United States Patent (19) (11) 4,307,034 Nakayama Et Al

United States Patent (19) (11) 4,307,034 Nakayama et al. 45) FDec. 22, 1981

54) INERT ORGANIC SOLVENT DISPERSION 52 U.S. Cl...... 260/465 G; 252/309; OF ALKALI. HYDROXDE AND REACTION 260/465 R; 260/465 D; 260/465 F; 260/465 H; USING THE SAME 260/465 K; 260/465.4; 260/465.8 R; 560/51; 560/82; 560/178; 560/190; 562/405; 562/459; 562/489; 562/495; 562/496; 562/590; 562/595; 75) Inventors: Yoshiki Nakayama, Shimizu; Taro 568/316; 568/376; 568/393; 568/433; 568/458; Izawa, Shizuoka; Yasushi Higuchi, 568/459 Shizuoka; Yutaka Ohishi, Shizuoka; 58) Field of Search ...... 260/465 R, 465 G, 465 H, Chihiro Yazawa, Yokohama, all of 260/465.4, 465 F, 465 D, 465 K, 465.8 R; Japan 560/51, 82, 190, 178; 562/489, 495, 496, 590, 595, 405, 459; 568/316, 376, 393, 458, 459, 433 56) References Cited 73) Assignee: Ihara Chemical Industry Co., Ltd., U.S. PATENT DOCUMENTS Tokyo, Japan 3,755,412 8/1973 Taranko et al...... 260/465 R 4,012,428 3/1977 Ohno et al...... 260/465 G 4,062,968 12/1977 Fujimoto et al...... 424/304X (21) Appl. No.: 75,314 Primary Examiner-Dolph H. Torrence Attorney, Agent, or Firm-Oblon, Fisher, Spivak, McClelland & Maier 22 Filed: Sep. 13, 1979 57 ABSTRACT An inert organic solvent dispersion of alkali hydroxide is prepared by mixing an alkali hydroxide, an inertor 30 Foreign Application Priority Data ganic solvent and a stabilizer and heating and stirring at the temperature for forming the pasty alkali hydroxide Sep. 26, 1978 JP Japan ...... 53/118501 and cooling the dispersion. The dispersion of alkali Oct. 30, 1978 JP Japan ...... 53/133379 hydroxide is used in a reaction of an active methylene Oct. 30, 1978 JP Japan ...... 53/133380 compound with an organoalkyl halide such as a reac tion of a halophenylacetonitrile with an isopropyl hal ide to obtain ot-isopropyl halophenylacetonitrile. 51) Int. Cl...... C07C 121/66; CO7C 53/34; CO7C 55/08; C07C 121/22 8 Claims, No Drawings 4,307,034 1. 2 lene compound with an organoalkyl halide in the pres INERT ORGANIC SOLVENT DISPERSION OF ence of an alkali hydroxide. ALKALI. HYDROXIDE AND REACTION USING (1) The reaction is carried out in the presence of an THE SAME alkali hydroxide (Organic Reactions Vo. 9, page 107). (2) The reaction is carried out in a reaction medium of BACKGROUND OF THE INVENTION an aprotic polar solvent such as dimethylsulfoxide (J. Org. Chem. Vol. 34, pages 226, 1969). 1. Field of the Invention (3) The reaction is carried out in the presence of a The present invention relates to a process for prepar catalyst of a quaternary ammonium salt (Acta. Chem. ing an inert organic solvent dispersion of an alkali hy 10 Scand. Vol. 23, page 2204, 1969; Tetrahedron Lett. Vol. droxide. More particularly, it relates to a process for 15, 1273, 1973; Tetrahedron Vol. 32, page 2235, 1976). preparing an inert organic solvent dispersion of fine One of the important examples of the reaction of the alkali hydroxide particles having a diameter of order of active methylene compound with an organoalkyl halide mu to u such as 100 mu to 500u. is the production of a-isopropyl halophenylacetonitrile. The present invention also relates to a reaction using 15 (1) The reaction is carried out in the presence of a the same. More particularly, it relates to the reaction of condensing agent such as alkali metals, alkali metal an active methylene compound with an organoalkyl alcoholates, alkali metal halides or alkali metal amides halide to produce methylene organoalkylated com (Japanese Unexamined Patent Publication No. pounds useful as intermediates of agricultural chemicals 5350/1975). and medicines. More particularly, it relates to a process (2) The reaction is carried out in the presence of a for producing methylene organoalkylated compounds condensing agent of an alkali hydroxide in a medium of by reacting an active methylene compound with an an aprotic polar solvent such as dimethylsulfoxide and organoalkyl halide in the presence of an alkali hydrox dimethylformamide (Japanese Unexamined Patent Pub ide. lication No. 154217/1975). 2. Description of the Prior Arts 25 (3) The reaction is carried out in the presence of a Heretofore, it has been difficult to obtain fine alkali condensing agent of an alkali hydroxide and a catalyst hydroxide particles because of strong hygroscopic of a quaternary ammonium salt (Japanese Unexamined property of the alkali hydroxide. patent Publication No. 6314.5/1976). On the other hand, an aqueous solution of a base such as alkali hydroxides or carbonates has been used for 30 SUMMARY OF THE INVENTION reactions of a halogenated compound with a compound It is an object of the present invention to provide a having an activated hydrogen atom, such as a condensa process for preparing an inert organic solvent disper tion reaction. sion of fine alkali hydroxide particles having a diameter When an aqueous solution of a base is used for the of 100 mu to 500. condensation reaction such as dehydrohalogenation, 35 It is another object of the present invention to pro the product may be decomposed because of the aqueous vide a process for preparing an inert organic solvent solution of a base. dispersion of alkali hydroxide which is used for a con In order to overcome the problem, it has been consid densation reaction of a halogenated compound with a ered to use a solid base such as alkali hydroxides or compound having an active hydrogen. carbonates. However, alkali hydroxides are hygro The foregoing and other objects of the present inven scopic and are insoluble in an inert organic solvents. tion have been attained by mixing a solid alkali hydrox However, these conventional processes have various ide, and an inert organic solvent and heating and stir disadvantages and are not satisfactory process as the ring the mixture and cooling the mixture in the dis industrial process. persed form. In the process (1), the condensing agent is remarkably 45 The mixture is heated so as to form a pasty alkali reactive with water and accordingly, the activity of the hydroxide in the inert organic solvent. condensing agent is decreased by the contamination of The stirring is carried out so as to form fine particles water to decrease the yield of the object compound. of the alkali hydroxide. The stirring is continued after The explosive reaction may be caused by reacting the starting the cooling. It is preferable to add a stabilizer. condensing agent with water to cause firing. Thus, the 50 The reaction of an active methylene compound with storage and maintenance of the starting materials and an organoalkyl halide is carried out by using the inert the operation for the reaction are quite difficult to be organic solvent dispersion of fine alkali hydroxide disadvantageous. whereby a methylene organoalkylated compound hav In the process (2), the expensive and water soluble ing high purity can be obtained in high yield without aprotic polar solvent such as dimethylsulfoxide is used 55 using an expensive aprotic polar solvent such as di as the solvent. This is not easily recovered. Thus, it is methyl sulfoxide and without a recovery of a catalyst disadvantageous from the economical viewpoint. such as a quarternary ammonium salts. In the process (3), the expensive and water soluble quaternary ammonium salt is used as the catalyst. The DETAILED DESCRIPTION OF THE discharge of the quaternary ammonium salt in a drain 60 PREFERRED EMBODIMENTS age can not be prevented whereby the nitrogen content The dispersion of the alkali hydroxide is prepared by in river, sea or lake is increased to cause the environ using the inert organic solvent which is suitable for mental pollution. Thus, it is disadvantageous from the swelling the alkali hydroxide to form the pasty alkali economical viewpoint. hydroxide in the solvent at the elevated temperature. It The inventors have studied to overcome these disad 65 is preferable to use the inert organic solvent which can vantages of the conventional processes. be used in the atmospheric pressure. The detail of the It has been well-known to produce methylene or operation for the preparation of the dispersion will be ganoalkylated compounds by reacting an active methy described. 4,307,034 3 4 Suitable inert organic solvents include aromatic hy Suitable quaternary ammonium salts include lauryl drocarbons such as benzene, toluene and xylene; halo trimethylammonium chloride and stearyltrimethylam genated aromatic hydrocarbons such as chlorobenzene monium chloride and alkylbenzyldimethylammonium and chlorotoluene; halogenated aliphatic hydrocarbons chloride. such as chloroform and carbon tetrachloride and other Suitable perfluoroalkyl surfactants include per solvents which have boiling point of higher than 100° C. fluoroalkylsulfonate, such as perfluorooctylsulfonate; preferably higher than 120° C. perfluoroalkylsulfonylamine derivatives such as per The stirring operation is easily carried out and the fluorooctylsulfonylamine hydrohalide, perfluorooctyl hygroscopic property of the alkali hydroxide can be sulfonylpropylamine ethyleneoxide adduct and -sul prevented and the formation of fine particles of the O fonylbenzylamine ethyleneoxide adduct. alkali hydroxide can be promoted by stirring and solid The amount of the stabilizer is usually more than alkali hydroxide in said inert organic solvent. 0.0001 wt.% preferably more than 0.001 wt.% espe The amount of the inert organic solvent should be cially more than 0.01 wt.% to the alkali hydroxide. The enough to stir the mixture and is preferably more than 2 stabilizer can be a mixture of said compounds. The times of the alkali hydroxide. 15 stabilizer is to prevent the coagulation of the dispersed The stabilizers can be the compounds having the alkali hydroxide in the inert organic solvent by adsorb formula ing it on the surface of the fine alkali hydroxide particles whereby the formation of fine particles of the alkali hydroxide is improved and to prevent a deposition of 20 the alkali hydroxide on the inner wall of the reactor. The stabilizer should have hydrophilic property so as to be adsorbed on the surface of the alkali hydroxide in wherein R and R are respectively hydrogen atom or the inert organic solvent which is not hydrophilic sol C1-C4 alkyl group and X represents oxygen or sulfur Vent. atom; m and n are respectively 1 or more than 1; and 25 The heating and stirring of the mixture of the alkali polyoxyethylene type nonionic surfactants, fatty acid hydroxide and the inert organic solvent are preferably sorbitan esters, fatty acid glycerol monoesters and fatty carried out near the boiling point of the solvent. When acid sugar esters, quaternary ammonium salts, fatty the inert organic solvent having low boiling point is amines and perfluoroalkyl surfactants. used, it is preferable to carry out under higher pressure. Suitable stabilizers include; monoalkyl glycol ethers 30 It is preferable to carry out the stirring at higher than e.g. monomethyl, monoethyl, monopropyl or mono 120° C. in the atmospheric pressure. The temperature stearyl glycol ethers; dialkyl glycol ethers e.g. di can be decreased under higher pressure. methyl, diethyl, dipropyl or dibutyl glycol ethers; gly The stirring should be enough to disperse the alkali cols such as polymethyleneglycol, ethyleneglycol, di hydroxide in the inert organic solvent, with or without ethyleneglycol, triethyleneglycol, tetraethyleneglycol, 35 the stabilizer. The stirring method is not critical. Suit hexaethyleneglycol, pentaethyleneglycol, iso able stirrer, homomixer, ultrasonic disperser orjet dis propyleneglycol, polyethyleneglycol, propyleneglycol, perser can be used to apply share enough to disperse the dipropyleneglycol, tripropyleneglycol, trapropyleneg alkali hydroxide. lycol, polypropyleneglycol and 1,4-butanediols; polyvi When a stirrer is used, the stirrer is preferably rotated nyl ethers; monoalkylsulfides e.g. monomethyl, mono 40 at greater than 500 rp.m. preferably greater than 1,000 ethyl, monopropyl and monobutyl sulfides; dialkylsul r.p.m. It is possible to stir at greater than 3,000 r.p.m. fides e.g. dimethyl, diethyl, dipropyl and dibutyl sul such as 10,000 r.p.m. as used in the homogenizer. fides; thioglycols such as ethylenethioglycol, die The ultrasonication or the jet dispersion is preferably thylenethioglycol, triethyleneglycol, tetraethylenethio applied together with the mechanical stirring so as to glycol, polyethylenethioglycol and polymethylenethio 45 share the alkali hydroxide. glycol; polyoxyethlene type nonionic surfactants; fatty The melting point of the alkali hydroxide is usually acid sorbitan esters; fatty acid glycerol monoesters; high as 360.4° C. of KOH and 328° C. of NaOH. In the Sugar esters; fatty amines; quaternary ammonium salts; operation, the alkali hydroxide is dispersed at lower and perfluoroalkyl surfactants. than the melting point of the alkali hydroxide, however Suitable polyoxyethylene type nonionic surfactants 50 the alkali hydroxide is preferably pasty in the inertor include polyoxyethylenealkyl esters such as polyoxye ganic solvent at the elevated temperature. thylenedodecyl ether, polyoxyethyleneoctadecyl ether The dispersion of fine alkali hydroxide particles hav and polyoxyethylenenonyl ether; polyoxyethylenealk ing orders of mu to u such as 100 mu to 500u can be ylaryl ethers such as polyoxyethylenenonylphenyl obtained by the process of the present invention. It is ehter, polyoxyethylene fatty acid esters such as polyox 55 possible to separate the organic solvent from the disper yethylenestearate and polyoxyethylenedistearate; po sion by a filtration or a distillation to obtain the fine lyoxyethylenesorbitane fatty acid esters such as polyox alkali hydroxide powder which can be dispersed in a yethylenesorbitanemonolaurate, -monoparamitate, desired solvent. It is preferable to use an inert organic -monostearate, -monooleate, -tristearate, and -trioleate; solvent which is used for the reaction of a halogenated polyoxyethylenealkylamine such as polyoxyethylene compound with a compound having active hydrogen dodecylamine. aton. The dispersion of the fine alkali hydroxide in said Suitable fatty acid sorbitane esters include sor solvent can be used for the reaction without the separa bitanemonolaurate, -monoparmitate, -monostearate, tion or the exchange of the solvent. -monooleate, -tristearate, -trioleate and -sesquioleate. In accordance with the process of the present inven Suitable fatty acid esters include glycerol monostea 65 tion, the dispersion of fine alkali hydroxide or fine alkali rate and glycerol monooleate. hydroxide powder can be easily obtained, and more Suitable fatty amines include oleyl dimethylamine, over the adhesion of the alkali hydroxide on the inner coconut oil dimethylamine and lauryl dimethylamine. wall of the reactor can be prevented. These are remark 4,307,034 5 6 ably advantageous. The size of the resulting particles of a-methylphenylacetonitrile, a-methoxyphenylacetoni the alkali hydroxides is controlled by the stirring trile, 3-cyanophenylpropionitrile, diphenylacetonitrile, method to give 100 mu to 500. propionaldehyde, cyclohexanone, and 2-methylcy The dispersion of fine alkali hydroxide is remarkably clohexanone and their derivatives. effective for condensation reactions such as alkylations Suitable organoalkyl halides include alkyl halides especially alkylation of active methylene group. such as methyl, ethy, propyl, butyl, pentyl, hexyl, octyl The inert organic solvent dispersion of an alkali hy and nonyl halides; dihalides thereof such as dihaloe droxide is the novel important reactant for the reaction thanes, dihalopropanes, dihalobutanes; trihalides of an active methylene compound with an organoalky thereof; aralkyl halides such as benzyl halides; vinyl halide. 10 halides; alkyl vinyl halides; haloacetyl compounds such The organoalkyl halide is added to the inert organic as haloacetonitriles and haloacetates. solvent dispersion of an alkyl hydroxide and the active The organoalkyl compound is used at molar ratio of methylene compound is added to it so as to react them. 1 to 5 based on the active methylene compound. The reaction of the active methylene compound with The example of the production of a-isopropyl halo the organoalkyl halide is carried out in a dispersion of 5 fine alkali hydroxide particles having diameter of less phenylacetonitrile will be further illustrated. than several hundred microns as the condensing agent. As one typical example, the reaction of halo A dispersion of fine potassium hydroxide in an inert phenylacetonitrile with isopropyl halide to produce organic solvent is preferably used. The reaction is a-isopropyl halopheylacetonitrile will be illustrated. smoothly performed without a special condensing agent 20 The dispersion of the alkali hydroxide in an inert nor a special solvent nor a special catalyst to obtain organic solvent can be used at a molar ratio of 1 to 10 a-isopropyl halophenylacetonitrile having high purity preferably 3 to 6 based on the halophenylacetonitrile. in high yield. Suitable halophenylacetonitriles include 2-chloro In the process of the present invention, a dispersion of phenylacetonitrile, 3-chlorophenylacetonitrile, 4 fine alkali hydroxide is admixed with the organoalkyl 25 chlorophenylacetonitrile, 4-bromophenylacetonitrile, halide and the active methylene compound is added to 3-fluorophenylacetonitrile and 4-fluorophenylacetoni react them. trile. The reaction temperature is in a range of 0 to 150 C. Suitable isopropyl halides include isopropyl bromide preferably 20' to 60° C. The reaction is carried out and isopropyl chloride. under the atmospheric pressure or the elevated pres 30 The isopropyl halide is used at a molar ratio of 1 to 5 sure. The reaction time is preferably 0.5 to 1 hour and is based on the halophenylacetonitrile. not critical. The alkali hydroxides include sodium hydroxide and The reaction solvent is not critical and is preferably potassium hydroxide. an inert organic solvent such as benzene, toluene, xy The process of the present invention is remarkably lene, chlorobenzene and dichlorotoluene. 35 effective and has the following advantages in compari The dispersion of fine alkali hydroxide can be ob son with the conventional process and is remarkably tained by mixing an alkali hydroxide such as potassium advantageous as an industrial process. hydroxide and a stabilizer and an inert organic solvent Firstly, a dimer of halophenylacetonitrile having the such as benzene, toluene, xylene, chlorobenzene and dichlorotoluene and heating and stirring the mixture to formula disperse the alkali hydroxide and cooling the dispersion. 40 The stabilizer can be the compound having the formula gN CH2C-CH R 45 NH RX---CH)x--R wherein Y represents a halogen atom is not substantially formed and amounts of the other by-products are also wherein R and R' are respectively hydrogen atom or remarkably small. Thus, the object compound having C1-C4 alkyl group; X represents oxygen or sulfur atom; high purity can be obtained in high yield. m and n are respectively 1 or more than 1; and polyoxy 50 ethylene type nonionic surfactants, fatty acid sorbitan Secondly, an aprotic polar solvent such as dimethyl esters, fatty acid glycerol monoesters, fatty acid sugar sulfoxide, is not used. Thus, the solvent can be easily esters, quaternary ammonium salts, fatty amines; perflu recovered. The a-isopropyl halophenylacetonitrile can oroalkyl surfactsnts, powdery titanium oxides and pow be obtained by an industrial process in low cost. dery zirconium oxides. 55 Thirdly, a catalyst such as a quaternary ammonium The amount of the fine alkali hydroxide is at a molar salt is not used. Thus, it is unnecessary to have a step of ratio of 1 to 10 preferably 3 to 6 based on the active recovery of a catalyst, the treatment of the discharged methylene compound. water can be easy to prevent an environmental pollu The active methylene compounds can be various tion. compounds having active methylene group. EXAMPLE 1. Suitable active methylene compounds include ma lonic nitrile, malonic acid, diethyl malonate, cyanoace In a 500 ml. reactor made of stainless steel (SUS) tic acid, methyl cyanoacetate, acetylacetic acid, methyl equipped with a stirrer, 52.08 g. of solid potassium hy acetylacetate, acetylacetone, phenylacetonitrile, 4 droxide (96% KOH), 200 ml. of xylene and 0.05 g. of ethylphenylacetonitrile, 3,4-dimethylphenylacetoni 65 polypropyleneglycol (M. W. 1,000) (0.1 wt.% to KOH) trile, 3-trifluoromethylphenylacetonitrile, phenylacetic were charged and heated at 140° C. and stirred at 2000 acid, 4-chlorophenyl acetic acid, 2-bromophenyl acetic r.p.m. for about 15 minutes and then, cooled to room acid, 4-ethylphenyl acetic acid, phenylthioacetonitrile, temperature during the stirring. 4,307,034 7 8 A dispersion of fine potassium hydroxide in xylene 10. No adhesion of potassium hydroxide on the inner was obtained. wall of the reactor was not found. According to the microscopic observation, the fine potassium hydroxide had particle sizes of 100 mu to EXAMPLE 9 10. No adhesion of potassium hydroxide on the inner In accordance with the process of Example 8 except wall of the reactor was not found. using solid sodium hydroxide instead of the solid potas sium hydroxide, the dispersion of fine sodium hydroxide EXAMPLE 2 was prepared. The result was the same as that of Exam In accordance with the process of Example 1 except ple 8. using polyethyleneglycol (M. W. 600) instead of poly 10 propyleneglycol, a dispersion of fine potassium hydrox REFERENCE 1 ide in xylene was prepared. The fine potassium hydrox In accordance with the process of Example 1 except ide had particle sizes of 100 mu to 10p. No adhesion of eliminating polypropyleneglycol, a dispersion of fine potassium hydroxide on the inner wall of the reactor potassium hydroxide in xylene was prepared. An adhe was found. 15 sion of potassium hydroxide on the inner wall of the EXAMPLE 3 reactor was found though a dispersion of fine potassium hydroxide was formed. In accordance with the process of Example 1 except using solid sodium hydroxide instead of the solid potas REFERENCE 2 sium hydroxide, the dispersion of fine sodium hydroxide 20 In accordance with the process of Example 1 except was prepared. The result was the same as that of Exam eliminating polypropyleneglycol, and using solid so ple 1. dium hydroxide instead of solid potassium hydroxide, a EXAMPLE 4 dispersion of fine sodium hydroxide in xylene was pre pared. An adhesion of sodium hydroxide on the inner In accordance with the process of Example 1 except 25 using polyoxyethylene sorbitanmonolaurate (E. O. 20) wall of the reactor was found though a dispersion of instead of polypropyleneglycol and sitrring for 30 min fine sodium hydroxide was formed. utes, a dispersion of fine potassium hydroxide in xylene REFERENCE 3 was prepared. The fine potassium hydroxide had parti In accordance with the process of Example 1 except cle sizes of 100 mu to 10. No adhesion of potassium 30 eliminating polypropyleneglycol, and stirring at room hydroxide on the inner wall of the reactor was found. temperature, a dispersion of potassium hydroxide in EXAMPLE 5 xylene was prepared. The particles of potassium hy In accordance with the process of Example 4 except droxide were polygon and coarse. using solid sodium hydroxide instead of the solid potas 35 EXAMPLE 10 sium hydroxide, the dispersion of fine sodium hydroxide was prepared. The result was the same with that of In a 500 ml. reactor made of stainless steel (SUS) Example 4. equipped with a stirrer, 52.08 g. of solid potassium hy droxide (96% KOH), 200 ml. of xylene and 0.05 g. of EXAMPLE 6 polypropyleneglycol (M. W. 1,000) (0.1 wt.% to KOH) In accordance with the process of Example 1 except were charged and heated at 140 C. and stirred at 2000 using chlorobenzene, chlorotoluene, toluene, chloro r.p.m. for about 15 minutes and then, cooled to room form or carbon tetrachloride, instead of xylene, each temperature during the stirring. dispersion of fine potassium hydroxide was prepared. A dispersion of fine potassium hydroxide in xylene The result was the same as that of Example 1. 45 was obtained. In the dispersion, 26 g. (0.33 mole) of isopropyl chlo EXAMPLE 7 ride was charged and then, 34 g. (0.22 mole) of 4 In accordance with the process of Example 1 except chlorophenylacetonitrile was added dropwise during 10 using polyoxyethylene stearate, polyoxyethylene non minutes at room temperature with stirring the mixture ylphenyl ether, polyoxyethylene dodecyl ether, sorbi 50 and then, the mixture was further stirred at 70 to 80 C. tan monolaurate, fatty acid sugar ester, or glycerin for 50 minutes to react them. monostearate instead of polypropyleneglycol, each dis After the reaction, the reaction mixture was poured persion of fine potassium hydroxide was prepared. The into 300 ml. of water. The organic layer was separated result was the same as that of Example 1. and concentrated to distill off xylene and the product These results are observed by the microscope as the 55 was distilled under a reduced pressure to obtain 40.4 g. microscopic photographs. of a-isopropyl-4-chloro-phenylacetonitrile having a boiling point of 104°-106° C./1 mmHg (yield 95%). EXAMPLE 8 In a 500 ml. reactor made of stainless steel (SUS) REFERENCE 4 equipped with a homomixer, 52.08 g. of solid potassium In a mortar, 50 g (0.89 mole) of potassium hydroxide hydroxide, 200 ml. of xylene and 0.05 g. of polyoxyeth was pulverized in 200 ml. of xylene to obtain a disper ylene sorbitan monolaurate (E. O. 20) were charged and sion of fine potassium hydroxide in xylene. heated at 140 C. (potassium hydroxide was pasty). The In accordance with the process of Example 10 except homomixer was rotated at 10,000 r. p.m. for 30 minutes using said dispersion of fine potassium hydroxide in and the dispersion was cooled to the room temperature 65 stead of the dispersion of fine potassium hydroxide during the stirring. having a diameter of less than 100pu in xylene, and vary According to the microscopic observation, the fine ing the reaction time to 8 hours, the process was re potassium hydroxide had particle sizes of 100 mu to peated to obtain. 29.8 g. of a-isopropyl-4-chloro 4,307,034 10 phenylacetonitrile having a boiling point of 102” to 106 After the reaction, the reaction mixture was poured C./1 mmHg (yield of 70%). into 300 ml. of water and the organic layer was sepa rated and concentrated to distill off xylene and the prod EXAMPLE 11 to 15 uct was distilled under a reduced pressure to obtain 43 In accordance with the the process of Example 10, 5 g. (yield of 91%) of a-isopropyl-4-chlorophenylacetic the halophenylacetonitrile and isopropyl halide shown acid (m.p. 88-89° C). in the following table were used to obtain the corre sponding a-isopropyl halophenylacetonitriles. EXAMPLE 23 The results are shown in Table. In accordance with the process of Example 22, ex 10 cept using 36 g. (0.89 mole) of sodium hydroxide instead TABLE of 50 g. (0.89 mole) of potassium hydroxide and using Starting material 40.6 g. (0.33 mole) ofisopropyl bromide instead of 26 g. halophenylacetonitrile isopropyl halide (0.33 mole) of isorpopyl chloride, the reaction and the Exp. 11 2-chlorophenylacetonitrile isopropyl bromide treatment were carried out to obtain 38.0 g (yield of Exp. 12 3-chlorophenylacetonitrile isopropyl chloride 15 Exp. 13 4-bromophenylacetonitrile 81.2%) of a-isopropyl-4-chlorophenyl acetic acid. Exp. 14 3-fluorophenylacetonitrile Exp. 15 4-fluorophenylacetonitrile EXAMPLE 24 to 44 In accordance with the process of Example 22 the active methylene compounds and the halides shown in 20 the following table were used to obtain the correspond Product ing product. The results are shown in Table. a-isopropyl halophenyl- Yield Boiling point TABLE acetonitrile (%) (C./mmHg) Exp. 11 a-isopropyl-2-chlorophenyl- 90.5 105-106/1.1 Starting materials acetonitrile Active methylene compound Halides Exp. 12 a-isopropyl-3-chlorophenyl- 92 105-107/0.3 Exp. 24 diethyl malonate 1,2-dibromoethane acetonitrile Exp. 25 ethyl cyanoacetate n-butyl iodide Exp. 13 a-isopropyl-4-bromophenyl- 95 92-94/0.12 Exp. 26 methyl acetylacetate benzyl chloride acetonitrile Exp. 27 4-t-butyl phenylacetonitrile isopropyl chloride Exp. 14 a-isopropyl-3-fluorophenyl- 91 87-88/4.97 Exp. 28 3-trifluoromethyl phenyl- isopropyl bromide acetonitrile 30 acetonitrile Exp. 15 a-isopropyl-4-fluorophenyl- 91.5 88-89/4.98 Exp. 29 phenylacetonitrile isopropyl chloride acetonitrile Exp. 30 a-ethylphenylacetonitrile 1,4-dichlorobutane Exp. 31 g-cyanophenyl propionitrile chloroacetonitrile Exp. 32 2-methyl cyclohexanone 3,3-dimethyl vinyl chloride EXAMPLE 16 35 Exp. 33 3,4-dimethoxyphenyl- methyl iodide acetonitrile In accordance with the process of Example 10 except Exp. 34 4-methoxyphenylacetic acid isopropyl bromide using 0.05 g. of polyoxyethylenesorbitane monolaurate Exp. 35 a-ethylphenylacetonitrile vinyl chloride Exp. 36 4-isopropylphenylacetonitrile isopropyl bromide as a stabilizer instead of polypropyleneglycol, the pro Exp. 37 4-methoxyphenylacetonitrile isopropyl bromide cess was repeated to obtain 40 g. of a-isopropyl-4- Exp. 38 3,4-dimethylphenylacetonitrile isopropyl chloride chlorophenylacetonitrile having a boiling point of 104 40 Exp. 39 phenylacetonitrile ethyl iodide to 106° C./mmHg (yield of 94%). Exp. 40 2,4-dichlorophenylacetonitrile methyl iodide Exp. 41 phenylacetic acid isopropyl bromide EXAMPLE 17 to 21 Exp. 42 4-isobutylphenylacetic acid methyl iodide Exp. 43 3,4-dichlorophenylacetonitrile methyl iodide In accordance with the process of Examples 11 to 15, Exp. 44 2,4,6-trimethylphenylacetonitrile ispropyl bromide the halophenylacetonitrile and isopropyl halide shown 45 in the above table were used except using polyoxye thylenesorbitane monolaurate as the stabilizer instead of TABLE polypropyleneglycol. Yield Melting point The results are as follows. Product (%) Boiling point 50 Exp. 24 cyclopropane-1,1-dicarboxylic 83 m.p. TABLE acid diethyl ester 139-141 C. Starting materials Product Yield (%) Exp. 25 ethyl a-n-butylcyanoacetate 91.3 bp. 129-131 C./ Exp. 17 same as Example 11 same as Example 11 90 22 mmHg Exp. 18 same as Example 12 same as Example 12 91 Exp. 26 methyl a-benzylacetylacetate 92.0 b.p. Exp. 19 same as Example 13 same as Example 13 94 55 98-09 C./ Exp. 20 same as Example 14 same as Example 14 89 0.05 mmHg Exp. 21 same as Example 15 same as Example 15 91 Exp. 27 a-isopropyl-4-t-butyl phenyl- 91.6 b.p. acetonitrile 92-95 C/ 0.25 mmHg EXAMPLE 22 Exp. 28 a-isopropyl-3-trifluoromethyl- 92.3 b.p. 60 phenylacetonitrile 96-97 C./ In the xylene dispersion of fine potassium hydroxide 5.1 mmHg Exp. 29 a-isopropylphenylacetonitrile 95.0 m.p. having particle diameter of less than 100 obtained by 50-52 C. the process of Example 1, 26 g. (0.33 mole) of isopropyl Exp. 30 a-ethyl-a-(1-chlorobutyl) 73.1 bp. chloride was charged, and then a solution of 37.5 g. phenylacetonitrile 152 C/ (0.22 mole) of 4-chlorophenylacetic acid in 50 ml. of 65 1.5 mmHg Exp. 31 g-cyano-6-(cyano acetyl) 86.0 m.p. xylene was added dropwise during about 10 minutes phenylpropionitrile 102-103' C. and then, the reaction was continued at 70-80 C. for Exp. 32 2-methyl-2-(3,3-dimethylvinyl)- 40.5 b.p. 50 minutes. cyclohexanone 190-200 C/ 4,307,034 11 12 TABLE-continued treating the mixture to form a dispersion of fine particles Yield Melting point of the alkali hydroxide having a diameter of 100 mu to Product (%) Boiling point 500u. 40 mmHg 5 2. A process according to claim 1 wherein a stabilizer Exp. 33 a-methyl-(3,4-dimethoxy- 90.2 b.p. is added to the inert organic solvent in the preparation phenyl)acetonitrile 52-155 C. of the dispersion of fine alkali hydroxide. Exp. 34 disopropyl-4-methoxyphenyl- 85.0 m.p. acetic acid 143-45 C. 3. A process according to claim 2 wherein the stabi Exp. 35 a-ethyl-a-vinylphenylaceto- 93.5 b.p. 116 C/ lizer is a hydrophilic compound which is adsorbed on nitrile 7 mmHg the surface of the alkali hydroxide in the inert organic Exp. 36 a-isopropyl-4-isopropylphenyl- 87.1 b.p. 10 solvent. acetonitrile 00-02 Cy 0.4 mmHg 4. A process according to claim 2 wherein the stabi Exp. 37 a-isopropyl-4-methoxyphenyl- 90.4 b.p. lizer is selected from the group consisting of com acetonitrile 95-96 C pounds having the formula 0.15 mmHg Exp. 38 a-isopropyl-3,4-dimethyl- 87.8 b.p. 15 phenylacetonitrile 93-95 C/ 0.5 mmHg Exp. 39 a-ethyl phenylacetonitrile 91.5 m.p. RX----CH)X--R 69-70 C. Exp. 40 a-methyl-2,4-dichlorophenyl- 92.0 b.p. wherein R and R' are respectively hydrogen atom or acetonitrile 102 CA 2O 0.9 mmHg C1-C4 alkyl group and X represents oxygen or sulfur Exp. 41 a-isopropyl phenylacetic acid 89.5 m.p. atom; n and n are respectively 1 or more than 1; and 62 C. polyoxyethylene type nonionic surfactants, fatty acid Exp. 42 a-methyl-4-isobutylphenyl- 88.7 m.p. aceticacid 75-76 C. sorbitan esters, fatty acid glycerol monoesters and fatty Exp. 43 a-methyl-3,4-dichlorophenyl- 89.6 b.p. 25 acid sugar esters, quaternary ammonium salts, fatty acetonitrile 08 C/ amines and perfluoroalkyl surfactants is added at a ratio 0.2 mmHg Exp. 44 at-isopropyl-2,4,6-trimethyl- 70.2 b.p. of more than 0.0001 wt.% to the alkali hydroxide. phenylacetonitrile 87-88 C.M 5. The method of claim 1 wherein said treating com 0.2 mmHg prises heating the mixture to form a paste and stirring 30 the mixture to form a dispersion of fine particles of the We claim: alkali hydroxide, and cooling the mixture in the dis 1. In a reaction of an active methylene compound persed form while continuing stirring to yield said di selected from the group consisting of malonic nitrile, ameter particles. malonic acid, diethyl malonate, cyanoacetic acid, 6. A process according to claim 5 wherein the mix methyl cyanoacetate, acetylacetic acid, methyl acety- 35 ture is heated near the boiling point of the solvent. lacetate, acetylacetone, phenylacetonitrile, 4-ethyl 7. A process according to claim 1 wherein the solvent phenylacetonitrile, 3,4-dimethylphenylacetonitrile, 3 is removed from the dispersion of the alkali hydroxide trifluoromethylphenylacetonitrile, phenylacetic acid, and another solvent is added to the alkali hydroxide. 4-chlorophenyl acetic acid, 2-bromophenyl acetic acid, 8. In a reaction of a halophenylacetonitrile with an 4-ethyl phenyl acetic acid, phenylthioacetonitrile, o- 40 isopropyl halide to produce a-isopropyl halo methylphenylacetonitrile, O-methoxyphenylacetoni phenylacetonitrile, the improvement characterized in trile, 3-cyanophenylpropionitrile, diphenylacetonitrile, that the reaction is carried out in an inert organic sol propionaldehyde, cyclohexanone and 2-methylcy vent dispersion of fine alkali hydroxide obtained by clohexanone with an organoalkyl compound selected mixing an alkali hydroxide and an inert organic solvent, from the group consisting of alkyl halides, aralkyl ha- 45 heating the mixture to form a paste and stirring the lides, vinyl halides, alkyl vinyl halides, haloacetonitriles mixture to form a dispersion of fine particles of the and haloacetates to produce a methylene organolk alkali hydroxide, and cooling the mixture in the dis ylated compound, the improvement characterized in persed form while continuing stirring to yield alkali that the reaction is carried out in an inert organic sol hydroxide particles having a diameter of 100 mu, to vent dispersion of fine alkali hydroxide obtained by 50 500u. mixing an alkali hydroxide and an inert organic solvent, 2 x k sk

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