Abstract:
A novel process for producing fluorinated organic compounds containing a difluoromethylene group, essentially characterized by reacting organic compounds containing a carbonyl function with molybdenum hexafluoride at room temperature and under atmospheric pressure.

Description:
FIELD OF INVENTION 
     This is a continuation of application Ser. No. 533,272, filed Dec. 16, 1974, now abandoned, which in turn is a Continuation-in-Part of copending application Ser. No. 185,362 filed Sept. 30, 1971, now U.S. Pat. No. 3,878,246. 
    
    
     The present invention relates to a new process for fluorinating organic compounds containing at least one ketone or aldehyde group in order to produce fluorinated organic compounds containing a difluoromethylene group. The present invention also relates to procedures for preparing substituted α,α-difluoroalkylbenzene compounds as well as to the compounds resulting from same. 
     BACKGROUND 
     Fluorinated organic compounds are well known and in recent years have gained technical importance in view of their particular chemical and physical properties such as good thermal resistance and resistance to oxidation. They are also in great demand in pharmaceutical chemistry. For these reasons, simple and economical processes have been sought for obtaining these products. 
     The fluorination processes up to the time of parent application Ser. No. 185,362, now U.S. Pat. No. 3,878,246 used reagents which are highly toxic or not easily obtainable, or which may even require the use of special equipment. They often lead to secondary polymerization and decomposition reactions. In particular, fluorination of carbonyl groups into difluoromethylene groups can be performed by the use of the reagent SF 4  (see U.S. Pat. No. 2,859,245). In addition to the fact that SF 4  is an extremely toxic gas, the process is difficult to perform. In fact, the solid or liquid reagents must be fed into a hastelloy autoclave under an atmosphere of nitrogen; thereafter one must cool to -80° C., sweep the gases, introduce SF 4 , react the mixture at the desired temperature (approx. 100° C.) under autogenous pressure, then cool to -80° C. and finally open the autoclave. The products are then separated. Moreover, it should be pointed out that there is a significant loss of the reagent SF 4  the molar excess of which is between 1.5 and 4 or even more. 
     SUMMARY 
     In parent application Ser. No. 185,362, the subject matter of which is hereby incorporated by reference, there is described a process of preparing fluorinated organic compounds that contain the difluoromethylene group, from compounds that contain at least one ketone or aldehyde group. This process, which is applicatle to the production of the compounds of the present invention, comprises reacting the organic starting compounds containing the ketone or aldehyde function with molybdenum hexafluoride, at ambient temperature and at atmospheric pressure and in anhydrous solvent medium in the presence of BF 3  or any other fluoride ion acceptor of the strong Lewis acid type. 
     There are various types of compounds which may be fluorinated in accordance with such process. In most of the examples of the parent application Ser. No. 185,362, there are no other functional groups in the organic starting compound to react with the MoF 6  except the ketone or aldehyde group desired to be fluorinated. 
     It is an object of the present invention to provide compounds of the substituted α,α-difluoroalkylbenzene type of the formula ##STR1## wherein X&#39; designates a substituent inert with respect to MoF 6 . 
     But there are also various types of compounds which cannot be fluorinated in accordance with such process e.g. compounds containing, besides the ketone or aldehyde groups, other functional group reacting with MoF 6 . 
     It is therefore another object of the invention to provide a process for preparing new compounds of the substituted α,α-difluoroalkylbenzene type of the formula ##STR2## wherein X designates a substituent which reacts with MoF 6 . 
     In such a case the starting compound cannot be: ##STR3## because reaction with MoF 6  would yield in a complex and unseparable mixture of various fluorinated products. 
     Now the applicants have solved this problem by choosing a starting compound of the formula ##STR4## wherein Y is such that: 
     (1) It does not react with MoF 6  so that the fluorination step leads to the product ##STR5## 
     (2) It allows the conversion of Y to X without altering the remaining part of the molecule i.e. it allows to perform the reaction: ##STR6## 
     Thus, one obtains the desired product which could not be prepared in a single step process. 
     The above mentioned objects are achieved in accordance with this invention by reacting, the starting organic compound with substantially anhydrous molybdenum hexafluoride as fluorinating agent, under substantially anhydrous conditions, in solution in a solvent inert with respect to the reactants, in a glass vessel at a temperature of about -20° C. to about +40° C. conveniently under atmospheric pressure and under an inert atmosphere, the molar ratio of MoF 6  to (C═O) group being about 1; and then, as the case may be, converting the product of the fluorination reaction II to the desired product (I) containing a group X which would have reacted with MoF 6  during the fluorination. 
     The new compounds of the type mentioned above are stable and can be used especially as intermediate products in organic synthesis, in particular in the field of pharmaceutical industry. It is in fact well known that modern sophisticated pharmaceuticals often contain fluorinated groups so that the products of the above type are potentially interesting. But these pharmaceuticals are outside the scope of the present invention. 
     According to the invention, the compounds correspond to the generic formula: ##STR7## where X, which may be situated in ortho, meta or para position, and preferably in the para or meta position, is --CN, --NO 2 , --F, --Cl, --COOH, --COCl, --CH 2  OH, --CONH 2 , --CHO, ##STR8## --COOR&#39;, --CONR&#39; 2 , CO--R&#34;, --NHCOOR&#39;, --CH 2  NH 2 , --COO(CH 2 ) n  NR&#39; 2  ; n is 2 or 3; R&#39; is an alkyl or aryl radical, preferably lower alkyl or phenyl; R&#34; is a heterocyclic amine of morpholine type; R is an alkyl or aryl group, preferably lower alkyl or phenyl, and may also be hydrogen in the case where X does not represent --NO 2 , --F, --Cl, --COOR&#39;, --CHO, --NHCOOR&#39;, or ##STR9## 
     It has actually been discovered that the substituent X, in this type of compound, leads to stabilization of the molecule and, for this purpose, it preferably consists of an electrophilic group. 
     When the desired compound ##STR10## contains an X group which reacts with the MoF 6 , the starting compound choosen is ##STR11## wherein Y is selected so that it can easily be later converted into X by these conventional methods of organic synthesis which do not affect the remaining part of the molecule. 
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
     The organic compounds used in the present process at the fluorination stage are all ketones and aldehydes whether aliphatic, cyclic or aromatic the only condition at this stage being that the molecule concerned does not contain any other group capable of reacting with MoF 6 . The groups capable of reacting with MoF 6  are Lewis bases (basic ethers, amines, groups with ethylenic or acetylenic bonds), or groups possessing labile hydrogen atoms (acids, alcohols, phenols, primary and secondary amides and the like). Indeed MoF 6  is a rather strong Lewis acid and thus will react with Lewis bases. 
     MoF 6  is also an oxidizing agent and like the higher halides of Mo, W and the like, it is readily hydrolized; accordingly it will react with double or triple carbon-carbon bonds and with compounds having labile hydrogen atoms as previously mentioned. 
     In the case of preparing substituted α,α-difluoroalkylbenzenes, wherein the substituent is a --CONH 2  or --COOH group, the process of the invention consists in preparing first of all the corresponding fluorinated cyanated compound, in anhydrous medium, by means of the abovementioned fluorination process, which is followed by the hydrolysis of such compound in alkaline medium. The total hydrolysis followed by an acidification of the medium leads to a --COOH carboxylated compound, while the partial hydrolysis in alkaline medium leads to a --CONH 2  aminated compound. 
     In the case of the preparation of substituted α,α-difluoroalkylbenzenes wherein the substituent is a --COCl, the process of the invention consists in reacting the --COOH compound described above with thionyl chloride at 60° C. for 2 hours, evaporating the excess of SOCl 2  then distilling the residue. 
     In the case of the preparation of substituted α,α-difluoroalkylbenzenes wherein the substituent is a --CONR&#39; 2  group, the process of the invention consists in reacting the acid chloride described above with double the theoretical amount of secondary amine R&#39; 2  NH. There is formed a precipitate of the amine chlorhydrate insoluble in the organic solvent; e.g. ether. The precipitate is filtered and the organic solvent is evaporated. The evaporation leads to the production of the sought amidated --CONR&#39; 2  derivative. 
     In regard to the preparation of substituted α,α-difluoroalkylbenzene derivatives wherein the substituent is a --CHO group, the process of the invention consists in reacting a cyanated derivative as described above with an aluminum hydride, e.g. LiAlH(OC 2  H 5 ) 3 , hydrolyzing the mixture with 6 N sulfuric acid and evaporating the organic solvent, e.g. ether, in order to obtain the sought aldehydic --CHO derivative. 
     In order to obtain the substituted α,α-difluoroalkylbenzene derivatives wherein the substituent is a --NHCOOR&#39; group, the process consists in reacting the corresponding amide with bromine and an alcohol in alkaline alcoholate medium. 
     In order to obtain the substituted α,α-difluoroalkylbenzene derivates wherein the substituent is a --CH 2  OH group, the corresponding acid is reacted with LiAlH 4 . 
     In order to obtain the substituted α,α-difluoroalkylbenzene derivatives wherein the substituent is a CH 2  NH 2  group, the corresponding nitrile is reacted with LiAlH 4  in excess. 
     For the amino esters of the type ##STR12## COO(CH 2 ) n  CONR&#39; 2 , the acid ##STR13## is reacted with ClCOO(CH 2 ) n  NR&#39; 2 , n being 2 or 3. 
     In regard to preparing the substituted α,α-difluorotoluene derivatives, the basic molecule is the ortho, meta, para α,α-difluoromethylbenzonitrile which, through the ordinary processes that are mentioned above, leads to the following derivatives: ##STR14## 
     The general reactions for producing the compounds of the invention are summarized below, 
     (a) for X equals --CN, --NO 2 , --F, --Cl, --COOR&#39;, and ##STR15## and R equals alkyl or aryl, the reaction is: ##STR16## and for X equals --CN and R equals H the reaction is: ##STR17## 
     (b) for X equals --COOH or --CONH 2  ; and R equals alkyl or aryl, the reaction is: ##STR18## 
     (d) for X equals COCl and R equals H, alkyl or aryl, the reaction is: ##STR19## 
     (e) for X equals CHO and R equals alkyl or aryl, the reaction is: ##STR20## 
     (f) for X equals --CONR&#39; 2  and R equals H, alkyl or aryl, the reaction is: ##STR21## 
     (g) for X equals NHCOOR&#39; and R equals alkyl or aryl, the reaction is: ##STR22## 
     (h) for X equals CH 2  OH and R equals H, alkyl or aryl, the reaction is: ##STR23## 
     (i) for R equals H, alkyl or aryl; and X equals CH 2  NH 2 , the reaction is: ##STR24## 
     (j) for R equals H, alkyl or aryl; and X equals COO(CH 2 ) n  NR&#39; 2  and where n is 2 or 3, the reaction is: ##STR25## 
     The molybdenum hexafluoride used as reagent during the fluorination stage can be prepared by any of the methods described in various papers, such as, for example, that of O. RUFF and E. ASHER (Z. ANORG. ALLG. CHEM. 196, 418, 1931) which involves the direct combustion of molybdenum in fluorine. Molybdenum hexafluoride is liquid at room temperature (b.p. 35° C. at atmospheric pressure); consequently it is very easy to use. 
     The solvent used for the fluorination stage is selected such that separation of the reagents and reaction products is maximized. The preferred solvent used is methylene chloride. 
     With regard to the preparation of compounds containing groups (X&#39;) not reactive with MoF 6 , these are prepared directly by the MoF 6  reaction without later conversion. 
     The following series of new compounds have been thus obtained: 
     
                       TABLE 1______________________________________R                 X&#39;______________________________________CH.sub.3          p . ClCH.sub.3          p . CNCH.sub.3          p . CO.sub.2 C.sub.2 H.sub.5CH.sub.3              ##STR26##CH.sub.3          p . FCH.sub.3          o . p . and m . NO.sub.2CH.sub.3          m . CNC.sub.2 H.sub.5   p . CNphenyl            p . CNH                 p . and m . CN______________________________________ 
    
     With reference to formulas (I) and (III) above, the following series of new compounds have been produced: 
     
                       TABLE 2______________________________________R           X               Initial Y______________________________________CH.sub.3 p . COOH           p . CNCH.sub.3 p . CONH.sub.2     p . CNCH.sub.3 p . NH . COOCH.sub.3                       p . CNCH.sub.3 p . CHO            p . CNCH.sub.3 m . CO . OH        m . CNCH.sub.3 p . COCl           p . CNCH.sub.3 p . CH.sub.2 OH    p . CNCH.sub.3 p . CH.sub.2 NH.sub.2                       p . CNH        p . CH.sub.2 NH.sub.2                       p . CNH        m . COOH           m . CNCH.sub.3 p . CO--N(CH.sub.2).sub.4 O                       p . CNCH.sub.3 p . COO(CH).sub.2 N(i-C.sub.3 H.sub.7).sub.2                       p . CNH        p . COOH           p . CN______________________________________ 
    
     The following examples are given merely by way of an illustration and are in no way intended to limit the invention. The starting materials in these examples have been selected from aromatic aldehydes or ketones according to the definition given above in order to show the applicability of the instant process. 
    
    
     EXAMPLE 1 
     para-alpha, alpha-difluoroethyl-nitrobenzene 
     200 ml of CH 2  Cl 2  freshly distilled over P 2  O 5 , 17 ml of MoF 6  (i.e. 0.2 mole) were introduced into a 500 ml flask equipped with a stirrer, a gas-inlet, a condenser and a drop funnel. The resulting yellow solution was cooled to 0° C. A slight stream of BF 3  gas was passed through the mixture and is maintained during the reaction. The mixture is then cooled to -15° C. and 34 gm of p-CH 3  COC 6  H 4  NO 2  (0.2 mole) in 100 ml of methylene chloride (MoF 6  /CO group molar ratio=1) were introduced dropwise. 
     The solution became dark red. The temperature of the solution was allowed to rise to room temperature. It was then treated with 20 gm of dry NaF and stirred during one hour. It was filtered. The filtrate, the colour of which was blue was discoloured by stirring with SiO 2 . The solution was evaporated and the resulting yellow residue submitted to chromatographic separation on a column of gel of silica in order to separate the constituents. Benzene is used as eluent. At the top of the column a product of the formula: ##STR27## is recovered with a yield of 41%. 
     m.p.=48° C. 
     
         ______________________________________Analysis    C          H          F______________________________________calculated  51.33%     3.74%      7.48%found       50.83%     3.81%      7.25%______________________________________ 
    
     EXAMPLE 2 
     para-alpha, alpha-difluoroethyl-cyanobenzene 
     150 ml of dry CH 2  Cl 2  and 6 ml of MoF 6  (0.07 mole) were introduced into a 250 ml flask equipped with a stirrer, a gas-inlet, a condenser and a drop funnel. The solution was cooled to 0° C. and a slight stream of BF 3  gas was passed through it. The solution was then cooled to -15° C. and 15.8 gm of p-CH 3  COC 6  H 4  CN in 50 ml of dry CH 2  Cl 2  (MoF 6  /CO group molar ratio=1) were introduced. The solution became red. Its temperature was then allowed to rise to room temperature and it was treated with 20 gm of dry NaF and the resulting blue solution was discoloured using SiO 2 . After evaporation, the resulting residue can be either chromatographed on a column (gel of silica with CH 2  Cl 2  as eluent) or distilled. 
     A yield of 42% of a product of formula ##STR28## was obtained 
     b.p. 02  =49° C. 
     
         ______________________________________Analysis    C          H          F______________________________________Calculated  64.67%     4.19%      8.39%found       64.42%     4.02%      7.81%______________________________________ 
    
     EXAMPLE 3 
     meta-alpha, alpha-difluoroethyl-nitrobenzene 
     Example 1 was repeated with 12 ml of MoF 6  and 24 gm of m-CH 3  -COC 6  H 4  NO 2  (MoF 6  /CO group molar ratio=1). After chromatographic separation on the column of gel of silica (benzene as eluent) a product of formula: ##STR29## was obtained with a yield of 15%. 
     m.p.=48° C. 
     
         ______________________________________Analysis    C          H          F______________________________________calculated  51.33%     3.74%      7.48%found       50.95%     3.53%      7.10%______________________________________ 
    
     EXAMPLE 4 
     ortho-alpha, alpha-difluoroethyl-nitrobenzene 
     Example 1 was repeated with 11 ml of MoF 6  and 22 gm of o-CH 3  COC 6  H 4  NO 2  (MoF 6  /CO group molar ratio=1). The separation of the constituents was carried out by chromatographic on a column of gel of silica (eluent: benzene 80--hexane 20) and a colourless liquid product of the formula ##STR30## was obtained. 
     The product was identified by NMR spectroscopy of the proton and of fluorine. 
     EXAMPLE 5 
     N-(p-alpha,alpha-difluoroethylbenzene)phthalimide ##STR31## 
     Example 1 was repeated with 20 ml of MoF 6   and 20 gm of N-(p-acetophenyl)phtalimide p-CH 3  COC 6  H 4  N (CO) 2  C 6  H 4  (MoF 6  /CO group molar ratio=1). By chromatographic separation of the constituents (eluent: CH 2  Cl 2 ), a product of formula: ##STR32## was obtained. 
     m.p. 205° C. 
     
         ______________________________________Analysis    C          H          F______________________________________calculated  66.90%     3.83%      4.88%found       66.30%     4.27%      4.30%______________________________________ 
    
     EXAMPLE 6 
     para-alpha, alpha-difluoroethyl-fluorobenzene 
     Example 2 was repeated with 11 ml of MoF 6  and 19 gm of p-CH 3  COC 6  H 4  F (MoF 6  /CO group molar ratio=1). After distillation of the reaction mixture, a product of formula: ##STR33## was obtained. 
     b.p. 10  =70° C. 
     n D   20  =1.4355 
     This product was identified by NMR spectroscopy of the proton and of fluorine. 
     EXAMPLE 7 
     para-alpha, alpha-difluoroethyl-chlorobenzene 
     Example 2 was repeated with 14 ml of MoF 6  and 26 gm of p-CH 3  COC 6  H 4  Cl (MoF 6  /CO group molar ratio=1). After distillation of the reaction mixture a product of formula: ##STR34## was obtained. 
     b.p. 8  =90° C. 
     This product was identified by NMR spectroscopy of the proton and of fluorine. 
     EXAMPLE 8 
     para-alpha, alpha-difluoroethyl ethyl benzoate 
     Example 1 was repeated with 7 ml of MoF 6  and 13.6 gm of p-CH 3  -COC 6  H 4  COOC 2  H 5  (MoF 6  /CO group molar ratio=1). There was obtained, after chromatography on the column of gel of silica (eluent: CH 2  Cl 2 ) a yield of 12.5%, with respect to the theoretical amount, of a product of formula: ##STR35## in the form of a colourless liquid. 
     EXAMPLE 9 
     para-alpha, alpha-difluoropropyl-cyanobenzene 
     Example 1 was repeated with 4.5 ml of MoF 6  and 8 gm of p-C 2  H 5  -COC 6  H 4  CN (MoF 6  /CO group molar ratio=1). There was obtained, after chromatography on the gel column of silica (eluent: benzene 50-hexane 10) a liquid product of the formula: ##STR36## n D   20  =1.4884; yield=16.5% 
     
         ______________________________________Analysis    C          H          F______________________________________calculated  66.00%     4.96%      7.73%found       65.26%     4.48%      7.44%______________________________________ 
    
     EXAMPLE 10 
     meta-alpha, alpha-difluoroethyl-cyanobenzene 
     Example 1 was repeated with 5 ml of MoF 6  and 6 gm of m-CH 3  COC 6  H 4  CN (MoF 6  /CO group molar ratio=1). There is obtained, after chromatography on the gel column of silica (eluent: benzene 80-hexane20) with a yield of 33%, a liquid product having the formula: ##STR37## 
     n D   20  =1.4825 
     
         ______________________________________Analysis    C          H          F______________________________________calculated  64.67%     4.19%      8.39%found       63.80%     3.75%      8.12%______________________________________ 
    
     EXAMPLE 11 
     difluorophenyl [4-cyanophenyl], methane 
     Example 1 was repeated with 5 ml of MoF 6  and 6 gm (MoF 6  /CO group molar ratio=1) of ##STR38## After chromatography on the gel column of silica (eluent: benzene) a yield of 27% with respect to the theoretical amount of ##STR39## was obtained. 
     m.p.=40° C. 
     
         ______________________________________Analysis    C          H          F______________________________________calculated  73.35%     3.96%      6.11%found       73.53%     3.43%      6.09%______________________________________ 
    
     EXAMPLE 12 
     meta-alpha, alpha-difluoro-cyanotoluene 
     Example 1 was repeated with 5 ml of MoF 6   and 7 gm of meta-cyanobenzaldehyde (MoF 6  /CO group molar ratio=1). After chromatography on the gel column of silica (eluent: benzene) a liquid product having the formula: ##STR40## was obtained with a yield of 20%. 
     
         ______________________________________Analysis    C          H          F______________________________________calculated  62.75%     3.29%      9.15%found       61.90%     2.81%      8.23%______________________________________ 
    
     EXAMPLE 13 
     Example 1 was repeated with 5 ml of MoF 6  and 7 gm (MoF 6  /CO group molar ratio=1) of ##STR41## After chromatography on the gel column of silica (eluent: CHCl 3 ), 1.65 gm of ##STR42## was obtained. 
     n D   10  =1.4990 
     
         ______________________________________Analysis    C          H          F______________________________________calculated  62.74%     3.29%      9.15%found       61.56%     3.26%      8.26%______________________________________ 
    
     EXAMPLE 14 
     para α,α-difluoroethyl benzoic acid. 
     7 gm of ##STR43## 4 gm of sodium hydroxide and 100 ml of water at 80°-90° C. were reacted during about 24 h. A clear solution was obtained. The heating was stopped when no further ammonia evolved. The cooled solution was then acidified with concentrated HCl. The formed white precipitate was washed with water and dried under vacuum. 7 gm of ##STR44## was thus obtained. 
     MP=182° C.; yield=90%. 
     EXAMPLE 15 
     para α,α-difluoro ethyl benzamide. 
     5 gm of p-CH 3  CF 2  C 6  H 4  CN, 200 ml of an aqueous solution of H 2  O 2  at 3% and 10 ml of an aqueous solution of NaOH at 25% were reacted at 60° C. during 4 hours. A white precipitate was progressively formed. The reaction medium was then cooled, filtered, washed with water and dried under vacuum. 5.5 gm of ##STR45## were obtained. 
     M.P.=170° C.; yield=99%. 
     EXAMPLE 16 ##STR46## 
     (methyl para-α,α-difluoroethylphenylcarbamate) 
     In a mixture of 1.7 gm of ##STR47## in 10 ml of pure methanol, there was added a solution obtained from 0.46 gm of sodium and 15 ml of methanol. 
     1.6 gm of bromine were then added and the mixture was heated 10 minutes at 60° C. The colourless solution was neutralized with acetic acid. It was evaporated under vacuum and the residue was washed with water in order to eliminate any traces of sodium bromide which may be present. The theoritical yield in ##STR48## was obtained. 
     M.P.=95° C. 
     EXAMPLE 17 
     para-α,α-difluoroethyl benzaldehyde 
     In a mixture obtained from 1.15 gm of LiAlH 4 , 2.2 gm of CH 3  COOC 2  H 5  and 30 ml of anhydrous ether (exothermic reaction), 5 gm of p-CH 3  -CF 2  C 6  H 4  CN in 10 ml of ether were slowly added. The reaction is lightly exothermic. The solution was then cautiously treated with 30 ml of 6 N sulphuric acid. The ether layer was washed with water, separated and dried. On evaporation there was obtained, with a yield of 20%, a yellow liquid of ##STR49## which crystallized very slowly. 
     EXAMPLE 18 
     meta-α,α-difluoroethyl benzoic acid 
     Example 14 was repeated with 0.5 gm of m-CH 3  -CF 2  C 6  H 4  CN. A white solid (0.5 gm) was obtained. M.P.=109°-110° C. Formula: ##STR50## 
     EXAMPLE 19 
     para-α,α-difluoroethyl benzoic acid chloride 
     7 gm of ##STR51## were reacted with 30 ml of SOCl 2  at 60° C. during 2 hours. The resulting solution was evaporated under vacuum. The residue was distilled to give 5 gm of ##STR52## 
     B.P. 0 .1 =45° C. 
     EXAMPLE 20 ##STR53## 
     4 gm of ##STR54## were poured in a solution of 3.5 gm of morpholine in 50 ml of anhydrous ether. A precipitate of morpholine hydrochloride was formed. The resulting solution was filtered and evaporated. The residue was washed with water and dried. 4 gm of ##STR55## were obtained. 
     M.P. 128° C. 
     This product can be recrystallized from ethanol. 
     EXAMPLE 21 
     Example 14 was repeated with 0.5 gm of ##STR56## and 0.5 gm of ##STR57## was obtained. 
     M.P.=128°-129° C. 
     EXAMPLE 22 
     para-α,α-difluoroethyl benzylic alcohol 
     1.8 gm of p-CH 3  CF 2  C 6  H 4  COOH were dissolved in 25 ml of ether and the reaction is alloved to proceed, during one hour, at room temperature, with a suspension of 0.5 gm of LiAlH 4  in 25 ml of ether. The excess of LiAlH 4  is hydrolized with diluted hydrochloric acid. After decantation, the ether layer is washed with water, dried on Na 2  SO 4  and then evaporated; the liquid residue is chromatographied on a column of gel of silica (with benzene as eluant). A yellow liquid (0.8 gm) was obtained. The formula of this produit is: p-CH 3  -CF 2  -C 6  H 4  -CH 2  OH. 
     Yield=48%. 
     EXAMPLE 23 
     diisopropyl aminoethanol para-α,α-difluoroethylbenzoate 
     1.9 gm of p-CH 3  CF 2  C 6  H 4  COOH were reacted with 1.6 gm of ClCH 2  CH 2  N (i-C 3  H 7 ) 2  in 50 ml of isopropanol (i-C 3  H 7  OH). The solution was refluxed for one hour. The isopropanol was then evaporated under vacuum. The residue was washed with water to eliminate any starting compound. The resulting crystals of the resulting hydrochloride which are insoluble in ether were then treated with a 5% Na 2  CO 3  aqueous solution, followed by an ether extraction. The ether solution was then dried on Na 2  SO 4 . The ether was evaporated and 1.9 gm of a slightly viscous yellow liquid of the formula: 
     
         p-CH.sub.3 CF.sub.2 C.sub.6 H.sub.4 COOCH.sub.2 CH.sub.2 N(i-C.sub.3 H.sub.7).sub.2 
    
     were recovered. 
     Yield: 60%. 
     EXAMPLE 24 
     para-α,α-difluoroethyl benzylic amine 
     1.67 gm (1/100 mole) of ##STR58## and 25 ml of anhydrous ether were poured in a mixture of 0.5 gm of LiAlH 4  and 25 ml of anhydrous ether. The reaction is slightly exothermic. A reflux heating was carried out for 8 hours. The excess of LiAlH 4  was then destroyed with distilled water. The ether layer was washed with water and dried on Na 2  SO 4 . The hydrochloride of the amine was precipitated by passing through the ether solution a stream of HCl gas until saturation was obtained. The resulting precipitate was then washed with ether and dried under vacuum. 
     1.25 gm of ##STR59## were thus obtained. 
     EXAMPLE 25 
     para-difluoromethyl benzylic amine 
     As described in example 23, 4.6 gm of ##STR60## were reacted with 2 gm of LiAlH 4  in 50 ml of ether. 2.6 gm of a white product corresponding to the following formula were thus obtained: ##STR61## 
     EXAMPLE 26 
     Example 14 was repeated with 0.5 gm of ##STR62## and there was obtained 0.45 gm of: