Cyanamide from amines

Cyanamides like 4 (from amines and cyanogen bromide) provide access to guanidines. This approach allows for introduction of different substituents, and alkylating intermediates can further increase the diversity of products produced. However, high temperatures are required, especially with aromatic amines, for the final addition to give the guanidine products (Scheme 5).9... 

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... 

Into a 750 ml. round-bottomed flask furnished with a reflux condenser place a solution of 34 g. (18-5 ml.) of concentrated sulphuric acid in 100 ml, of water add 33 g. of di-n-butyl cyanamide and a few fragments of porous porcelain. Reflux gently for 6 hours. Cool the resulting homogeneous solution and pour in a cold solution of 52 g. of sodium hydroxide in 95 ml. of water down the side of the flask so that most of it settles at the bottom without mixing with the solution in the flask. Connect the flask with a condenser for downward distillation and shake it to mix the two layers the free amine separates. Heat the flask when the amine with some water distils continue the distillation until no amine separates from a test portion of the distillate. Estimate the weight of water in the distillate anp add about half this amount of potassium hydroxide in the form of sticks, so that it dissolves slowly. 

Ammonia is used in the fibers and plastic industry as the source of nitrogen for the production of caprolactam, the monomer for nylon 6. Oxidation of propylene with ammonia gives acrylonitrile (qv), used for the manufacture of acryHc fibers, resins, and elastomers. Hexamethylenetetramine (HMTA), produced from ammonia and formaldehyde, is used in the manufacture of phenoHc thermosetting resins (see Phenolic resins). Toluene 2,4-cHisocyanate (TDI), employed in the production of polyurethane foam, indirectly consumes ammonia because nitric acid is a raw material in the TDI manufacturing process (see Amines Isocyanates). Urea, which is produced from ammonia, is used in the manufacture of urea—formaldehyde synthetic resins (see Amino resins). Melamine is produced by polymerization of dicyanodiamine and high pressure, high temperature pyrolysis of urea, both in the presence of ammonia (see Cyanamides). 

Guanidines have been prepared by a wide variety of methods, of which two are of much greater importance than the others. These two methods, (a) the addition of amines to cyanamides and (b) the displacement of an alkylmercaptan by an amine from an alkylisothiouronium salt, together with close variants, are discussed first, and this discussion is followed by a survey of less frequently used procedures. 

Reaction between an amine salt and cyanamide has been used successfully for the synthesis of many mono- and poly-alkylguanidines [84-95], and also of alkoxyguanidines [96, 97] and aryloxyguanidines [98]. The reaction is usually carried out in boiling water or ethanol for from 1 to 24 hours. Higher temperatures have been employed using sealed tubes [99,100] or butanol as a solvent [82,101]. 

Odo studied the formation of methylguanidine from cyanamide and aqueous mixtures of methylamine and methylamine hydrochloride in various proportions [ 110]. He concluded that the reaction occurred by a reversible nucleophilic attack of the free amine on cyanamide, and that an acid was required to shift the equilibrium in the direction of the guanidine. 

A useful method for the synthesis of 5-chloro-l,2,4-thiadiazoles (206) is the reaction of amidines with trichloromethylsulfenyl chloride (see Equation (30)). 3-Halo derivatives (349) (X = Cl, Br, I) (Equation (57)) have been obtained in moderate yields from the corresponding amines (348) via the Sandmeyer-Gatterman reaction <84CHEC-I(6)463>. 3-Chloro-l,2,4-thiadiazolin-5-ones (350) and (351) can be prepared by reacting chlorocarbonylsulfenyl chloride with carbodiimides or cyanamides respectively (Scheme 79) <84CHEC-I(6)463>. 

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. 

Diallyl amine has been prepared from allyl amine and allyl bromide,1 and from allyl amine and allyl chloride.2 Experiments on these methods showed that the resulting product contained relatively large amounts of triallyl amine and mono-allyl amine and it was very difficult to isolate pure diallyl amine. The above synthesis from diallyl cyanamide, which has recently appeared in the literature,3 is more satisfactory than the older methods. 

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. 

It is worth noting that HCN is also an important by-product of propylene ammonoxidation to acrylonitrile (the yield may be as large as 20% in relation to acrylonitrile). Other methods have been used in the past, for example, the conversion of nitrogen to cyanamide (NHj C=N) followed by a subsequent further hydrogenation to hydrogen cyanide, or the thermolysis of trimeihyl-amine obtained from niolasses. 

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