Amino compounds nitriles

The reactivity of 5-amidinoisothiazoles (221) was explored to demonstrate the equilibrium 221 222 (Scheme 37). However, on reacting with nitriles or imidates, 5-amino compounds 220 (R = Me, Ph) give directly the rearranged thiadiazoles 222. The equilibrium between the two heterocycles (in different solvents at room temperature) is not observed, and this result is attributed to the greater stability of the 1,2,4-thiadiazole... 

In general, the method of enzymatic cyanohydrin synthesis promises to be of considerable value in asymmetric synthesis because of the synthetic potential offered by the rich chemistry of enantiomerically pure cyanohydrins, including their stereoselective conversion into other classes of compounds such as a-hydroxy carboxylic acids or respective esters, w c-diols, / -aminoalcohols, aziridins, a-azido(amino/fluoro)nitriles, and acyloins [501, 516]. 

Arylsulphonyl chlorides may be readily converted into the corresponding arylsulphonamides (e.g. by treatment with solid ammonium carbonate or with concentrated ammonia solution) or into a substituted arylsulphonamide (by reaction with the appropriate amino compound). Arylsulphonylhydrazides (for use in the preparation of aliphatic nitriles, Section 5.13.2, p. 712) may be prepared by a similar reaction using anhydrous hydrazine.20... 

Thiazolecarboxylic acids, esters or acid chlorides react readily with ammonia or various amines, affording the corresponding carboxamides. Dehydration of the amides with phosphorus pentoxide or phosphoryl chloride occurs readily and gives the corresponding nitriles (Scheme 99). Thiazolecarboxylic acid hydrazides are obtained in a similar way, using hydrazine or substituted hydrazines instead of ammonia or amines. The Raney nickel reduction of cyanothiazoles leads to the corresponding amino compounds, the 4-cyano derivative being the isomer most readily reduced. 

Substituted 1,2-benzoseIenazoles are synthesized by the reaction of 6H, 1H-benzo[fc]selenophene-6,7-dione (31) with bromine followed by ammonia. The amide (14 Scheme 10) may be used for the preparation of the nitrile (15) or the amino compound (16) (75JHC1091). 

As both nitration and sulphonation take place with comparative ease, with either hydrocarbons or acids, and as the nitro compounds yield amino compounds and these yield diazo compounds, with their numerous reactions, in particular the Sandmeyer reaction for obtaining nitriles and as sulphonic acids are easily converted into phenols or nitriles it will be seen that by a combination of these synthetic reactions practically any desired ring-substituted mono-basic or poly-basic ring-carboxy acid may be obtained. 

Complexes of organotin with amidines have been found to be excellent catalysts for the preparation of polyurethane foams, which do not have the disadvantage of any amine odor and, in addition, delayed onset of the isocyanate-hydroxyl reaction An example of a mercapto-delayed organotin catalyst is 2,2,4,4-tetrakis(alkyl)- l,3,2,4-dithia-stannetane.55 Amine salts of amino acids, tertiary amino acids, and tertiary amino acid-nitrile compositions, have been found to be effective as delayed action catalysts for polyurethane synthesis. They are particularly effective when used in combination with an organometallic compound, such as an organotin. ... 

In a general annulation method, 4-aminonicotinonitriles are treated with ethyl orthoformate to give the corresponding (ethoxymethylene)amino compounds. The nitrile group is then converted with sodium hydrogen sulfide into a thioamide function which cyclizes to yield the 2-sulfanylpyrimidine moiety. An application of this method is the synthesis of 6-benzyl-5,6,7,8-tetrahydropyrido[4,3-t/]pyrimidine-2-thiol (3) from l-benzyl-4-[(ethoxymethylene)amino]-l,2,5,6-tetrahydropyridine-3-carbonitrile (2).491 492... 

Similarly, pteridine-6-carbaldehyde 2a after conversion to the oxime 3 can be transformed to the corresponding nitrile oxide with (V-chlorosuccinimide in dimethyl formamide, followed by treatment with friethylamine in the presence of a dipolarophile, to give good yields of cycloaddition products 4.254 These adducts are hydrolyzed to the 2-amino compounds by heating to 70-80°C with 1 M hydrochloric acid in dioxane. 

Reaction of compound 8 with a-halo nitriles (R CHHalCN) gave the 3-amino compounds 7 after cyclization of the intermediate S-alkylated products 12 with aqueous potassium hydroxide. Similarly reaction of 2-amino-3-chloropyrazine (13) with the mercapto esters 14 in the presence of sodium ethoxide gave the 3-oxo derivatives 16 on refluxing in dioxan. The intermediates 15 are involved in the reaction. The most convenient synthesis of these compounds involves reaction of 2-amino-3-chloropyrazines with thioglycollic acid in alkali and acid-catalyzed cyclization of the carboxymethylthio derivative. ... 

Reaction of 2-chloro 3-substituted quinoxalines 22 with hydrazines provides another simple preparation of pyrazolo[3,4-h]quinoxalines. The parent heterocycle 23 has been obtained by treating the aldehyde 22 (R = CHO) or the dibromomethyl derivative 22 (R = CHBr2) with hydrazine. Similarly the nitrile 22 (R = CN) has given the 3-amino compound 24 in 72% yield, and methylhydrazine with the ester 22 (R = COjEt) gave the 3-hydroxy derivative 25. In spite of the ready cyclization of the aldehyde 22 (R = CHO) with hydrazine, the corresponding... 

This compound, like any nitrile can be catalytically reduced to its corresponding amino compound. To prevent the formation of any byproducts, the nitrile is treated with the catalyst, hydrogen and a mixture of sodium acetate in acetic anhydride. This protects the primary amine and the final product is isolated by alkaline hydrolysis. Summarizing ... 

Reduced nitrogen (as in ammonium ions, amino compounds, amides, nitriles) normally retains its oxidation stage of -3 exceptions are possible. 

Scheme 12.28. A representation of the use of sodium azide as a nucleophile to convert a-halo carboxylic acids and their amide and nitrile derivatives to the corresponding amino compounds. The example shows the formation of glycine (Gly, G) by this method.

The overall reproducibility of this nitrogen determination method is 5% in the nitrogen content range 0.002 to 75%. The sodium sulfate-selenium-copper sulfate mixture is particularly suitable for the quantitative digestion of all compounds in which the nitrogen is present in an easily decomposed form (e.g., as amine, amino compounds, amino acids, amide or nitrile and their simple derivatives). Forms of nitrogen for which accurate results are not usually obtained include those with -N-N (e.g., diazo) and N-0 (e.g., nitro) linkages and some resistant heterocyclic structures. 

The Kjeldahl digestion procedure described quantitatively decomposes amines, amino compounds, amino acids, amides, nitriles and their simple derivatives and also many refractory nitrogen compounds. Quantitative decomposition of nitrogen containing polymers, e.g., styrene-acrylonitrile copolymers and polyacrylonitrile, is achieved. 

Nucleophilic Reactions.—Nucleophilic substitution in the isothiazole nucleus, as well as a variety of nucleophilic ring fissions, continue to attract a good deal of attention. The methylsulphonyl group is particularly prone to nucleophilic replacement 3,5-bis(methylsulphonyl)isothiazole-4-carbo-nitrile, readily accessible from malononitrile and carbon disulphide, yields the 5-(substituted)amino-compounds on treatment with ammonia, amines, or hydrazine, and the 5-ethoxy-compound when treated with ethanol in the presence of sodium carbonate. The electron-attracting cyano-group appears to promote the nucleophilic displacement, since 3,5-bis(methyIsuIphonyl)-4-phenylisothiazole displays reduced reactivity. ... 

---