Nitriles amidines

From To — Akanes CycJoaikanes Akenes Akynes Aryls Halogen compounds Alcohols Phenols Ethers, Quinones B, 5 and Si compounds P and BI compounds Nttro. Nitroso, Azo. Azoxy, Hydrazo Azides Amines Organometahic compounds Adehydes Ketones Acids. AnHyd rides. Esters Amides, Amidines. Nitriles Hydroxy-aldehydes or -ketones. Sugars. Hydroxy acids Ammo acids. Peptides Heterocycles Nucleosides Miscellaneous, including heterocycles... 

Amidines. Nitriles are converted to amidines on reaction with MeAlfCONH in toluene at slightly elevated temperatures. 

Amidines are best made in two stages a nitrile reacts with dry HCl and anhydrous alcohols to give an imidic ester (imino-ether) which yields an amidine with NH3. 

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). 

The reaction of ethyleneimine with nittiles in the presence of HBF gives A -imidazolines (229). If trichloroacetonitrile [545-06-2] (R = Cl) is used as the nitrile component, the intermediate amidine can be isolated (230). 

The other main reaction in this class is the Dieckmann-type cyclization of the intermediates (163) from 4(6)-halo-5-ethoxycarbonylpyrimidines with AC-substituted /3-alanine esters and nitriles, and related compounds, to give 5,6,7,8-tetrahydro-5-oxopyrido[2,3-[Pg.221]

Peifluorinated nitriles are highly electrophihc compounds because of the adjacent electron-accepting substituent Therefore, the addition of amines, alcohols, and mer-captans forming amidines, imidates, and thiobnidates is well-documented [63]. 

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. 

This reaction is believed to proceed via an amidine (34) and it has been shown that the reactivity of the nitrile group toward nucleophiles is a more important factor than amine basicity in controlling cyclization. 

Among other bicyclic amidine catalysts, 3,4,6,7,8,9-hexahydro-2//-pyrido[l,2-n]pyrimidine was also applied in the preparation of /3-alkoxy nitriles from Q ,/3-unsaturated nitriles and alcohols (99GEP 19803515). The azido group could be smoothly converted into a trifluoroacetylamido group by treatment with (Cp3CO)2 in the presence of Ph3P and 2,3-dihydro-2//-pyrido[l,2-n]pyrimidin-2-one under Ar in THE (99HCA2380). 

Intermediate arylamidine, 6S, is prepared by the aluminum chloride-catalyzed addition of aniline to the nitrile function of 4-cyanothiazole (67), Amidine, 65, is then converted to its N-chloro analog (69) by means of sodium hypochlorite. On base treatment, this apparently undergoes a nitrene insertion reaction to produce thiabendazole (70), ... 

The imidazole nucleus is often found in biologically active molecules,3 and a large variety of methods have been employed for their synthesis.4 We recently needed to develop a more viable process for the preparation of kilogram quantities of 2,4-disubstituted imidazoles. The condensation of amidines, which are readily accessible from nitriles,5 with a-halo ketones has become a widely used method for the synthesis of 2,4-disubstituted imidazoles. A literature survey indicated that chloroform was the most commonly used solvent for this reaction.6 In addition to the use of a toxic solvent, yields of the reaction varied from poor to moderate, and column chromatography was often required for product isolation. Use of other solvents such as alcohols,7 DMF,8 and acetonitrile9 have also been utilized in this reaction, but yields are also frequently been reported as poor. 

The synthesis of pyrido[2,3-d]pyrimidin-7(8H)-ones has also been achieved by a microwave-assisted MCR [87-89] that is based on the Victory reaction of 6-oxotetrahydropyridine-3-carbonitrile 57, obtained by reaction of an Q ,/3-unsaturated ester 56 and malonitrile 47 (Z = CN). The one-pot cyclo condensation of 56, amidines 58 and methylene active nitriles 47, either malonitrile or ethyl cyanoacetate, at 100 °C for benzamidine or 140 °C for reactions with guanidine, in methanol in the presence of a catalytic amount of sodium methoxide gave 4-oxo-60 or 4-aminopyridopyrimidines 59, respectively, in only 10 min in a single-mode microwave reactor [87,88]... 

A catch and release synthesis of tetrazoles and cyclic amidines has been reported making use of solid-supported oximes [94]. When bound sulpho-nyloximes, obtained by reacting polymer supported sulfonyl chloride with oximes, were reacted with nucleophiles, tetrazoles or cychc amidines were obtained (Scheme 19). Alternatively, the use of TMS-CN affords imino nitriles, which have been used as intermediates for the preparation of indoles, 1,2,3,4-tetrahydropyridines, quinoxalines and benzimidazoles. 

Unsubstituted amidines (in the form of their salts) can be prepared by addition of ammonia to nitriles. Many amidines have been made in this way. Dinitriles of... 

Removing the piece with the two heteroatoms from (43) leaves acetoacetate as one starting material the other is an amidine, easily made from nitrile (45). 

Xylamidine (87) is an amidine which serves as a serotonin inhibitor. This agent is prepared by alkylation of m-methoxyphenol with a-chloropropio-nitrile, KI and potassium carbonate in methylethyl ketone to give 85, which is in turn reduced with... 

A number of amidines have anthelmintic activity. Bunamidine (25), indicated for treatment of human pinworm infestations, is prepared from a-naphthylhexyl-ether (23) by Friedel-Crafts type reaction with cyanogen bromide and aluminum chloride to give nitrile (24). This, then, is reacted with the magnesium bromide salt of di-n-propylamine leading to the naph-thamidine structure (25). -... 

Reactions of nitriles may be promoted by the presence of divalent Co. The conversion of sterically unhindered nitriles RCN (R = Me, Et, n-Pr, w-Bu) into the corresponding amidines RC(NH2) = NH occurs in the presence of Co(N03)2.6H20 and the ketoxime Me2C=NOH. The metal free amidinium ions were crystallized as their nitrate salts.358... 

The formation of compounds 2-503 proceeds via the addition of a hydrazide 2-500 onto the central carbon of an isothiocyanate 2-499. Subsequent cyclization by attack of the hydrazide nitrogen in the formed 2-501 onto the nitrile moiety gives intermediate 2-502. A further attack of the newly formed amidine nitrogen onto the carbonyl group followed by extrusion of water affords the triazoloquinolines 2-503. 

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