United States Patent (19) 11) Patent Number: 4,605,521 Eubanks et al. 45) Date of Patent: Aug. 12, 1986

(54) PROCESS FOR THE PREPARATION OF 56 References Cited ORGANIC NTRILES FROM ORGANIC CARBOXYLECACID PRIMARY AMIDES U.S. PATENT DOCUMENTS 3,317,585 5/1967 Herschmann ...... 260/465.2 (75) Inventors: Robert J. I. Eubanks; James G. Primary Examiner-Dolph H. Torrence Pacifici, both of Batesville, Ark. Attorney, Agent, or Firm-Clyde L. Tootle; J. Frederick (73) Assignee: Eastman Kodak Company, Thomsen Rochester, N.Y. 57 ABSTRACT (21) Appl. No.: 717,926 This invention relates to a process for the preparation of organic nitriles. More particularly, the invention relates 22) Fied: Mar. 29, 1985 to a process for the preparation of organic nitriles by reacting organic carboxylic acid primary amides with a 51 Int. Cl." ...... C07C 120/10 dehydrating agent in the presence of a catalytic amount (52) U.S. Cl...... 558/313; 546/286 of a particular quaternary ammonium salt. (58) Field of Search ...... 260/465 B, 465.2, 464; 546/286 12 Claims, No Drawings 4,605,521 1 2 The quaternary ammonium salt used in a catalytic PROCESS FOR THE PREPARATION OF amount has the formula: ORGANIC NTRILES FROM ORGANC CARBOXYLIC ACID PRIMARY AMIDES DESCRIPTION This invention relates to a process for the preparation of organic nitriles. More particularly, the invention relates to a process for the preparation of organic ni wherein triles by reacting organic carboxylic acid primary am O R1, R2, R3, and R4 are each independently selected ides with a dehydrating agent in the presence of a cata from alkyl of from 1 to 18 carbon atoms, alkylaryl of lytic amount of a particular quaternary ammonium salt. from 7 to 18 carbon atoms, arylalkyl of from 7 to 18 The organic nitriles are used in many organic synthe carbon atoms, and aryl of from 6 to 18 carbon atoms and sis processes. Such compounds have been well known 15 X is an anion such as hydroxyl, halogen, hydrogen in the art for many years. Such organic nitriles can be sulfate, perchlorate, hydroxide anion and the like. The prepared by reacting an aliphatic, cycloaliphatic or quaternary ammonium salts in which R1, R2 and R3 aromatic carboxylic acid primary amide with a dehy each independently contain 1 to 4 carbon atoms and R4 drating agent such as thionyl chloride. Other dehydrat contains 1 to 4 carbon atoms or a benzyl group are ing agents are known in the art such as, for example, 20 preferred. Such preferred quaternary ammonium salts phosphorous pentoxide, acetic anhydride and the like. include tetraethylammonium chloride, tetraethylammo Generally, the preferred dehydrating agent is thionyl nium bromide, tetraethylammonium hydroxide, benzyl chloride since it can be easily handled and forms gase triethylammonium chloride, benzyltriethylammonium ous by products, hydrogen chloride and sulfur dioxide, hydroxide, benzyltriethylammonium bromide, and which allows relatively simple workups. The use of 25 ethyltrimethylammonium chloride, ethyltrimethylam thionyl chloride however in many reactions reacts monium hydroxide, propyltrimethylammonium hy slowly, requires long reaction times, elevated reaction droxide, butyltrimethylammonium hydroxide, tetraeth temperatures and large excesses of thionyl chloride for ylammonium bromide, tetrabutylammonium bromide, dehydration reactions. The use of large excesses of tetrabutylammonium hydroxide, tetraethylammonium thionyl chloride in dehydration reactions is undesirable 30 acetate, and mixtures thereof. Such salts are disclosed as since any unreacted thionyl chloride must be removed being useful as catalysts in heterogeneous reactions in before the product is isolated and recovered. In addi U.S. Pat. No. 3,992,432. tion, the use of an excess amount of thionyl chloride in The quaternary ammonium salts of this process gen combination with high reaction temperatures and long erally are employed in a catalytic amount, that is, any 35 amount which exhibits a favorable comparison in the stripping times at temperatures greater than 60° C. will reaction as compared to the use of the dehydrating rapidly darken organic nitriles and increase residual agent alone. Typically this amount will be about 0.01 sulfur content which is also undesirable. mol percent to about 0.1 mol percent of the organic acid In an attempt to eliminate or reduce the above unde primary amide reactant, preferably 0.02 to 0.05 mol sirable aspects, catalysts such as N,N-dimethylforma percent, most preferably about 0.03 mol percent. mide (DMF) have been widely used in preparing a Suitable organic carboxylic acid primary amides use variety of organic nitriles. The DMF catalyst provides ful in the present invention can be aliphatic, cycloali dehydration reactions at shorter reaction times, at lower phatic, heterocyclic or aromatic carboxylic acid pri temperatures and with a less amount of thionyl chlo mary amides. The aliphatic carboxylic acid primary ride. However, relatively large amounts of DMF are 45 amides can be straight or branched chain acid primary necessary. Moreover, when DMF is exposed to thionyl amides containing 2 to 22 carbon atoms. The organic chloride and other such dehydration agents such as carboxylic acid primary amides such as the longer chain. phosphorous pentoxide and the like, there is formed length or high molecular weight are generally slower N,N-dimethylcarbamoyl chloride (DMCC) which is a reacting than the short chain aliphatic acid primary proven-carcinogen in mice and a possible carcinogen in 50 amides. The aliphatic, cycloaliphatic, heterocyclic, and humans. Therefore, when dehydration processes are aromatic carboxylic acid primary amides can be substi carried out where DMCC may be produced there are tuted or unsubstituted. Substituents include any substit procedures which must be carried out to ensure that uent which does not hinder the dehydration, block the there is no human exposure in the work place to the dehydration or which react more easily with the car DMCC. Therefore, dehydration processes where DMF 55 boxyl primary amide group thereby preventing forma is present and could form DMCC during the dehydra tion of the organic nitrile. Suitable substituents include, tion which could result in human exposure to such for example, alkyl groups, phenyl groups, nitro groups, formed DMCC are highly undesirable. cyano groups, halogens and the like. Examples of such Therefore, it would be an advance in the state of the aliphatic, cycloaliphatic, heterocyclic and aromatic art to provide a dehydration process to prepare organic carboxylic acid primary amides are acetamide, propana nitriles in high yields and efficiency where DMCC was mide, butanamide, isobutanamide, stearamide, benza not formed in the dehydration process and only a small mide, pentamide, 3-methylbutamide, hexanamide, hep amount of catalyst is required. tamide, octamide, nonamide, decamide, undecamide, In accordance with the present invention, it has been dodecamide, tetradecamide, hexadecamide, heptadeca found that the use of a quaternary ammonium salt as a 65 mide, octadecamide, eicosanoic acid amide, cyclo catalyst in the dehydration of organic carboxylic acid propanecarboxylic acid amide, cyclopentanecarboxylic primary amides to form organic nitriles provides a acid amide, cyclohexanecarboxylic acid amide, benza highly efficient and safe dehydration process. mide, p-toluic acid amide, m-toluic acid amide, 1-naph 4,605,521 3 4. thalene carboxylic acid amide, phenyl acetic acid am 95%) and high purity which can be used without fur ide, p-chlorobenzoic acid amide, p-nitrobenzoic acid ther purification. amide, m-nitrobenzoic acid amide, p-methylbenzoic The process of this invention therefore provides the acid amide, p-methoxybenzoic acid amide, 3,4-dime desired organic nitrile product in good yield and purity thoxybenzoic acid amide, nicotinamide and the like. without the use of long reaction times, large excesses of The dehydration reaction can be carried out in the dehydrating agent, elevated reaction temperatures or presence or absence of a solvent depending on the reac the preparation of possibly carcinogens. tants employed. The process is a homogeneous process. The novel process of the present invention therefore Generally the organic carboxylic acid amide used in the provides organic nitriles which are useful as intermedi present invention are liquids and are miscible with the 10 dehydrating agents, such as thionyl chloride, and the ates in the synthesis of organic compounds and other quaternary ammonium salt. It may be desirable in dehy useful materials in a unique and efficient manner. drating the organic carboxylic acid primary amides The invention will be further illustrated by the fol which have high melting points to carry out the dehy lowing Examples although it will be understood that dration in non-polar organic solvents such as heptane, 15 these Examples are included merely for purposes of hexane, benzene, toluene and the like. The solvent after illustration and are not intended to limit the scope of the dehydration can, if desired, be recovered by conven invention. tional stripping methods. Suitable dehydration agents include phosgene, oxyal EXAMPLE 1 oyl chloride, oxyaloyl bromide, oxyaloyl iodide, phos 20 A homogeneous mixture of benzamide (1.0 mol) and phorous trichloride, phosphorous tribromide, phospho benzyltriethylammonium chloride (0.02 mol percent) rous triiodide, thionyl chloride, thionyl bromide, thio was heated to and maintained at 60 to 65 C. while nyl iodide, phosphorous pentachloride, phosphorous thionyl chloride (1.1 mol) was added over a one-hour oxychloride and the like. The preferred dehydration period. After the addition was completed, the batch was agent is thionyl chloride due to its ease of handling and 25 held at 60° C. to 65 C. for one hour. Unreacted thionyl Sc. chloride and water was removed by distillation at re Stoichiometric quantities of organic acid primary duced pressure (ca 200 mm) to a pot temperature of 85 amide and dehydrating agent are employed. If desired, to 90° C. The product was cooled to room temperature a slight excess of dehydrating agent may be employed, and stored. Approximately 93.7 grams of a clear, pale generally up to about 10 mol %, preferably about 5 mol 30 yellow liquid was isolated which assayed 95.6 percent %. The dehydration is carried out attemperatures gener by GC (0.474 mol, 95 percent of theory). The IR and ally in the range of about 25 C. to 90° C., preferably NMR (H) matched those of benzonitrile. about 50° C. to 60° C. Similar results can be obtained using thionyl bromide The dehydration can be carried out at atmospheric 35 or thionyl iodide in place of thionyl chloride. pressure and may advantageously be conducted under a EXAMPLE 2 nitrogen sweep. This effectively allows degassing of strong acid such as HCl, in the case of thionyl chloride, Example 1 was repeated except that stearamide (1.0 generated in the process which may aid in the formation mol) was substituted for benzamide. Approximately of unwanted by-products. 40 95% of the stearamide was converted to stearonitrile. The process of this invention can be carried out by adding the dehydrating agent to a homogeneous reac EXAMPLE 3 tion mixture of the organic carboxylic acid primary Example 2 was repeated except that the benzyltrie amide and quaternary ammonium salt. Equally good thylammonium chloride was deleted and the reaction results may be achieved by adding the organic carbox 45 was maintained at reflux for four hours. Approximately ylic acid primary amide to a homogeneous reaction 80 percent of the stearamide was converted to stearyl mixture of dehydrating agent and the catalyst. The rate nitrile. of addition of dehydrating agent can be widely varied This Example shows that without the quaternary but generally should be a sufficient rate to utilize the ammonium salt and maintaining the reaction for four dehydrating agent efficiently. On a laboratory scale, 50 hours gave a conversion of only 80% of the stearamide such as disclosed in the experimental examples set out to the corresponding stearyl nitrile as compared to ap hereinbelow, addition of thionyl chloride was complete proximately 95% with the quaternary ammonium salt. in about one hour. Of course, the time can be expected to vary depending on the size of the reaction, the reac EXAMPLE 4 tion conditions, the reactants, the equipment used, and 55 the like. During the addition of the thionyl chloride in Example 3 was repeated except that N,N-dimethyl the examples which follow water, hydrogen chloride formamide (DMF) (0.2 mol) was added to the steara and sulfur dioxide gases are evolved, thereby minimiz mide as a catalyst in place of the quaternary ammonium ing harsh strong acid reaction conditions. After addition salt and the reaction maintained for one hour. Approxi of the thionyl chloride the reaction mixture is held at 60 mately 90 percent of the stearamide was converted to the same temperature (25 C-90° C) for a period of the stearyl nitrile. time sufficient to ensure completion of the reaction. This Example shows that with a conventional dehy About 0.25 to 1.0 hour on a small laboratory scale nor dration catalyst, DMF, in an amount ten times greater mally is sufficient. Any unreacted thionyl chloride and than the amount of the quaternary ammonium salt used water which may be present is then removed, i.e., by 65 in Example 2, provided a conversion of only about 90 vacuum distillation, and the product readily isolated by percent whereas with only a tenth the amount of the cooling the reaction mixture to room temperature. The quaternary ammonium salt of Example 2 provided resulting product is obtained in good yield (up to about about a 95 percent conversion. 4,605,521 5 6 90° C. in the presence of a catalytic amount of a quater EXAMPLE 5 nary ammonium salt having the formula: Example 2 was repeated except that butamide was used in place of stearamide. Similar results were ob tained with a conversion of about 95 percent of the R1 butamide to butyl nitrile. R!--R. X Similar results were obtained substituting propyla R3 mide, pentamide, hexamide and octamide for butamide. EXAMPLE 6 wherein 10 R, R2, R3, and R are each independently selected Example 5 was repeated except that dodecamide was from alkyl of from 1 to 18 carbon atoms, alkylaryl substituted for butamide. Similar results were obtained of from 7 to 18 carbon atoms, arylalkyl of from 7 to with a conversion of about 95 percent of the dodeca 18 carbon atoms, and aryl of from 6 to 18 carbon mide to dodecanyl nitrile. atoms and X is an anion. Similar results are obtained when octamide, nona 15 2. A process according to claim 1 wherein said dehy mide, decamide, undecamide, tetradecamide, pen drating agent is thionyl chloride. tadecamide, hexadecamide, heptadecamide, octadeca 3. A process according to claim 2 wherein said qua mide and nonadecamide were substituted for dodeca ternary ammonium salt is benzyltriethylammonium mide. chloride. 20 4. A process according to claim 2 wherein said or EXAMPLE 7 ganic carboxylic acid primary amide is an aromatic Example 2 was repeated except that cyclohexamide carboxylic acid primary amide containing about 7 to was substituted for stearamide. Similar results were about 22 carbon atoms. obtained with a conversion of about 95 percent of the 5. A process according to claim 4 wherein said aro cyclohexamide to cyclohexyl nitrile. 25 matic carboxylic acid primary amide is substituted or Similar results were obtained when 4-methyl cy unsubstituted benzamide. clohexamide, 4-chlorocyclohexamide and 3,4,5-tri 6. A process according to claim 5 wherein said substi chlorocyclohexamide were substituted for cyclohexa tuted or unsubstituted benzamide is benzamide. mide. 7. A homogeneous process for preparing organic 30 nitriles which comprises reacting an organic carboxylic EXAMPLE 8 acid primary amide selected from the group consisting of aliphatic carboxylic acid primary amide, cycloali Example 2 was repeated except that the amount, of phatic carboxylic acid primary amide, heterocyclic benzyltriethylammonium chloride was reduced to 0.01 carboxylic acid primary amide and aromatic carboxylic mol percent. Similar results were obtained but the 35 acid primary amide containing about 2 to about 22 car amount of stearamide converted was only about 88 bon atoms with at least a stoichiometric amount of a percent. Extending the reaction time to two hours gave dehydrating agent at a temperature of about 25 C. to a conversion of about 95 percent. 90° C. in the presence of a quaternary ammonium salt Repeating this Example increasing the amount of having the formula catalyst to 0.1 mol percent converted about 95 percent 40 of the stearamide in about one hour. This Example shows that with only 0.01 percent R1 catalyst the process provides good conversions of the organic carboxylic acid primary amide to the organic nitrile under acceptable conversion rates. Increasing the 45 amount of catalyst greater than 0.1 percent only used more catalyst than necessary with no detectable in wherein crease in conversion rates. R1, R2, and R3 each independently contain 1 to 4 carbon atoms and R contains 1 to 4 carbon atoms The present process provides an effective and cost or a benzyl group and Xishalide, hydrogen sulfate, efficient process for the preparation of organic nitriles 50 perchlorate or hydroxide anion. in good conversion rates and good yields. 8. A process according to claim 7 wherein said dehy The invention has been described in detail with par drating agent is thionyl chloride. ticular reference to preferred embodiments thereof, but 9. A process according to claim 8 wherein said qua it will be understood that variations and modifications ternary ammonium salt is benzyltriethylammonium can be effected within the spirit of the invention. 55 chloride. We claim: 10. A process according to claim 9 wherein said or 1. A homogeneous process for preparing organic ganic carboxylic acid primary amide is an aromatic nitriles which comprises reacting an organic carboxylic carboxylic acid primary amide containing about 7 to acid primary amide selected from the group consisting about 22 carbon atoms. of aliphatic carboxylic acid primary amide, cycloali 11. A process according to claim 10 wherein said phatic carboxylic acid primary amide, heterocyclic aromatic carboxylic acid primary amide is substituted carboxylic acid primary amide and aromatic carboxylic or unsubstituted benzamide. acid primary amide containing about 2 to about 22 car 12. A process according to claim 11 wherein said bon atoms with at least a stoichimetric amount of a 65 substituted or unsubstituted benzamide is benzamide. dehydrating agent at a tenperature of about 25 C. to k . k . k UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT NO. : 4, 605, 52 DATED : August l2, l986 INVENTOR(S) : Robert J. I. Eubanks and James G. Pacifici It is certified that error appears in the above-identified patent and that said Letters Patent is hereby corrected as shown below:

Column 5. line 66, delete "tenperature" and insert therefor - - -temperature---. Column 6 line 28, delete "benzanide" and insert therefor ---benzyl amide---.

Signed and Sealed this Ninth Day of December, 1986

Attest:

DONALD J. QUIGG Artesting Officer Commissioner of Patents and Trademarks