Abstract:
The present invention provides a unique and novel way of producing carbinols such as 4-hydroxyphenylmethylcarbinol (HPMC). In this new process, a ketone such as 4-hydroxyacetophenone (4-HAP) is heated under suitable hydrogenation conditions of temperature and pressure in the presence of a suitable catalyst and a basic material, and for a sufficient period of time to form HPMC.

Description:
RELATED APPLICATIONS 
     This patent application is a continuation-in-part of Commonly assigned patent application Ser. No. 08/529,931 filed Sep. 18, 1995, now abandoned which is a continuation-in-part patent application of Ser. No. 08/406,350 filed Mar. 17, 1995, now U.S. Pat. No. 5,498,804. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a process for the production of 4-hydroxyphenylmethylcarbinol (HPMC) [sometimes referred to as 1-(4-hydroxyphenyl)ethanol-( 1,4-HPE)]by the hydrogenation of 4-hydroxyaeetophenone (4-HAP). 
     2. Description of the Prior Art 
     It is known in the art to produce 4-hydroxystyrene (HSM) and derivatives thereof such as poly(4-hydroxystyrene) (PHS), which have applications in the production of adhesives, coating compositions, photoresists, and the like. In the PHS area, there is a need to produce such material in the least amount of process steps in order to provide efficiency. The prior art has utilized a five-step process in order to produce PHS. We have now found that PHS can be produced in three steps or less. 
     The following prior art references are disclosed in accordance with the terms of 37 CFR 1.56, 1.97, and 1.93. 
     U.S. Pat. No. 5,087,772 (issued Feb. 11, 1992) discloses the preparation of HSM by reacting 4-acetoxystyrene (ASM) with a suitable alcohol in the presence of a catalytic amount of a suitable base. 
     European Patent Application No. 0-128-984 (publication no.), filed Aug. 30, 1983, discloses a process for the production of para-vinyl phenol (HSM) by dehydrogenation of para-ethyl phenol. 
     European Patent Application No. 0-108-624 (publication no.), filed Nov. 4, 1983, discloses a process for the production of p-vinyl phenol polymer (polyhydroxystyrene polymer - PHS) by polymerizing p-vinyl phenol (HSM) in the presence of water and iron. 
     U.S. Pat. No. 4,032,513 (issued Jun. 28, 1977) discloses a process of producing PHS by cationically polymerizing HSM in the presence of a nitrile, such as CH 3  CN, using a cationic polymerization initiator in a homogeneous reaction system. 
     U.S. Pat. No. 5,041,614 discloses a method for the preparation of 4-acetoxystyrene (ASM) from 4-acetoxyphenylmethylcarbinol. (Note Formula I for the structural formula for ASM). 
     U.S. Pat. No. 5,084,533 discloses a process for the neat hydrogenation of 4-acetoxyaceto-phenone in the production of 4-acetoxystyrene (ASM). 
     U.S. Pat. No. 5,151,546 discloses a process for preparing 4-acetoxystyrene (ASM) by heating 4-acetoxyphenylmethylcarbinol with an acid catalyst. 
     U.S. Pat. No. 5,245,074 discloses a process for preparing 4-acetoxystyrene (ASM) through the 4-acetoxyacetophenone/4-acetoxyphenylmethylcarbinol route. 
     U.S. Pat. No. 5,247,124 discloses a process for preparing substituted styrenes such as ASM by reacting a bisarylalkyl ether in the presence of an acid catalyst. 
     J. Org. Chem., (1954), 19, 1205, discloses the use of copper chromite catalysts in the hydrogenation of ketones. 
     Other prior art references which relate to the present invention include U.S. Pat. Nos. 2,276,138; 3,547,858; 4,544,704; 4,678,843; 4,689,371; 4,822,862; 4,857,601; 4,868,256; 4,877,843; 4,898,916; 4,912,173; 4,962,147; 4,965,400; 4,880,487; 5,264,528; 5,342,727; and U.S. Pat. No. Re. 34,122. 
     All of the above-cited prior art and any other references mentioned herein are incorporated herein by reference in their entirety. 
     SUMMARY OF THE INVENTION 
     The present invention provides a unique and novel way of producing 4-hydroxy-phenylmethylcarbinol (HPMC). In this new process, 4-hydroxyacetophenone (4-HAP) is heated under suitable hydrogenation conditions of temperature and pressure in the presence of a suitable palladium catalyst and for a sufficient period of time to form the HPMC. Subsequently, HPMC can be dehydrated and polymerized to form PHS. 
     DETAILED DESCRIPTION OF THE INVENTION 
     In the overall scheme of preparing PHS in a limited number of process steps, it has been unexpectedly found that the intermediate product, i.e. 4-hydroxymethylcarbinol (HPMC) can be efficiently prepared by hydrogenating 4-hydroxyacetophenone (4-HAP) under certain conditions. Specifically, it has been found that 4-HAP can be heated under suitable hydrogenation conditions of temperature and pressure in the presence of a suitable palladium catalyst and for a sufficient period of time to form HPMC in relatively high yields. The heating is conducted at a temperature of at least about 20° C., preferably from about 20° C. to about 100° C., in the presence of at least a stoiehiometric amount of hydrogen and a catalyst selected from the group consisting of Pd/C; Pd/Al 2  O 3  ; Pd/SiO 2  ; and Pd/CaCO 3 . 
     In a preferred embodiment, the reaction is conducted until a substantial completion of hydrogenation is indicated by a lack of H 2  uptake, normally about one to twelve hours. 
     In a preferred embodiment, when Pd/C is used, the reaction proceeds at a pressure of from about 14.7 psig to about 5,000 psig, more preferably at a pressure of from about 50 psig to about 500 psig, and most preferably at a pressure of from about 100 psig to about 400 psig. 
     The hydrogenation conditions also include the use of a suitable solvent/diluent. Diluents/solvents which can be used in the present invention include: (a) water; (b) hydrocarbons such as benzene, toluene, xylene, and low-boiling point petroleum fractions; (c) inorganic gases such as carbon monoxide, carbon dioxide, nitrogen, helium, and argon; (d) dipolar protic or aprotic solvents; and (e) mixtures thereof. The dipolar aprotie solvents employed are solvents which have a high dielectric constant and a high dipole moment but no acid hydrogen atoms; for example, such solvents include dimethylsulfoxide (DMSO), acetonitrile, dimethylformamide (DMF), dimethylacetamide, hexamethylphosphoric acid triamide (HMPT), and n-methyl pyrrolidone (NMP). Solvents such as ethanol, methanol, or tetrahydrofuran (THF) may be used alone or in combination with the preceding solvents/diluents. Water, ethanol, methanol, benzene, and toluene (and mixtures thereof) are preferred diluents. The diluents are used in an amount of 2 to 200 mols, preferably 3 to 20 mols per mol of 4-HAP. It is to be understood that any diluent may be used under any temperature and reaction conditions so long as the hydrogenation of 4-HAP is effected smoothly. 
     The amount of catalyst employed is that which is catalytically effective in promoting the reaction. Usually, this amount is from about 0.001 weight percent to about 10.0 weight percent based on the weight of the starting material, i.e. 4-HAP. 
     The length of time which this heating/hydrogenation (reaction) step is conducted is not critical and the only requirement is that the heating be conducted for a period sufficient to form HPMC. Generally, this period is at least five minutes and may be as long as 25 hours, generally from about one to about twelve hours. 
     After the hydrogenation of 4-HAP, the end product (HPMC) is recovered from the reaction product and the residual fraction containing any unreacted 4-HAP can be recycled as the starting material for the next cycle of hydrogenation. The end product (HPMC) may be recovered from the reaction product by any method. One example is to recover the HPMC as a polymerized product, i.e. the reaction product is first subjected to a decomposition and a polymerization step to polymerize the HPMC to the resulting polymer--polyhydroxystyrene (PHS). 
     The following specific example is supplied for the purpose of better illustrating the invention. This example is not intended, however, to limit or restrict the scope of the invention in any way and should not be construed as providing conditions, parameters, or values which must be utilized exclusively in order to practice the present invention. 
     While the above has been described using 4-hydroxyacetophenone (4-HAP) as the starting material, it is also within the scope of the present invention to use (1) other hydroxyacetophenones (wherein the hydroxy substituents are positioned at different locations on the phenyl ring), and (2) substituted hydroxyacetophenones wherein the remaining four hydrogen atoms (on the phenyl ring) are selectively replaced by an R group, said R being selected from the group consisting of (a) C 1  -C 8  alkyl; (b) C 6  H 5  ; (c) halogen (F, Cl, Br, I); (d) hydroxy; and (e) OR where R is the same as defined above. These hydroxyacetophenones and substituted hydroxyacetophenones are all suitable starting materials for use in the present invention process. The resultant product will be a hydroxyphenylcarbinol or substituted hydroxyphenylcarbinol (&#34;carbinol&#34;). 
     In another facet of the present invention, it was also found that the utilization of a basic material in the hydrogenation step results in substantial increases in the selectivity to the desired product, i.e. the carbinol. The basic material is selected from the group consisting of (a) alkali metal hydroxides (e.g. NaOH, KOH); (b) alkaline earth metal hydroxides (e.g. Ca(OH) 2  ; (c) alkali metal carbonates (e.g. K 2  CO 3 ); (d) alkali metal alkoxides (e.g. NaOCH 3  and KOC(CH 3 ) 3 ); (e) alkali metal organic acid salts (e.g. an ionic organic base such as potassium acetate); and (f) amines (a non-ionic organic base) such as pyridine or a tri-lower-alkylamine (e.g. tripropylamine, trimethylamine, and triethylamine). Such basic material is present in any amount which will achieve the desired end result. Thus, an effective amount will be at least 1 ppm (part per million), preferably from about 1 ppm to about 10,000 ppm, more preferably from about 25 ppm to about 1,000 ppm. The exact mechanism is not known, however it was surprising to find that such addition of the basic material to the hydrogenation step resulted in significant increases in selectivity. 
    
    
     EXAMPLE I 
     Hydrogenation of 4-Hydroxyacetophenone 
     4-Hydroxyacetophenone (13.6 g, 0.1 mol) was charged in a 500 ml Zipper autoclave reactor, absolute alcohol (100 ml), and 5% Pd/C (Johnson Matthey&#39;s 21R) (1.2 g) was added. The autoclave was first checked for leaks with 100 psig of nitrogen. The autoclave was later pressurized to 300 psig with hydrogen and stirred at 35° C. for three hours. During this time, 0.095 mole of hydrogen was consumed (95% of the theoretical value). The reaction was vented and the contents filtered through a millipore filter yielding a colorless solution. Concentration of this solution in vacuo gave a solid. Traces of ethanol were removed via azeotropic distillation with toluene to afford a white solid (13.8 g). Liquid chromatographic analysis of the product showed 1,4-HPE (or HPMC) (99.0%), 4-HAP (0.2%), and 4-EP (ethylphenol) (0.8%).  1  H NMR spectrum of the product showed it to be mainly 1,4-HPE, with traces of 4-HAP. 
     EXAMPLES II-XII 
     Using the same procedure set forth in Example I, Examples II-XII were carried out using different reaction conditions as outlined in Table 1. The results are shown in Table 1. 
     
                                           TABLE 1__________________________________________________________________________ANALYTICAL              REACTION CONDITIONSExam-    ex. std        RUN  4-HAP                       CATALYST TYPE                                 SOLVENT/ H.sub.2ple No.    HPMC   4-HAP       HSM EP TIME (g.)                       &amp; AMOUNT  AMOUNT   ADDED                                               COMMENTS__________________________________________________________________________II  84.79   11.08       0.00           0.57              1.6 HRS                   12.0                       0.6 g. 5% Pd/C                                 48 g.                                     MeOH 227  45° C., white                                               crystalsIII 74.11   0.33       0.00           16.00              1.1 HRS                   18.0                       1.3 g. 5% Pd/C                                 42 g.                                     MeOH 323  55° C., white                                               crystalsIV  83.33   0.00       0.00           10.60              3.2 HRS                   6.0 0.2 g. 5% Pd/C                                 54 g.                                     MeOH 108  35° C., white                                               crystalsV   35.97   48.96       5.97           2.46              2.0 HRS                   6.9 0.6 g. 5% Pd/C                                 51 g.                                     EtOH 270  35° C., RXN                                               PSI 300,                                               white crystalVI  47.30   41.48       5.22           2.64              1.0 HRS                   6.0 0.6 g. 5% Pd/C                                 51 g.                                     EtOH **** 35° C., RXN                                               PSI 300,                                               white crystalVII 78.95   0.00       0.00           16.57              3.0 HRS                   6.0 0.6 g. 5% Pd/C                                 50 g.                                     MeOH **** 35° C., RXN                                               PSI 300,                                               white crystalVIII               2.5 HRS                   6.0 0.6 g. 5% Pd/C                                 45.5 g.                                     MeOH/                                          740  81° C., RXN                                               PSI 300,                                 5.6 g.                                     H.sub.2 O liquid after rotovapIX  86.90   0.00       *** 10.11              2.0 HRS                   8.0 0.4 g. 5% Pd/C                                 53.4 g.                                     MeOH 780  35° C., RXN                                               PSI 300,                                               white crystalX   81.36   0.86       *** 3.55              2.0 HRS                   8.0 0.2 g. 5% Pd/C                                 53.4 g.                                     MeOH 530  35° C., RXN                                               PSI 300,                                               white crystalXI  28.52   69.22       *** 2.26              4.0 HRS                   20.0                       1.0 g. 5% Pd/C                                 40 g.                                     MeOH 390  35° C., RXN                                               PSI 300,                                               white crystalXII                4.5 HRS                   20.0                       1.0 g. 5% Pd/C                                 39.9 g.                                     MeOH 1140 35° C., RXN                                               PSI 300,                                               white__________________________________________________________________________                                               crystal 
    
     EXAMPLE XIII 
     Synthesis of 4-Hydroxyphenylmethylcarbinol 
     To a five-gallon stainless steel reactor, a solution of 4-hydroxyacetophenone (2500 g, 18.4 moles) and a 25% solution of sodium methoxide in methanol (39.1 g, 0.26 moles) in methanol (10,000 g, 312.5 moles), and palladium on carbon catalyst (ESCAT 10, 125 g) were charged. The reactor is purged three times with nitrogen (100 psi). Hydrogen is then charged to a pressure of 300 psi and the reactor is heated to 45° C. The temperature is maintained at 45° C. for three hours at a constant hydrogen pressure of 500 psi. The reactor is cooled to 30° C. and then discharged (12,245 g). The analysis of the solution gave a conversion of 97.6% and a selectivity of 96.0% (note Table 2). 
     EXAMPLES XIV-XXII 
     Example XIII was repeated nine times using the conditions set forth in Table 2. The results are shown in Table 2. 
     The results of these Examples XIII-XXII are compared to those of Examples I-XII (i.e. without the use of a basic material) and it can readily be seen that the use of a basic material surprisingly results in a significant increase (e.g. Example VI-47.30% HPMC vs. Example XV-86.4% HPMC) in selectivity of the HPMC. 
     
                                           TABLE 2__________________________________________________________________________Temp    Pressure         %   % CatalystExample°C.    psig 4-HAP             vs 4-HAP                   Conversion                         Selectivity                               Yield__________________________________________________________________________XIII 45  500  20  5     97.6  96.0  93.7XIV  35  300  10  3     92.7  96.4  89.4XV   55  300  30  3     99.2  86.4  85.7XVI  35  700  10  7     99.6  93.8  93.4XVII 45  500  20  5     99.4  88.8  88.3XVIII55  700  10  3     92.1  95.5  88.0XIX  35  700  30  3     99.4  93.5  92.9XX   35  300  30  7     98.2  98.0  96.2XXI  55  300  10  7     99.3  93.9  93.2XXII 45  500  20  5     98.4  96.9  95.3__________________________________________________________________________ 
    
     EXAMPLE XXIII 
     Hydrogenation of 4-Hydroxyacetophenone 
     4-Hydroxyacetophenone (13.6 g, 0.1 mol) was charged in 500 mL Zipper autoclave reactor, absolute alcohol (100 mL), the indicated amount (Table 3) of Et 3  N (triethylamine), and 5% pd/C (Johnson Matthey&#39;s 21R) (1.2 g) was added. The autoclave was first checked for leaks with 100 psig of nitrogen. The autoclave was later pressurized to 300 psig with hydrogen and stirred at 35° C. for three hours. During this time, 0.095 mole of hydrogen was consumed (95% of the theoretical value). The reaction was vented and the contents filtered through a millipore filter yielding a colorless solution. Concentration of this solution under vacuum gave a solid. Traces of ethanol were removed via azeotropic distillation with toluene to afford a white solid (13.8 g). Liquid chromatographic analysis of the product showed 97.8% conversion and 99.2% selectivity to 4-HPMC.  1  H NMR spectrum of the product showed it to be mainly 4-HPMC with traces of 4-HAP. The results are shown in Table 3. 
     Example XXIII was repeated four times using the conditions set forth in Table 3. The results are shown in Table 3. 
     
                                           TABLE 3__________________________________________________________________________HYDROGENATION OF 4-HYDROXY ACETOPHENONE (4-HAP) TO4-HYDROXYPHENYLMETHYLCARBINOL (4-HPMC)Example 4-HAP            (Additive)  H.sub.2 Press.                                   Convrs.                                        Selectivity                                                     4-HPMCNo.   (mole)     Solvent          Catalyst (g)                  (mole) t,h                            t,C                              psig %    4-HPMC                                             4-EP                                                 4-VPM                                                     Yield__________________________________________________________________________                                                     %XXIV  0.1 Ethanol          5% Pd/C.sup.a (1.0)                  Et.sub.3 N (0.01)                         3.3                            50                              100  55.2 83.5 0.0 3.6 46.1XXV   0.1 Ethanol          5% Pd/C.sup.a (1.0)                  Et.sub.3 N (0.005)                         3.5                            50                              150  91.4 86.5 0.0 0.9 84.2XXVI  0.1 Ethanol          5% Pd/C.sup.a (1.3)                  Et.sub.3 N (0.005)                         5.0                            40                              200  74.9 93.7 0.0 0.4 80.4XXVII 0.1 Ethanol          5% Pd/C.sup.a (1.2)                  Et.sub.3 N (0.005)                         4.0                            35                              250  99.4 87.3 0.0 0.6 87.5__________________________________________________________________________ .sup.a Johnson Matthey&#39;s 21R catalyst lot no. 8D4906 was used. 
    
     Although the invention has been illustrated by the preceding examples, it is not to be construed as being limited thereby; but rather, the invention encompasses the generic area as hereinbefore disclosed. Various modifications and embodiments can be made without departing from the spirit and scope thereof.