United States Patent (19) 11) 4,189,580 Findeisen (45) Feb. 19, 1980

54 PROCESS FOR THE PREPARATION OF 3,457,293 7/1969 Sonobe et al...... 260/465 B NTRILES Primary Examiner-Dolph H. Torrence 75 Inventor: Kurt Findeisen, Odenthal, Fed. Rep. Attorney, Agent, or Firm-Sprung, Felfe, Horn, Lynch of Germany & Kramer 73 Assignee: Bayer Aktiengesellschaft, 57 ABSTRACT Leverkusen, Fed. Rep. of Germany A process for the preparation of a nitrile of the formula (21) Appl. No.: 932,599 22 Filed: Aug. 10, 1978 30 Foreign Application Priority Data wherein R represents an optionally substituted alkyl, Aug. 18, 1977 (DE) Fed. Rep. of Germany as a 2737210 cycloalkyl or aryl radical or an optionally substituted 5 51) Int. Cl...... CO7C2O/OO or 6-membered heterocyclic radical which may addi 52 U.S. Cl...... 544/301; 260/346.3; tionally be fused with a benzene ring and n' represents 1 260/359; 260/464; 260/465 B; 260/465.2; to 6 which comprises contacting a carboxylic acid of 544/334; 544/356 the formula 58) Field of Search ...... 260/464, 465 B, 465.2, 260/329 R, 346.3,359; 544/301, 334,356 R-(COOH) 56 References Cited wherein R and n' have the meanings given above with U.S. PATENT DOCUMENTS cyanogen chloride and/or cyanogen bromide at a tem 2,800,496 7/1957 Toland, Jr...... 260/465 B perature in the range of 100 to 300° C. 3,012,059 12/1961 Bezman ...... 260/465 B 3,131,209 4/1964 King ...... 260/465 B 3,341,566 9/1967 Nakaoka et al...... 260/465 B 8 Claims, No Drawings 4,189,580 1. 2 dehydration. However, the high temperatures required PROCESS FOR THE PREPARATION OF of 300' to 500 C. restrict this method to carboxylic NTRLES acids and nitriles which are particularly resistant to heat. (for example J. Amer. Chem. Soc. 38,2128 (1916)). The invention relates to a process for the preparation 5 A further process for the preparation of nitriles was of nitriles by reacting carboxylic acids with cyanogen described in U.S. Pat No. 2,377,795. From low-molecu chloride and/or cyanogen bromide. lar nitriles which are used in a large excess nitriles form A large number of methods are known for the prepa in the presence of an acid, the nitriles corresponding to ration of nitriles. It is possible to obtain nitriles for ex the acids. The disadvantages of this process are the high ample by 10 temperatures and the use of a silver-plated autoclave as the addition of HCN to C-C double bonds, well as the industrially unsatisfactory yields and the use the addition of HCN to C-O double bonds, of low-boiling nitriles, which have to firstofall be synthe the addition of HCN to C-N double bonds, sized. Furthermore, this process seems to be restricted the reaction of alkyl mineral acid esters with metal to the preparation of adipic acid dinitrile. cyanides, the condensation of aromatic diazonium salts 15 A process was found for the preparation of nitriles of with metal cyanides (Sandmeyer reaction), the conden the formula sation of cyanohalogens with Grignard compounds, Friedel-Crafts reactions of aromatic compounds with R-(CN), (I) dicyanogen, the dehydrogenation of amines, the elimi nation of water from aldoximes, the elimination of 20 in which water from amides, the action of ferrocyanide com R represents an optionally substituted alkyl, cycloal pounds or copper cyanide at elevated temperatures on kyl or aryl radical or for an optionally substituted 5- or aromatic halogen compounds, the reaction of ethers 6-membered hetero-cyclic radical, which can addition with HCN or cyanides (Houben-Weyl, Methoden der ally be fused with a benzene ring and organischen Chemie (Methods of Organic Chemistry), 25 n' represents 1 to 6, characterised in that carboxylic 4th edition, Vol. VIII, page 335-338). acids of the formula The preparation of nitriles from carboxylic acids is also described in detail in literature (Houben Weyl, R-(COOH), (II) Methoden der organischen Chemie, 4th edition, Vol. VIII, page 335-338). 30 in which R and n' have the above-mentioned meaning, The preparation of nitriles by the elimination of water are reacted with cyanogen chloride and/or cyanogen from carboxylic acids can be conducted either using bromide at temperatures in the range of 100 to 300° C. chemical means or by thermal methods. Both methods Preferably, in the case of the process according the are associated with a number of disadvantages and have invention, carboxylic acids of the formula (II) are used not been very widely used in preparative chemistry. 35 with n' representing 1 to 3. Alkyl radicals with up to 24 Thus although the ammonium salts of organic acids carbon atoms, preferably with up to 18 carbon atoms, are converted, using water-elimination agents (phos which can optionally be substituted by chlorine, bro phorous pentoxide, glycerol), into nitrile in a heteroge mine, or methoxy, alkoxy-, nitrilo-, methoxycarbonyl nous reaction in order to obtain good yields, it is neces or ethoxycarbonyl-groups may represent the radical R sary to first of all synthesize the amide (Comp. rend. in the above-mentioned formulae. The following op 25,383 (1847) and Ber. 19, 2459 (1886). tionally substituted alkyl radicals may for example be Although nitriles are also obtained by melting acids mentioned: methyl-, ethyl-, propyl-, butyl-, pentyl-, with potassium thiocyanate or lead thiocyanate, the best hexyl-, heptyl-, 2-ethylhexyl-, dodecyl-, tetradecyl-, yields are obtained if instead of the acids their zinc salts hexadecyl-, octadecyl-, -chloro-propyl-, pivaloyl-, ol are used. This method is time-consuming and thus un 45 eyl-, cyanmethyl-, 3-bromopropyl-, co-methoxy-hexyl-, economical because of the lengthy preparation and co-ethoxyhexyl-, co-methoxycarbonyl-butyl- and co drying of these salts (J. Amer. Chem. Soc. 38, 2120 ethoxycarbonyi-butyl-. (1916). Higher molecular fatty acids or dicarboxylic Further, the radical R can represent cycloalkyl radi acids are converted into nitrile when heated with urea cals with up to 10 carbon atoms, preferably with up to or cyanuric acid to temperatures of 250' to 310' C., but 50 6-carbon atoms, which can be substituted by chlorine, the yields are low. They vary between 32% and 49% bromine or methoxy-, ethoxy-, nitrilo-, methoxycarbo (Org. Synth. 25, 95 (1949)). nyl-, ethoxycarbonyl-, methyl-, ethyl-, propyl- or iso A process for the preparation of aromatic nitriles is propyl-groups, or also for arylradicals, with up to 14 known from J. Chem. Soc. 1946, 763, based on the carbon atoms, preferably with up to 10 carbon atoms, reaction of aromatic acids with aryl sulphamides in the 55 optionally substituted by chlorine, bromine, nitro, or presence of phosphorous pentachloride or by heating to methoxy, ethoxy-, nitrilo-, methoxycarbonyl-, ethox temperatures of over 200° C. Both process variations ycarbonyl-, methyl-, ethyl-, propyl-, isopropyl- or tert give very different yields (between 11 and 83%). What butyl-groups. Examples which may be mentioned of is disadvantageous in this process is that per mol of optionally substituted cycloalkyl radicals are: nitrile 1 mol of p-toluene sulphonyl chloride is formed, 60 2-methyl-cyclohexyl-, 4-ethyl-cyclohexyl-2- if phosphorous pentachloride, a substance which is very chlorocyclohexyl- and 4-methoxycarbonyl-cyclohexyl difficult to work with, is used as the condensation agent. , and of optionally substituted aryl radicals: o-, m-, p In the condensation at above 200 C. one mol of p-tol chlorophenyl-, 2,3-dichlorophenyl-, 3,4-dichlorophe uene sulphonic acid and 1 mol of the ammonium salt of nyl-, 4-chloro-3-nitrophenyl-, 2-chloro-4-nitrophenyl-, the p-toluene sulphonic acid are obtained per mol of 65 2-chloro-5-nitrophenyl-, 3,4- and 3,5-dinitrophenyl-, o-, nitrile. m-, or p-tolyl-, 3-methyl-4-nitrophenyl-, 4-tert.-butyl Nitriles can also be prepared directly from organic phenyl-4-methoxycarbonyl-phenyl o-, m-, p-bromophe acids catalytically using ammonia by means of thermal nyl- and 4-ethoxycarbonyl-phenyl-radicals. 4,189,580 3 4. The following may be mentioned as the 5- or 6-mem cyanide, iron-(III)-chloride, tin-(IV)-chloride, alumi bered heterocyclic radicals with up to 9 carbon atoms, num chloride and boron trifluoride. preferably with up to 5 carbon atoms, optionally substi According to the process of the invention nitriles of tuted with methyl-, ethyl-, chloro-, bromo-, nitro-, me the formula (I) can be obtained in good yields and high thoxycarbonyl-, ethoxycarbonyl-, or nitrile, which radi purities. Apart from hydrogen chloride and carbon cal may be additionally fused with a benzene ring: 2,4,6- dioxide no secondary products are formed. Of particu trioxopyrimidyl-, 2,4,6-trichloro-pyrimidyl-, dichloro lar industrial significance is the general applicability of quinoxalinyl-, thiophenyl as well as the phthalic anhy the process of the invention. It is not restricted to partic dride and hexahydrophthalic anhydride radicals. ular carboxylic acids. The working up of the reaction Preferably the following carboxylic acids of the for 10 mixture does not present any problems since the reac mula (II) are used in the process according to the inven tion products are obtained in many cases in such a pure tion: acetic acid, propionic acid, butyric acid, valeric form that a purification process is not required. acid, hexanoic acid, heptanoic acid, 2-ethyl hexanol A further advantage is that the starting products, i.e. carboxylic acid, dodecanic acid, tetradecanic acid, hex the carboxylic acids as well as cyanogen chloride and adecanic acid, octadecanic acid, 3-chloroproponic acid, 15 cyanogen bromide are easily accessible technically. If pivalic acid, 10-undecanic acid, oleic acid, sorbic acid, the products are not available in large quantities they cyanoacetic acid, succinic acid, glutaric acid, adipic can easily be synthesized according to known methods. acid, sebacic acid, dodecane diacid, cyclohexan carbox The nitriles according to the invention are valuable ylic acid, 3-cyclohexene-1-carboxylic acid, benzoic intermediary products for the synthesis of dyes, such as acid, o,m,p-chlorobenzoic acid, dichlorobenzoic acid, 20 azo dyes, polyisocyanates or polyamides (Polyure o, m, p-nitrobenzoic acid, 4-chloro-3-nitrobenzoic acid, thanes, Chemistry and Technology, Saunders-Frisch, 2-chloro-5-nitro-benzoic acid, 2-chloro-4-nitrobenzoic Interscience Publishers, New York, London, Vol. I and acid, 3,4- and 3,5-dinitrobenzoic acid, phenylacetic acid, II, 1962). o-, m-, p-toluic acid, 3-methyl-4-nitrobenzoic acid, 4 The process according to the invention may be illus tert-butyl benzoic acid, naphthalene carboxylic acid, 25 4'-nitro-bis-phenyl-4-carboxylic acid, isophthalic acid, trated with the aid of the following examples, without 4-chloroisophthalic acid, 4-nitroisophthalic acid, ter the process being however limited to the examples. ephthalic acid, nitroterephthalic acid, chlorotereph EXAMPLE 1 thalic acid, dichloroterephthalic acid, trimesic acid, In a three-necked flask 122 g benzoic acid (1 mol) are anisic acid, 3-nitroanisic acid, 4,4'-oxybisbenzoic acid, 30 heated to 180-200 C. and after 1 g zinc chloride has 2,4'carbonyl bisbenzoic acid, 3-chloroanthraquinone been added 61 g (51 ml) cyanogen chloride (cyanogen carboxylic acid and 4,4'-carbonyl bisbenzoic acid. bromide can also be used instead of cyanogen chloride) The aromatic carboxylic acids mentioned are particu are introduced dropwise over 60 minutes. CO2 and HCl larly preferred. begin to evolve rapidly. The cyanogen chloride is sepa The reaction of the carboxylic acids of formula (II) 35 rated from the gases by intensive cooling and drops with cyanogen chloride and/or cyanogen bromide, back into the reaction vessel. After the cyanogen chlo preferably with cyanogen chloride, may be conducted ride has been consumed distillation is conducted. in the presence of solvents or diluents. As solvent or Yield: 95 g benzonitrile (92% of theory), bp 1s: diluent all inert organic solvents may be used which do 76-78° C. not enter into a chemical reaction with either the car 40 As described in Example 1 the following acids were boxylic acids or the cyanogen halide. Such solvents or converted into their nitriles with cyanogen chloride: diluents are for example o, m, p-xylenes, chlorbenzene, o-dichlorobenzene, the 1,2,3-, 1,2,4-, 1,2,5-, or 1,3,5-tri chlorobenzenes, nitrobenzene, tetramethylene sul nitriles phone, N-methylpyrrolidone and hexamethylphosphor 45 p-methyl-benzoic acid (89% of theory, b.p. 11:91. C.) ic-acid-triamide. As the solvent or the diluent the end o-nitrobenzoic acid (85% of theory, m.p.: 108-109' C.) product, carboxylic acid nitrile, may also be used and in many cases successfully. The solvents or diluents may be used alone or in a mixture with each other. EXAMPLE 2 The quantity of the solvent or diluent added is in 50 144.2 g 2-ethylhexanoic acid (1 mol) are dissolved in general 1 to 10% times, preferably 1 to 5% times, the 100 g 2-ethylhexanoic acid nitrile, reacted with 1 g zinc amount of carboxylic acid used. cyanide and heated to 190-210 C. Within 3 hours 123 The reaction temperature may be varied within a g cyanogen chloride (2 mols) are added dropwise. Fol large range. In general the process is conducted at tem lowing this addition stirring is continued for 15 minutes peratures in the range of 100° C. to 300° C., preferably 55 at the reaction temperature, and distillation is then con in the range of 150 C. to 250 C. The reactants, carbox ducted under vacuum. ylic acid and cyanogen halide, are in general reacted in Yield: 110 g 2-ethylhexanoic acid nitrile (88% of a ratio of approx. 1:1. If the cyanogen halide is used in theory), b.p. 10: 71-73 C. excess, this factor is of no significance to the reaction. 100 g 2-ethylhexanoic acid nitrile are recovered un The reaction is in general conducted under normal 60 changed. pressure. When using low boiling, aliphatic carboxylic acids a slight excess pressure is desirable to achieve the EXAMPLE 3 reaction temperature. The reaction pressure is in gen 201 g 6-chloro-3-nitrobenzoic acid (1 mol) are melted eral approx. 1 to 10, preferably 1 to 5 mm Hg. and heated to 170°-190° C. and rapidly reacted drop By adding catalytic amounts of Lewis acids (approx. 65 wise with 92 g cyanogen chloride (1.5 mols). After 0.001 to 0.1 mol, preferably 0.01 to 0.05 mol) the reac approx. 40 minutes the reaction is complete and no tion can be accelerated. Suitable Lewis acids which can more hydrogen chloride evolves. The reaction product for example be mentioned are zinc-II-chloride, zinc is distilled by aid of an oil pump.

H 4,189,580 5 6 Yield: 175 g 6-chloro-3-nitrobenzonitrile (96% of theory). wherein R represents unsubstituted alkyl or substituted b.p.: 160-163' C/0.3 mm Hg. alkyl substituted by chlorine, bromine, methoxy, alk oxy, nitrilo, methoxycarbonyl, or ethoxycarbonyl, un EXAMPLE 4. substituted cycloalkyl or substituted cycloalkyl substi 146 g adipic acid (1 mol) are dissolved in 200 ml tuted by chlorine, bromine, methoxy, ethoxy, nitrilo, tetramethylene sulphone and reacted dropwise with 215 methoxycarbonyl, ethoxycarbonyl, methyl, ethyl, pro g cyanogen chloride (3.5 mols) in the presence of lig pyl or isopropyl, unsubstituted aryl radical or substi iron-III-chloride at approx. 200 C. After four hours the tuted aryl substituted by chlorine, bromine, nitro, me reaction is complete. 10 thoxy, ethoxy, nitrilo, methoxycarbonyl, ethoxycarbo The reaction mixture is allowed to cool, is poured nyl, methyl, ethyl, propyl, isopropyl or tert-butyl or into water, the oily phase is separated off, the reaction unsubstituted 5- or 6-membered heterocyclic radical or mixture is then dried over sodium sulphate, the sodium substituted 5- or 6-membered heterocyclic radical sulphate is filtered off and the reaction mixture is then which may additionally be fused with a benzene ring distilled. 15 where the substituents are methyl, ethyl, chloro, bromo, Yield: 91 g adipic acid dinitrile (84% of theory), b.p.: nitro, methoxycarbonyl, ethoxycarbonyl or nitrile and 179-182' C. at 20 mm Hg. n' represents l to 6 which comprises contacting a car EXAMPLE 5 boxylic acid of the formula 83 g isophthalic acid (0.5 mol) are added to 200 ml 20 R-(COOH) tetramethylene sulphone and heated to 210-220 C. At this temperature 61.5 g cyanogen chloride (1 mol) are wherein R and n' have the meanings given above with added dropwise within 2 hours, the mixture is stirred cyanogen chloride and/or cyanogen bromide at a tem for a further 15 minutes, filtered, allowed to cool, perature in the range of 100 to 300 C. poured into water and the reaction product precipitated 25 2. A process according to claim 1 wherein a carbox is filtered. ylic acid of the formula given in claim 1 is employed Yield: 58 g isophthalic acid dinitrile (91% of theory), wherein m.p.: 162 C. (from ethyl acetate). R represents substituted or unsubstituted alkyl radical EXAMPLE 6 with up to 18 carbon atoms, substituted or unsubsti 30 tuted cycloalkyl radical with up to 6 carbon atoms As described in Example 5, the following acids are or substituted or aryl unsubstituted radical with up converted with cyanogen chloride into the di- or trini to 10 carbons atoms or substituted or unsubstituted triles: 5- or 6-membered heterocyclic radical with up to 5 carbon atoms which heterocyclic radical can addi 35 tionally be fused with a benzene ring and n' repre dinitries sents 1 to 3. terephthalic acid (95%, m.p.: 223 C.) 3. A process according to claims 1 or 2 wherein the 5-nitroisophthalic acid (98%, m.p.: 190 C.) 4-chloroisophthalic acid (96%, m.p.: 149 C) reaction is conducted in the presence of an inert organic 2-chloro-terephthalic acid (98%, m.p.: 156' C.) solvent or diluent. trinitrile 4. A process according to claim 3 wherein the inert benzene tricarboxylic acid (98%, m.p.: 2.54 C.) solvent or diluent is o-, m-, or p-xylene, chlorobenzene, (1,3,5) o-dichlorobenzene, 1,2,3-, 1,2,4-, 1,2,5-, 1,3,5-trichloro benzene, nitrobenzene, tetramethylene sulphone, N methylpyrrollidone or hexamethylphosphoric acid tri EXAMPLE 7 45 amide. 128 g cyclohexanoic carboxylic acid (1 mol) are 5. A process according to claim 3 wherein the quan heated to 180-200 C., reacted with 1 g aluminium tity of solvent or diluent employed is 1 to 10 times the chloride and 123 g cyanogen chloride (2 mols) are amount of the carboxylic acid employed. added dropwise within 3 hours. After the evolution of 6. A process according to claim 1, wherein the reac CO2 and HCl has ended, distillation takes place. 50 tion is conducted in the presence of a Lewis acid. Yield: 94 g cyclohexylnitrile (86% of theory), b.p.: 7. A process according to claim 6 wherein the Lewis 68-70° C. at 12 mm Hg. acid is zinc-II-chloride, zinc-cyanide, iron-III-chloride, What is claimed is: tin-IV-chloride, aluminum-chloride and/or boron tri 1. A process for the preparation of a nitrile of the fluoride. formula 55 8. A process according to claim 6 wherein the Lewis acid is employed in an amount of 0.001 to 0.1 mol. is a

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