Amidines acidity

Nitriles react with ammonia, or primary or secondary amines in the presence of an acid catalyst to give amidines (Scheme 26) (75, 77, 81). The catalysts used are hydrochloric acid and aluminium chloride. The amidines are anthelmintics for animals such as sheep, goats, cattle, horses, and Swine. 

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

Carbamic acid is the monoamide of carbonic acid the diamide is the weU-known compound urea [57-13-6] also called carbamide (see Urea). Guanidine [113-00-8] could be regarded as the amidine of carbamic acid (see Cyanamides). 

The simplest [3 + 3] reactions in the pyridine series involve reaction of o-chloropyridinecarboxylic acid derivatives with three-atom fragments such as urea, thiourea(s), amidines and guanidines, e.g. (240) (241). Examples are known mainly in... 

The reactivity of the amino groups at the pteridine nucleus depends very much upon their position. All amino groups form part of amidine or guanidine systems and therefore do not behave like benzenoid amino functions which can usually be diazotized. The 4-, 6-and 7-amino groups are in general subject to hydrolysis by acid and alkali, whereas the 2-amino group is more stable under these conditions but is often more susceptible to removal by nitrous acid. 

A -Imidazolines (294 Z = NH) are cyclic amidines and exhibit the characteristic resonance stabilization and high basicity. A -Oxazolines (294 Z = 0) are cyclic imino ethers, and A"-thiazolines (294 Z = S) are imino thioethers both are consequently easily hydrolyzed by dilute acid. 

Several related derivatives have also been utilized in this type of synthesis. Imino-chloromethanesulfenyl chlorides (184), prepared by the controlled addition of chlorine to isothiocyanates, react with amidines (161) to give 1,2,4-thiadiazolines (185) (71T4117). Chlorocarbonylsulfenyl chloride (186), prepared by the hydrolysis of trichloromethanesulfenyl chloride with sulfuric acid, reacted with ureas, thioureas and guanidines to give 1,2,4-thiadiazolidine derivatives (187) <70AG(E)54, 73CB3391). 

There are differences in the high temperature behavior. While oxaziridines almost always isomerize to acid amides, a similar reaction of diaziridines, which should lead to amidines, has not been observed. Sensitivity towards bases, often encountered in oxaziridines, is observed only in some special substituted diaziridines. The tendency of some classes of oxaziridines to transfer the nitrogen function also lacks in the diaziridine field. On homolytic reactions of diaziridines there are only a few observations. 

Cleavage of N—N by potassium f-butoxide to give amidine (164) was observed with diaziridine (134). This is the only known analog of the generally observed acid amide formation from oxaziridines (74JPR999). 

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

The third step is hydrolysis of the N-phosphorylated amidines which is carried out by either acid or alkali depending on the substrate. 

The condensation of 1,3-dicarbonyl compounds 1 with amidines 2 catalyzed by acids or bases to give pyrimidine derivatives 3 is regarded as the Pinner pyrimidine synthesis. ... 

Substances of this type have hitherto received little attention. One of the reasons appears to be the limited possibilities of preparation. The only known method of preparation, described by Woolley et ai./ proceeds from the derivatives of 4-aminoimidazole-5-carboxylic acid. The amide of this acid (142) is treated with nitrous acid to yield 4-hydroxyimidazo [4,5-d]-i -triazine (2-azahypoxanthine) (143), the amidine (144) yielding the 4-amino derivative (2-azaadenine) (145) under the same conditions. 2-Azahypoxanthine was probably obtained in the same way earlier but was not identified. ... 

It was found inadvisable to use more than four molecules of form-amide [ (47) when R = H] per molecule of anthranilic acid and the condensation produces best results when the mixture is heated at 120 -130°C for 2 hr followed by further heating at 170°-180 C for 2 hr. Other variants of this reaction involve the use of ammonium o-acylaminobenzoates, anthranilic acid in the presence of nitriles and acetic anhydride, o-acetamidonitrile with acetic anhydride or hydrogen peroxide, anthranilic esters and aliphatic or aromatic amides or amidines, isatoic anhydride with amides or amidines, and anthranilic esters with aryl iminochlorides in acetoned The mechanism proposed by Bogert and Gotthelf has had experimental supporR and is represented in Scheme 12. 

During a study of azonitrones (70), Forrester and Thomson showed that reaction with toluene-p-sulfinic acid resulted in nitrogen evolution and formation of the hydroxamic acid (66) together with the pyrrolidone (71) and the amidine (72). These workers suggested the following reaction course. Although the yield of hydroxamic acid was high, the method is not likely to be of preparative value. 

Furthermore we found that kasugamycin forms a chelate compound with basic cupric carbonate (7), which is stable to acid and unstable to heat and base. This evidence together with the results obtained above strongly supports the amidine structure (13) for kasugamycin. Finally the amidine compound was successfully prepared by the reaction of kasuganobiosamine with the diethyl ester of oxalimidic acid (14) and... 

This is the first case to observe 2,4-diamino-2,3,4,6-tetradeoxy-D-arafoino-hexopyranose in natural products and the first isolation of d-inositol from microbial products. Kasugamycin is the first compound possessing a unique group of an amidine carboxylic acid. 

The route of kasugamycin s biosynthesis, especially of the amidine carboxylic acid moiety, is interesting. Either C-l or C-2 labeled glycine... 

The amidines 10, prepared by condensation of the corresponding imidates with aminoacetal-dehyde dimethyl acetal, undergo cyclization with a variety of acids to l//-3-benzazcpin-2-amines 11 45 Method A has proved to be successful on an industrial scale. 

Chromium, (ri6-benzene)tricarbonyl-stereochemistry nomenclature, 1,131 Chromium complexes, 3,699-948 acetylacetone complex formation, 2,386 exchange reactions, 2,380 amidines, 2,276 bridging ligands, 2,198 chelating ligands, 2,203 anionic oxo halides, 3,944 applications, 6,1014 azo dyes, 6,41 biological effects, 3,947 carbamic acid, 2,450 paddlewheel structure, 2, 451 carboxylic acids, 2,438 trinuclear, 2, 441 carcinogenicity, 3, 947 corroles, 2, 874 crystal structures, 3, 702 cyanides, 3, 703 1,4-diaza-1,3-butadiene, 2,209 1,3-diketones... 

Iron, tris(hexafluoroacetylacetone)-structure, 1,65 Iron, tris(oxalato)-chemical actinometer, 1,409 photoreduction, 1,471 relief-image-forming systems, 6,125 Iron, tris(l,10-phenanthroline)-absorptiometry, 1,549 racemization, 1,466 solid state, 1,467 structure, 1, 64 lron(III) chloride amino acid formation prebiotic systems, 6,871 Iron complexes acetonitrile. 4,1210 acetylacetone, 2,371 amidines... 

However, more-rigorous treatment (5% acetic acid, 100°C, 17 hours) opened the imidazole ring and produced /V -cyclohexyl-a-formylaminoacetamidine (57), characterized as the crystalline picrate. Amidine 57 produced no dye in the Bratton-Marshall assay. The same behavior can be expected from AIR (46), although the product of hydrolytic ring-opening was not actually isolated. On the other hand, it was observed that a solution of AIRs (0.2 mM in 0.01-M ammonium hydroxide) prepared by biosynthesis, when stored at 4°C, did not change appreciably within a day. A decrease in the concentration of AIRs of about 30% occurred within a month. 

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