United States Patent (19) 11 Patent Number: 4,835,312 Itoh et al. 45 Date of Patent: May 30, 1989

54 PRODUCTION PROCESS OF 3,242,213 3/1966 Raleigh et al...... 564/142 X N-SUBSTITUTED AMDE COMPOUNDS 3,833,597 9/1974 Hardy et al...... 564/143 X 3,852,350 12/1974 Wilson, Jr. et al...... 564/142 X 4,008,066 2/1977 Moser ...... 564/143 X 75 Inventors: Hiroshi Itoh, Yokohama; Toshimi Nakagawa, Fujisawa; Atsuhiko Nitta, 4,113,774 9/1978 Surrey et al...... 564/42 X Yokohama, all of Japan 4,288,592 9/1981 Rauhut et al...... 564/143 X 73) Assignee: 501 Mitsui Chemicals, Incorporated, OTHER PUBLICATIONS Tokyo, Japan Johnstone et al., “Tetrahedron', vol. 35, pp. 2169-2173 (21) Appl. No.: 881,087 (1979). 22 Filed: Jul. 2, 1986 Primary Examiner-Robert V. Hines Attorney, Agent, or Firm-Schmeiser, Morelle & Watts Related U.S. Application Data 63 Continuation-in-part of Ser. No. 556,563, Nov. 30, 57 ABSTRACT 1983, abandoned. An N-substituted amide compound is produced with a 51) Int. Cl." ...... C07C 103/133 high yield by initiating a reaction among a starting 52 U.S. Cl...... 564/205; 564/207 amide compound such as a saturated or unsaturated, 58 Field of Search ...... 564/204, 205, 142, 207, aliphatic or aromatic carboxylic acid amide, a halogen 564/143, 80 substituted compound such as an alkyl halide and a strongly basic substance while maintaining the basic (56) References Cited substance in a suspended state. U.S. PATENT DOCUMENTS 3,057,861 10/1962 Florey et al...... 564/142 X 1 Claim, No Drawings 4,835,312 1 2 inconvenience, as shown in Comparative Examples 1 PRODUCTION PROCESS OF N-SUBSTITUTED through 3 which will be described later, this process AMDE COMPOUNDS involves such problems that the yield of an intended final product is low, the halogen-substituted compounds This application is a continuation-in-part of applica 5 reactable with the alkali metal substituted amide com tion Ser. No. 556,563, filed Nov. 30, 1983 and now pound are limited to specific ones and the reaction prod abandoned. uct is exclusively an N-monosubstituted amide com BACKGROUND OF THE INVENTION pound and, where an N,N-disubstituted amide com pound is intended, the process has to be repeated simi (a) Field of the Invention 10 larly. For the reasons mentioned above, this process has This invention relates to an improved production not been adopted in an industrial large scale as a pro process of N-monosubstituted amide compounds. It also duction process for general N-substituted amide com relates to a novel production process of N,N-disub pounds. stituted amide compounds. Alternatively, as disclosed on Page 266 of G. L. Isele, (b) Description of the Prior Art 15 Since N-substituted amide compounds generally con A. Littringhous, Synthesis 1971 (5), it has been known tain well-balanced hydrophilic groups and hydrophobic to use a two-step production process in which, after groups in their molecules, they have such advantages reacting an amide compound with a strongly basic sub that their miscibility with various substances are good, stance in an aprotic polar solvent to form an alkali met they exhibit strong resistance to hydrolysis, and unsatu 20 al-substituted amide compound, the alkali metal-sub rated amide compounds pertain excellent homopoly stituted amide compound is reacted with a halogen-sub merization or copolymerization property. Owing to stituted compound such as an alkyl halide to obtain an such advantages, a wide variety of application fields are N-alkyl-substituted-amide compound. However, even if known for N-substituted amine compounds, including this process was followed, no satisfactory results have adhesive, paint, paper-processing agents, textile-proc 25 been obtained as described in Comparative Example 2. essing agents, emulsion, urethane stiffeners, pigment In addition, USSR Certificate of Inventorship No. dispersants, plastics additives, polymeric coagulants, 667,547 discloses a production process of N-alkylated ion-exchange resins, etc. They are also useful as starting organic compounds, in which a basic substance such as materials or intermediates for or even final products of caustic soda is added in the form of an aqueous solution compounds having a complex structure such as pharma 30 and the substitution reaction is initiated while keeping ceutical products, agricultural chemicals, amino acids, all the basic substance in a liquid state. According to the naturally-occurring substances, etc. and, also, as a start disclosure of the certificate, it is mentioned that, in the ing material for the production of amines. Notwith above process, the presence of water in the reaction standing such advantages and usefulness of N-sub mixture is extremely convenient for the proceeding of stituted amide compounds, they have not yet been used 35 the reaction. According to a study made by the present in a great quantity as no inexpensive industrial produc inventors, as will be apparent from a comparison be tion process has yet been established for N-substituted tween Examples 1, 3 and 4 and Comparative Example 4 amide compounds. which will also be described later, this process is accom As known industrial production processes of N-sub panied by a considerable occurrence of reaction by-pro stituted amide compounds, may be mentioned a produc 40 ducts, whereby making its selectivity of an intended tion process relying upon the reaction between a car N-substituted amide compound poor and, depending on boxylic chloride and an amine as well as another pro an N-substituted amide compound intended, resulting in duction process which makes use of the Ritter reaction. a considerable reduction of its yield. However, under the current circumstances, N-sub In the case where the starting amide compound, to stituted amide compounds produced in accordance with 45 such conventional processes are either expensive or are which the present invention is directed, is an unsatu limited to certain specific types, thereby limiting their rated compound, N,N-substitution reaction does not applications to specific fields. take place in the same manner as in the case of the Furthermore, as a general production process of N saturated compounds disclosed in Johnstone et al., Tet substituted amide compounds, there has been known to 50 rahedron, Vol. 35, pages 2169-2173. In this regard, the convert an amide compound to an amide compound general alkylation procedure recited on page 2173, left substituted by one or more alkali metals under the influ column, of the Johnstone et al. reference, shows an ence of a strongly basic substance such as alkali metal example of the use of potassium hydroxide in an amount alkoxide and then to convert the thus-alkali metal sub of 4 m moles per replaceable hydrogen of substrate, i.e., stituted amide compound to an N-substituted amide 55 8 moles per one mole of the substrate. However, in the compound under the influence of a halogen-substituted case where such a large amount of potassium is used in compound such as alkyl halide. Reference may, for an N-substitution reaction of unsaturated compounds, example, be made to Hikkinbottom, W. J., Reactions of polymerization and other side reactions take place. Organic Compounds (Vol. 3), Longmans, Green and SUMMARY OF THE INVENTION Co., (1957) and U.S. Pat. No. 3,084,191. However, this 60 process involves varied inconvenience such that the An object of this invention is to provide a production process comprises two steps; it requires as a reaction process, which can produce not only an N-monosub solvent a protonic solvent having high reactivity in the stituted amide compound but also an N,N-disubstituted presence of a basic catalyst with a halogen-substituted amide compound in a single-step reaction. compound, such as liquid ammonia or an alcohol; it also 65 Another object of this invention is to provide a pro requires an extremely strong basic substance which is duction process, which is substantially free of side reac irksome to handle, such as an alkali metal amide, alkali tions and can thus produce an intended N-substituted metal hydride, or alkali metal alkoxide. Due to such amide compound with good selectivity. 4,835,312 3 4. A further object of this invention is to provide a least one of at least one type of substituent groups such production process, which is suitable for the production as nitro, cyano, amino, carboxyl, sulfo, alkoxy and car of a wide variety of N-substituted amide compounds. boxylic acid ester groups. Unsaturated aliphatic carbox According to a process of this invention, a wide vari ylic acid amides are represented by a general formula ety of N-monosubstituted amide compounds and N,N- CnH2n-1-2m,CONH2, in which n and m stand respec disubstituted amide compounds can each be produced tively for integers of 2-20 and 1-5. These amides con with a high yield without substantially causing side tain at least one carbon-to-carbon double or triple bond reactions to occur by bringing a strongly basic sub in their molecules. Also included are those containing at stance, a starting amide compound and a halogen-sub least one of at least one type of substituent groups such stituted compound into a simultaneous contact in a 10 as nitro, cyano, amino, carboxyl, sulfo, alkoxy and car reaction system containing an aprotic polar solvent to boxylic acid ester groups. Aromatic carboxylic acid initiate a reaction while maintaining the strongly basic amides contain in their molecules an aromatic ring. As substance in a suspended state. the aromatic ring, may be mentioned a benzene, naph thalene or anthracene ring or the like. Also included are DETAILED DESCRIPTION OF THE 15 those containing at least one of at least one type of INVENTION substituent groups such as nitro, cyano, alkoxy, amino, The process according to this invention features very carboxyl, sulfo, carboxylic acid ester, alkyl, alkenyl and little occurrence of side reactions and thus a high yield aryl groups, which substituent groups are attached to of an intended product. It is capable of producing a the aromatic ring. Also included are aromatic carbox wide variety of N-substituted amide compounds as it 20 ylic acid amides in which one or more of the above permits reactions between an extremely wide range of substituent groups or aromatic ring is each attached to amide compounds and an extremely broad variety of another aromatic ring through oxygen, sulfonyl group, halogen-substituted compounds by combining them sulfur or the like. Alicyclic carboxylic acid amides are suitably. Moreover, it enables to produce each of N those containing in their molecules an alicyclic struc monosubstituted amide compounds and N,N-disub 25 ture and also include heterocyclic compounds formed stituted amide compounds in a single-step reaction by of different elements. Urea and its derivatives are those selecting suitable production conditions. It is also possi containing an N-CO-N or N-CO-N-N atomic ble to produce an N,N-disubstituted amide compound group, as led by urea. having different substituent groups. The above success Examples of the above-described monoamide com ful process of the present invention is based on the pres pounds are, as saturated aliphatic carboxylic amides, ent inventors' finding that the presence of water in the formamide, acetamide, propionamide, butylamide, val reaction system, which has heretofore been considered eramide, isovaleramide, pivalamide, lauramide, myrista to be convenient, serves to induce side reactions con mide, palmitamide, stearamide, methoxyacetamide, trary to what has been believed and impedes the pro ethoxyacetamide, methoxypropionamide, ethoxypro duction of an intended N-substituted amide compound; 35 pionamide, cyanovaleramide, nitropropionamide, and, instead of reacting an amide compound and a aninopropionamide, carbamoyl propane sulfonic acid, strongly basic substance first and then causing a halo carbamoyl propanoic acid, methyl carbamoyl propa gen-substituted compound to react with a reaction nate, etc. product of the amide product and basic substance as Exemplary unsaturated aliphatic carboxylic acid am proposed by the prior art, it is necessary to bring the ides include acrylamide, methacrylamide, vinylaceta strongly basic substance, amide compound and halogen mide, crotonamide, decenamide, nonadecenamide, pro substituted compound into a simultaneous contact to pionamide, butynamide, hexadiene carboxamide, pen react them together. tinamide, heptinamide, ethoxyacrylamide, ethoxyme Accordingly, either one of the following processes thacrylamide, cyanobutenamide, nitrobutenamide, may be suitably selected in the present invention: 45 aminobutynamide, carbamoyl propene sulfonic acid, (a) The three starting materials are simultaneously carbamoyl crotonic acid, methyl carbamoyl crotonate, added to and mixed in an aprotic polar solvent and the etc. strongly basic substance is suspended therein to react Among the aromatic carboxylic acid amides, there them together; are included for example benzamide, naphthamide, an (b) The strongly basic substance is suspended in an 50 thracene carboxamide, anthraquinone carboxamide, aprotic polar solvent and the amide compound and biphenylcarboxamide, phenylacetamide, phenylpro halogen-substituted compound are then simultaneously pionamide, phenyldecanamide, nitrobenzamide, ni supplied into the suspension to react them together; and tronaphthamide, nitrocinnamide, cyanobenzamide, me (c) The amide compound and halogen-substituted thoxybenzamide, ethoxybenzamide, methoxynaphtha compound are dissolved or suspended in an aprotic 55 mide, N,N-dimethylaminobenzamide, N,N-dime polar solvent and the strongly basic substance is then thylaminonaphthamide, carbamoyl benzene sulfonic added and suspended. acid carbamoyl benzene sulfonic acid, carbamoyl naph Amide compounds, to which the present invention is thalene sulfonic acid, toluamide, propylbenzamide, directed, may be roughly divided into two groups, one decylbenzamide, carbamoyl naphthoic acid, vinylben being monoamide compounds and the other polyamide zamide, allylbenzamide, butenylbenzamide, phenylcar compounds higher than diamide compounds. bamoyl phenyl ether, vinylcarbamoyl phenyl ether and As monoamide compounds, may be mentioned satu phenylcarbamoyl phenyl sulfide. rated aliphatic carboxylic amides, unsaturated aliphatic As alicyclic carboxylic acid amides, may be men carboxylic amides, aromatic carboxylic amides, alicyc tioned for example cyclopropane carboxamide, cyclo lic carboxylic amides as well as urea and its derivatives. 65 butane carboxamide, cyclopentane carboxamide, cyclo Saturated aliphatic carboxylic amides are represented pentene carboxamid cyclohexane carboxamide, cyclo by a general formula CnH2n-1CONH2 in which n is an heptane carboxamide, cyclooctane carboxamide, cy integer of 0-20. Also included are those containing at clooctene carboxamide, pyrrole carboxamide, furan 4,835,312 5 6 carboxamide, thiophene carboxamide, cyclohexylaceta dicarboxamide, octadecene dicarboxamide, butene tet mide, cyclohexylpropionamide, pyridine carboxamide, racarboxamide, hexadiene dicarboxanide, pentyne pyrrolidine carboxamide, morpholine carboxamide, dicarboxamide, methoxy butene dicarboxamide, imidazole carboxamide, quinoline carboxamide, etc. cyanobutene dicarboxanide nitrobutene dicarboxa Examples of urea and its derivatives include, for exam mide, amonbutenedicarboxamide, dicarbamoylbutene ple, urea, biuret, thiobiuret, triuret, semi-carbazide, car sulfonic acid, dicarbamoylbutenoic acid, methyl dicar bonohydrazide, and carbazone. bamoylbutenoate, etc. Among these amide compounds exemplified above, Aromatic polycarboxylic acid amides are, for exam unsubstituted amide compounds are preferred in permit ple, phthalamide, isophthalamide, terephthalamide, ting a reaction to proceed efficiently. As another pre 10 naphthalene dicarboxamide, anthracene dicarboxamide, ferred types of compounds, there may be used conju anthraquinone dicarboxamide, biphenyl dicarboxamide, gated amide compounds in which an amido group is phenyl citraconamide, naphthalene tricarboxamide, conjugated with a double bond, for example, unsatu pyromellitamide, nitrophthalide, cyanophthalide, ami rated aliphatic amide compounds such as acrylamide, nophthalide, methoxyphthalide, N,N-dime methacrylamide and crotonamide; and aromatic amide 15 thylaminophthalide, dicarbamoyl benzene sulfonic acid, compounds such as benzamide, tolylamide, isopropyl dicarbamoyl benzoic acid, dicarbamoyl benzylacetate, benzamide and naphthamide. methylphthalamide, propylphthalamide, allylphthala On the other hand, polyamide compounds include mide, phenyldicarbamoyl phenylether, vinyldicarbam saturated aliphathic polycarboxylic acid amides, unsatu oyl phenylether, phenyldicarbamoyl phenylsulfon, phe rated aliphatic polycarboxylic aid amides, aromatic nyldicarbamoyl phenylsulfide, etc. polycarboxylic acid amides and alicyclic polycarbox As exemplary aliphatic polycarboxylic acid amides, ylic acid amides. may be mentioned cyclopropanedicarboxamide, cyclo Saturated aliphatic polycarboxylic acid amides are pentane dicarboxamide, camphoramide, cyclohexane represented by 2. general formula dicarboxamide, cyclohexene dicarboxamide, pyrone CnH2n-m-2(CONH2)n, in which n and m are each an 25 dicarboxamide, pyridine dicarboxamide and pyridine integer and are respectively 0-20 and 2-4. Also in tricarboxamide. cluded are those containing at least one of at least one Among these amide compounds exemplified above, type of substituent groups such as nitro, cyano, amino, unsubstituted amide compounds are preferred in that carboxyl, sulfo, alkoxy and carboxylic acid ester they allow reactions to proceed efficiently. As another groups. 30 types of preferred compounds, there may be used con Unsaturated aliphatic polycarboxylic acid amides are jugated amide compounds in which an amido group is represented by general formula conjugated with a double bond, for example, unsatu CnH2n-2-n-2(CONH2)n, in which n, m and r denote rated aliphatic polyamides such as fumaramide, malea individually an integer and are respectively 2-20, 2-4 mide, and citraconamide; and aromatic polyamide com and 1-4. Also included are those containing at least one 35 pounds such as phthalamide, isophthalamide, tereph of at least one type of substituent groups such as nitro, thalamide and benzene tricarboxamide. cyano, amino, carboxyl, sulfo, alkoxy and carboxylic As a halogen-substituted compound to be reacted acid ester groups. with a starting amide compound, a wide variety of Aromatic polycarboxylic acid amides contain in their compounds may be mentioned, including for example molecules an aromatic ring, which is for example a alkyl halides, alkyl polyhalides, halogenated alicyclic benzene, naphthalene or anthracene ring or the like. compounds, aryl halides, alkylaryl halides, alkenyl ha They may be substituted by 2-6 substituent groups. lides, alkenylaryl halides, carboxylic halides, sulfonic Also included are those containing at least one of at halides, halogen-substituted carboxylic acids and their least one type of substituent groups such as nitro, cyano, esters, halogen-substituted ethers, heterocycle-contain amino, carboxyl, sulfo, alkoxy, carboxylic acid ester, 45 ing halides and heteroatom-containing halides. alkyl, alkenyl and aryl groups, which substituent groups Alkyl halides are represented by a general formula are attached to an aromatic ring. Also included are CnH2n-1X, in which X denotes a halogen atom and n is those containing one or more of such substituent groups an integer of 1-20. Alkyl polyhalides are represented by or aromatic ring each coupled with another aromatic a general formula CnH2n-2-nXn, in which X means a ring through oxygen, sulfonyl sulfur or the like. 50 halogen atom and n and n are respectively integers of Alicyclic polycarboxylic acid amides contain an ali 1-20 and 2-4. Halogenated alicyclic compounds are cyclic structure in their molecules and may include those having in their molecules an alicyclic structure heterocyclic compounds formed of different elements. and substituted by at least one halogen atom. Their They may be substituted by 2-5 substituent groups. rings are each formed of 3-8 carbon atoms. Aryl halides Certain specific examples of such polycarboxylic acid 55 have an aromatic ring substituted by at least one halo amide compounds will next be described. As saturated gen atom. The aromatic ring may include benzene ring, aliphatic carboxylic acid amides, may be mentioned for naphthalene ring or anthracene ring. Also included are example oxalamide, malonamide, succinamide, glutara those containing at least one of at least one type of mide, adipamide, pimelamide, suberamide, azelamide, substituent groups such as alkyl, alkenyi, aryl, nitro, sebacamide, carbamoylmethyl methylglutaramide, bu 60 cyano, amino, carboxyl, sulfo, alkoxy and carboxylic tane tetracarboxamide, tetradecane dicarboxamide, me acid ester groups, which substituent groups are attached thoxy adipamide, cyanoadipamide, nitroadipamide, to an aromatic ring. Also included are those containing aminoadipamide, dicarbamoyl butane sulfonic acid, one or more of the above substituent groups or aromatic dicarbamoyl butanoic acid and dicarbamoyl butylace ring each coupled with another aromatic ring through tate. 65 oxygen, sulfonyl group, sulfur or the like. Exemplary unsaturated aliphatic polycarboxylic acid Alkenyl halides are unsaturated halogen-substituted amides include maleamide, fumaramide, citraconamide, compounds represented by a general formula methaconamide, decene dicarboxamide, tetradecene CnH2n+2-m-2Xn, in which X means a halogen atom 4,835,312 7 8 and n,m and rare all integers and stand respectively for respectively 1-20, 1-4 and 0-5 and s stands for 1-4. Also 2-10, 1-4 and 1-4. included are their salts. Esters of halogen-substituted Alkenylaryl halides are represented by a general for carboxylic acids are represented by a general formula mula Arm.CnH2n+2-2s-m-X, in which X and Ar XCnH2n-1-2-n(COOR), in which X means a halo denote respectively a halogen atom and an aromatic gen atom, n, m and rare all integers, and n, m, r and S ring and n, m, r and s are all integers and stand respec stand respectively for 1-20, 1-4, 0-5 and 1-4. In the tively for 2-20, 1-4, 1-4 and 1-4. Here, as the aromatic above formula, R is a saturated aliphatic hydrocarbon, ring, a benzene, naphthalene or anthracene ring may be unsaturated aliphatic hydrocarbon or aromatic hydro employed. Also included are those containing at least carbon group. Where R represents aromatic hydrocar one of at least one type of substituent groups such as 10 bon groups, the above general formula embraces those alkyl, alkenyl, aryl, nitro, cyano, amino, carboxyl, sulfo, containing at least one of at least one type of substituent alkoxy and carboxylic acid ester groups and halogen groups such as alkyl, alkenyl, aryl, nitro, cyano, amine, atoms, such substituent groups and/or atoms being at carboxyl, sulfo, alkoxy and carboxylic acid ester tached to the aromatic ring as well as those containing groups, which substituent groups are attached to an one or more of such substituent groups and/or atoms or 15 aromatic ring, as well as those containing one or more aromatic ring each coupled with another aromatic ring of such substituent groups or aromatic ring each cou through oxygen, sulfonyl group, sulfur or the like. pled with another aromatic ring through oxygen, sulfo Carboxylic halides may be divided into aliphatic car nyl group, sulfur or the like. These substituent groups boxylic halides, aromatic carboxylic halides and alicyc may be the same or different. Halogen-substituted esters lic carboxylic halides. Aliphatic carboxylic halides may 20 of carboxylic acids are divided into esters of saturated be divided further into saturated aliphatic carboxylic aliphatic carboxylic acids, esters of unsaturated ali halides and unsaturated aliphatic carboxylic halides. phatic carboxylic acids and esters of aromatic carbox Aliphatic carboxylic halides are represented by a ylic acids. Esters of saturated aliphatic carboxylic acids general formula CnH2n+2-m-2(COX)n, in which X are represented by a general formula means a halogen atom and n,m and rare all integers and 25 CnH2n-1COORXn, in which X is a halogen atom, in stand respectively for 2-20, at least 1 and 0-4. When and m are each an integer and stand respectively for r= 0, the general formula corresponds to saturated car 0-20 and 1-4, and R represents a saturated aliphatic boxylic halides while, when r = 1-4, the general for hydrocarbon group, unsaturated aliphatic hydrocarbon mula corresponds to unsaturated carboxylic halides. group or aromatic hydrocarbon group. Also included in Also included are those containing at least one of at 30 this category are those containing at least one of at least least one type of substituent groups such as nitro, cyano, one type of substituent groups such as alkyl, alkenyl, amino, carboxyl, sulfo, alkoxy and carboxylic acid ester aryl, nitro, cyano, amino, carboxyl, sulfo, alkoxy and groups. carboxylic acid ester groups, which substituent groups Aromatic carboxylic halides are carboxylic halides are attached to an aromatic ring, as well as those con containing in their molecules an aromatic ring. The 35 taining one or more of such substituent groups or aro aromatic carboxylic halides contain at least one substit matic ring each coupled with another aromatic ring uent group. Here, as the aromatic ring, may be men through oxygen, sulfonyl group, sulfur or the like. Es tioned a benzene, naphthalene or anthracene ring. Also ters of unsaturated aliphatic carboxylic acids are repre included are those containing at least one of at least one sented by a general formula CnH2n-1-2COORXn, in type of substituent groups such as alkyl, alkenyl, aryl, which X means a halogen atom, n, m and r are all inte nitro, cyano, amino, carboxyl, sulfo, alkoxy and carbox gers and stand respectively for 2-20, 1-4 and 1-4. R ylic acid ester groups, the substituent groups being denotes a saturated aliphatic hydrocarbon, unsaturated attached to the aromatic ring, as well as those contain aliphatic hydrocarbon or aromatic hydrocarbon group. ing one or more of such substituent groups or aromatic Also included are those containing at least one of at ring each coupled with another aromatic ring through 45 least one type of substituent groups such as alkyl, alke oxygen, sulfonyl group, sulfur or the like. nyl, aryl, nitro, cyano, amino, carboxyl, sulfo, alkoxy Sulfonic halides are for example aliphatic and aro and carboxylic acid ester groups, the substituent groups matic sulfonic halides and contain at least one substitu being attached to an aromatic ring, as well as those ent group. Aliphatic sulfonic halides include both satu containing one or more of such substituent groups or rated and unsaturated aliphatic sulfonic halides, both 50 aromatic ring each coupled with another aromatic ring usable in the present invention. Aromatic sulfonic ha through oxygen, sulfonyl group, sulfur or the like. Es lides contain as their aromatic rings a benzene, naphtha ters of aromatic carboxylic acids are represented by a lene or anthracene ring or the like. Also included are general formula Ar.COORXn, in which X means a those containing at least one of at least one type of halogen atom and m is an integer of 1-4 and Ardenotes substituent groups such as alkyl, alkenyl, aryl, nitro, 55 a hydrocarbon group containing an aromatic ring. Also cyano, amino, carboxyl, sulfo, alkoxy and carboxylic included are those containing at least one of at least one acid ester groups, the substituent groups being attached type of substituent groups such as alkyl, alkenyl, aryl, to the aromatic ring, as well as those containing one or nitro, cyano, amino, carboxyl, sulfo, alkoxy and carbox more of such substituent groups or aromatic group each ylic acid ester groups, the substituent groups being coupled to another aromatic ring through oxygen, sul 60 attached to the aromatic ring, as well as those contain fonyl group, sulfur or the like. ing one or more of such substituent groups or aromatic Halogen-substituted carboxylic acids and their esters ring each coupled with another aromatic ring through include halogen-substituted carboxylic acids, esters of oxygen, sulfonic group, sulfur or the like. halogen-substituted carboxylic acids and halogensub Halogen-substituted ethers mean ethers substituted stituted esters of carboxylic acids. Halogen-substituted 65 by at least one halogen atom. They may be roughly carboxylic acids are represented by a general formula divided into aliphatic ethers and aromatic ethers. Halo XmCnH2n+1-2r-m(COOH); in which X represents a gen-substituted aliphatic ethers consist of saturated ali halogen atom, n, m and r are all integers and denote phatic ethers and unsaturated aliphatic ethers. In an 4,835,312 10 unsaturated aliphatic ether, there are two types of Halogenated alicyclic compounds include for exam ethers, one having one or more halogen atoms attached ple chlorocyclobutane, chlorocyclopentane, chlorocy to a saturated hydrocarbon group and the other having clohexane, chlorocycloheptane, chlorocyclooctane, one or more halogen atoms attached to an unsaturated dichlorocyclooctane, chlorocyclopentene, chlorome hydrocarbon group. Aromatic ethers are also divided thylcyclohexane, and chloroethylcyclohexane. into two groups, one being a combination of an aliphatic Among aryl halides, may be mentioned for example residue and an aromatic residue and the other being a benzylchloride, bezylidenedichloride, phenethylchlo combination of aromatic residues. Furthermore, they ride, phenylpropylchloride, chloromethylnaphthalene, may also be divided into those having one or more chloromethylanthracene, diphenylmethylchloride, tri halogen atoms attached to an aliphatic moiety and those O phenylmethylchloride, chloromethyltoluene, chlo having one or more halogen atoms attached to an aro romethylethylbenzene, chloromethylxylene, chloro matic moiety. Also included are those containing at methylstyrene, nitrobenzylchloride, chlorome least one of at least one type of substituent groups such thylamisole, chloromethylbenzoic acid, methyl chlo as alkyl, alkenyl, aryl, nitro, cyano, amino, carboxyl, romethylbenzoate, ethyl chloromethylbenzoate, phenyl sulfo, alkoxy and carboxylic acid ester groups, the sub 15 chloromethylbenzoate, chloromethylbenzonitrile, chlo stituent groups being attached to an aromatic ring, as romethylaniline, chloromethyl benzenesulfonic acid, well as those containing one or more of such substituent chloromethylbiphenyl, chlorobenzylchloride, chlo groups or aromatic ring each coupled with another romethylphenyl phenyl ether, chloromethylphenyl aromatic ring through oxygen, sulfonyl group, sulfur or phenyl sulfon and chloromethylphenyl phenyl sulfido. the like. 20 As alkenyl halides, may be mentioned for example Heterocycle-containing halides are halides of com vinylchloride, vinylidenechloride, allylchloride, chlo pounds containing a heterocycle in their molecules. roallylchloride, propargyl chloride, methallyl chloride, They contain at least one halogen atom as a substituent. chloromethallyl chloride, pentenyl chloride, hexene There are two types of heterocycle-containing halides, dichloride and octenyl chloride. 25 Alkenylaryl halides include for example styryl chlo one having one or more halogen atoms attached to a ride, cinnamyl chloride, naphthylpropenyl chloride, heterocycle and the other containing one or more halo anthrylpropenyl chloride, phenanthrylpropenyl chlo gen atoms as a haloalkyl, haloalkenyl or carboxylic ride, ethylstyryl chloride, chlorovinyl styrene, nitrosty halide group, which is attached to a heterocycle. De ryl chloride, cyanostyryl chloride, chlorovinyl aniline, pending on the heteroatom making up each heterocy 30 chlorovinyl benzoic acid, ethyl chlorovinyl benzoate, cle, they may be divided into those containing an oxy N,N-dimethylaminomethylstyrylchloride, chlorostyryl gen atom as the heteroatom, those having a nitrogen chloride, phenylstyryl chloride, methoxystyryl chlo atom as the heteroatom and those containing a sulfur ride, chlorovinylphenyl phenyl ether, chlorovinylphe atom as the heteroatom. In addition, where two or more nyl phenyl sulfon and chlorophenyl phenyl sulfido. heteroatoms are contained to make up a heterocycle, 35 Among carboxylic halides, may be mentioned for they may be the same or different. example formyl chloride, acetyl chloride, propionyl Heteroatom-containing halides are represented by a chloride, butyryl chloride, valleryl chloride, pivaloyl general formula X-R-Y, in which X denotes a halogen chloride, lauroyl chloride, myristoyl chloride, palmit atom, R means an alkylene, alkenylene or like group, oyl chloride, stearoyl chloride, oxalyl chloride, malonyl and Y is a substituent group containing one or more chloride, succinyl chloride, adipoyl chloride, suberoyl heteroatoms, such as cyano, nitro, amino, sulfo, sulfido, chloride, sebacoyl chloride, nitropropionyl chloride, or sulfonyl group. Also included in the present inven cyanopropionyl chloride, aminopropionyl chloride, tion are those substituted by two or more halogen atoms adipic monochloride, sulfopropionyl chloride, ethoxy and those containing two or more of at least one type of propionyl chloride, methoxycarbonyl butanoic chlo the above substituent groups containing one-or more 45 ride, acryloyl chloride, propioloyl chloride, methacryl heteroatoms. oyl chloride, crotonoyl chloride, oleoyl chloride, male Although each of chlorine-substituted bromine-sub oyl chloride, fumaroyl chloride, citraconoyl chloride, stituted and iodine-substituted compounds are encom mesaconoyl chloride, decene dicarbonyl chloride, bu passed by the present invention, following chlorine-sub tene tetracarbonyl chloride, nitrocrotonoyl chloride, stituted compounds are given as representative exam 50 cyanocrotonoyl chloride, aminocrotonoyl chloride, ples of halogen-substituted compounds. Where two or maleic monochloride, sulfocrotonoyl chloride, ethox more halogen atoms are incorporated, it is not neces yacryloyl chloride, methoxycarbonyl acryloyl chloride, sary that such substituent halogen atoms be the same. benzoyl chloride, naphthoyl chloride, anthracene car They may be combinations of chlorine(s)-bromine(s), bonyl chloride, biphenyl carbonyl chloride, phenyla chlorine(s)-iodine(s) and bromine(s)-iodine(s). How 55 cetyl chloride, phenylpropionyl chloride, nitrobenzoyl ever, in the following specific examples of halogen-sub chloride, nitrocinnamoyl chloride, cyanobenzoyl chlo stituted compounds, substituent halogen atoms are lim ride, aminobenzoyl chloride, phthalic monochloride, ited to substituent chlorine atoms only. acetoxybenzoyl chloride, methoxybenzoyl chloride, As alkyl halides, may be mentioned for example chlo chioroformyl benzene sulfonic acid, toluoyl chloride, romethane, chloroethane, chloropropane, chlorobu 60 allylbenzoyl chloride, phenylchloroformyl phenyl tane, chloropentane, chlorohexane, chloroheptane, ehter, phenylchloroformyl phenyl sulfon, phenyl chlorodecane, chlorododecane, chlorotetradecane, and chloroformyl sulfido, phthaloyl chloride, cyclobutane chlorooctadecane. Among alkyl polyhalides, there are carbonyl chloride, cyclohexane carbonyl chloride, cy for example dichloromethane, chloroform, tetra cloheptane carbonyl chloride, cyclooctane carbonyl chloromethane, dichloroethane, trichloroethane, tetra 65 chloride, cyclooctene carbonyl chloride, pyrrole car chloroethane, dichloropropane, trichloropropane, di bonyl chloride, thiophene carbonyl chloride, pyridine chlorobutane, dichloroheptane, dichlorohexane and carbonyl chloride, camphoroyl chloride, and pyridine dichlorodecane. tricarbonyl chloride. 4,835,312 11 12 Exemplary sulfonic acid chlorides include methane chloromethoxycarbonyl benzoate, chloromethoxycar sulfonyl chloride, ethane sulfonyl chloride, propane bonylphenyl phenyl ether, chloromethoxycarbonylphe sulfonyl chloride, hexane sulfonyl chloride, decane nyl phenyl sulfon, chloromethoxycarbonylphenyl sulfonyl chloride, ethylene sulfonyl chloride, allylsulfo phenyl sulfido, chloronitrobenzyl benzoate, chlo nyl chloride, methallylsulfonyl chloride, crotonosulfo rocyanophenyl benzoate, chloroaminophenyl benzoate, nyl chloride, hexene sulfonyl chloride, benzene sulfonyl benzoyloxychlorobenzoic acid, chlorosulfophenylben chloride, naphthalene sulfonyl chloride, anthracene zoate, chloroanisyl benzoate, ethyl benzoyloxychloro sulfonyl chloride, anthraquinone sulfonyl chloride, benzoate, chlorotolyl benzoate, chlorostyryl benzoate, tosyl chloride, biphenylsulfonyl chloride, styrene sulfo chlorobiphenyl benzoate, benzoyloxychlorophenyl nyl chloride, nitrobenzene sulfonyl chloride, dinitro 10 phenyl ether, benzoyloxychlorophenyl phenyl sulfon, benzene sulfonyl chloride, aminobenzene sulfonyl chlo benzoyloxychlorophenyl phenyl sulfido, chlorostyryl ride, cyanobenzene sulfonyl chloride, methoxybenzene nitrobenzoate, and chlorosulfophenyl cyanobenzoate. sulfonyl chloride, chlorosulfonyl benzoic acid, chloro Among halogen-substituted ethers, there are for ex sulfonyl benzene sulfonic acid, methyl chlorosulfonyl ample chloromethyl methyl ether, chloromethyl ethyl benzoate, phenyl chlorosulfonyl benzoate, phenyl 15 ether, chloromethyl propyl ether, chloromethyl butyl chlorosulfonyl phenyl ether, phenyl chlorosulfonylphe ether, chloromethyl hexyl ether, chloroethyl ethyl nyl sulfon, and phenyl chlorosulfonylphenyl sulfido. ether, chloroethyl butyl ether, chloromethyl vinyl As halogen-substituted carboxylic acids and their ether, chloroethyl vinyl ether, chloromethyl allyl ether, esters, may be mentioned for example chloroacetic acid, chloromethyl methallyl ether, chloroethyl vinyl ether, chloropropionic acid, chlorobutyric acid, chlorovaleric 20 chloroethyl allyl ether, chloroethyl methallyl ether, acid, chlorocaproic acid, chloroheptanoic acid, chloro chloroallyl methyl ether, chloromethallyl ethyl ether, palmitic acid, chlorostearic acid, chloromalonic acid, chloromethyl phenyl ether, chloromethyl naphthyl chloroacrylic acid, chloromethacrylic acid, chlorocro ether, chloromethyl benzyl ether, chloromethyl phen tonic acid, chlorooleic acid, methyl chloroacetate, ethyl ethyl ether, chloroethyl benzyl ether, chlorophenyl chloroacetate, butyl chloroacetate, hexylchloroacetate, 25 methyl ether, chlorobenzyl propyl ether, chloromethyl diethyl chloromalonate, vinyl chloroacetate, allyl chlo phenyl methyl ether, chloromethyldiphenyl methyl roacetate, methallyl chloroacetate, phenyl chloroace ether, chloromethyl tolyl ether, chloromethyl nitrophe tate, benzyl chloroacetate, phenethyl chloroacetate, nyl ether, chloromethyl cyanophenyl ether, chloro phenyl chloropropionate, tolyl chloroacetate, styryl methyl aminophenyl ether, chloromethoxy benzoic chloroacetate, nitrophenyl chloroacetate, cyanophenyl 30 acid, chloromethyl sulfophenyl ether, chloromethox chloroacetate, chloroacetoxy benzenesulfonate, biphe yphenyl methyl ether, methyl chloromethoxybenzoate nyl chloroacetate, aminophenyl chloroacetate, chlo chloromethylstyryl ether, chloromethoxyphenyl roacetoxy benzoic acid, anisyl chloroacetate, diethyl phenyl ether, chloromethoxyphenyl phenyl sulfon, and chloromalonate, methyl chloroacetoxybenzoate, chlo chloronitrophenyl ethyl ether. roacetoxyphenyl phenyl ether, chloroacetoxyphenyl 35 As heterocycle-containing halides, may be mentioned phenyl sulfon, chloroacetoxyphenyl phenyl sulfido, for example chloropyridine, chloroquinolin, chloroacri chloromethyl formate, chloromethyl acetate, chloro dine, chlorofuran, ethyl chlorothiophen, chloroben methyl propionate, chloromethyl laurate, chloromethyl zofuran, chlorodioxane, chlorobenzothiophen, chloroe stearate, chloroethyl acetate, chlorobutyl acetate, chlo thylpiperidine, chloroethylpyridine, N-chloropentyl ropropenyl acetate, chlorobutenyl acetate, chloro piperidine, N-chloromethyl carbazole, N-chloropropyl phenyl acetate, chlorobenzyl acetate, chlorophenethyl carbazole, epichlorohydrin, methylepichlorohydrin, acetate, chlorotolyl acetate, chlorostyryl acetate, chlo chloromethylfuran, chloroethylfuran, chloromethyl ronitrophenyl acetate, chlorocyanophenyl acetate, nitrofuran, chloroethylthiophen, chloromethylthio chlorosulfophenyl acetate, chloroaminophenyl acetate, phen, bischloromethylthiophen, chlorobutylthiophen, acetoxy chlorobenzoic acid, anisylbiphenyl acetate, 45 chloromethylbenzophenone, and chloromethylphenyl methyl acetoxy chlorobenzoate, chlorobiphenyl ace dihydrobenzofuran. tate, acetoxychlorophenyl phenyl ether, acetoxy Examples of heteroatom-containing halides include chlorophenyl phenyl sulfon, acetoxychlorophenyl for example chloropropionitrile, chlorobutylonitrile, phenyl sulfido, chloroethyl acrylate, chlorobutyl acry chlorovaleronitrile, chloroacrylonitrile, chloronitroe late, chloromethyl methacrylate, chloropropenyl acry 50 thane, chloronitropropane, dichloropropionitrile, di late, chlorobutenyl methacrylate, chlorophenyl acry chloronitroethane, dichloronitropropane, chloroethane late, chlorophenyl oleate, chlorobenzyl crotonate, chlo sulfonic acid, chloropropane sulfonic acid, chlorobu ronitrobenzyl crotonate, chlorocyanobenzyl methacry tane sulfonic acid, chloroethylamine, chloropropyla late, chlorotolyl acrylate, chlorostyryl acrylate, chlo mine, N-(chloroethyl)dimethyl amine salts, N-(chloroe robiphenyl acrylate, acryloyloxy chlorobenzoic acid 55 thyl)diethylamine salts, chloromethyl methyl sulfido, acryloyloxy benzene sulfonate, chloroanisyl acrylate, chloromethyl ethyl sulfido, and chloroethyl ethyl sul methyl acryloyloxy benzoate, acryloyloxychlorophe fido. nyl phenyl ether, acryloyloxychlorophenyl phenyl sul Among the halogen-substituted compounds exempli fon, acryloyloxychlorophenyl phenyl sulfido, chloro fied above, those containing no substituent groups, methylbenzoate, chlorobutyl naphthoate, chloroprope which in turn contain one or more heteroatoms, are nyl benzoate, chlorobutenyl naphthoate, chlorophenyl preferred in allowing the reaction to proceed efficiently benzoate, chlorobenzyl benzoate, chlorophenyl naph where such compounds contain one or more aromatic thoate, chloromethoxycarbonyl toluene, chloromethox rings therein. As halogen-substituted compounds suit ycarbonyl styrene, chloromethoxycarbonyl biphenyl, able to cause the reaction to take place more efficiently, chloromethyl nitrobenzoate, chloromethyl cyanoben 65 alkyl halides, alkyl polyhalides, alkylaryl halides, alke Zoate, chloropropenyl aminobenzoate, chloromethox nyl halides, carboxylic halides, heterocycle-containing ycarbonyl benzoic acid, chloropropenyl sulfobenzoate, halides, etc. may be used. The reactivity of each of such chloromethoxycarbonylphenyl methyl ether, methyl halogen-substituted compounds varies depending on 4,835,312 13 14 the conformation of a carbon atom to which a halogen cesium hydroxide. As alkaline earth metal hydroxides, atom is attached. For the reaction of this invention, it is may be mentioned for example beryllium hydroxide, preferable to employ a compound which has one or magnesium hydroxide, calcium hydroxide, strontium more halogen atoms substituted at a primary or second hydroxide and barium hydroxide. ary carbon. Exemplary alkali metal carbonates are for example The reaction solvent used in the present invention sodium carbonate, potassium carbonate, lithium carbon may be selected from aprotic polar solvents, including, ate, rubidium carbonate and cesium carbonate. As alkali for example, acetonitrile, dioxane, nitromethane, nitro metal hydrides, may be mentioned for example sodium ethane, nitrobenzene, pyridine, dimethoxyethane, tetra hydride, potassium hydride, and lithium hydride. As hydrofuran, tetrahydropyran, 2-meth-1-ytetrahydrofu O alkaline earth metal hydrides, may be mentioned for ran, benzonitrile, N,N-dimethylformamide, N,N-dime example beryllium hydride, magnesium hydride and thylacetamide, N,N-diethylformmide, dimethylsulfox calcium hydride. Alkali metal amides are alkali metal ide, N-methylpyrrolidone, hexamethyl phosphoramide substituted compounds of ammonia and include for Sulforan, orepane and glimes such as monoglime, di example sodium amide, potassium amide, and lithium glime, triglime and tetraglime. Among the above sol 15 amide. Alkali metal alkoxides are each a compound vents, acetonitrile, N,N-dimethylformamide, N,N- obtained by substituting the proton of an hydroxyl dimethylacetamide, dimethylsulfoxide, sulforan and group of an alcohol and embrace for example sodium tetraglime may be used as particularly preferable sol methoxide, sodium ethoxide, sodium t-butoxide, potas vents. These solvents generally have strong miscibility sium methoxide, potassium ethoxide, and potassium with water and thus tend to induce mixing of water due t-butoxide. to water absorption or upon recycling for re-use. There As anion-exchange resin, either OH-type or free-type fore, care must be exercised upon handling such sol strong basic resin can be employed. The ion-exchange Vents. resin contains water preferably in an amount of 15% or In a reaction system for carrying out the process of less. As other ion-exchange substances, any substances this invention, it is necessary that the reaction is initi 25 may be used as far as they induce an anion exchange ated while at least a part of the strongly basic substance phenomenon. Exemplary ion-exchange substances in is suspended therein. In this state, water is present nor clude anion-exchange cellulose, anion-exchange Sepha mally in an amount of 6% by weight or so in the reac dex, anion-exchange solutions, basic dolomite, hydrated tion system. If the water content exceeds this figure, iron oxide, and hydrated zirconium oxide. They must be side reactions such as hydrolysis of a halogen-sub 30 in a form capable of undergoing a neutralization reac stituted compound or amide compound tend to occur tion with hydrochloric acid. easily, thereby considerably lowering the yield of an Among the strongly basic substances described intended product. To make the reaction to proceed above, as substances suitable for practising the process efficiently and to increase the yield of an intended prod of this invention, may be mentioned for example alkali uct, as will be appreciated from Examples 3 and 4 and 35 metal hydroxides, alkaline earth metal hydroxides, al Comparative Example 4, it is required to control the kali metal oxides, alkaline earth metal oxides, alkali water content in the reaction system below at most 5% metal carbonates, ion-exchange resins and other ion-ex by weight, preferably, below 2.5% by weight, and more change substances. As particularly preferred sub preferably, below 10,000 ppm. stances, may be mentioned for example alkali metal There is no special limitation to the amount of solvent 40 hydroxides, alkaline earth metal hydroxides, alkali to be employed. However, it may account for 5-95% by metal oxides, alkaline earth metal oxides, alkali metal weight, preferably, 10-90% by weight of the whole carbonates, ion-exchange resins and other ion-exchange weight of the reactants including the solvent per se. substances. Next, the strongly basic substance to be employed in These strongly basic substances are generally sub the present invention is required to be a solid material 45 jected to their respective reactions in a solid form and and, when dissolved or suspended in water, to make the the reactions are initiated while at least parts of the pH of the aqueous solution be at least 10, preferably, substances still remain in a suspended state. above 11. However, where an ion-exchange resin or In practising this invention, the relative amounts of other ion-exchange substance is employed, it is ex the raw materials, starting amide compound, halogen empted from the above requirements. Requirements for 50 substituted compound and strongly basic substance to such an ion-exchange resin or other ion-exchange sub be used vary depending on the reactivity between the stance will be explained later. As such strongly basic halogensubstituted compound and starting amide com Substances, there are for example alkali metal oxides, pound or depending whether the intended product is an alkaline earth metal oxides, alkali metal hydroxides, N-monosubstituted amide compound or an N,N-disub alkaline earth metal hydroxides, alkali metal carbonates, 55 stituted amide compound, or by another reason. It is alkali methyl hydrides, alkaline earth metal hydrides, thus rather difficult to limit their relative amounts to alkali metal amides, alkali metal alkoxides, ion-exchange specific ranges. However, generally speaking, where resins and other ion-exchange substances. an N-monosubstituted amide is intended, the halogen Specific examples of the above materials or sub substituted compound may be used in an amount of stances are as follows: 60 0.2-10 moles, more preferably, 0.3-7 moles per mole of As alkali metal oxides, may be mentioned for example the starting amide compound. On the other hand, the sodium oxide, potassium oxide, lithium oxide, rubidium strongly basic substance may be used in an amount of oxide, and cesium oxide. Exemplary alkaline earth 0.3-10 moles, more preferably, 0.5-7 moles per mole of metal oxides include for example beryllium oxide, mag the starting amide compound. nesium oxide, calcium oxide, strontium oxide and bar 65 When producing an N,N-disubstituted amide com ium oxide. Among alkali metal hydroxides, may be pound, the halogen-substituted compound may be used mentioned for example sodium hydroxide, potassium in an amount of 1.0-20 moles, more preferably, 1.5-15 hydroxide, lithium hydroxide, rubidium hydroxide, and moles per mole of the starting amide compound. 4,835,312 15 16 It is also possible to produce an N,N-disubstituted gas chromatography or high-speed liquid chromatogra amide compound having different substituent groups. phy. Here, two halogen-substituted compounds of different Upon completion of the reaction, by-produced metal types may be reacted simultaneously with the starting chloride is filtered off in a known manner and, by sub amide compound The relative amounts of the two halo 5 jecting the filtrate to a distillation under a reduced pres gen-substituted compounds of different types vary de sure, the intended product of high purity is obtained. pending on their reactivity. One of the halogen-sub However, where the metal chloride is dissolved in the stituted compounds may be used generally in an amount reaction solution or sublimable starting amide com of 1.0-20 moles, preferably, 1.0-15 moles per mole of pound remains in the reaction solution, the solvent is the other halogen-substituted compound, the reactivity O distilled off from the reaction solution and the above of the latter compound being supposed to be high. Also, substance is then removed with a mixed solvent, which as a process for producing an N,N-disubstituted amide forms two layers, such as benzene-water, chloroform compound whose substituent groups are different, it water or the like. Upon subjecting the organic layer to may be possible to react the starting amide compound a distillation under a reduced pressure, the intended with a first halogen-substituted compound to obtain an 5 product can be obtained with high purity. Where the N-monosubstituted amide compound and then to react intended product has a high boiling point or tends to the N-monosubstituted amide compound with a second decompose by heat, it may be purified in accordance halogen-substituted compound. When an unsaturated with a purification method such as solvent extraction or amide compound is employed as a starting amide com recrystallization. pound, it is preferable to incorporate a polymerization 20 Moreover, where the reaction solvent has great mis inhibitor to avoid the polymerization of raw materials cibility with water, such as dimethyl sulfoxide and the and reaction product during the reaction step or purifi intended product is highly hydrophobic such as an cation step. The polymerization inhibitor is not neces N-alkylsubstituted amide compound, it is possible to sarily be limited to any specific one, but, may generally add water to the reaction solution after the completion be mentioned phenoltype polymerization inhibitors, 25 of the reaction and separate the intended product as an amine-type polymerization inhibitors, mercaptan-type oil layer, or to extract the intended product with a polymerization inhibitors, and copper powder. solvent capable of forming two layers with water, such To carry out the reaction, a conventional reaction as benzene, toluene, or chloroform. tank may be used. However, where a strongly basic According to this invention, it is possible to economi substance having low solubility is used, the basic sub 30 cally produce N-substituted amide compounds which stance may be packed in a column and a mixture solu have an extremely wide variety of functions. Thus, tion of a starting amide compound and halogen-sub N-substituted amide compounds can be supplied to stituted compound may be recycled through the col various application fields, to which conventional N-sub umn. From the standpoint of the maintenance and con stituted amide compounds could not be applied. trol of the reaction facilities, it is more convenient to use 35 a reaction tank. Since the present invention is carried out with the When carrying out he reaction in a reaction tank, the same reaction pattern, it brings about an advantage that raw materials may be charged in an arbitrary order. many types of N-substituted amide compounds can be However, where a halogen-substituted compound hav produced in the same reaction vessel, thereby making ing high reactivity is employed, it is convenient for the the process of this invention suitable for the production purpose of suppressing side reactions to add the halo of many types of N-substituted amide compounds in gen-substituted compound lastly so that it undergoes an small quantities. intended reaction with the other two raw materials. The invention will further be explained by reference The reaction temperature depends on the reactivity to the following examples: of a starting amide compound and halogen-substituted 45 EXAMPLE compound to be used. However, a low reaction temper ature tends to retard the proceeding of the reaction Preparation of N-n-Propylacrylamide whereas a high reaction temperature induces side reac To 150 ml of N,N-dimethylformamide, was added tions such as hydrolysis of the amide compounds and and suspended 14 g of potassium hydroxide, followed leads to a low yield. Accordingly, the reaction is usually 50 by a further addition of 14 g of acrylamide and 0.05 g of carried out in a temperature range of -20-10020 C., phenothiazine as polarization inhibitor. The mixture preferably, -10'-70° C. Except for certain specific was subjected to a reaction for 3 hours, at 40 C., and halogen-substituted compounds, the reaction tempera with stirring. After the reaction, the reaction solution ture is more preferably in the range of 0-50 C. As long was analyzed by gas chromatography, using a column as the reaction temperature is kept within the above 55 packed with 20M of polyethylene glycol. As a result, it temperature ranges, it is not always necessary to keep was confirmed that N-n-propylacrylamide had been the temperature constant during the reaction. The reac formed in a true weight of 21 g(conversion: 92%). The tion temperature may be suitably set while maintaining reaction solution was filtered and N,N-dimethylfofma a full control on the progress of the reaction so as to mide and unreacted n-propylbromide were distilled off allow the reaction to take place efficiently. under a reduced pressure. The reaction time varies, similar to the reaction tem After adding 100 ml of benzene and 50 ml of distilled perature, depending on the types of starting amide com water to the residue and stirred thoroughly, the solution pound and halogen-substituted compound to be used. It was separated into two layers. The aqueous solution is however within 30 hours at the longest, generally, layer was extracted twice with 50 ml of benzene. The within 10 hours. The progress of the reaction may be 65 resulting benzene layers were combined together and determined by watching the state of the reaction system dried with magnesium sulfate. Then, the benzene layer or by checking the concentrations of the raw materials was subjected to a distillation under reduced pressure. and intended product in the reaction system by virtue of A fraction was collected at 81-83 C./ 1 mmHg, 4,835,312 17 18 thereby obtaining 18g. of N-n-propylacrylanide(yield: and the reaction mixture was reacted at room tempera 79%). ture for 5 hours in a pressure-resistant reaction tube. In the above reaction, the water content in the reac Then, 57 g of 2-chloroethyl acetate was added to the tion system was about 1000 ppm or so. Under such a reaction solution, followed by a further reaction for 3 low content of water, the conversion of acrylamide was 5 hours at room temperature. After the completion of the 95% and the selectivity to N-n-propylacrylamide was reaction, ammonia was distilled off and 10% aqueous 97%. hydrochloric acid solution was added to the resulting COMPARATIVE EXAMPLE 1. residue so as to obtain an aqueous solution of pH 5. The aqueous solution was extracted twice with 100 ml of Preparation of N-N-propylacrylamide 1O ethylacetate. The ethylacetate layers were dried with To 150 ml of t-butanol containing 22 g of potassium magnesium sulfate, followed by the distillation-off of t-butoxide dissolved therein, was added at room tem ethylacetate. The residual substance was subjected to a perature 14 g of acrylamide. The resulting mixture was distillation under reduced pressure but the intended allowed to stand until the deposition of N-potassiumac- is product, N-acetoxyethylacetamide(138-140 C./ 2 rylamide was completed. Then, 31 g of n-propylbro mmHg) did not come out. mide and 0.05 g of phenothiazine were incorporated and thereafter allowed to react for 3 hours with stirring. EXAMPLE 3 Thereafter, deposited potassium bromide was filtered Preparation of N-n-Propylacrylamide off. The filtrate was subjected to a distillation under a 20 A reaction and treatment after the reaction were reduced pressure. At 81-83 C./ 1 mmHg, a fraction carried out in the same manner as in Example 1, except was collected, thereby obtaining 6.0 g of N-n-propyla for the use of N,N-dimethylformamide containing 3.5% crylamide(yield: 25%). by weight of water. The reaction was initiated, similar COMPARATIVE EXAMPLE 2 25 to Example i, while potassium hydroxide remained in To 150 ml of N,N-dimethylformamide, were added the suspended state. In this reaction, the conversion, 14 g of potassium hydroxide, 14 g of, acrylamide and selectivity and yield were 93%, 90% and 84% respec 0.05 g of phenothiazine. The reaction mixture was al tively. The water content in the reaction system was 2.5 lowed to initiate a reaction at 40 C. % by weight. Thirty minutes after the initiation of the reaction, a 30 EXAMPLE 4 white substance deposited on the surfaces of particles of potassium hydroxide and further agitation was not feasi Preparation of N-n-Propylacrylamide ble. The reaction mixture was allowed to react for fur A reaction and treatment after the reaction were ther one hour in the same state and, then, 31 g of n-pro carried out in the same manner as in Example 1, except pyl bromide was added and the reaction was continued 35 for the use of N,N-dimethylformamide containing 7.0% for further two hours. The treatment of the reaction by weight of water. The reaction was initiated, similar mixture was carried out in the same manner as in Exam to Example 1, while potassium hydroxide remained in ple 1. N-n-Propylacrylamide was obtained in an amount the suspended state. In this reaction, the conversion, as little as 20 g only(yield: 9%). selectivity and yield were respectively 87%, 81% and EXAMPLE 2. 70%. The reaction system contained water in an Preparation of N-Acetoxyethylacetamide amount of 5.0% by weight. Tengrams of sodium hydroxide was suspended in 50 COMPARATIVE EXAMPLE 4 ml of N,N-dimethylacetamide, followed by a further Preparation of N-n-Propylacrylamide addition of 12 g of acetamide, 0.05 g of phenothiazine 45 To 150 ml of N,N-dimethylformamide, were added and 36 g of 2-chloroethyl acetate. A reaction was al 14 g of acrylamide, 0.05 g of phenothiazine and 31 g of lowed to take place at 40 C. for 4 hours with stirring. n-propyl bromide. After stirring the mixture to dissolve After the completion of the reaction, the reaction solu the latter in the former, 19.9 ml of a 47.5% aqueous tion was filtered to separate off all the undissolved ma solution of potassium hydroxide was added to initiate a terials. Under reduced pressures, N,N-dimethylacetoa 50 reaction. At this stage, the reaction solution was sepa mide and unreacted 2-chloroethyl acetate were distilled rated in two layers and potassium hydroxide was in a off. After adding 100 ml of benzene and 50 ml of dis completely dissolved state. Thereafter, the procedure of tilled water to the residue, the mixture was thoroughly Example 1 was followed exactly. In this reaction, the agitated and separated into two layers. The aqueous 55 conversion, selectivity and yield were 63%, 48% and solution layer was extracted twice with 50 ml of ben 30% respectively. The reaction system contained water Zene. The benzene layers were combined and dried with in an amount of 7.2% by weight. magnesium sulfate. The thus-dried benzene layer was subjected to a distillation under reduced pressure. A EXAMPLES 5-13 fraction was collected at 138-140 C./ 2 mmHg, With the combinations of raw materials, strongly thereby obtaining 22 g of N-acetoxyethylacetamide basic substances and solvents described in Table 1, their (yield: 74%). The reaction system in the above reaction respective reactions were carried out under the reaction contained water of the order of 5000 ppm or so. conditions also described in Table 1. In Examples 8-13, COMPARATIVE EXAMPLE 3 each reaction was conducted by adding 0.05 g of phe 65 nothiazine. After the completion of each reaction, the Preparation of N-acetoxyethylacetamide resulting reaction solution was treated in the same man To 150 ml of liquid ammonia in which 7.8g of sodium ner as in Example 1, thereby giving results shown in amide had been dissolved, was added 12 g of acetamide Table 2. 4,835,312 19 20 TABLE 1. Amide compound Halogen-substituted Strongly basic Sovent Reaction temp. (C.)/ Example (g) compound (g) substance (g) (ml) reaction time (hr.) 5 Acetamide (12) Ethylbromide (21) Potassium DMF (150) 30/3 hydroxide (12) 6 Acetamide (12) n-Propylchloride Sodium DMF (150) 40/3 (20) hydroxide (9) 7 Acetamide (12) Laurylbromide (75) Sodiurn oxide DMSO 40/4 (14) (150) 8 Acrylamide n-Heptyichloride Potassium DMF (150) 40/4 (14) (33) hydroxide (12) 9 2-Ethoxyacryl n-Propylchloride Potassium Nitro- 40/3 amide (23) (24) hydroxide (12) methane (150) 10 Acrylanide (14) i-Propylbromide Potassium DMF (150) 40A4 (36) hydroxide (16) 11 Methacryl- Chloromethyi Potassium DMF (150) 40/4 amide (17) ethyl ether (33) hydroxide (16) 12 Acrylamide 2-Bronoethyl Potassium DMF (150) 40/4 (14) acrylate (53) hydroxide (16) 13 Acetamide (12) N-(5-bromopentyl) Potassium DMF (150) 40/4 piperidine (70) hydroxide (16) Note: DMF: N,N-Dimethylformamide; DMSO: Dimethylsulfoxide

TABLE 2. Example Reaction product Dist'n conditions (temp. C./press. mmHg) Yield (g) 5 N-Ethylacetamide 87-89/7 2 6 N-n-Propylacetamide 98-100/16 16 7 N-Laurylacetamide 224-229/17 29 8 N-Heptylacrylamide 8-120/2 24 9 N-n-Propyl-2-ethoxyacrylamide 20-121/10 24 O N-i-Propylacrylamide 85-88/1 15 N-Ethoxymethylmethacrylamide 98-00/0.5 20 12 N-2-Acrylethylacrylamide 118-20/0.15 24 13 N-5-Piperidinopentylacetamide 170-171/2 33

EXAMPLE 14 EXAMPLES 15-26 Preparation of N,N-Dimethylacetamide 35 With the combinations of the raw materials, strongly To 150 ml of acetonitrile, were added 12 g of acetam basic substances and solvents shown in Table 3, their ide and 18 g of sodium hydroxide. While stirring the respective reactions were carried out under the reaction mixture, 30g of methylchloride was blown into the conditions also shown in Table 3. In Examples 16, 20, mixture at 50 C. and a reaction was carried out for 3 and 23-26, 0.05 g of phenothiazine was added prior to hours. After the completion of the reaction, undissolved the reactions. substances were filtered off and the filtrate was distilled. After the completion of reactions, resulting reaction A fraction was collected at 166-167 C./760 mmHg, solutions were treated in the same manner as in Exam thereby providing 16 g of N,N-dime ple 14. The reaction products given in Table 4 were thylacetamide(yield: 90%). isolated under their respective distillation conditions 45 shown in the same table. TABLE 3 Amide compound Halogen-substituted Strongly basic Solvent Reaction temp. (C.)/ Example (g) compound (g) Substance (g) (ml) reaction time (hr.) 5 Lauramide (40) Methylchloride (29) Potassium HMPA 40/3 hydroxide (25) (150) 6 Acrylamide (14) Methylchloride (31) Potassium DMF 40/3 hydroxide (25) (150) 17 Benzanide (24) Methylchloride (29) Sodium DMF 40/3 hydroxide (18) (150) 18 Cyclohexane Methylchloride (30) Sodium Aceto- 50/3 carboxanide hydroxide (18) nitriie (25) (150) 19 Urea (12) Methylchloride (50) Potassium DMF SO/3 carbonate (62) (150) 20 3-Ethoxyacryl Methylchloride (31) Barium Diglime 50/3 amide (23) hydroxide (103) (200) 2 Acetamide (12) Ethylchloride (32) Barium Dioxane 50/3 oxide (92) (200) 22 P-Nitrobenz- Ethylbromide (54) Lithium Benzo- 50/3 amide (33) hydroxide (15) nitrile (200) 23 Acrylamide 1,4-Dichlorobutane Potassium EMSO 40/4 (14) (38) hydroxide (22) (150) 24 Ethoxyacet- Allylchloride (39) Sodium THF 40/3 amide (21) hydroxide (20) (150) 25 Methacrylanide Methyl chloro- Potassium DMF 40/5 (17) acetate (76) hydroxide (18) (150) 4,835,312 21 22 TABLE 3-continued Amide compound Halogen-substituted Strongly basic Solvent Reaction temp. (C.)/ Example (g) compound (g) substance (g) (ml) reaction time (hr.) 26 n-Butylamide 2-Chloroallyi Potassium DMF 40/5 (17) chloride (66.6) hydroxide (18) (150) Note: HMPA: Hexamethylphosphoramide; THF: Tetrahydrofuran

TABLE 4 Example Reaction product Dist'n conditions (temp. C./press. mmHg) Yield (g) 15 N,N-Dimethyllauramide 178-180/15 39 16 N,N-Dimethylacrylamide 80-81/20 16 17 N,N-Dimethylbenzamide 131-133/15 25 8 N,N-Dimethylcyclohexane 119-121/12 27 carboxanide 19 Tetramethylurea 89-91A18 14 20 3-Ethoxy-N,N-dimethylacryl- 118-120/6 17 amide 21 N,N-Diethylacetamide 93-94/35 14 22 p-Nitro-N,N-diethylbenzamide 212-24/18 29 23 1-Acryloyl-pyrrolidine 106-08/10 9 24 2-Ethoxy-N,N-diallylacetamide 74-75/0.6 28 25 N,N-Bis(methoxycarbonylmethyl) 144-145/1 23 methacrylamide 26 N,N-Bis(2-chloroallyl)- 80-182/5 33 n-butylamide

then extracted twice with 50 ml of benzene. All the EXAMPLE 27 benzene layers were combined and dried with magne Preparation of 2-Phenyl-N-n-butylacetamide sium sulfate. The residue, resulted from a distillation To 150 ml of N,N-dimethylformanide, were added under reduced pressure of the benzene layers, was re 14 g of potassium hydroxide, 27 g of phenylacetamide 30 crystallized from benzine, thereby obtaining 30 g of and 41 g of n-butyl bromide. The mixture was subjected 2-phenyl-N-n-butyl-acetamide having a melting point of to a reaction at 40 C. for 4 hours. After the completion 56-57 C.(yield: 78%). of the reaction, the reaction solution was analyzed through high-speed liquid chromatography, using a EXAMPLES 28-50 column packed with silica which had been pretreated 35 With the combinations of raw materials, strongly with octadecyl silane. As a result, it was confirmed that basic substances and solvents given in Table 5, their 2-phenyl-N-n-butyl-acetamide had been prepared in a respective reactions were carried out under reaction true amount of 34 g (yield: 89%). After subjecting the conditions shown in the same table. In Examples 29-33, reaction solution to filtration to remove any substances 44 and 45, 0.05 g of phenothiazine was added prior to which had not been dissolved, N,N-dimethylformamide the reactions. and unreacted n-butyl bromide were distilled off under After the completion of the reactions, the resulting reduced pressure from the filtrate. The residue was reaction solutions were treated in the same manner as in mixed with 100 ml of benzene and 50 ml of distilled Example 27. The reaction products shown in Table 6 water. They were thoroughly stirred and then sepa were obtained in a crystalline form from the recrystalli rated into two layers. The aqueous solution layer was zation solvents given in the same table. TABLE 5 Amide compound Halogen-substituted Strongly basic Solvent Reaction temp. (C.)/ Example (g) compound (g) substance (g) (ml) reaction time (hr.) 28 Benzamide (24) Cyclohexyi methyi Sodium DMF 40/4 chloride (40) hydroxide (11) (150) 29 Methacrylamide Cyclohexylbromide potassium DMF 50/4 (17) (49) hydroxide (15) (150) 30 Methacrylamide 4-Bromotoluene Potassium DMF 60/3 (17) (51) hydroxide (15) (150) 31 Benzamide (24) 4-Chloromethyl- Potassium DMA 50/3 m-xylene (39) hydroxide (15) (150) 32 Methylacrylamide p-Bromoanisole Potassium DMF 70/3 (17) (46) hydroxide (15) (150) 33 Acrylamide 4-Bromostyrene Potassium DMF 70/3 (14) (38) hydroxide (15) (150) 34 Benzamide (24) 2-Chloroethyl- Sodium Dimethoxy 40/4 benzene (35) hydroxide (11) ethane (150) 35 Benzamide (24) Cyclohexylchloride Potassium DMF 60/3 (47) hydroxide (16) (150) 36 Cyclohexane 2-Chloroethyl Sodium DMF 40/4 carboxamide benzene (35) hydroxide (10) (150) (25) 37 3-Cyclohexyl Cyclohexylbromide Potassium DMF 60/3 propioamide (41) hydroxide (16) (150) (31) 38 Acetamide (12) Diethyl 2-bromo- Potassium DMF 50/3 4,835,312 23 2 4. TABLE 5-continued Amide compound Halogen-substituted Strongly basic Solvent Reaction temp. (C.)/ Example (g) compound (g) substance (g) (ml) reaction time (hr.) malonate (59) hydroxide (15) (150) 39 p-Nitrobenz- 2-Chloroethyl p- Potassium DMF 50/3 amide (33) nitrobenzoate (51) hydroxide (15) (150) 40 Acetamide (12) 1-Chloromethyl Sodium Nitro- 40/4 naphthalene (32) hydroxide (10) ethane (150) 4. Acetamide (12) 1-Bromonaphtha- Potassium DMF 50/3 lene (39) hydroxide (16) (150) 42 Acetamide (12) 3-Bromoacridine Potassium DMF 60/3 (49) hydroxide (15) (150) 43 Acetamide (12) 3-Chloropropio- Potassium Benzo- 50/3 nitrile (22) hydroxide (15) nitrile (150) 44 Cinnamide (29) Bromobenzene (39) Potassium Nitro- 60/3 hydroxide (15) methane (150) 45 Malonamide (20) Benzylchloride Potassium DMF 40/4 (42) hydroxide (29) (150) 46 Adipamide (29) Benzylchloride Sodium DMF 40/4 (41) hydroxide (20) (150) 47 Furmaramide (23) Benzylchloride Potassium DMF 40/4 (41) hydroxide (29) (150) 48 Terephthal- Benzylchloride Potassium DMF 40/4 amide (33) (41) hydroxide (29) (150) 49 Oxamide (17) Ethyl chloro- Potassium DMF 50/4 acetate (64) hydroxide (28) (150) 50 Urea (12) Benzylchloride Sodium DMF 40/4 (62) hydroxide (20) (150) Note: DMA: N,N-Dimethylacetamide

TABLE 6 Example Reaction product M.P. ("C.) (recryn solvent) Yield (g) 28 N-Cyclohexylmethylbenzamide 106.0-106.5 (Ethanol) 33 29 N-Cyclohexyl methacrylamide 110-111 (Petroleum ether) 17 30 N-p-Tolylmethacrylamide 86-87 (Water-ethanol) 31 N-2,4-Dimethylbenzyl- 97-98 (Ethylacetate-petroleum ether) 35 benzamide 32 N-p-Methoxyphenyl- 89-90 (Water-ethanol) 18 methacrylamide 33 N-p-Styryl acrylamide 128-130 (Water-ethanol) 17 34 N-Phenethylbenzanide 117-118 (Water-ethanol) 34 35 N-Cyclohexyl benzamide 147-148 (Ethanol) 20 36 N-Phenethyl cyclohexane 93-94 (Cyclohexane) 35 carboxamide 37 3,N-Dicyclohexylpropioamide 108-109 (Methanol) 23 38 N-(Diethoxycarbonyl)methyl 95-97 (Water) 41 acetamide 39 N-Nitro-N2-(4-nitrobenzoyl- 189.5-190.5 (Acetone) 48 oxy)ethylbenzamide 40 N-(1-Napthylmethyl)acetamide 127-128 (Ethanol) 29 41 N-1-Napthyl acetamide 158.5-159.5 (Ethanol) 20 42 3-Acetylaminoacridine 235-236 (Water-ethanol) 23 43 N-(2-Cyanoethyl)acetamide 64-65 (Chloroform-carbon tetrachloride) 16 44 N-Phenyl cinnamide 138-140 (Water-ethanol) 23 45 N,N'Dibenzyl malonamide 140-141 (Ethanol-benzine) 42 46 N,N'-Dibenzyi adipamide 188-189 (Water-ethanol) 47 47 N,N'-Dibenzyi fumaramide 313-314 (Ethanol) 42 48 N,N'-Dibenzyl phthalamide 264-266 (Acetone) 49 49 N,N'-Bisethoxycarbonyl 133-134 (Ethanol) 34 methyloxamide 50 N,N'-Dibenzylurea 170-171 (Chloroform) 34

EXAMPLE 51 ethanol, thereby giving 27 g of N,N,N',N'-tetramethyl Preparation of N,N,N',N'-Tetramethylfumaramide fumaramide having a melting point of 130-131 To 150 ml of N,N-dimethylformamide, were added 60 C.(yield: 79%). 56 g of potassium hydroxide and 23 g of fumaramide. While stirring the mixture, 56 g of methylchloride was EXAMPLES 52-55 blown at 40 C. into the mixture. A reaction was carried With the combinations of the raw materials, strongly out for 4 hours. After the reaction, undissolved sub basic substances and solvents given in Table 7, their stances were filtered off and the resulting filtrate was 65 respective reactions were carried out under the reaction subjected to distillation under reduced pressure so as to conditions also given in the same table. After the com remove the solvent and unreacted raw materials. The pletion of each reaction, the reaction solution was residue of the distillation was then recrystallized from treated in the same manner as in Example 51. The reac 4,835,312 25 26 tion products shown in Table 8 were obtained by re solution under stirring conditions, thereby allowing a crystallizing them from their respective recrystalliza reaction to take place for 4 hours. Upon completion of tion solvents also indicated in the same table. the reaction, undissolved substances were filtered off TABLE 7 Amide compound Halogen-substituted Strongly basis Solvent Reaction temp. (C.)/ Example (g) compound (g) substance (g) (ml) reaction time (hr.) 52 Succinamide (23) Methylchloride (50) Potassium DMAC 40/4 hydroxide (50) (200) 53 Phthalanide Ethylbromide (55) Sodium DMF 40/4 (16) hydroxide (37) (150) 54 4,4-Dimethyl- Methylchloride (25) Sodium DMF 40/4 pent-2-inamide (25) hydroxide (18) (150) 55 Succinamide 3-Bromopropio- Potassium DMAC 40/4 (12) nitrile (67) hydroxide (28) (150)

TABLE 8 Example Reaction product M.P. (C.) (recry'n solvent) Yield (g) 52 N,N',N',N'-Tetramethylsuccinamide 83-86 (Diethyl ether) 27 53 N,N,N',N'-Tetraethylphthalamide 38-39 (Ethyl acetate) 34 54 4,4,N,N-Tetramethyl pent-2- 65-66 (Diethyl ether-petroleum ether) 23 inamide 55 Tetrakis-N-2-cyanoethyl 175-176 (Water) 26 succinanide and the filtrate was distilled under reduced pressure. A EXAMPLE 56 fraction was collected at 113-116° C./1 mmHg, result Preparation of N-Allyl-N-ethylacetamide ing in the preparation of 18 g of N-2-cyanoethyl-Nime To 150 ml of N,N-dimethylformamide, were added thylmethacrylamide(yield: 65%). 30g of potassium hydroxide, 12g of acetamide, 54 g of 30 EXAMPLE 58 ethyl bromide, 23 g of allyl chloride and 0.05 g of phe nothiazine. They were subjected to a reaction under Preparation of Diacetylamide stirring conditions at 30° C. for 5 hours. To 150 ml of dioxane, were added 14 g of calcium After removing undissolved substances from the re oxide and 12g of acetamide. Under stirring conditions, action solution, the filtrate was distilled under reduced 35 16 g of acetylchloride was added dropwise at 5° C. A pressure. A fraction was collected at 185-186 C./633 reaction was continued for 2 hours. mmHg, thereby providing 18 g of N-allyl-N- After the reaction, undissolved substances were fil ethylacetamide(yield: 70%). tered off and the solvent and unreacted raw materials were distilled off from the filtrate. The distillation resi EXAMPLE 57 40 due was recrystallized from petroleum ether, obtaining Preparation of 15 g of diacetylamide having a melting point of 80-81 N-2-cyanoethyl-N-methylmethacrylamide C. (yield: 72%). To 150 ml of N,N-dimethylformamide, were added EXAMPLES 59-63 2823 g ofof potassium3-chloropropionitrile hydroxide, and17 g 0.05of methacrylamide, g of phenothi 45 With the combinations of raw materials, strongly azine. A reaction was carried out at 40 C. for 3 hours basic substances and solvents given in Table 9, their with stirring. respective reactions were conducted under the reaction After the completion of the reaction, a 20g portion of conditions also shown in the same table. In Examples 59 the reaction solution was collected. Subsequent to the and 60, 0.05 g of phenothiazine was added prior to the removal of undissolved substances, the filtrate was dis 50 reactions. tilled under reduced pressure. The distillation residue After each reaction, the reaction solution was treated was recrystallized from water, thereby obtaining 1.8g in the same manner as in Example 58. The reaction of N-2-cyanoethylmethacrylamide having a melting products given in Table 10 were recrystallized from point of 46-48 C.(yield: 68%). Twenty grams of their respective recrystallization solvents also shown in methyl were blown at 40 C. into the remaining reaction 55 the same table. TABLE 9 Amide compound Halogen-substituted Strongly basic Solvent Reaction temp. (C.)/ Example (g) compound (g) substance (g) (ml) reaction time (hr.) 59 Acrylamide (14) Acryloylchloride Sodium DMF 5/3 (18) hydroxide (8) (150) 60 Methacylamide Benzene sulfonyl- Barium THF 5/3 (17) chloride (35) hydroxide (19) (150) 6 Benzanide Benzene sulfonyl- Calcium DMA 20/3 (24) chloride (35) hydroxide (9) (150) 62 Benzanide Acetylchloride Sodium Aceto- 5/3 (24) (16) hydroxide (8) nitrile (150) 63 Maonamide Acetylchloride Potassium Dimethoxy 5/3 (20) (16) hydroxide(23) ethane 4,835,312

TABLE 9-continued Amide compound Halogen-substituted Strongly basic Solvent Reaction temp. (C.)/ Example (g) compound (g) substance (g) (ml) reaction time (hr.) (150)

TABLE 10 Example Reaction product M.P. (C.) (recry'n solvent) yield (g) 59 Diacrylamide 176-178 (methanol-benzene) 18 60 N-phenylsulfonyl methacrylanide 128-129 (water) 24 61 N-phenylsulfonyl benzamide 146-147 (ethanol) 27 62 N-acetylbenzamide 116-117 (diethylether) 23 63 N,N'-diacetylmalonamide 137-38 (ethanol) 22 hexylacetamide having a melting point of 73-74 EXAMPLE 64 C.(yield: 45%). Preparation of N-3-Acryloylaminopropyl carbazole EXAMPLE 68 To 150 ml of N,N-dimethylformamide, were added 20 Preparation of N-Allylcrotonamide 14 g of acrylamide, 14 g of potassium hydroxide, and 58 To 200 ml of N,N-dimethylformamide, were added g of N-3-bromopropyl carbazole. A reaction was car 17 g of crotonamide, 105 g of LEWATITMP-500(trade ried out with stirring for 3 hours at 50° C. After the mark, product of Beyer AG) which had been subjected reaction, undissolved substances were filtered off and to a pretreatment described below, 19 g of allylchloride solvent was removed through distillation from the fil 25 and 0.05 g of phenothiazine. They were reacted at 40 trate. Then, the distillation residue was recrystallized C. for 5 hours with stirring. from a mixed solvent of acetone-n-hexane, thereby pro After the reaction, the ion-exchange resin was filtered viding 39 g of N-3-acryloylaminopropyl carbazole hav off and the filtrate was then distilled under reduced ing a melting point of 121.5-122.5 C.(yield: 70%). pressure. A fraction was collected at 90-91 C./0.8 mmHg, thereby obtaining 18 g of N-allylcrotonamide EXAMPLE 65 (yield: 71%). Treatment of Ion-exchange Resin: Preparation of N-3-carboxy-2-propenylacetamide As a strongly basic ion-exchange resin, was used To 150 ml of N,N-dimethylformamide, were added LEVATIT MP-500. The resin was preconditioned and 12 g of acetamide, 14 g of potassium hydroxide, 37 g of then converted to an OH-type resin with 1N-aqueous sodium 4-chloro-2-butynoate, and 0.05 g of phenothi-35 sodium hydroxide solution. It was then thoroughly azine. They were reacted at 50 C. for 4 hours with washed with water. After removing water, it was dried stirring. at 65 C. for 5 hours. After the reaction, undissolved substances were fil EXAMPLE 69 tered off and 30 g of conc. hydrochloric acid was added to the filtrate. The solvent and unreacted raw materials Preparation of N-Cyclohexylacetamide were distilled off under reduced pressure. The resulting To 200 ml of nitroethane, were added 12 g of acetam distillation residue was recrystallized from a mixed ide, 105 of MP-500, which was also used in Example 68, solvent of methanol-chloroform, thereby obtaining 16g and 41 g of cyclohexylbromide. They were reacted at of N-3-carboxy-2-propenylacetamide having a melting 60° C. for 5 hours with stirring. After the reaction, the point of 139-140° C.(yield: 56%). 45 ionexchange resin was filtered off and the resulting filtrate was distilled under reduced pressure to remove EXAMPLE 66 the solvent and unreacted raw materials. The resulting Preparation of Hippuric Acid distillation residue was recrystallized from petroleum To 150 ml of N,N-dimethylformamide, were added ether, thereby obtaining 16 g of N-cyclohexylacetamide 24 g of benzamide, 14 g of potassium hydroxide and 40 having a melting point of 108-109 C.(yield: 57%). g of sodium bronoacetate. They were reacted at 60° C. EXAMPLE 70 for 4 hours with stirring. After the reaction, the reaction Solution was treated in the same manner as in Example Preparation of N-Benzylacetamide 65. The resulting distillation residue was recrystallized To 200 ml of N,N-dimethylformamide, were added from distilled water, thereby obtaining 34 g of hippuric 12g of acetamide, 105 g of LEVATIT MP-500, which acid having a melting point of 187 C.(yield: 69%). was also used in Example 68, and 32 g of benzylchlo ride. They were reacted at 50 C. for 4 hours with EXAMPLE 67 stirring. After the reaction, the reaction solution was Preparation of N,N-Bis-6-carboxyhexylacetamide treated in the same manner as in Example 69, the result To 250 ml of N,N-dimethylformamide, were added ing distillation residue was recrystallized from benzene, 12g of acetamide, 30 g of potassium hydroxide and 116 thereby providing 22 g of N-benzylacetamide having a g of sodium 7-bromoheptanoate. They were reacted at melting point of 61-62 C. 80 C. for 5 hours with stirring. After the reaction, the EXAMPIE 71 reaction solution was treated in the same manner as in Example 65. The resulting distillation residue was re Preparation of N-Benzylcrotonamide crystallized from a mixed solvent of acetone-die To 200 ml of N,N-dimethylformamide, were added thylether, thereby giving 29 g of N,N-bis-6-carboxyl 17 g of crotonamide, 105 g of LEVATIT MP-500, 4,835,312 29 30 which was also used in Example 68, and 32 g of benzyl the mixture was analyzed and it was found that 0.043 chloride. They were reacted at 50 C. for 4 hours with grams of N,N-dimethylmethacrylamide were formed stirring. After the reaction, the reaction solution was (yield 38%). The degree of conversion of the methac treated in the same manner as in Example 69, the result rylamide was measured at 97%. ing distillation residue was recrystallized from benzine, It will be noted that in fact in above Example 1, 31g and 25 of N-benzylcrotonamide having a melting point of n-propylbromide were added together with the 14g of 112.5-113.6° C. was obtained (yield: 71%). of acrylamide and 0.05g of phenothiazine to the potas sium hydroxide suspension, and further that in the ex EXAMPLE 72 periment such strongly basic substance was used in an Preparation of N,N-Dimethylmethacrylamide 10 amount of 0.6 moles per mole of replaceable hydrogen To 150 ml of dimethylsulfoxide, were added 17 g of of the starting amide compound. methacrylamide. 0.05 g of phenothiazine and 18 g of In above Comparative Example 2, the amount of sodium hydroxide. While stirring the mixture, 30 g of N-n-propylacrylamide obtained was in fact only 2.0g methylchloride was blown at 40 C. into the mixture. (yield 9%). They were reacted for 3 hours. After the reaction, un 15 In above Example 47, after the completion of the dissolved substances were filtered off. Then, 150 ml of reaction and prior to filtration to remove substances benzene and 150 ml of water were added to the result which had not been dissolved, the reaction solution was ing filtrate. They were thoroughly agitated and allowed analyzed through high speed liquid chromatography, to stand, resulting in the formation of two separate using a column packed with silica which had been pre layers. The benzene layer was placed aside. The water 20 treated with octadecyl silane, and as a result it was layer was extracted twice with 100 ml of benzene. All confirmed that N,N-dibenzylfumaramide had been pre the benzene layers were combined and dried with mag pared in a true amount of 45 g (yield 94%). nesium sulfate. It was thereafter subjected to distillation Exemplary base/replaceable hydrogen mole ratios under reduced pressure. A fraction was collected at (moles of the strongly basic substance per one mole of 65-67 C./100 mmHg, thereby obtaining 19 g of N,N- 25 replaceable hydrogen of the starting amide compound) dimethylmethacrylamide(yield: 86%). and corresponding intended product yields of preferred production process examples of this invention from EXAMPLE 73 among the above Examples are as follows: Preparation of N,N-dimethylacrylamide 30 To 2 ml of dimethylsulfoxide were added in suspen Example Base/Hydrogen Moie Ratio Yield g (2%) sion 0.17 grams of KOH (base/hydrogen ratio = 1.5). 0.6 18 (79) After stirring at room temperature for 5 minutes, 0.07 3 0.6 - (84) grams of acrylamide and 0.57 grams of methyl iodide 4. 0.6 - (70) 8 0.5 24 (72) were added for effecting reaction with agitation for 5 35 9 0.5 24 (76) minutes. After the reaction was completed, the reaction 10 0.7 15 (67) mixture was analyzed by means of gas chromatography 16 1.15 16 (82) using a column with 20M polyethylene glycol. As a 20 5 i7 (60) 23 O 19 (77) result, it was found that 0.090 grams of N,N-dimethyla 47 0.6 42 (88) crylamide were formed (yield 91%). 51 1.2 27 (79) 72 1. 19 (86) COMPARATIVE EXAMPLE 5 73 1.5 0.090 (91) Preparation of N,N-dimethylacrylamide 74 1.4 0.106 (94) The reaction was carried out in the same manner as in Example 73, except that 0.45 grams of KOH (base/hy 45 Examplary results confirming the adverse influence drogen ratio=8) were used. After the reaction, the of water in the reaction system on the conversion, selec mixture was analyzed in the same manner as in Example tivity and yield of the intended product of preferred 73, and it was found that 0.034 grams of N,N-dimethyla production process examples of this invention from crylamide were formed (yield 34%). The degree of among the above Examples are as follows: conversion of the acrylamide was measured at 99%. 50 Water Content in Conversion Selectivity Yield EXAMPLE 74 Reaction System % % % Preparation of N,N-dimethylmethacrylamide - Example The reaction was carried out in the same manner as in l 1000 ppm 95 97 92 55 3 2.5 wt % 93 90 84 Example 73, except that 0.085 grams of methacrylam 4 5.0 wt.% 87 8 70 ide, instead of the 0.07 grams of acrylamide, were used, Comp. Ex. 7.2 wt.% 63 48 30 and that 0.15 grams of KOH (base/hydrogen ratio = 1.4) 4. were also employed. After the reaction, the mixture was analyzed as in Example 73 and it was found that 0.106 60 It will be seen from the above Examples and from grams of N,N-dimethylmethacrylamide were formed what is stated hereinafter that, notwithstanding the (yield 94%). earlier stated features of the general production process, COMPARATIVE EXAMPLE 6 the present invention is particularly directed to an im proved preferred production process for unsaturated Preparation of N,N-dimethylmethacrlamide 65 N-substituted amide compounds. The reaction was effected in the same manner as in It will be realized that unlike aromatic N-substituted Example 73, except that 0.45 grams of KOH (base/hy amide compounds and saturated N-substituted amide drogen ratio = 8) were employed. After the reaction, compounds which have a very low polymerization 4,835,312 31 32 property or no such property, unsaturated amide com keeping all the basic substance in a liquid state, the pounds, i.e. unsaturated aliphatic N-substituted carbox presence of water in the reaction mixture is considered ylic acid amide compounds, as earlier stated, have an extremely convenient for the proceeding of the reac excellent homopolymerization or copolymerization tion. As is apparent from a comparison between the property. Despite the earlier stated advantages and above Examples 1, 3 and 4 and Comparative Example 4, otherwise wide variety of application fields and useful this known process is accompanied by a considerable ness known for such unsaturated N-substituted amide occurrence of reaction by-products, thereby making its compounds, these compounds have not yet been used in selectivity of an intended N-substituted amide com a great quantity as no inexpensive industrial production pound poor and, depending on an unsaturated N-sub process has yet been established for them. O stituted amide compound intended, resulting in a con In this regard as to the earlier stated known industrial siderable reduction of its yield. production processes of N-substituted amide com Lastly, as earlier stated, in the case where the starting pounds, relying upon the reaction between a carboxylic amide compound to which the present invention is di chloride and an amine, as well as another such produc rected is particularly an unsaturated compound, i.e. tion process which makes use of the Ritter reaction, 5 unsaturated aliphatic N-substituted amide compound, under current circumstances such unsaturated N-sub N,N-substitution reaction does not take place in the stituted amide compounds produced in accordance with same manner as in the case of the saturated compounds these stated conventional processes are either expensive disclosed in Johnstone et al. (Tetrahedron, Vol. 35, or are limited to certain specific types, thereby limiting pages 2169-2173), as is confirmed especially by a com their applications to specific fields. 20 parison between the above Examples 73 and 74 and As to the earlier stated known two step production Comparative Examples 5 and 6. Following the general process for N-substituted amide compounds, (Hikkin alkylation procedure recited on page 2173, left column, bottom, W. J., Reactions of Organic Compounds, Vol. 3, of the Johnstone et al. reference, which shows an Exam 1957; and U.S. Pat. No. 3,084,191), in which first the ple of the use of potassium hydroxide in an amount of 4 amide compound is converted to an amide compound 25 m moles per replaceable hydrogen of the substrate, i.e. substituted by one or more alkali metals under the influ 8 moles per one mole of the substrate, the above Com ence of a strongly basic substance such as alkali metal parison Examples 5 and 6 confirm that in the case where alkoxide, and second the thus-alkali metal substituted such a large amount of potassium is used in an N-substi amide compound is converted to an N-substituted tution reaction of unsaturated amide compounds, poly amide compound under the influence of a halogensub 30 merization and other side reactions take place. This may stituted compound such as alkyl halide, this process be attributed to the earlier stated excellent homopoly involves the inconvenience, in addition to the need for merization or copolymerization property of unsaturated two separate successive steps, that it requires a protonic amide compounds in particular. solvent such as liquid ammonia or an alcohol as reaction On the other hand, the above Examples 73 and 74 solvent, having high reactivity in the presence of a basic 35 show that under the particular conditions of the pre catalyst with a halogen-substituted compound; and an ferred production process of the present invention, the extremely strong basic substance which is irksome to unsaturated N-substituted amide compounds result in handle, such as an alkali metal amide, alkali metal hy high yields of the intended final product. This is further dride, or alkali metal alkoxide. As is shown in particular confirmed by the above Examples 1, 3, 4, 8, 9, 10, 16, 20, in Comparative Examples 1 and 3 above, this known 23, 47, 51 and 72. process involves such problems that the yield of an Thus, in accordance with the particular aspects of the intended unsaturated N-substituted amide compound preferred production process of the present invention, it final product is low, the halogen-substituted compounds is among its special objects to provide a production reactable with the alkali metal substituted amide com process, which can produce not only an unsaturated pound are limited to specific ones and the reaction prod 45 N-monosubstituted amide compound but also an unsatu uct is exclusively an N-monosubstituted amide com rated N,N-disubstituted amide compound in a single pound and, where an N,N-disubstituted amide com step reaction; which is substantially free of side reac pound is intended, the process has to be repeated simi tions and can thus produce an intended unsaturated larly. For the reasons mentioned above, this process has N-substituted amide compound with good selectivity; not been adopted in an industrial large scale as a pro 50 and which is suitable for the production of a wide vari duction process for general unsaturated N-substituted ety of unsaturated N-substituted amide compounds. amide compounds. According to the particular aspects of this invention, As to the earlier stated alternative known two step a wide variety of unsaturated N-monosubstituted amide production process (G. L. Isele et al., Synthesis, 1971 compounds and unsaturated N,N-disubstituted amide (5)), in which, after reacting an amide compound with a 55 compounds can each be produced with a high yield strongly basic substance in an aprotic polar solvent to without substantially causing side reactions to occur by form an alkali metal-substituted amide compound, the an improved preferred production process which com alkali metal-substituted amide compound is reacted prises bringing a strongly basic substance, a starting with a halogen-substituted compound such as an alkyl amide compound and a halogen-substituted compound halide to obtain an N-alkyl-substituted-amide com into simultaneous contact in an aprotic polar solvent to pound, even if this process is followed, no satisfactory react them together, including the improvement result is obtained, as is clear from Comparative Example wherein in the reaction system the starting amide com 2 above. pound is an unsaturated aliphatic monocarboxylic acid In addition, as to the earlier stated production process amide represented by the general formula CH2. of N-alkylated organic compounds (USSR Certificate 65 1CONH2 in which in stands for an integer of 2-3, said of Inventorship No. 667,547), in which a basic substance unsaturated aliphatic amide optionally containing alk Such as caustic soda is added in the form of an aqueous oxy substituent groups, or an unsaturated aliphatic di solution and the substitution reaction is initiated while carboxylic acid amide represented by the general for 4,835,312 33 34 mula CnH2n-2(CONH2)2 in which n stands for an integer vinylacetamide, crotonamide, ethoxyacrylamide and of 2-3; the strongly basic substance, is an alkali metal ethoxymethacrylamide. hydroxide or an alkaline earth metal hydroxide; the Unsaturated aliphatic dicarboxylic acid amides are halogensubstituted compound is an alkyl halide, alkyl represented by the general formula CnH2n-2(CONH2)2 polyhalide, aralkyl halide or alkenyl halide compound; in which in stands for an integer of 2-3. the amount of the strongly basic substance is 0.5-1.5 Exemplary unsaturated aliphatic dicarboxylic acid moles per mole of replaceable hydrogen of the starting amides include maleamide and fumaramide and ci amide compound; the amount of aprotic polar solvent is traconamide. 10-90% by weight; the amount of water present at the As a halogen-substituted compound to be reacted beginning of the reaction is 5% by weight or less; and 10 with a starting amide compound, a wide variety of the reaction is initiated while maintaining the basic compounds may be mentioned, including for example substance in a suspended state. alkyl halides, alkyl dihalides, aralkyl halides and alkenyl It is clear from the foregoing that the preferred pro halides. duction process according to the particular aspects of Alkyl halides are represented by the general formula this invention features very little occurrence of side 15 CnH2n-1X, in which X denotes a halogen atom and n is reactions and thus a high yield of an intended product. an integer of 1-20. Alkyl polyhalides are represented by It is capable of producing a wide variety of unsaturated the general formula CnH2n-2-mXn, in which X means a N-substituted amide compounds as it permits reactions halogen atom and n and m are respectively integers of between an extremely wide range of amide compounds 1-20 and 2-4. and an extremely broad variety of halogen-substituted 20 Alkenyl halides are unsaturated halogen-substituted compounds by combining them suitably. Moreover, it compounds represented by the general formula CnH2n+2-m-2Xm, in which X means a halogen atom and enables the production of each of unsaturated N n, m and r are all integers and stand respectively for monosubstituted amide compounds and unsaturated 2-10, 1-4 and 1-4. N,N-disubstituted amide compounds in a single-step Aralkyl halides are represented by the general for reaction by selecting suitable production conditions. mula Arm. CnH2n-2-m-X, in which X and Ar denote The above successful preferred production process of respectively a halogen atom and an aromatic ring and n, the present invention is based on the present inventors' m and rare all integers and stand respectively for 1-20, finding that the presence of water in the reaction sys 1-4 and 1-4. Here, as the aromatic ring, a benzene, tem, which has heretofore been considered to be conve 30 naphthalene or anthracene ring may be employed. Also nient, serves to induce side reactions contrary to what included are those containing at least one of at least one has been believed and impedes the production of an type of substituent groups such as alkyl, alkenyl and intended unsaturated N-substituted amide compound; aryl groups and halogen atoms, such substituent groups and, instead of reacting an unsaturated amide com and/or atoms being attached to the aromatic ring. pound and a strongly basic substance first and then 35 Although each of chlorine-substituted, bromine-sub causing a halogen-substituted compound to react with a stituted and iodine-substituted compounds are encom reaction product cf the unsaturated amide product and passed by the preferred production process of the pres basic substance as proposed by the prior art, it is neces ent invention, the following chlorine-substituted com sary to bring the strongly basic substance, unsaturated pounds are given as representative examples of halogen amide compound and halogen-substituted compound substituted compounds. Where two or more halogen into a simultaneous contact to react them together. atoms are incorporated, it is not necessary that such Accordingly, either one of the following processes substituent halogen atoms be the same. They may be may be suitably selected in the present invention, as combinations of chlorine(s)-bromine(s) chlorine(s)- earlier stated: iodine(s) and bromine(s)-iodine(s) However, in the fol (a) The three starting materials are simultaneously 45 lowing specific examples of halogen-substituted com added to and mixed in an aprotic polar solvent and the pounds, substituent halogen atoms are limited to substit strongly basic substance is suspended therein to react uent chlorine atoms only. them together; As alkyl halides, may be mentioned for example chlo (b) The strongly basic substance is suspended in an romethane, chloroethane, chloropropane, chlorobu aprotic polar solvent and the unsaturated amide com SO tane, chloropentane, chlorohexane, chloroheptane, pound and halogensubstituted compound are then si chlorodecane, chlorododecane, chlorotetradecane, and multaneously supplied into the suspension to react them chlorooctadecane. Among alkyl polyhalides, there are together; and for example dichloromethane, chloroform, tetra (c) The unsaturated amide compound and halogen chloromethane, dichloroethane, trichloroethane, tetra substituted compound are dissolved or suspended in an 55 chloroethane, dichloropropane, trichloropropane, di aprotic polar solvent and the strongly basic substance is chlorobutane, dichloroheptane, dichlorohexane, and then added and suspended. dichlorodecane. According to the particular aspects of the preferred Among aryl alkyl halides, i.e. aralkylhalides, may be production process of the present invention, the follow mentioned for example benzychloride, benzylidenedi ing features are especially contemplated. chloride, phenethylchloride, phenylpropylchloride, Unsaturated aliphatic carboxylic acid amides are rep chloromethylnaphthalene, chloromethylanthracene, resented by the general formula CnH2n-1CONH2, in diphenylmethylchloride, triphenylmethylchloride, which n stands for an integer of 2-3. These amides chloromethyltoluene, chloromethylethylbenzene, chlo contain at least one carbon-to-carbon double bond in romethylxylene, chloromethylstyrene, chloromethyl their molecules. Also included are those containing 65 biphenyl and chlorobenzylchloride. alkoxy substituent groups. As alkenyl halides, may be mentioned for example Exemplary unsaturated aliphatic monocarboxylic vinylchloride, vinylidenechloride, allylchloride, chlo acid amides include acrylamide, methacrylamide, roallylchloride, propargyl chloride, methallyl chloride, 4,835,312 35 36 chloromethallyl chloride, pentenyl chloride, hexene the reactions are initiated while at least parts of the dichloride, and octenyl chloride. substances still remain in a suspended state. The reactivity of each of the halogen-substituted In practising the preferred production process of this compounds exemplified above, varies depending on the invention, the relative amounts of the raw materials, i.e. conformation of a carbon atom to which a halogen atom starting unsaturated amide compound, halogen-sub is attached. For the reaction of the preferred production stituted compound and strongly basic substance, to be process of this invention, it is preferable to employ a used vary depending on the reactivity between the compound which has one or more halogen atoms substi halogen-substituted compound and starting unsaturated tuted at a primary or secondary carbon. amide compound or depending on whether the intended The reaction solvent used in the preferred production O product is an unsaturated N-monosubstituted amide process of the present invention may be selected from compound or an unsaturated N,N-disubstituted amide aprotic polar solvents, including, for example, acetoni compound, or for another reason. It is thus rather diffi trile, dioxane, nitromethane, nitroethane, nitrobenzene, cult to limit their relative amounts to specific ranges. pyridine, dimethoxyethane, tetrahydrofuran, tetrahy However, generally speaking, where an unsaturated dropyran, 2-methyl-tetrahydrofuran, benzonitrile, N,N- 15 N-monosubstituted amide is intended, the halogen-sub dimethylformamide, N,N-dimethylacetamide, N,N-die stituted compound may be used in an amount of 0.2-10 thylformamide, dimethylsulfoxide, N-methylpyrroli moles, more preferably, 0.3-7 moles, per mole of the done, hexamethyl phosphoramide, sulforan, oxepane starting amide compound. On the other hand, the and glimes such as monoglime, diglime, trigline and strongly basic substance may be used in an amount of tetraglime. Among the above solvents, acetonitrile, 20 0.5-1.5 moles per mole of replaceable hydrogen of the N,N-dimethylformamide, N,N-dimethylacetamide, di starting amide compound as per the above Examples. methylsulfoxide, sulforan and tetraglime may be used as When the strongly basic substance is in excess particularly preferable solvents. These solvents gener amount, that is above 1.5 moles per mole of replaceable ally have strong miscibility with water and thus tend to hydrogen, polymerization of the unsaturated compound 25 and other side reactions will take place. On the other induce mixing of water due to water absorption or upon hand, when the amount used is below the 0.5 mole ratio recycling for re-use. Therefore, care must be exercised amount the desired reaction fails to take place in a satis upon handling such solvents. factory manner. In a reaction system for carrying out the preferred When producing an N,N-disubstituted amide com production process of this invention, it is necessary that 30 pound, the halogen-substituted compound may be used the reaction is initiated while at least a part of the in an amount of 1.0-20 moles, more preferably 1.5-15 strongly basic substance is suspended therein. In this moles, per mole of the starting amide compound. state, water is present normally in an amount of 6% by It is also possible to produce an unsaturated N,N- weight or so in the reaction system. If the water content disubstituted amide compound having different substit exceeds this figure, side reactions such as hydrolysis of 35 uent groups. Here, two halogen-substituted compounds a halogen-substituted compound or amide compound of different types may be reacted simultaneously with tend to occur easily, thereby considerably lowering the the starting amide compound. The relative amounts of yield of an intended product. To make the reaction the two halogen-substituted compounds of different proceed efficiently and to increase the yield of an in types vary depending on their reactivity. One of the tended product, as will be appreciated from the above halogen-substituted compounds may be used generally Examples 3 and 4 and Comparative Example 4, it is in an amount of 1.0-20 moles, preferably, 1.0-15 moles, required to control the water content in the reaction per mole of the other halogen-substituted compound, system below at most 5% by weight, preferably, below the reactivity of the latter compound being supposed to 2.5% by weight, and more preferably, below 10,000 be high. Also, as to a process for producing an unsatu ppm. 45 rated N,N-disubstituted amide compound whose sub There is no special limitation to the amount of solvent stituent groups are different, it may be possible to react to be employed. However, it may account for 5-95% by the starting amide compound with a first halogen-sub weight, preferably, 10-90% by weight of the whole stituted compound to obtain an unsaturated N weight of the reactants including the solvent per se. monosubstituted amide compound and then to react the Next, the strongly basic substance to be employed in 50 unsaturated N-monosubstituted amide compound with the preferred production process of the present inven a second halogen-substituted compound. In the reaction tion is required to be a solid material and, when dis system of the preferred production process of this in solved or suspended in water, to make the pH of the vention it is preferable to incorporate a polymerization aqueous solution be at least 10, preferably, above 11. As inhibitor to avoid the polymerization of raw materials such strongly basic substances, there are for example 55 and reaction product during the reaction step or purifi alkali metal hydroxides and alkaline earth metal hydrox cation step. The polymerization inhibitor is not neces ides. sarily to be limited to any specific one, but there may Specific examples of the above materials are as fol generally be mentioned phenol-type polymerization lows: inhibitors, amine-type polymerization inhibitors, mer Among alkali metal hydroxides, may be mentioned captan-type polymerization inhibitors, and copper pow for example sodium hydroxide, potassium hydroxide, der. lithium hydroxide, rubidium hydroxide, and cesium To carry out the reaction of the preferred production hydroxide. As alkaline earth metal hydroxides, may be process of this invention, a conventional reaction tank mentioned for example beryllium hydroxide, magne may be used. However, where a strongly basic sub sium hydroxide, calcium hydroxide, strontium hydrox 65 stance having low solubility is used, the basic substance ide and barium hydroxide. may be packed in a column and a mixture solution of a These strongly basic substances are generally sub starting amide compound and halogen-substituted com jected to their respective reactions in a solid form and pound may be recycled through the column. From the 4,835,312 37 38 standpoint of the maintenance and control of the reac Moreover, where the reaction solvent has great mis tion facilities, it is more convenient to use a reaction cibility with water, such as dimethyl sulfoxide, and the tank. intended product is highly hydrophobic such as an When carrying out the reaction in a reaction tank, the unsaturated N-alkylsubstituted amide compound, it is raw materials may be charged in an arbitrary order. 5 possible to add water to the reaction solution after the However, where a halogen-substituted compound hav completion of the reaction and separate the intended ing high reactivity is employed, it is convenient for the product as an oil layer, or to extract the intended prod purpose of suppressing side reactions to add the halo uct with a solvent capable of forming two layers with gen-substituted compound lastly so that it undergoes an water, such as benzene, toluene, or chloroform. O It is clear from the foregoing, that according to the intended reaction with the other two raw materials. preferred production process of this invention, it is The reaction temperature of the preferred production possible to economically produce unsaturated N-sub process of this invention depends on the reactivity of a stituted amide compounds which have an extremely starting unsaturated amide compound and halogen-sub wide variety of functions. Thus, unsaturated N-sub stituted compound to be used. However, a low reaction 15 stituted amide compounds can be supplied to various temperature tends to retard the proceeding of the reac application fields, to which conventional unsaturated tion whereas a high reaction temperature induces side N-substituted amide compounds could not be applied. reactions such as hydrolysis of the unsaturated amide Since the preferred production process of the present compounds and leads to a low yield. Accordingly, the invention is carried out with the same reaction pattern, reaction is usually carried out in a temperature range of it brings about an advantage that many types of unsatu -20 to 100 C., preferably -10 to 70° C. Except for rated N-substituted amide compounds can be produced certain specific halogen-substituted compounds, the in the same reaction vessel, thereby making the process reaction temperature is more preferably in the range of of this invention suitable for the production of many 0-50 C. As long as the reaction temperature is kept types of unsaturated N-substituted amide compounds in within the above temperature ranges, it is not always 25 small quantities. necessary to keep the temperature constant during the In short, according to the preferred production pro reaction. The reaction temperature may be suitably set cess of the present invention, an unsaturated N-sub while maintaining a full control on the progress of the stituted amide compound is produced with a high yield reaction so as to allow the reaction to take place effi by initiating a reaction among a starting amide com ciently. 30 pound such as an unsaturated aliphatic mono or dicar The reaction time varies, similar to the reaction tem boxylic acid amide, a halogen-substituted compound perature, depending on the types of starting amide con such as an alkyl halide, alkyl polyhalide, aralkylhalide pound and halogensubstituted compound to be used. It or alkenyl halide, and a strongly basic substance while is however within 30 hours at the longest, and generally maintaining the basic substance in a suspended state, in is within 10 hours. The progress of the reaction may be 35 conjunction with the above stated preferred production determined by watching the state of the reaction system process requirements. or by checking the concentrations of the raw materials What is claimed is: and intended product in the reaction system by virtue of 1. In a process for producing an unsaturated N-sub gas chromatography or high-speed liquid chromatogra stituted amide compound by bringing a strongly basic 40 substance, a starting amide compound and a halogen phy. substituted compound into simultaneous contact in an Upon completion of the reaction, by-produced metal aprotic polar solvent to react them together, the im halide is filtered offin a known manner and, by subject provement wherein the reaction system the starting ing the filtrate to a distillation under a reduced pressure, amide compound is acrylamide or methacrylamide; the the intended product of high purity is obtained. How 45 strongly basic substance is an alkali metal hydroxide; ever, when the metal halide is dissolved in the reaction the halogen-substituted compound is an allyl halide solution or sublimable starting amide compound re alkyl polyhalide, aralkyl halide or allyl halide com mains in the reaction solution, the solvent is distilled off pound; the amount of the strongly basic substance is from the reaction solution and the above substance is 0.5-1.5 moles per mole of replaceable hydrogen of the then removed with a mixed solvent, which forms two 50 starting amide compound; the amount of aprotic polar layers, such as benzenewater, chloroform-water or the solvent is 10-90% by weight of the whole weight of the like. Upon subjecting the organic layer to a distillation reactants including the solvent per se; the amount of under a reduced pressure, the intended product can be water present at the beginning of the reaction is 5% by obtained with high purity. Where the intended product weight or less of the reaction system; and the reaction is has a high boiling point or tends to decompose by heat, 55 initiated while maintaining the basic substance in a sus it may be purified in accordance with a purification pended state. method such as solvent extraction or recrystallization. is

65 UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT NO. : 2,835,312 DATED May 30, 1989 INVENTOR (S) : Itoh et al. It is certified that error appears in the above-identified patent and that said Letters Patent is hereby Corrected as shown below: On the first page of the patent document, at 73, Assignee data, change the Assignee from "Mitsui Chemicals, Incorporated" to --Mitsui Toatsu Chemicals, Incorporated--.

Signed and Sealed this Sixteenth Day of January, 1990

Attest

JEFFREY M. SAMUELS Attesting Officer Acting Commissioner of Patents and Trademarks