Secondary amines cyanamide

By the hydrolysis of dialkyl cyanamides with dilute sulphuric acid this method gives pure secondary amines. The appropriate dialkyl cyanamide is prepared by treating sodium cyanamide (itself obtained in solution from... 

A convenient way of obtaining secondary amines without contamination by primary or tertiary amines involves treatment of alkyl halides with the sodium or calcium salt of cyanamide NH2—CN to give disubstituted cyanamides, which are then hydrolyzed and decarboxylated to secondary amines. Good yields are obtained when the reaction is carried out under phase-transfer conditions. The R group may be primary, secondary, allylic, or benzylic. 1, co-Dihalides give cyclic secondary amines. 

A second method is due to J. von Braun and consists in the addition of cyanogen bromide to tertiary cyclic bases.1 In the unstable addition product a C—N-linkage is broken and at the same time the bromine wanders to a new position. A brominated derivative of cyanamide is produced and this, on hydrolysis, yields a secondary amine which can be broken down further, e.g. 

Conversion of Alkyl Halides to Secondary Amines with Cyanamide Imino-de-dihalo-aggre-substitution (overall transformation)... 

This reaction represents a general method for the preparation of secondary amines thus, di-n-butyl amine has been obtained from di-w-butyl cyanamide in yields of 75 per cent of the theoretical amount. 

The preparation of pure symmetrical secondary amines (e.g. dibutylamine, Expt 5.199) is conveniently achieved by the hydrolysis of dialkylcyanamides with dilute sulphuric acid. The appropriate dialkyl cyanamide is prepared by treating sodium cyanamide (itself obtained from calcium cyanamide and aqueous sodium hydroxide solution) with an alkyl halide. In this case the reagent [ —C=N]20 may be regarded as a masked NH group. 

A method for the preparation of secondary amines from cyanamides has been demonstrated for the preparation of the amine (22) using dihydroisoconessimine (21) as the starting material. Under alkaline conditions, hydrogen peroxide... 

Benzo[Z>]thiophen 5-Oxides. - Mild methods for the oxidation of 2,3-dihydrobenzo[Z>] thiophens to the sulphoxide have been developed. The photochemical reactions of various 2- and 3-substituted benzo[ ]-thiophen 1-oxides led to different photodimers. From 3-chlorobenzo[b]-thiophen-2-carboxylic acid 1,1-dioxide, 1,3-oxazinones of biological interest were obtained through cyclization reactions with cyanamides and carbodi-imides. Secondary amines add to 2-phenylbenzo [b] thiophen 1,1-dioxide to give 3-amino-substituted 2,3-dihydro-2-phenylbenzo[b]thiophen 1,1-dioxides. " ... 

Daphniphylline/ —On oxidation with sodium metaperiodiate followed by reduction with sodium borohydride and acetylation, daphniphylline (1) was converted into daphnialcohol acetate (91)." Treatment of (91) with excess cyanogen bromide afforded the cyanamide (92). On heating (92) with 6-M methanolic HCl, an amine (94) containing a new heterocyclic skeleton was obtained, possibly via the intermediate (93). Compound (94) was transformed into the original cyanamide (92) by von Braun degradation and acetylation. The secondary amine (95) proposed as a biogene tic intermediate" could not be obtained. 

Secondary amines can occasionally be prepared by alkylation of cyanamide and hydrolysis of the product, and it is an advantage that the cheap commercial calcium cyanamide may be used as starting material. 

For the preparation of disubstituted cyanamides it is often better, not to treat a secondary amine with cyanogen bromide, but, instead, to subject a tertiary amine to von Braun degradation604 in which it is generally the smallest alkyl group that is split off as alkyl bromide. 

Alkylation of cyanamide makes dialkylcyanamides accessible and, by their hydrolysis, also secondary amines. For instance, dimethylamine was obtained... 

Pyrazole reacts with cyanamide very efficiently to produce an A-derivative which can be utilised, by reaction with primary or secondary amines, to synthesise guanidines. Conversion of the pyrazolyl guanidine to a doubly r-butoxycarbonyl-protected pyrazolyl guanidine then allows this to be used for the direct synthesis of protected guanidines, as illustrated. ... 

Guanidine derivatives of tetrahydroisoquinoline are generally prepared by the route shown in Scheme 5.21. The von Braun reaction converts the secondary amine (84) into the cyanamide (85) and hydrogen sulphide addition in pyridine-triethylamine gives the thiourea (86). Alkylation with bromoethane and treatment with ammonia complete the preparation of debrisoquin (87) and guanisoquin (88) [95], Recently, direct reaction of (85) with anhydrous ammonia to give (87) has been achieved [96]. The two guanidines are antihypertensives of which debrisoquin is the more useful. It appears to act in part by inhibition of neuronal monoamine oxidases [97]. 

The nickel(o)-catalysed oligomerization of butadiene has been further studied. Cyclo-octa-1,5-diene is a major product in hydroxylic solvents, and a minor product in the presence of secondary amines." The oligomerization of butadiene in the presence of nickel(ii)acetylacetonate, triethylamine, alkyl cyanamides, and miscellaneous heterocycles has also been studied, and catalyst systems causing an almost quantitative conversion into trans,trans,trans-, cis,trans,trans-, or cis,cis,trans-cyclododeca-l,5,9-triene were found." The ability of some hydrides, trans-MHX-(PR3)2 (M = Ni or Pd), to act as catalysts for butadiene oligomerization has been found to depend upon the substituent, X, and the solvent the reactions of some cationic palladium hydrides with butadiene was also examined. Unlike other organo-cobalt catalyst systems, CoCUPPhjjj has been found to catalyse the dimerization... 

The reaction has found use in the degradation of alkaloids . Unlike the Hofinann exhaustive methylation procedure which may be repeated until the nitrogen of the natural product is freed as tertiary amine, the cyanogen bromide reaction is only practicable with tertiary amines. With secondary amines, cyanogen bromide yields disubstituted cyanamides direcdy and these react further with the amine hydrobromide formed at the same time to give guanidines (equation 53) . 

Alkylation of cyanamide (anion), followed by hydrolysis, has been used for the preparation of some symmetrically sutetituted secondary amines (reaction 52) . It is clear from alkaloid studies that reduction... 

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