Sodium cyanide, in DMSO

Halogeno-l-methyl-l,2,3-triazoles undergo substitution reactions with amines, but the 4-halogeno analogs do not. 5-Chloro-l,4-diphenyl-l,2,3-triazole with sodium cyanide in DMSO gives the cyano derivative (63JCS2032). 1-Substituted 3-chloro- and 5-chloro-l,2,4-triazoles both react with amines. 

Pentynenitrile from Homopropargyl Tosylate and Sodium Cyanide in DMSO... 

Diimines of a-diketones—reaction of aromatic aldimines with sodium cyanide in DMSO at 20°C (72 hr) [57]. 

Alkylation of appropriate a-alkylhomoterephthalate esters with the bromide (160) afforded 10-alkyl-10-carboxy-4-amino-4-deoxy-8,10-dideazapteroic acid diesters, whose ester cleavage and decarboxylation were accomplished by heating with sodium cyanide in DMSO to afford the 2,4-diamino- 10-alkyl-8,10-dideazapteroic acids. These acids were coupled with diethyl glutamate, followed by saponification, to give the products (163 R = H) <84JMC376>. 

Three tetracyclic systems, triphenylene, benz(c)phenanthrene and chrysene can be derived by angular benzannelation of phenanthrene and hence these hydrocarbons may be synthesized from corresponding phenanthreneacetonitriles. The phenanthrene-1-acetonitrile (81) used for the preparation of the chrysenes (82) was obtained from phenanthrene-l-carbonitrile (72a) in a sequence of conventional steps hydrolysis to the acid (84%) by KOH in triglycol, reduction to the carbinol (82%) by sodium dihydrido-bis(methoxyethoxy)aluminate, conversion by thionyl chloride in benzene to the chloromethyl derivative (98%), and finally reaction of the latter with sodium cyanide in DMSO to (81) (94%). 

Readily accessible also are derivatives of benzo(a)pyrene, e.g., 123) applying the usual benzannelation method using pyrene-1-acetonitrile 121 d). The latter was prepared starting from pyrene- 1-carbaldehyde67 121 a) by reduction with sodium bismethoxyethoxy-dihydroaluminate in benzene to the carbinol 121 b), this by thionyl chloride to 121 c), and finally with sodium cyanide in DMSO leading to 121 d). 

To achieve a further benzannelation, benzo(b)thiophen-7-carbonitrile (196 b) has been converted by a four-step sequence — hydrolysis by KOH in cellosolve (150°, 1 h), reduction of the acid by sodium bis(methoxyethoxy)aluminiumdi-hydride, action of thionyl chloride on the carbinol, and reaction of the chloromethyl compound with sodium cyanide in DMSO — in a 75% overall yield to the oily benzo(b)thiophen-7-acetonitrile (197), which finally afforded the naphtho(l,2-b)-thiophen-9-carbonitriles (198a, b) ... 

The reaction was found to be useful in a total synthesis of dihydrocleavamines and related alkaloids. The key intermediate was (3, R = COOC2H5), but this contains an unwanted ethoxycarbonyl group. This group was removed by sodium cyanide in DMSO in 70% yield to give the desired intermediate (4, R = H).3... 

A new acid catalyst of potential use in the Bischler-Napieralski cyclization is P2O5 in methanesulfonic acid. The phenethylamines used in isoquinoline syntheses are usually prepared from the reduction of the corresponding /S-nitrostyrenes. A more versatile procedure starts with a substituted benzyl chloride which is converted to the nitrile using sodium cyanide in DMSO (dimethylsulfoxide). Reduction of the nitrile with LiAlH4 in the presence of AICI3 gives the desired amine in excellent yield. Benzylamines or their quaternary salts may also be utilized in appropriate solvents in place of benzylic chlorides, so that they too may act as nitrile precursors. ... 

Reaction of compound 37 with bromine in chloroform results in mono-bromination a to the sulfur. Treatment of this brominated derivative with NaBH3CN in AcOH gives a mixture of products resulting from reduction of the C=N double bond and of elimination of HBr. Reaction of 44 with sodium ethoxide results in the ethoxy-substituted derivative 45, whereas reaction with pyridine gives the dehydrobrominated derivative 46. Reaction of either 44 or 46 with sodium cyanide in dimethyl sulfoxide (DMSO) gives the cyano-derivative 47 <1983HCA971> (Scheme 13). 

Although 1,2-dicarbonyl substrates (especially unsymmetrical benzils) are often difficult to make, there are a number of approaches which may be appropriate. Propane-1,3-dithiol reacts with aldehydes to give cyclic thioacetals (in 52-91% yields) which form stable dithiane anions when treated with butyllithium. Subsequent quenching with an acid chloride followed by mercury(ll) chloride treatment gives a 1,2-dicarbonyl species. Alternatively, substitution of an aldehyde for the acid chloride gives rise eventually to an a-hydroxycarbonyl derivative (Scheme 5.1.2) [16j. An alternative approach to a-ketoaldehydes (82-86% yields) reacts an a-ketonitrate ester with sodium acetate in DMSO [17]. Aryl a-diketones can be made from a-ketoanils, which are in turn made by cyanide ion-catalysed transformation of aromatic aldimines [18], and the range of unsymmetrical benzils has been increased by... 

Hydrazonium salts (117) with sodium hydride in DMSO give azirines (118), which react further with ketones to give 2f/-pyrroles (119) benzyl cyanide similarly gives 120 (Scheme 43).114-116 This reaction is claimed to be the most convenient general route to 2H-pyrroles (yields 20-80%).114... 

Although phase transfer catalysis is certainly an important and extremely versatile tool for the chemical modification of chloromethyl polystyrene, it is not necessarily always the best method as excellent results can also be obtained for some nucleophilic displacements when DMF or even DMSO (at low temperature to avoid oxidation to the carboxaldehyde polymer) are used as solvent for the nucleophile. For example, we prefer to use a solution of sodium cyanide in DMF to prepare cyanomethyl polystyrene from I rather than using a different solvent and phase transfer conditions, and we routinely prepare iodomethyl polystyrene from I by reaction with sodium or potassium iodide in acetone rather than under the conditions of Gozdz (Ref. 25). Recent work by Bied-Charreton et al. (Ref. 32) has also shown that excellent results could be obtained even under classical conditions in the transformation of I into its malononitrile derivative if the chloromethylated polymer is first transformed into the more reactive iodomethyl derivative this is in sharp contrast with earlier data from the same laboratory (Ref. 33). 

DMSO is dried over calcium hydride and distilled, bp 64°/4 mm, before use. Sodium cyanide is dried at 110° for 12 hours and stored in a tightly stoppered bottle. 

Alkali metal 1-methyl- and 1-phenyl-borinates are also available from bis(borinato)cobalt complexes (see below) on treatment with sodium or potassium cyanide in an aprotic solvent like acetonitrile. Cobalt cyanide precipitates and the alkali borinate remains in solution. After addition of thallium(I) chloride to some complexes, thallium 1-methyl- or 1-phenyl-borinate could be isolated as pale yellow solids, the only main group borinates isolated hitherto. They are insoluble in most organic solvents but readily soluble in pyridine and DMSO. The solids are stable on treatment with water and aqueous potassium hydride, but are decomposed by acids <78JOM(153)265). 

Cyclization of a,a-dichloro-/3-mesyloxyimines 171 by means of potassium carbonate in DMSO constitutes a novel approach to a relatively unexplored class of azaheterocycles, that is, 3,3-dichloroazetidines 172 (Equation 43) <1998JOC6>. The use of nucleophilic reagents like potassium cyanide or sodium borohydride in methanol afforded 2-cyano-3,3-dichloroazetidines 173 (Equation 44) and 2-methoxy-3,3-dichloroazetidines 174 (Equation 45), respectively. 

D-(-)-Tartaric acid, the unnatural enantiomer, was converted to the known ditosylate A. Two-carbon elongation of A with sodium cyanide was problematic. When the required amount (2 moles) of sodium cyanide was added in one portion to a DMSO solution of A, crystalline (2 ,4 )-2,4-hexadienedinitrile... 

A. Casarini, P. Denbeck, G. Reginato, A. Ricci, G. Secondi, Tetrahedron Lett. 1991, 32, 2169-2170. In a recent method for the preparation of cyanoalkynes, terminal acetylenes are coupled with cuprous cyanide in the presence of trimethylsilyl chloride water, catalytic amounts of sodium iodide and acetonitrile in DMSO at 50 C F.-T. Luo, R.-T. Wang, Tetrahedron Lett. 1993, 34, 5911-5914. 

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