CA1292996C - Process for the preparation of 4-(2'-chloroethyl)- benzoic acid - Google Patents
Process for the preparation of 4-(2'-chloroethyl)- benzoic acidInfo
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- CA1292996C CA1292996C CA000553206A CA553206A CA1292996C CA 1292996 C CA1292996 C CA 1292996C CA 000553206 A CA000553206 A CA 000553206A CA 553206 A CA553206 A CA 553206A CA 1292996 C CA1292996 C CA 1292996C
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- chloroethyl
- benzoic acid
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- acetophenone
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Abstract
Abstract of the disclosure:
The invention relates to a process for the preparation of 4-(2'-chloroethyl)benzoic acid or an aqueous solution of its sodium and/or potassium salt from 4-(2'-chloroethyl)-acetophenone. In this process, 4-(2'-chloroethyl)-acetophenone is reacted with an aqueous alkaline solution of sodium hy-pochlorite and/or potassium hypochlorite at temperatures between 25°C and 110°C. The free acid can be pre-cipitated by acidification using a strong inorganic acid from the thus obtained aqueous solution of the sodium and/or potassium salt of the 4-(2'-chloroethyl)benzoic acid.
The invention relates to a process for the preparation of 4-(2'-chloroethyl)benzoic acid or an aqueous solution of its sodium and/or potassium salt from 4-(2'-chloroethyl)-acetophenone. In this process, 4-(2'-chloroethyl)-acetophenone is reacted with an aqueous alkaline solution of sodium hy-pochlorite and/or potassium hypochlorite at temperatures between 25°C and 110°C. The free acid can be pre-cipitated by acidification using a strong inorganic acid from the thus obtained aqueous solution of the sodium and/or potassium salt of the 4-(2'-chloroethyl)benzoic acid.
Description
~Z~29g6 HOECHST AKTIENGESELLSCHAFT HOE 86/F292 Dr.MA/mù
Description:
Process for the preparation of 4-(2'-chloroethyl)benzoic acid The invention relates to a process for the preparation of 4-~2'-chloroethyl)benzoic acid from 4-(2'-chloroethyl)-acetophenone.
Such a process is already known. According to US Patent2,969,385, 4-(2'-chLoroethyl)acetophenone is reacted with an alkaline sodium hypobromite solution at 0C. This temperature is maintained during the total reaction period of 4 to 8 hours. The reaction is carried out in a mix-ture of about 60 parts of water and 40 parts of 1,4-dioxa-ne:
H3C-C- ~ -CH2-CH2-C1 ~ 3NaOBr ~ Na00~- ~ -CH2-CH2-C1 ~ HCBr3 1 2NaOH
~ H00C- ~ CH2-CH2-C1 ~ HCBr3 + 3NaC1 ~ 2H20 The process described yields 4-(2'-chloroethyl)benzoic acid while using a very large amount of brom;ne: 3 mol of bromine - 479.5 9 are requ;red for the preparation of 3 mol of NaOBr, with which 1 mol of 4-(2'-chloroethyl)aceto-phenone = 1~2.65 9 are brought to reaction. In this pro-cess more of the ~aste product bromoform is formed than the reaction product 4-(2'-chloroethyl)benzoic acid.
On account of the use of a reaction mixture of 60 parts of water and 40 parts of 1,4-dioxane, a large amount of a solvent which is today considered as hazardous and which is only recoverable from this mixture with difficulty must be employed. Finally, maintaining the reaction tem-perature of 0C requires a considerable amount of cooling.The process for the preparation of 4-(2'-chloroethyl)-benzoic acid known from the literature is thus hardly suitable for industrial execution.
lZ9Z996 The object was therefore to develop a process for the preparation of the carboxylic acid mentioned which is free of these disadvantages. This object is solved by the present invention.
Accordingly, the invention relates to a process for the preparation of 4-(2'-chloroethyl)benzoic acid from 4-(2'-chloroethyl)acetophenone, which process comprises reacting 4-(2'-chloroethyl)acetophenone with an aqueous alkaline solution of sodium hypochlorite and/or potassium hypo-chlorite at temperatures between 25C and 110C and then acidifying the solution using a strong inorganic acid.
The 4-(2'-chloroethyl)benzoic acid is ~iberated from its initially resulting sodium or potassium salt by acidifi-cation. The reaction equation reads:
o H3C-C ~ CH2-CH2-Cl ~ 3NaOCl ~ NaOOC ~ CH2-CH2-Cl ~ HCCl3 ~ 2NaOH
~ HOOC ~ -CH2-CH2-Cl ~ HCCl3 1 3NaCl ~ 2H20 The reaction with hypochlorite can be carried out in the presence of a solubilizer.
Suitable solubilizers are substances which are misc;ble both with 4-(2'-chloroethyl)acetophenone and also with water, but which are simultaneously chemically inert towards sodium hypochlorite or potassium hypochlorite. These requirements are fulfilled both by cycloaliphatic ethers, such as tetrahydrofuran, and also by aliphatic ethers, such as 1,2-dimethoxyethane, d;ethylene glycol dimethyl ether, 3û triethylene glycol dimethyl ether, and their higher homologs.
The reaction can then be carried out by adding the solution of 4-(2'-chloro-ethyl)acetophenone in one of the previously mentioned solubilizers ~or in any des;red mixture thereof) to the aqueous alkaline sodium hypochlorite and/or potassium hypochlorite solution and this reaction mixture is stirred 1~9Z996 w;thout external warm;ng.
After a short t;me, appreciable warming occurs, the rise in temperature accelerating with increasing temperature. The temperature ;s preferably mainta;ned in the range of 28 to 60C by external cooling.
Surprisingly, the reaction proceeds substantially without formation of 4-vinylbenzoic acid, although the molecular structure of 4-(2'-chloroethyl)benzoic acid would suggest easy elimination of HCl.
The reaction can, however, also be carried out without the addition of a solubilizer. In this case, the aqueous alkaline sodium hypochlorite and/or potassium hypochlorite solution is stirred only with the 4-(2'-chloroethyl)-acetophenone; the reaction temperature is preferably again limited to 28 to 60C by cooling. In an otherwise com-pletely analogous reaction procedure to that in the presence of a solubilizer, the carboxylic acid is obtained in practically the same yield and purity. The time be-tween the start of the reaction and the beginning of the exothermic reaction phase is lengthened slightly in this procedure.
If it is desirable on process technology grounds to work without cooling, this is achieved by a appropriately slow addition of the reactants (alone or together with one of the mentioned solubilizers) to the prewarmed sodium hypochlorite and~or potassium hypochlorite solution. The exothermic reaction can be controlled without cooling in this process variant, so that the reaction temperature can easily be maintained in the range up to 60C. The amount of substance available for the exothermic reaction is in each case small, limited by the slow addition.
The amount of solubilizer is generally 0 to 50 Z by weight, preferably 0 to 10 % by weight.
lZ9Z996 The reaction temperature is between 25C and the boiling point of the batch (about 110C), preferably between 28C and 60C.
The duration of the reaction is generally between 0.5 and 8 hours, preferably between 1 and 5 hours.
The concentrations of the hypochlorite solutions are gen-erally between 5 and 25 % by weight of sodium hypochlorite or potassium hypochlorite, preferably between 8 and 20 %
by weight. The preparation of these solutions (for example by passing chlorine into aqueous NaOH solutions) is described in Gmelins Handbuch der Anorganischen Chemie [Gmelin's Handbook of Inorganic Chemistry]: volume on chlorine, 1927, p. 265 et seq. and the literature cited there.
The 4-~2'-chloroethyl)benzoic acid is initially present after reaction with the hypochlorite solution as the dis-solved sodium or potassium salt and is precipitated byaddit;on of a strong inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid at pH of 1 to 6, preferably at pH 1 to 3.
The process can also be carried out continuously.
Naturally, when it is wished to obtain the solution of the sodium or potassium salt instead of the free acid, the addition of the strong inorganic acid can be omitted.
The invention also relates to the preparation of such a solution.
4-(2'-Chloroethyl)benzoic acid is the starting point for the preparation of 4-vinylbenzoic acid by HCl elimination, for example with the aid of potassium hydroxide in a sol-vent. 4-Vinylbenzoic acid is an important monomer for the preparation of specific polymers, such as, for example, are described in Chemical Abstracts 65, 12362h (1966) lZ9Z996 (Copolymer with specific acrylamides for improving the propert;es of gelatin layers against water); Chemical Abstracts 74, P 133057y (1971) ~Copolymer with ethyl acrylate and lauryl methacrylate as part of a developer for electrophotography); US Patent 4,364,924 ~Alkali metal salts of polyvinylbenzo;c acid for prevent;ng plaque);
Chemical Abstracts 98, P 207,5659 (1983) (Copolymer with styrene as part of a photothermographic material).
Experimental section Example 1 4.8 mol of sodium hypochlorite (357.3 g) were initially introduced in the form of an aqueous alkaline solution (about 2Z60 ml of sodium hypochlorite solution having an NaOCl content of 0.158 9 per ml and a pH of 12 to 13 due to NaOH) at about 25C. 1.5 mol of 4-(2'-chloroethyl)-acetophenone ~274 ~), d;ssolved in 90 ml of 1,Z-dimethoxy-ethane, were added thereto, and the reaction mixture wasst;rred without additional warming. The 4-~2'-chloroethyl)acetophenone employed was (according to gas chromatography) a 94% pure product; the remaining 6 percent were the isomeric 2-(2'-chloroethyl)acetophenone.
After stirring for about one hour the reaction m;xture began to warm noticeably. The reaction temperature was kept at 32 to 35C by external cooling. In this way the exothermic reaction pha~e lasted for 1 to 1.5 hours. The mixture was then stirred for an additional 2 hours and 3û during this the temperature in the reaction vessel was allowed to fall to room temperature. The 4-~2'-chloro-ethyl)benzoic acid - dissolved as the sodium salt - was then precipitated by addition of hydrochloric acid tabout 475 ml of conc. HCl) at a pH of 1 to 2. The precipitate was filtered off under suction, the 4-~2'-chloroethyl)-benzoic acid was added to 1 liter of warm water at about 60C and the solid was stirred for several minutes in order to free it from adhering hydrochloric acid and salt ~Z9Z9~6 traces.
After cool;ng to room temperature, the solid was aga;n filtered off under suction and the st;ll moist reaction product ~as then dried under reduced pressure for about 20 hours at 50 to 70C.
Z70 9 of 4-(2'-chloroethyl)benzoic acid (97.5% of theory) having a melting point of 177 to 180C were obtained.
Sample content: 95X of 4-(2'-chloroethyl)benzoic acid;
determined by GC after silylation using MSTFA (N-methyl-N-trimethylsilyltrifluoroacetamide) After recrystallization from methanol, the melting point ~as 187 to 188C, the sample content was greater than 99%
of 4-(2'-chloroethyl)benzoic acid.
1H-NMR data (solvent: DMSO-D6) ~ values ;n ppm coupling ass;gned protons 20 _ constants ~riplet 3.11 7 Hz Ar-CH2-~riplet 3.90 7 Hz -CH2-Cl Doublet 7.41 8 Hz aromat. H, ortho to alkyl Doublet 7.91 8 Hz aromat. H, ortho to carbo-%yl Singlet 12.9 -COOH
(broad) Example 2 4.8 mol of sodium hypochlorite (357.3 9) were initially introduced in the form of an aqueous alkaline solution (about 2335 ml of sodium hypochlorite solution having an NaOCl content of 0.153 g/ml and a pH of 12 to 13 due to NaOH) at about 25C. 1.5 mol of 4-(2'-chloroethyl)-acetophenone (274 9 having a content of 94 g by ~eight, as in Example 1), dissolved in 90 ml of 1,2-d;methoxyethane, were added thereto, and the react;on m;xture was stirred ~32~39~i without additional warming. After stirring for about one hour, the reaction mixture began to warm noticeably. The reaction temperature was kept between 3~ and 42C by external cooling. In this way the exothermic reaction phase lasted for about one hour. The mixture was then st;rred for an additional 2 hours and during this the temperature was allowed to fall to room temperature. The 4-(2'-chloro-ethyl)benzoic acid was liberated from its sodium salt by addition of hydrochloric acid at a pH of 1 to 2. The solid was filtered off under suction, the 4-(2'-chLoroethyl)-benzoic acid was added to 1 liter of water at 60C, the mixture was stirred for several minutes and the solid was again filtered off under suction after cooling to room temperature. The moist reaction product was dried at 50 to 70C for 20 hours under reduced pressure.
264 9 of 4-~2'-chloroethyl)benzoic acid (95~3% of theory) having a melting point of 179 to 182C were obta;ned.
Sample content: 95% of 4-(2'-chloroethyl)benzoic acid;
determined by GC after silylation using MSTFA.
Example 3 4.~ mol of sodium hypochlorite t357.3 9) were initially introduced in the form of an aqueous alkaline NaOH solution (about 2206 ml of sodium hypochlorite solution having an NaOCl content of 0.162 g/ml and a pH of 12 to 13) at about 25C. 1.5 mol of 4-~2'-chloroethyl)acetophenone 274 9 having a content of 94 % by weight, as in Example 1), ~dissolved in 90 ml of 1,2-dimethoxyethane, were added thereto, and the reaction mixture was stirred without addit;onal warming. After stirring for about one hour, the reaction mixture began to warm noticeably. The reaction temperature was kept between 45 and 52C by external cool-ing. In this way, the exothermic reaction phase lastedabout 0.5 to 1 hour. The reaction mixture was then stir-red for a further 2 hours and during this the temperature was allowed to fall to room temperature. The work-up of 1~9~99~
this batch was as described in Examples 1 and 2.
2h8 9 of 4-(2'-chloroethyl)benzoic acid (96.8% of theory) hiaving a melting point of 178 to 181C were obtained.
Sample content: 94% of 4-(2'-chloroethyl)benzo;c acid;
determined by GC after silylation using MSTFA.
Example 4 1.6 mol of sodium hypochlorite (119.1 9) were initially introduced in the form of an aqueous alkaline NaOH solution (about 713 ml of sodium hypochlorite solution having an NaOCl content of 0.167 g/ml and a pH of 12 to 13) at about 25C. 0.5 mol of 4-(2'-chloroethyl)aceto-phenone (91.3 9 having a content of 94 % by weight, as in Example 1), dis-solved in 30 ml of 1,2-dimethoxyethane, was added thereto, and the reaction mixture was stirred without additional warming. After stirring for about one hour, the reaction m;xture began to warm not;ceably. The temperature was allowed ~o ;ncrease w;thout any cool;ng. Th;s 1nitially occured very slowly, but accelerated with increasing tempe-rature. Above about 50C the temperature then cl;mbed to the boiling point within a few minutes, and the reaction mixture boiLed. The vigorous exothermic reaction lasted only a few minutes ;n th;s case. Thereafter the internal temperature was allowed to fall to room temperature and the mixture ~as stirred for a little longer, lasting ;n total for 2 hours. The reaction product was precipitated at pH 1 to 2 by addition of hydrochloric acid and it was worked up in the manner described in Example 1.
After drying at about 50 to 60t under reduced pressure for 20 hours, 88.2 9 of white solid were obtained. Th;s reaction product showed no uniform melting point; it softened at a temperature as low as 170C and melted between about 174 and 181C, without a clear melt being obtained. In the 1H-NMR spectrum of the reaction product, the signals for 4-vinylbenzoic acid, formed by HCL
:~9Z~96 _ 9 _ elimination, can be clearly detected in addition to the usual s;gnals for 4-(2'-chloroethyl)ben-zoic acid (see Example 1).
1H-NMR data (solvent: DMSO-D6) of 4-vinylbenzoic acid:
values in ppm coupling assigned protons constants Doublet-doublet 5.41 10 Hz + 1 Hz Ar-C=C-H, trans Doublet-doublet 5.97 18 Hz + 1 Hz Ar-C=C-H, cis Doublet-doublet 6.82 18 Hz +10 Hz Ar-CH=C
Doublet (broad) 7.60 8 Hz aromat. H, ortho to vinyl Doublet (broad) 7.94 8Hz aromat. H, ortho to carboxyl Singlet tbroad) 12.95 -COOH
Sample content according to GC after silylation with MSTFA:
88% of 4-~2'-chloroethyl~benzoic acid 6% of 4-vinylbenzoic acid about 6% of additional substances.
Example 5 25 4.6 mol of sodium hypochlorite ~342.4 g) were initially introduced in the form of an aqueous alkaline NaOH solution (about 2167 ml of sodium hypochlorite solution having an NaOCl content of 0.158 g/ml and a pH of 12 to 13) at about 25C. 1.5 mol of 4-(2'-chloroethyl)aceto-phenone (274 9 having a content of 94 % by weight, as in Ex-ample 1), dissolved in 90 ml of diethylene glycol dimethyl ether, were added thereto, and the reaction mixture was stirred without additional warming. After stirring for about one hour, the reaction mixture began to warm noticeably, and the reaction temperature was kept between 34 and 45C by external cooling~ The exothermic reaction phase lasted about an hour. The mixture was then stirred for an additional two hours, during which the internal temperature fell to room ~Z9Z996 temperature. The 4-(2'-chloroethyl)benzoic acid was precipitated at a pH of 1 to 2 by addition of hydrochloric acid, filtered off under suction and ~ashed ~ith water.
After drying, 269 9 of 4-(2'-chloroethyl)benzoic acid ~97.1X of theory) having a melting point of 177 to 180C
~ere obtained.
Sample content: 94% of 4-(2'-chloroethyl)benzoic acid, determined by GC after silylation using MSTFA.
Example 6 4.7 mol of sodium hypochlorite (349.9 9) were initially introduced in the form of an aqueous alkaline NaOH
solution ~about 2200 ml of sodium hypochlorite solution having an NaOCl content of 0.159 g/ml and a pH of 12 to 13) at 25C. 1.5 mol of 4-~2'-chloroethyl)acetophenone (274 9 having a content of 94 % by weight, as in Example 1), dissolved ;n 90 ml of tetrahydrofuran, were added thereto, and the react;on mixture was stirred without additional warming. After stirring for about one hour, the reaction mixture warmed noticeably, and the reaction temperature ~as kept between 35 and 40C by external cool-ing. After the end of the exothermic reaction phase, the internal temperature was allowed to fall to room tempera-ture and the 4-(2'-chloroethyl)benzoic acid was isolated as described in Examples 1 and 2. 263 9 of 4-(2'-chloro-ethyl)benzoic acid (95X of theory) were obtained after drying; the melting point was 178 to 180C.
Sample content: 94Z of 4-(2'-chloroethyl)benzoic acid;
determined by GC after silylation using MSTFA.
Example 7 3.2 mol of sodium hypochlorite (238.2 9) ~ere initially introduced in the form of an aqueous alkaline HaOH solution at 25C (about 1517 ml of a sodium hypochlorite solution having an NaOCl content of 0.157 g/ol and a pH of 12 to ~Z9~996 13). 1 mol of 4-(2'-chloroethyl)acetophenone (182.65 9 having a content of 94 Z by ~eight, as in Example 1) was added thereto. The mixture was stirred without additional warming. After stirr;ng for about 1.5 hours, the tempera-ture of the batch began to climb noticeably, and thereaction temperature was kept between 37 and 40C by external cooling. In this ~ay, the exothermic reaction phase lasted about an hour. The mixture was then stirred for a further 2 hours, during which the internal tempera-ture fell to room temperature. The isolation, purifica-tion and drying of the product was as described in Examples 1 and 2.
After drying 176 9 of 4-(2'-chloroethyl)benzoic acid (95.3%
of theory) having a melting point of 178 to 182C
remained.
Sample content: 95% of 4-(2'-chloroethyl)benzo;c acid;
determined by 6C after s;lylation using MSTFA.
Example 8 3.2 mol of sodium hypochlorite (238.2 g) ~ere initially introduced in the form of an aqueous alkaline NaOH solution - prewarmed to 40C - (about 1567 ml of a sodium hypochlo-rite solution having an NaOCl content of 0.152 g/ml and a pH of 12 to 13). A solution of 1 mol of 4-(2'-chloroethyl)-acetophenone (182.65 9 having a content of 94 X by weight, as in Example 1), dissolved in 80 ml of 1,2-dimethoxyethane, was steadily added drop~ise thereto during the course of 2.5 hours, with continuous stirring.
About half an hour after beginning the addition a tem-perature increase above 40C was observed. ~y gentle external cooling, it was easily possible to keep the re-action temperature in the range from 40 to 45C, since due to the slow rate of addit;on, only a small amount of substance was available for the exothermic reaction in each lZ9Z996 case. After the end of the addition and the subsiding of the exothermic reaction phase, the mixture was stirred for a further 2 hours at about 35C. The 4-(2'-chloroethyl)-benzo;c acid was precipitated from its sodium salt at a pH
of 1 to 2 by addition of hydrochloric acid~ The precipitate was filtered off under sùction and washed with water.
After drying at 50 to 60C under reduced pressure for about 20 hours, 177 9 of 4-(2'-chloroethyl)benzoic acid (95.8%
of theory) having a melting point of 177 to 183C were obtained.
Sample content: 93% of 4-(2'-chloroethyl)benzoic acid;
determined by GC after silylation using MSTFA.
After recrystallization from methanol the melting point was 186 to 187C; the recrystallized 4-(2'-chloroethyl)-benzoic acid was an at least 99% pure product.
Example 9 (Convers;on of 4-~2'-chloroethyl)benzoic acid into 4-vinyl-benzoic ac;d) 2.0 mol of 4-(2'-chloroethyl)benzoic acid (369.2 g) were introduced in portions, bùt rapidly, with continuous stirring into a solution of 6.0 mol of potassiu~ hydroxide (336.7 g) in 1000 ml of methanol, prewarmed to 70C, and an exothermic reaction was observed. The mixture was then heated to boiling for 5 hours. ~hen the reaction was com-plete, the reaction mixture was cooled to about 0C and the precipitated potassium salt of 4-vinylbenzoic acid was filtered off under suction~ This salt was dissolved in 1800 ml of water and the 4-vinylbenzoic acid was liberated at pH 1 to 2 by addition of hydrochloric acid.
The acid was filtered off under suction, washed with water and the still wet 4-vinylbenzoic acid was taken up in methyl tert.-butyl ether. After removal of the remain;ng water, the solution was dried over sodium sulfate, and concentrated to obtain 249.7 g of 4-vinylbenzoic acid lZ9Z996 (B4.3% of theory) having a melting point of 136 to 139C
(with decomposition).
The 1H-NMR data were identical with the data given in Ex-ample 4 for the 4-vinylbenzoic acid resulting as a by-product there.
Sample content: 96~ of 4-vinylbenzoic ac;d; determ;ned by GC after silylation using MSTFA.
Description:
Process for the preparation of 4-(2'-chloroethyl)benzoic acid The invention relates to a process for the preparation of 4-~2'-chloroethyl)benzoic acid from 4-(2'-chloroethyl)-acetophenone.
Such a process is already known. According to US Patent2,969,385, 4-(2'-chLoroethyl)acetophenone is reacted with an alkaline sodium hypobromite solution at 0C. This temperature is maintained during the total reaction period of 4 to 8 hours. The reaction is carried out in a mix-ture of about 60 parts of water and 40 parts of 1,4-dioxa-ne:
H3C-C- ~ -CH2-CH2-C1 ~ 3NaOBr ~ Na00~- ~ -CH2-CH2-C1 ~ HCBr3 1 2NaOH
~ H00C- ~ CH2-CH2-C1 ~ HCBr3 + 3NaC1 ~ 2H20 The process described yields 4-(2'-chloroethyl)benzoic acid while using a very large amount of brom;ne: 3 mol of bromine - 479.5 9 are requ;red for the preparation of 3 mol of NaOBr, with which 1 mol of 4-(2'-chloroethyl)aceto-phenone = 1~2.65 9 are brought to reaction. In this pro-cess more of the ~aste product bromoform is formed than the reaction product 4-(2'-chloroethyl)benzoic acid.
On account of the use of a reaction mixture of 60 parts of water and 40 parts of 1,4-dioxane, a large amount of a solvent which is today considered as hazardous and which is only recoverable from this mixture with difficulty must be employed. Finally, maintaining the reaction tem-perature of 0C requires a considerable amount of cooling.The process for the preparation of 4-(2'-chloroethyl)-benzoic acid known from the literature is thus hardly suitable for industrial execution.
lZ9Z996 The object was therefore to develop a process for the preparation of the carboxylic acid mentioned which is free of these disadvantages. This object is solved by the present invention.
Accordingly, the invention relates to a process for the preparation of 4-(2'-chloroethyl)benzoic acid from 4-(2'-chloroethyl)acetophenone, which process comprises reacting 4-(2'-chloroethyl)acetophenone with an aqueous alkaline solution of sodium hypochlorite and/or potassium hypo-chlorite at temperatures between 25C and 110C and then acidifying the solution using a strong inorganic acid.
The 4-(2'-chloroethyl)benzoic acid is ~iberated from its initially resulting sodium or potassium salt by acidifi-cation. The reaction equation reads:
o H3C-C ~ CH2-CH2-Cl ~ 3NaOCl ~ NaOOC ~ CH2-CH2-Cl ~ HCCl3 ~ 2NaOH
~ HOOC ~ -CH2-CH2-Cl ~ HCCl3 1 3NaCl ~ 2H20 The reaction with hypochlorite can be carried out in the presence of a solubilizer.
Suitable solubilizers are substances which are misc;ble both with 4-(2'-chloroethyl)acetophenone and also with water, but which are simultaneously chemically inert towards sodium hypochlorite or potassium hypochlorite. These requirements are fulfilled both by cycloaliphatic ethers, such as tetrahydrofuran, and also by aliphatic ethers, such as 1,2-dimethoxyethane, d;ethylene glycol dimethyl ether, 3û triethylene glycol dimethyl ether, and their higher homologs.
The reaction can then be carried out by adding the solution of 4-(2'-chloro-ethyl)acetophenone in one of the previously mentioned solubilizers ~or in any des;red mixture thereof) to the aqueous alkaline sodium hypochlorite and/or potassium hypochlorite solution and this reaction mixture is stirred 1~9Z996 w;thout external warm;ng.
After a short t;me, appreciable warming occurs, the rise in temperature accelerating with increasing temperature. The temperature ;s preferably mainta;ned in the range of 28 to 60C by external cooling.
Surprisingly, the reaction proceeds substantially without formation of 4-vinylbenzoic acid, although the molecular structure of 4-(2'-chloroethyl)benzoic acid would suggest easy elimination of HCl.
The reaction can, however, also be carried out without the addition of a solubilizer. In this case, the aqueous alkaline sodium hypochlorite and/or potassium hypochlorite solution is stirred only with the 4-(2'-chloroethyl)-acetophenone; the reaction temperature is preferably again limited to 28 to 60C by cooling. In an otherwise com-pletely analogous reaction procedure to that in the presence of a solubilizer, the carboxylic acid is obtained in practically the same yield and purity. The time be-tween the start of the reaction and the beginning of the exothermic reaction phase is lengthened slightly in this procedure.
If it is desirable on process technology grounds to work without cooling, this is achieved by a appropriately slow addition of the reactants (alone or together with one of the mentioned solubilizers) to the prewarmed sodium hypochlorite and~or potassium hypochlorite solution. The exothermic reaction can be controlled without cooling in this process variant, so that the reaction temperature can easily be maintained in the range up to 60C. The amount of substance available for the exothermic reaction is in each case small, limited by the slow addition.
The amount of solubilizer is generally 0 to 50 Z by weight, preferably 0 to 10 % by weight.
lZ9Z996 The reaction temperature is between 25C and the boiling point of the batch (about 110C), preferably between 28C and 60C.
The duration of the reaction is generally between 0.5 and 8 hours, preferably between 1 and 5 hours.
The concentrations of the hypochlorite solutions are gen-erally between 5 and 25 % by weight of sodium hypochlorite or potassium hypochlorite, preferably between 8 and 20 %
by weight. The preparation of these solutions (for example by passing chlorine into aqueous NaOH solutions) is described in Gmelins Handbuch der Anorganischen Chemie [Gmelin's Handbook of Inorganic Chemistry]: volume on chlorine, 1927, p. 265 et seq. and the literature cited there.
The 4-~2'-chloroethyl)benzoic acid is initially present after reaction with the hypochlorite solution as the dis-solved sodium or potassium salt and is precipitated byaddit;on of a strong inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid at pH of 1 to 6, preferably at pH 1 to 3.
The process can also be carried out continuously.
Naturally, when it is wished to obtain the solution of the sodium or potassium salt instead of the free acid, the addition of the strong inorganic acid can be omitted.
The invention also relates to the preparation of such a solution.
4-(2'-Chloroethyl)benzoic acid is the starting point for the preparation of 4-vinylbenzoic acid by HCl elimination, for example with the aid of potassium hydroxide in a sol-vent. 4-Vinylbenzoic acid is an important monomer for the preparation of specific polymers, such as, for example, are described in Chemical Abstracts 65, 12362h (1966) lZ9Z996 (Copolymer with specific acrylamides for improving the propert;es of gelatin layers against water); Chemical Abstracts 74, P 133057y (1971) ~Copolymer with ethyl acrylate and lauryl methacrylate as part of a developer for electrophotography); US Patent 4,364,924 ~Alkali metal salts of polyvinylbenzo;c acid for prevent;ng plaque);
Chemical Abstracts 98, P 207,5659 (1983) (Copolymer with styrene as part of a photothermographic material).
Experimental section Example 1 4.8 mol of sodium hypochlorite (357.3 g) were initially introduced in the form of an aqueous alkaline solution (about 2Z60 ml of sodium hypochlorite solution having an NaOCl content of 0.158 9 per ml and a pH of 12 to 13 due to NaOH) at about 25C. 1.5 mol of 4-(2'-chloroethyl)-acetophenone ~274 ~), d;ssolved in 90 ml of 1,Z-dimethoxy-ethane, were added thereto, and the reaction mixture wasst;rred without additional warming. The 4-~2'-chloroethyl)acetophenone employed was (according to gas chromatography) a 94% pure product; the remaining 6 percent were the isomeric 2-(2'-chloroethyl)acetophenone.
After stirring for about one hour the reaction m;xture began to warm noticeably. The reaction temperature was kept at 32 to 35C by external cooling. In this way the exothermic reaction pha~e lasted for 1 to 1.5 hours. The mixture was then stirred for an additional 2 hours and 3û during this the temperature in the reaction vessel was allowed to fall to room temperature. The 4-~2'-chloro-ethyl)benzoic acid - dissolved as the sodium salt - was then precipitated by addition of hydrochloric acid tabout 475 ml of conc. HCl) at a pH of 1 to 2. The precipitate was filtered off under suction, the 4-~2'-chloroethyl)-benzoic acid was added to 1 liter of warm water at about 60C and the solid was stirred for several minutes in order to free it from adhering hydrochloric acid and salt ~Z9Z9~6 traces.
After cool;ng to room temperature, the solid was aga;n filtered off under suction and the st;ll moist reaction product ~as then dried under reduced pressure for about 20 hours at 50 to 70C.
Z70 9 of 4-(2'-chloroethyl)benzoic acid (97.5% of theory) having a melting point of 177 to 180C were obtained.
Sample content: 95X of 4-(2'-chloroethyl)benzoic acid;
determined by GC after silylation using MSTFA (N-methyl-N-trimethylsilyltrifluoroacetamide) After recrystallization from methanol, the melting point ~as 187 to 188C, the sample content was greater than 99%
of 4-(2'-chloroethyl)benzoic acid.
1H-NMR data (solvent: DMSO-D6) ~ values ;n ppm coupling ass;gned protons 20 _ constants ~riplet 3.11 7 Hz Ar-CH2-~riplet 3.90 7 Hz -CH2-Cl Doublet 7.41 8 Hz aromat. H, ortho to alkyl Doublet 7.91 8 Hz aromat. H, ortho to carbo-%yl Singlet 12.9 -COOH
(broad) Example 2 4.8 mol of sodium hypochlorite (357.3 9) were initially introduced in the form of an aqueous alkaline solution (about 2335 ml of sodium hypochlorite solution having an NaOCl content of 0.153 g/ml and a pH of 12 to 13 due to NaOH) at about 25C. 1.5 mol of 4-(2'-chloroethyl)-acetophenone (274 9 having a content of 94 g by ~eight, as in Example 1), dissolved in 90 ml of 1,2-d;methoxyethane, were added thereto, and the react;on m;xture was stirred ~32~39~i without additional warming. After stirring for about one hour, the reaction mixture began to warm noticeably. The reaction temperature was kept between 3~ and 42C by external cooling. In this way the exothermic reaction phase lasted for about one hour. The mixture was then st;rred for an additional 2 hours and during this the temperature was allowed to fall to room temperature. The 4-(2'-chloro-ethyl)benzoic acid was liberated from its sodium salt by addition of hydrochloric acid at a pH of 1 to 2. The solid was filtered off under suction, the 4-(2'-chLoroethyl)-benzoic acid was added to 1 liter of water at 60C, the mixture was stirred for several minutes and the solid was again filtered off under suction after cooling to room temperature. The moist reaction product was dried at 50 to 70C for 20 hours under reduced pressure.
264 9 of 4-~2'-chloroethyl)benzoic acid (95~3% of theory) having a melting point of 179 to 182C were obta;ned.
Sample content: 95% of 4-(2'-chloroethyl)benzoic acid;
determined by GC after silylation using MSTFA.
Example 3 4.~ mol of sodium hypochlorite t357.3 9) were initially introduced in the form of an aqueous alkaline NaOH solution (about 2206 ml of sodium hypochlorite solution having an NaOCl content of 0.162 g/ml and a pH of 12 to 13) at about 25C. 1.5 mol of 4-~2'-chloroethyl)acetophenone 274 9 having a content of 94 % by weight, as in Example 1), ~dissolved in 90 ml of 1,2-dimethoxyethane, were added thereto, and the reaction mixture was stirred without addit;onal warming. After stirring for about one hour, the reaction mixture began to warm noticeably. The reaction temperature was kept between 45 and 52C by external cool-ing. In this way, the exothermic reaction phase lastedabout 0.5 to 1 hour. The reaction mixture was then stir-red for a further 2 hours and during this the temperature was allowed to fall to room temperature. The work-up of 1~9~99~
this batch was as described in Examples 1 and 2.
2h8 9 of 4-(2'-chloroethyl)benzoic acid (96.8% of theory) hiaving a melting point of 178 to 181C were obtained.
Sample content: 94% of 4-(2'-chloroethyl)benzo;c acid;
determined by GC after silylation using MSTFA.
Example 4 1.6 mol of sodium hypochlorite (119.1 9) were initially introduced in the form of an aqueous alkaline NaOH solution (about 713 ml of sodium hypochlorite solution having an NaOCl content of 0.167 g/ml and a pH of 12 to 13) at about 25C. 0.5 mol of 4-(2'-chloroethyl)aceto-phenone (91.3 9 having a content of 94 % by weight, as in Example 1), dis-solved in 30 ml of 1,2-dimethoxyethane, was added thereto, and the reaction mixture was stirred without additional warming. After stirring for about one hour, the reaction m;xture began to warm not;ceably. The temperature was allowed ~o ;ncrease w;thout any cool;ng. Th;s 1nitially occured very slowly, but accelerated with increasing tempe-rature. Above about 50C the temperature then cl;mbed to the boiling point within a few minutes, and the reaction mixture boiLed. The vigorous exothermic reaction lasted only a few minutes ;n th;s case. Thereafter the internal temperature was allowed to fall to room temperature and the mixture ~as stirred for a little longer, lasting ;n total for 2 hours. The reaction product was precipitated at pH 1 to 2 by addition of hydrochloric acid and it was worked up in the manner described in Example 1.
After drying at about 50 to 60t under reduced pressure for 20 hours, 88.2 9 of white solid were obtained. Th;s reaction product showed no uniform melting point; it softened at a temperature as low as 170C and melted between about 174 and 181C, without a clear melt being obtained. In the 1H-NMR spectrum of the reaction product, the signals for 4-vinylbenzoic acid, formed by HCL
:~9Z~96 _ 9 _ elimination, can be clearly detected in addition to the usual s;gnals for 4-(2'-chloroethyl)ben-zoic acid (see Example 1).
1H-NMR data (solvent: DMSO-D6) of 4-vinylbenzoic acid:
values in ppm coupling assigned protons constants Doublet-doublet 5.41 10 Hz + 1 Hz Ar-C=C-H, trans Doublet-doublet 5.97 18 Hz + 1 Hz Ar-C=C-H, cis Doublet-doublet 6.82 18 Hz +10 Hz Ar-CH=C
Doublet (broad) 7.60 8 Hz aromat. H, ortho to vinyl Doublet (broad) 7.94 8Hz aromat. H, ortho to carboxyl Singlet tbroad) 12.95 -COOH
Sample content according to GC after silylation with MSTFA:
88% of 4-~2'-chloroethyl~benzoic acid 6% of 4-vinylbenzoic acid about 6% of additional substances.
Example 5 25 4.6 mol of sodium hypochlorite ~342.4 g) were initially introduced in the form of an aqueous alkaline NaOH solution (about 2167 ml of sodium hypochlorite solution having an NaOCl content of 0.158 g/ml and a pH of 12 to 13) at about 25C. 1.5 mol of 4-(2'-chloroethyl)aceto-phenone (274 9 having a content of 94 % by weight, as in Ex-ample 1), dissolved in 90 ml of diethylene glycol dimethyl ether, were added thereto, and the reaction mixture was stirred without additional warming. After stirring for about one hour, the reaction mixture began to warm noticeably, and the reaction temperature was kept between 34 and 45C by external cooling~ The exothermic reaction phase lasted about an hour. The mixture was then stirred for an additional two hours, during which the internal temperature fell to room ~Z9Z996 temperature. The 4-(2'-chloroethyl)benzoic acid was precipitated at a pH of 1 to 2 by addition of hydrochloric acid, filtered off under suction and ~ashed ~ith water.
After drying, 269 9 of 4-(2'-chloroethyl)benzoic acid ~97.1X of theory) having a melting point of 177 to 180C
~ere obtained.
Sample content: 94% of 4-(2'-chloroethyl)benzoic acid, determined by GC after silylation using MSTFA.
Example 6 4.7 mol of sodium hypochlorite (349.9 9) were initially introduced in the form of an aqueous alkaline NaOH
solution ~about 2200 ml of sodium hypochlorite solution having an NaOCl content of 0.159 g/ml and a pH of 12 to 13) at 25C. 1.5 mol of 4-~2'-chloroethyl)acetophenone (274 9 having a content of 94 % by weight, as in Example 1), dissolved ;n 90 ml of tetrahydrofuran, were added thereto, and the react;on mixture was stirred without additional warming. After stirring for about one hour, the reaction mixture warmed noticeably, and the reaction temperature ~as kept between 35 and 40C by external cool-ing. After the end of the exothermic reaction phase, the internal temperature was allowed to fall to room tempera-ture and the 4-(2'-chloroethyl)benzoic acid was isolated as described in Examples 1 and 2. 263 9 of 4-(2'-chloro-ethyl)benzoic acid (95X of theory) were obtained after drying; the melting point was 178 to 180C.
Sample content: 94Z of 4-(2'-chloroethyl)benzoic acid;
determined by GC after silylation using MSTFA.
Example 7 3.2 mol of sodium hypochlorite (238.2 9) ~ere initially introduced in the form of an aqueous alkaline HaOH solution at 25C (about 1517 ml of a sodium hypochlorite solution having an NaOCl content of 0.157 g/ol and a pH of 12 to ~Z9~996 13). 1 mol of 4-(2'-chloroethyl)acetophenone (182.65 9 having a content of 94 Z by ~eight, as in Example 1) was added thereto. The mixture was stirred without additional warming. After stirr;ng for about 1.5 hours, the tempera-ture of the batch began to climb noticeably, and thereaction temperature was kept between 37 and 40C by external cooling. In this ~ay, the exothermic reaction phase lasted about an hour. The mixture was then stirred for a further 2 hours, during which the internal tempera-ture fell to room temperature. The isolation, purifica-tion and drying of the product was as described in Examples 1 and 2.
After drying 176 9 of 4-(2'-chloroethyl)benzoic acid (95.3%
of theory) having a melting point of 178 to 182C
remained.
Sample content: 95% of 4-(2'-chloroethyl)benzo;c acid;
determined by 6C after s;lylation using MSTFA.
Example 8 3.2 mol of sodium hypochlorite (238.2 g) ~ere initially introduced in the form of an aqueous alkaline NaOH solution - prewarmed to 40C - (about 1567 ml of a sodium hypochlo-rite solution having an NaOCl content of 0.152 g/ml and a pH of 12 to 13). A solution of 1 mol of 4-(2'-chloroethyl)-acetophenone (182.65 9 having a content of 94 X by weight, as in Example 1), dissolved in 80 ml of 1,2-dimethoxyethane, was steadily added drop~ise thereto during the course of 2.5 hours, with continuous stirring.
About half an hour after beginning the addition a tem-perature increase above 40C was observed. ~y gentle external cooling, it was easily possible to keep the re-action temperature in the range from 40 to 45C, since due to the slow rate of addit;on, only a small amount of substance was available for the exothermic reaction in each lZ9Z996 case. After the end of the addition and the subsiding of the exothermic reaction phase, the mixture was stirred for a further 2 hours at about 35C. The 4-(2'-chloroethyl)-benzo;c acid was precipitated from its sodium salt at a pH
of 1 to 2 by addition of hydrochloric acid~ The precipitate was filtered off under sùction and washed with water.
After drying at 50 to 60C under reduced pressure for about 20 hours, 177 9 of 4-(2'-chloroethyl)benzoic acid (95.8%
of theory) having a melting point of 177 to 183C were obtained.
Sample content: 93% of 4-(2'-chloroethyl)benzoic acid;
determined by GC after silylation using MSTFA.
After recrystallization from methanol the melting point was 186 to 187C; the recrystallized 4-(2'-chloroethyl)-benzoic acid was an at least 99% pure product.
Example 9 (Convers;on of 4-~2'-chloroethyl)benzoic acid into 4-vinyl-benzoic ac;d) 2.0 mol of 4-(2'-chloroethyl)benzoic acid (369.2 g) were introduced in portions, bùt rapidly, with continuous stirring into a solution of 6.0 mol of potassiu~ hydroxide (336.7 g) in 1000 ml of methanol, prewarmed to 70C, and an exothermic reaction was observed. The mixture was then heated to boiling for 5 hours. ~hen the reaction was com-plete, the reaction mixture was cooled to about 0C and the precipitated potassium salt of 4-vinylbenzoic acid was filtered off under suction~ This salt was dissolved in 1800 ml of water and the 4-vinylbenzoic acid was liberated at pH 1 to 2 by addition of hydrochloric acid.
The acid was filtered off under suction, washed with water and the still wet 4-vinylbenzoic acid was taken up in methyl tert.-butyl ether. After removal of the remain;ng water, the solution was dried over sodium sulfate, and concentrated to obtain 249.7 g of 4-vinylbenzoic acid lZ9Z996 (B4.3% of theory) having a melting point of 136 to 139C
(with decomposition).
The 1H-NMR data were identical with the data given in Ex-ample 4 for the 4-vinylbenzoic acid resulting as a by-product there.
Sample content: 96~ of 4-vinylbenzoic ac;d; determ;ned by GC after silylation using MSTFA.
Claims (4)
1. A process for the preparation of 4-(2'-chloroethyl)ben-zoic acid from 4-(2'-chloroethyl)acetophenone, which process comprises reacting 4-(2'-chloroethyl)acetophenone with an aqueous alkaline solution of sodium hypochlorite and/or potassium hypochlorite at temperatures between 25°C
and 110°C and then acidifying the solution using a strong inorganic acid.
and 110°C and then acidifying the solution using a strong inorganic acid.
2. The process as claimed in claim 1, wherein the reaction is carried out at temperatures between 28°C and 60°C.
3. A process for the preparation of an aqueous solution of the sodium and/or potassium salt of 4-(2'-chloroethyl)-benzoic acid from 4-(2'-chloroethyl)acetophenone, which process comprises reacting 4-(2'-chloroethyl)acetophenone with an aqueous alkaline solution of sodium hypochlorite and/or potassium hypochlorite at temperatures between 25°C
and 110°C.
and 110°C.
4. The process as claimed in claim 3, wherein the reaction is carried out at temperatures between 28°C and 60°C.
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| CA000553206A CA1292996C (en) | 1987-12-01 | 1987-12-01 | Process for the preparation of 4-(2'-chloroethyl)- benzoic acid |
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| CA000553206A CA1292996C (en) | 1987-12-01 | 1987-12-01 | Process for the preparation of 4-(2'-chloroethyl)- benzoic acid |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115888844A (en) * | 2022-11-22 | 2023-04-04 | 华烁科技股份有限公司 | Palladium catalyst, preparation method and application thereof, and synthetic method of p-vinylbenzoic acid |
-
1987
- 1987-12-01 CA CA000553206A patent/CA1292996C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115888844A (en) * | 2022-11-22 | 2023-04-04 | 华烁科技股份有限公司 | Palladium catalyst, preparation method and application thereof, and synthetic method of p-vinylbenzoic acid |
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