Primary amines cyanamide

Primary amines RNH2 cannot be converted to their anions, under PTC conditions, except if R is an electron-withdrawing substituent, such as CN or ArSOj. Thus cyanamide (23) has been alkylated, by Jonczyk et al.,55 with a.oj-dihalogeno alkanes (24) or a,a -dibromo-oxylene to yield N-cyanopyrro-lidine, /V-cyano-piperidine, AT-cyanohexahydroazepine, and 3-cyano-l,3-dihydroisoindole. 

The alternative 5-amino-1-substituted imidazoles are usually made by reactions between primary amines and alkyl 7/-cyanoalkylimidates (see Section 3.2). Other possibilities include ring closure of formylglycineamidines by heating them alone or with phosphoryl chloride (yields are usually low) (see Section 2.1.1), cyclization of or-cyanoalkylcyanamides (to form 5-amino-2-bromoimidazoles) (see Section 2.2), alkylation of arylamino-methylene cyanamides or cyanoimidothiocarbanates with or-halogenocarbonyl compounds (gives 4-acyl-5-aminoimidazoles) (see Section 2.3), and cycliza-tions of DAMN with amidrazones (to 1,5-diaminoimidazoles) (see Section 2.2.1). 

Halides derived from hydrogen cyanide also react smoothly with primary amines. Reaction with cyanogen bromide is to be recommended as a method of preparing cyanamides, but it is advisable to arrange for good cooling so as to avoid formation of guanidines. 

When the racemic ornithine (Scheme 12.35) was treated with benzoyl chloride in the presence of pyridine, the bisbenzoate was formed, and after purification, it was subjected to hydrolysis using aqueous barium hydroxide [Ba(OH)2]. The benzoyl group attached to the primary amine underwent hydrolysis to produce a-benzoylamino-5-aminopentanoate, which, after acidification, was treated with cyanamide (N=C-NH2) to form a-benzoylamino-5-guanidopentanoic acid. A final hydrolysis of the benzoyl group with dilute aqueous hydrochloric acid (HCl) generated arginine (Arg, R) (Scheme 12.36). 

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. 

The formation of a biguanide as a by-product in a condensation of a cyanamide and amine (225) (which would normally be expected to yield a guanidine) and as main product in the reaction of glucosamine and cyanamide (437) has been noted. In the former example, the small amount of biguanide probably arose by further reaction of the primary guanidine (which formed the main product) with C5 namide. In the second example the biguanide may be the result of the interaction of the amine and intermediate cyanoguanidine. 

In primary synthesis 2-perimidinamines (660) can be prepared from the naphthalene diamine with bromocyanogen or cyanamide (Scheme 106). 2-Anilino derivatives have been obtained in reactions with aryl isothiocyanates. 2-iV,7V-Dimethylamino derivatives (662) have been obtained via the alkylated amine (661) using dimethylamino(trichloro)methane. Nucleophilic substitution by amine readily occurs in the 2-position when carrying a halo, sulfenyl, or sulfonyl substituent <81RCR816>. 

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. ... 

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