744509 
                 3986842 
               
               
                 2 
                 2184706 
                 1632958 
                 3817664 
               
               
                 3 
                 2156436 
                 1714115 
                 3870551 
               
               
                 4 
                 2176410 
                 1687458 
                 3863868 
               
               
                 5 
                 2159765 
                 1581961 
                 3741726 
               
               
                 6 
                 2107640 
                 1637102 
                 3744742 
               
               
                 Average 
                 2171215.0 
                 1666350.5 
                 3837565.5 
               
               
                 Std. Dev 
                 43950.124 
                 59879.62368 
                 91935.65117 
               
               
                 % RSD 
                 2.02 
                 3.59 
                 2.4 
               
               
                   
               
             
          
           
               
                 % Conversion 
               
             
          
           
               
                   
                 Sample 
                   
                   
                   
                 % 
               
               
                   
                 weight 
                   
                   
                 Total peak 
                 Con- 
               
               
                 S. No. 
                 (g) 
                 Peak-1 
                 Peak-2 
                 area 
                 version 
               
               
                   
               
               
                 1 
                 198.2 
                 2234443 
                 1709801 
                 3944244.0 
                 87.49 
               
               
                 2 
                 199.4 
                 2213491 
                 1619436 
                 3832927.0 
                 84.51 
               
               
                 Average 
                   
                 2223967.00 
                 1664618.50 
                 3888585.5 
                 86.00 
               
               
                   
               
               
                 
                   
                     
                       
                         
                           % 
                            
                           
                               
                           
                            
                           Conversion 
                         
                         = 
                         
                           
                             
                               
                                 
                                   Total 
                                    
                                   
                                       
                                   
                                    
                                   sample 
                                    
                                   
                                       
                                   
                                    
                                   area 
                                    
                                   
                                       
                                   
                                   × 
                                   standard 
                                    
                                   
                                       
                                   
                                    
                                   weight 
                                    
                                   
                                       
                                   
                                    
                                   
                                     ( 
                                     mg 
                                     ) 
                                   
                                   × 
                                 
                               
                             
                             
                               
                                 
                                   % 
                                    
                                   
                                       
                                   
                                    
                                   Conversion 
                                    
                                   
                                       
                                   
                                    
                                   of 
                                    
                                   
                                       
                                   
                                    
                                   the 
                                    
                                   
                                       
                                   
                                    
                                   standard 
                                 
                               
                             
                           
                           
                             
                               
                                 
                                   Average 
                                    
                                   
                                       
                                   
                                    
                                   total 
                                    
                                   
                                       
                                   
                                    
                                   standard 
                                    
                                   
                                       
                                   
                                    
                                   area 
                                   × 
                                 
                               
                             
                             
                               
                                 
                                   Sample 
                                    
                                   
                                       
                                   
                                    
                                   weight 
                                    
                                   
                                       
                                   
                                    
                                   
                                     ( 
                                     mg 
                                     ) 
                                   
                                 
                               
                             
                           
                         
                       
                     
                   
                 
               
             
          
         
       
     
         [0067]    GC analysis was performed using Agilent GC 6890N series equipped with G188 Head space Auto sampler. Nitrogen was the carrier gas with flame ionized detector. 
         [0068]    GC Calculation ( FIG. 25  to  FIG. 29 ): 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 4 
               
               
                   
               
               
                 RESIDUAL MONOMER REPORT 
               
               
                 Product: Poloxamer 
               
               
                 Batch No.: FS09458-037 
               
               
                 A.R. No.: A532877 
               
               
                   
               
             
             
               
                 System suitability: 
               
             
          
           
               
                 S. No. 
                 Monomer 
                 Wt. 
               
               
                   
               
               
                 1 
                 THF 
                 0.1142 
               
               
                 2 
                 IPA 
                 0.1146 
               
               
                 3 
                 MAA 
                 0.2013 
               
               
                 4 
                 BHT 
                 0.0923 
               
               
                   
               
             
          
           
               
                   
                   
                 THF 
                 IPA 
                 MAA 
                 BHT 
               
               
                   
                   
               
               
                   
                 STD-1 
                 96.264 
                 |85.868 
                 139.706 
                 119.094 
               
               
                   
                 STD-2 
                 98.787 
                 86.458 
                 145.900 
                 123.176 
               
               
                   
                 STD-3 
                 97.908 
                 86.339 
                 142.939 
                 128.183 
               
               
                   
                 Average 
                 97.653 
                 86.399 
                 142.848 
                 123.484 
               
               
                   
                 Std. Dev 
                 1.28 
                 0.08 
                 3.10 
                 4.55 
               
               
                   
                 % RSD 
                 1.31 
                 0.10 
                 2.17 
                 3.69 
               
               
                   
                   
               
             
          
           
               
                   
                 Area of 
                 % Residual 
                   
               
             
          
           
               
                 Mono- 
                 Test 
                 Test 
                 Test 
                 Test 
                   
               
               
                 mer 
                 sample-1 
                 sample-2 
                 sample-1 
                 sample-2 
                 Result 
               
               
                   
               
               
                 THF 
                 10.626 
                 10.825 
                 0.0631 
                 0.0643 
                 0.0637 
               
               
                 IPA 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
               
               
                 MAA 
                 16.737 
                 17.311 
                 0.1198 
                 0.1240 
                 0.1219 
               
               
                 BHT 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
               
             
          
           
               
                 Total Residual solvent (%) 
                 0.1830 
                 0.1883 
                 0.19  
               
               
                   
               
               
                 Sample weight (g) = 0.0984 
               
             
          
         
       
     
         [0069]    High Molecular Component was Identified Using HPLC System: 
         [0070]    Chromatogram is given below. It is found that HMW component is 0.55% was present in this sample ( FIG. 30 ). 
         [0071]    Turbidity measurement of the Poloxamer 407 DM was measured in NTU units using HF Scientific Turbidity meter (Make): Model-Micro 100 Turbid meter. Solution was prepared in 10% water and THF. The turbidity in water showed 5 NTU and in THF 200 NTU. 
         [0072]    GPC: 
         [0073]    GPC was performed using Agilent 1200 Series with Addon GPC software. PEG-PPg were used as the GPC standards ( FIG. 31 ). 
         [0074]    Methacrylic Acid Content: 
         [0075]    Titration method was followed. The Methacrylic acid content: 0.002% (for this sample). 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Reaction performed using BHT as an inhibitor for the synthesis of Poloxamer 407 DM 
               
               
                 Compilation of Poloxamer 407 DM with different concentrations of BHT 
               
             
          
           
               
                   
                   
                   
                 BHT used 
                   
                   
                   
                 BHT level 
                   
                 Turbidity 
                   
               
               
                 SL. 
                   
                 Batch 
                 for process 
                   
                 % conversion 
                 % conversion 
                 by GC method 
                 GPC 
                 In THF 
               
               
                 No 
                 Batch. No 
                 size (g) 
                 (ppm) 
                 THF grade 
                 by NMR 
                 by HPLC 
                 (ppm) 
                 % of HMW 
                 (NTU) 
                 Yield (g) 
               
               
                   
               
             
          
           
               
                 SET-1 
               
             
          
           
               
                 1 
                 FS09458-032 
                 500 
                 0 
                 Dry 
                 80 
                 99.8 
                 0 
                 0.3 
                 25.1 
                 455 
               
               
                 2 
                 FS09458-033 
                 500 
                 500 
                 Dry 
                 83.5 
                 92.3 
                 10 
                 0.2 
                 125 
                 460 
               
               
                 3 
                 FS09458-036 
                 500 
                 1500 
                 Dry 
                 85.77 
                 96.4 
                 40 
                 0.4 
                 10 
                 455 
               
               
                 4 
                 FS09458-035 
                 500 
                 0 
                 Commercial 
                 85.0 
                 94.4 
                 5 
                 0.1 
                 57.4 
                 460 
               
             
          
           
               
                 SET-2 
               
             
          
           
               
                 1 
                 FS09458-037 
                 500 
                 0 
                 Dry 
                 83.6 
                 86 
                 0 
                 0.6 
                 340 
                 465 
               
               
                 2 
                 FS09458-038 
                 500 
                 500 
                 Dry 
                 81.7 
                 87.1 
                 15 
                 0.8 
                 50 
                 460 
               
               
                 3 
                 FS09458-040 
                 500 
                 1500 
                 Dry 
                 81.9 
                 93.01 
                 60 
                 0.7 
                 12.7 
                 470 
               
               
                 4 
                 FS09458-039 
                 500 
                 0 
                 Commercial 
                 85.6 
                 89.7 
                 10 
                 0.4 
                 500 
                 475 
               
             
          
           
               
                 SET-3 
               
             
          
           
               
                 1 
                 FS09458-042 
                 500 
                 0 
                 Dry 
                 80.7 
                 89.5 
                 0 
                 1.3 
                 410 
                 470 
               
               
                 2 
                 FS09458-043 
                 500 
                 500 
                 Dry 
                 80.7 
                 84.3 
                 10 
                 0.6 
                 832 
                 475 
               
               
                 3 
                 FS09458-041 
                 500 
                 1500 
                 Dry 
                 82.4 
                 92.5 
                 120 
                 0.5 
                 22 
                 475 
               
               
                 4 
                 FS09458-044 
                 500 
                 0 
                 Commercial 
                 83 
                 88.8 
                 0 
                 0.6 
                 82.3 
                 470 
               
               
                   
               
             
          
         
       
     
         [0076]    Advantage of BHT: 
         [0077]    The formation of undesirable High MW contaminant is minimized and inhibitor is not carried over with the reaction product when used as part of a device forming monomer mix. 
         [0078]    Disadvantage of BHT: 
         [0079]    Did not completely stop the formation of the High MW contaminant. 
         [0080]    Limitations of BHT: 
         [0081]    Because BHT radical is stable &amp; its sterically hindered this cannot further react with the radicals 
         [0000]    
       
                 
         
             
             
         
       
     
         [0082]    The activity of BHT radical is limited which cannot alone stop the formation of high molecular weight impurities, combination of inhibitor system was performed. The new inhibitor is MEHQ. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0083]    Mechanism (Action of Inhibitor): Usage of MEHQ 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]                                                                                                                          TABLE 6                   Reaction performed using BHT &amp;MEHQ as inhibitors for the synthesis of       Poloxamer 407 DM.                Inhibitor   GPC   GPC       GPC            SL. No   Descrip&#39;n   Batch No.   MeHQ   BHT   % HMW   % HMW   NMR   % HMW                    1   Set-1   FS09903-023   1000 ppm   0   ND   ND   72.5   ND       2       FS09903-024       500   ND   ND   66   ND       3       FS09903-025       1000   ND   ND   71.25   ND       4       FS09903-026       1500   ND   ND   73.75   ND       1   Set-2   FS09903-030   2000 ppm   0   . . .   . . .   87.5   ND       2       FS09903-031       500   0.06   0.03   83.5   0.09       3       FS09903-032       1000   0.04   ND   75.25   ND       4       FS09903-033       1500   ND   . . .   67.5   ND       1   Set-3   FS09903-034   3000 ppm   0   ND   ND   93   0.04       2       FS09903-035       500   ND   ND   92   ND       3       FS09903-036       1000   ND   ND   81   ND       4       FS09903-037       1500   ND   0.06   95   ND       1   Set-4   FS09903-038   4000 ppm   0   ND   ND   85   ND       2       FS09903-039       500   . . .   ND   73   ND       3       FS09903-040       1000   ND   ND   61   ND       4       FS09903-041       1500   ND   ND   79.25   ND       1   Set-5   FS09903-042   5000 ppm   0   ND   . . .   91   ND       2       FS09903-043       500   ND   . . .   95   ND       3       FS09903-044       1000   ND   . . .   89.7   ND       4       FS09903-045       1500   ND   . . .   94.5   ND                    
The usage of MEHQ along with BHT shown no High molecular weight impurity in Poloxamer 407 DM
 
         [0000]    
       
         
               
             
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 Comparative data: BHT &amp;MEHQ as a inhibitors 
               
               
                 for the synthesis of Poloxamer 407 DM 
               
             
          
           
               
                   
                 BHT 
               
             
          
           
               
                   
                 0 ppm 
                 500 ppm 
                 1000 ppm 
                 1500 ppm 
               
               
                 MEHQ 
                 % of 
                 % of 
                 % of 
                 % of 
               
               
                 level (ppm) 
                 conversion 
                 conversion 
                 conversion 
                 conversion 
               
               
                   
               
               
                 1000 
                 73 
                 66 
                 71 
                 74 
               
               
                 2000 
                 88 
                 84 
                 75 
                 68 
               
               
                 3000 
                 93 
                 92 
                 81 
                 95 
               
               
                 4000 
                 84 
                 73 
                 61 
                 79 
               
               
                 5000 
                 91 
                 95 
                 90 
                 95 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 Reaction performed using BHT &amp;MEHQ as a inhibitors for the synthesis of Poloxamer 407 DM 
               
             
          
           
               
                   
                 GPC 
                   
               
             
          
           
               
                   
                   
                 HMW 
                   
                   
                   
               
               
                   
                 Main Peak 
                 Peak 
                   
                 GC (ppm) 
               
             
          
           
               
                   
                 % Conversion 
                   
                   
                 Area 
                 Area 
                 % HMW 
                   
                 BHT + 
                   
                 Turbidity 
                 Titration 
               
             
          
           
               
                 Sl. No. 
                 Batch No. 
                 NMR 
                 HPLC 
                 Mw 
                 Mn 
                 (nRlu) 
                 (nRlu) 
                 (nRlu) 
                 THF 
                 MeHQ 
                 n-Heptane 
                 IPA 
                 THF 
                 MAA (%) 
               
               
                   
               
             
          
           
               
                 1 
                 FS09903-010 
                 94 
                 92.29 
                 8815 
                 7224 
                 682531.68 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 3.69 
                 0.0051 
               
               
                 2 
                 FS09903-011 
                 91 
                 90.58 
                 8855 
                 7447 
                 805058.96 
                 658.05 
                 0.08 
                 ND 
                 ND 
                 2779 
                 ND 
                 Not done 
                 0.0034 
               
               
                 3 
                 FS09903-015 
                 96 
                 87.98 
                 8842 
                 7447 
                 732759.25 
                 ND 
                 ND 
                 ND 
                 ND 
                 2323 
                 ND 
                 7.05 
                 0.0085 
               
               
                 4 
                 FS09903-016 
                 87 
                 94.59 
                 8893 
                 7461 
                 799899.87 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 Not done 
                 0.0032 
               
               
                 5 
                 FS09903-017 
                 92 
                 92.16 
                 8784 
                 7362 
                 790396.46 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 1062 
                 Not done 
                 0.0034 
               
               
                 6 
                 FS09903-018 
                 92 
                 93.31 
                 8930 
                 7443 
                 805179.62 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 23.7 
                 0.005 
               
               
                 7 
                 FS09903-019 
                 100 
                 90.98 
                 9033 
                 7579 
                 700435.68 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 8.76 
                 0.0052 
               
               
                 8 
                 FS09903-020 
                 89 
                 90.9 
                 8930 
                 7597 
                 708862 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 29 
                 0.0051 
               
               
                   
               
             
          
         
       
     
       Example 2 
     Improved Synthesis of Functionalized Surfactants 
       [0084]    100 g of PLURONIC F 127 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF) (700 mL) stabilized with 1500 ppm of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 13.6 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 9.5 mL of freshly distilled methacryloyl chloride which was stabilized with 3000 ppm of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove one third volume of THF. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. The NMR analysis of the final polymer showed greater than 89% conversion. 
       Example 3 
     Optimized Improved Large Scale Process for Manufacturing of Poloxamer 407 DM: with Double Inhibitor System (BHT and MeHQ as Inhibitors) 
       [0085]    Observations: When 2,6 ditert-butyl 4 methyl phenol (BHT) &amp; Hydroquinone monomethyl ether (MeHQ) was used as an inhibitor, the High Molecular Weight component was eliminated and the Turbidity of the product in THF and Water was drastically reduced 
         [0086]    Typical Procedure: 
         [0087]    1200 g of PLURONIC F-127 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 8400 mL) stabilized with 12600 mg of 2,6 ditert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 163.2 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 114 mL of freshly distilled methacryloyl chloride which was stabilized with 342 mg of Hydroquinone monomethyl ether (MeHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0088]    Work Up: 
         [0089]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 600 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 600 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 2800 mL of THF to get 5600 mL of mass. The mass was precipitated into 32000 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
         [0090]    Analytical Characterization 
         [0091]    % Conversion by  1 H-NMR: 
         [0092]    1H-NMR spectrum of FS09903-070 was recorded in DMSO-d6 on a Bruker Avance 400 MHz. The conversion was 82.3% ( FIG. 32 ). Calculation: No. of protons at 6.1 ppm 1.89+No. of protons at 5.6 ppm 1.92/4=3.81/4×100=95.2% 
         [0093]    Conversion by HPLC: Determination of Poloxamer 407 Dimethacrylate 
         [0094]    (FS09903-070): The HPLC analysis was performed on Agilent 1200 series HPLC system with SHODEX KB-804(300×8) mm column a using SODIUM ACETATE BUFFER as Mobile Phase. 
         [0095]    Calculation: % conversion by HPLC ( FIG. 33  to  FIG. 39 ) 
         [0000]    
       
         
               
               
             
               
             
               
               
               
               
             
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 9 
               
               
                   
               
               
                   
                 Product: Poloxamer 407 Dimethacrylate 
               
               
                   
                 Study: % Conversion (By HPLC) 
               
               
                   
                 B. No.: FS09903-070 
               
               
                   
                 AR No.: A576683 
               
               
                   
                 Standard weight (mg) = 200.5 
               
               
                   
                 % Conversion for standard = 84.7 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 System precision: 
               
             
          
           
               
                   
                   
                   
                 Total peak 
               
               
                 S. No. 
                 Peak-1 
                 Peak-2 
                 area 
               
               
                   
               
               
                 1 
                 5941334 
                 2720732 
                 8662066 
               
               
                 2 
                 6069470 
                 2866854 
                 8936324 
               
               
                 3 
                 5992173 
                 2775991 
                 8768164 
               
               
                 4 
                 5989656 
                 2704351 
                 8694007 
               
               
                 5 
                 6070184 
                 2792707 
                 8862891 
               
               
                 6 
                 6069636 
                 2822317 
                 8891953 
               
               
                 Average 
                 6022075.5 
                 2780492.0 
                 8802567.5 
               
               
                 Std. Dev 
                 55293.83487 
                 61230.54855 
                 111560.8785 
               
               
                 % RSD 
                 0.92 
                 2.2 
                 1.27 
               
               
                   
               
             
          
           
               
                 % Conversion 
               
             
          
           
               
                   
                 Sample 
                   
                   
                   
                 % 
               
               
                   
                 weight 
                   
                   
                 Total peak 
                 Con- 
               
               
                 S. No. 
                 (mg) 
                 Peak-1 
                 Peak-2 
                 area 
                 version 
               
               
                   
               
               
                 1 
                 200.4 
                 6389350 
                 3407932 
                 9797282.0 
                 94.32 
               
               
                 2 
                 200.3 
                 6407197 
                 3519536 
                 9926733.0 
                 95.61 
               
               
                 Average 
                   
                 6398273.50 
                 3463734.00 
                 9862007.5 
                 94.97 
               
               
                   
               
               
                 
                   
                     
                       
                         
                           % 
                            
                           
                               
                           
                            
                           Conversion 
                         
                         = 
                         
                           
                             
                               
                                 
                                   Total 
                                    
                                   
                                       
                                   
                                    
                                   sample 
                                    
                                   
                                       
                                   
                                    
                                   area 
                                    
                                   
                                       
                                   
                                   × 
                                   standard 
                                    
                                   
                                       
                                   
                                    
                                   weight 
                                    
                                   
                                       
                                   
                                    
                                   
                                     ( 
                                     mg 
                                     ) 
                                   
                                   × 
                                 
                               
                             
                             
                               
                                 
                                   % 
                                    
                                   
                                       
                                   
                                    
                                   Conversion 
                                    
                                   
                                       
                                   
                                    
                                   of 
                                    
                                   
                                       
                                   
                                    
                                   the 
                                    
                                   
                                       
                                   
                                    
                                   standard 
                                 
                               
                             
                           
                           
                             
                               
                                 
                                   Average 
                                    
                                   
                                       
                                   
                                    
                                   total 
                                    
                                   
                                       
                                   
                                    
                                   standard 
                                    
                                   
                                       
                                   
                                    
                                   area 
                                   × 
                                 
                               
                             
                             
                               
                                 
                                   Sample 
                                    
                                   
                                       
                                   
                                    
                                   weight 
                                    
                                   
                                       
                                   
                                    
                                   
                                     ( 
                                     mg 
                                     ) 
                                   
                                 
                               
                             
                           
                         
                       
                     
                   
                 
               
             
          
         
       
     
         [0096]    GC analysis was performed using Agilent GC 6890N series equipped with G188 Head space Auto sampler. Nitrogen was the carrier gas with flame ionized detector. 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 10 
               
               
                   
               
               
                 RESIDUAL MONOMER REPORT 
               
               
                 Product Poloxamer 
               
               
                 Batch No. FS09903-070 
               
               
                 A.R.No. A576683 
               
               
                   
               
             
             
               
                 System suitability: 
               
             
          
           
               
                 S. No. 
                 Monomer 
                 Wt. 
               
               
                   
               
               
                 1 
                 HEPTANE 
                 0.0218 
               
               
                 2 
                 THF 
                 0.0187 
               
               
                 3 
                 IPA 
                 0.0187 
               
               
                 4 
                 MAA 
                 0.0186 
               
               
                 4 
                 BHT 
                 0.0194 
               
               
                 5 
                 MEHQ 
                 0.0201 
               
               
                   
               
             
          
           
               
                   
                 HEPTANE 
                 THF 
                 IPA 
                 MAA 
                 BHT 
                 MEHQ 
               
               
                   
               
               
                 STD-1 
                 66.441 
                 33.875 
                 28.533 
                 28.222 
                 54.747 
                 32.643 
               
               
                 STD-2 
                 66.139 
                 33.923 
                 28.318 
                 27.711 
                 54.686 
                 35.663 
               
               
                 STD-3 
                 66.529 
                 34.366 
                 29.157 
                 27.212 
                 56.565 
                 33.533 
               
               
                 STD-4 
                 65.676 
                 33.979 
                 28.818 
                 27.631 
                 56.005 
                 37.052 
               
               
                 STD-5 
                 64.806 
                 33.774 
                 28.489 
                 27.215 
                 55.321 
                 31.885 
               
               
                 STD-6 
                 64.033 
                 33.563 
                 28.329 
                 26.93 
                 55.382 
                 34.797 
               
               
                 Average 
                 65.604 
                 33.91333 
                 28.60733 
                 27.48683 
                 55.451 
                 34.262 
               
               
                 Std. Dev 
                 1.00 
                 0.27 
                 0.32 
                 0.46 
                 0.73 
                 1.941 
               
               
                 % RSD 
                 1.52 
                 0.78 
                 1.14 
                 1.68 
                 1.31 
                 5.66 
               
               
                   
               
             
          
           
               
                   
                 AREA OF 
                   
                 % RESIDUALS 
                   
               
             
          
           
               
                   
                 RESIDUALS 
                 TS-1 
                 TS-2 
                 TS-1 
                 TS-2 
               
               
                   
                   
               
               
                   
                 HEPTANE 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
               
               
                   
                 THF 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
               
               
                   
                 IPA 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
               
               
                   
                 MAA 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
               
               
                   
                 BHT 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
               
               
                   
                 MEHQ 
                 N.D 
                 N.D 
                 N.D 
                 N.D 
               
             
          
           
               
                   
                 Total residuals 
                   
                 N.D 
                 N.D 
               
             
          
           
               
                   
                 Average 
                   
                 N.D 
               
               
                   
                   
               
               
                   
                 *TS—Test sample 
               
               
                   
                 **N.D—Not detected 
               
               
                   
                 Weight of test sample-1 (g) = 0.1001 
               
               
                   
                 Weight of test sample-2 (g) = 0.1005 
               
             
          
         
       
     
         [0097]    GC Calculation ( FIG. 40 ): 
         [0098]    High Molecular Component was Identified Using HPLC System: 
         [0099]    Chromatogram is given below. It is found that HMW component is not detected in this sample ( FIG. 41 ). 
         [0100]    GPC: 
         [0101]    GPC was performed using Agilent 1200 Series with Addon GPC software. PEG-PPg was used as the GPC standards ( FIG. 42  and  FIG. 43 ). 
         [0102]    Turbidity measurement of the Poloxamer 407 DM was measured in NTU units using HF Scientific Turbidity meter (Make): Model-Micro 100 Turbid meter. Solution was prepared in 10% water and THF. The turbidity in water showed 5 NTU and in THF 4 NTU. 
         [0103]    Methacrylic Acid Content: 
         [0104]    Titration method was followed. The Methacrylic acid content: 0.001% (for this sample). 
       Comparative Example 3 
     Prior Art Synthesis of Functionalized Surfactants 
       [0105]    6.00 g of PLURONIC F127 was placed in a round bottom flask and dried thoroughly via azeotropic distillation of toluene (100 ml). The round bottom flask was then fitted with a reflux condenser and the reaction was blanketed with Nitrogen gas. Anhydrous tetrahydrofuran (THF) (60 ml) was added to the flask and the reaction was chilled to 5° C. with 15 equivalents (based upon the hydroxyl end groups) of triethylamine (TEA) was added (2.0 ml). 1.4 ml of methacryloyl chloride (15 equivalents) was dropped into the reaction mixture through an addition funnel and the reaction mixture was allowed to warm to room temperature and then stirred overnight. The reaction mixture was then heated to 65° C. for 3 hours. Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was concentrated to a volume of around 355 mL and precipitated into cold heptane. Two further precipitations were performed to reduce the amount of TEA-HCl salt to less than 0.2% by weight. NMR analysis of the final polymer showed greater than 90% conversion of the hydroxyl end groups to the methacrylated end groups. 
       Example 4 
       [0106]    100 g of PLURONIC F-108 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 11.5 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 8.01 mL of freshly distilled methacryloyl chloride which was stabilized with 24 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0107]    Work Up: 
         [0108]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 5 
       [0109]    100 g of PLURONIC F-108 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of hydroquinone (HQ) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 11.5 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 8.01 mL of freshly distilled methacryloyl chloride which was stabilized with 24 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0110]    Work Up: 
         [0111]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 6 
       [0112]    100 g of PLURONIC F-127 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of phenothiazine (PTZ) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 13.6 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 9.5 mL of freshly distilled methacryloyl chloride which was stabilized with 28.5 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0113]    Work Up: 
         [0114]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 7 
       [0115]    100 g of PLURONIC F-68 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 19.78 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 13.95 mL of freshly distilled methacryloyl chloride which was stabilized with 41.8 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0116]    Work Up: 
         [0117]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 8 
       [0118]    100 g of PLURONIC P-105 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 25.73 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 18 mL of freshly distilled methacryloyl chloride which was stabilized with 54 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0119]    Work Up: 
         [0120]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 9 
       [0121]    100 g of PLURONIC F-108 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of phenothiazine (PTZ) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 11.5 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 8.01 mL of freshly distilled methacryloyl chloride which was stabilized with 24 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0122]    Work Up: 
         [0123]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 10 
       [0124]    100 g of PLURONIC L-101 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 43.9 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 30.84 mL of freshly distilled methacryloyl chloride which was stabilized with 92.5 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0125]    Work Up: 
         [0126]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 11 
       [0127]    100 g of PLURONIC F-108 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of phenothiazine (PTZ) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 11.5 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 8.01 mL of freshly distilled methacryloyl chloride which was stabilized with 24 mg of hydroquinone (HQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0128]    Work Up: 
         [0129]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 12 
       [0130]    100 g of PLURONIC F-127 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 13.6 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 9.5 mL of freshly distilled methacryloyl chloride which was stabilized with 28.5 mg of hydroquinone (HQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0131]    Work Up: 
         [0132]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 13 
       [0133]    100 g of PLURONIC F-127 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of phenothiazine (PTZ) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 13.6 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 9.5 mL of freshly distilled methacryloyl chloride which was stabilized with 28.5 mg of hydroquinone (HQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0134]    Work Up: 
         [0135]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 14 
       [0136]    100 g of PLURONIC F-38 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 35.54 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 24.93 mL of freshly distilled methacryloyl chloride which was stabilized with 74.8 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0137]    Work Up: 
         [0138]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 15 
       [0139]    100 g of PLURONIC F-127 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of hydroquinone (HQ) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 13.6 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 9.5 mL of freshly distilled methacryloyl chloride which was stabilized with 28.5 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0140]    Work Up: 
         [0141]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 16 
       [0142]    100 g of PLURONIC F-108 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 11.5 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 8.01 mL of freshly distilled methacryloyl chloride which was stabilized with 24 mg of phenothiazine (PTZ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0143]    Work Up: 
         [0144]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 17 
       [0145]    100 g of PLURONIC F-108 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 11.5 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 8.01 mL of freshly distilled methacryloyl chloride which was stabilized with 24 mg of hydroquinone (HQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0146]    Work Up: 
         [0147]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 18 
       [0148]    100 g of PLURONIC F-127 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 13.6 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 9.5 mL of freshly distilled methacryloyl chloride which was stabilized with 28.5 mg of phenothiazine (PTZ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0149]    Work Up: 
         [0150]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 19 
       [0151]    100 g of PLURONIC P-123 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 28.99 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 20.78 mL of freshly distilled methacryloyl chloride which was stabilized with 61.14 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0152]    Work Up: 
         [0153]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum 
       Example 20 
       [0154]    100 g of PLURONIC F-87 was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 di tert-butyl 4 methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 21.57 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 15.21 mL of freshly distilled methacryloyl chloride which was stabilized with 45.6 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0155]    Work Up: 
         [0156]    The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum. 
       Example 21 
       [0157]    100 g of Tetronic 1107 (Poloxamine) was placed in a round bottom flask fitted with reflex condenser and the reaction was blanketed with nitrogen gas Anhydrous tetrahydrofuran (THF; 700 mL) stabilized with 1050 mg of 2,6 ditert-butyl-4-methyl phenol (BHT) was added to the flask and heated to 30° C. under stirring till it formed a clear solution. 11.21 mL of triethylamine (TEA) was added to the above solution and the stirring continued. To this was added drop wise 7.81 mL of freshly distilled methacryloyl chloride which was stabilized with 23.42 mg of Hydroquinone monomethyl ether (MEHQ) at 30-32° C. through an addition funnel. The reaction mixture was heated to 63° C. upon stirring with nitrogen gas for 3 hours. Then the reaction mass was cooled for 12 h at RT. 
         [0158]    Work Up: The Precipitated salt (TEA-HCl) was filtered from the reaction mixture and the filtrate was treated with 50 g of Basic alumina under stirring for 30 minutes and filtered. The filtrate was treated with 50 g of basic resin (PUROLITE) under stirring for 30 minutes and filtered through celite bed. The filtrate was concentrated to remove 233 mL of THF to get 467 mL of mass. The mass was precipitated into 3200 mL of n-heptane. The precipitate was filtered and dried at 45° C. under high vacuum.