Hydrazines reaction with cyanates

Potassium [ C]cyanate is most easily prepared by oxidation of K CN with KMn04 . Addition of ammonia and amines to K CNO is its main application in carbon-14 synthesis. The ammonolysis of K CNO upon heating with aqueous ammonia is one of the standard procedures for preparing [ C]urea . Upon its reaction with primary or secondary amines, unsymmetrical [ CJureas such as iV-[ C]carbamoyl aspartic acid 108 are obtained (Figure 7.29). Reaction of two equivalents of K CNO with hydrazine produced... 

Hydrazine sulphate (52 g.) and 21 g. of anhydrous sodium carbonate are dissolved in 200 c.c. of boiling water. The solution is cooled to 50°, a solution of 35 g. of potassium cyanate in 100 c.c. of water is added, and the whole is allowed to stand over night. After small amounts of hydrazodicarbonamide, produced in the reaction H2N.CO.NH.NH2 + 0=C=NH —> H2N.CO.NH.NH.CO.NH2, have been removed by filtration, 60 c.c. of acetone are added to the solution, which is again allowed to stand, with frequent shaking, for twenty-four hours. The acetone semicarbazone which has then crystallised out is filtered dry at the pump, washed with a little water, and dried on a porous plate or in vacuo. 

The reaction of hydrazines with sodium or potassium cyanate or thiocyanate gives semicarhazides or thiosemicarbazides in good yields. Monosubstituted alkylhydrazines give 2-semicarbazides (Eq. 8). 

Mesoionic pyrido[2,l- >][1,3]oxazines (54) afforded 4-oxo-4//-pyrido[l,2-a]pyrimidin-l-iumolates (55) and 4//-quinolizin-4-one (56) with phenyl iso(thio)cyanates [78LA1655 79CB1585 82ZN(B)222] and dimethyl acetylenedicarboxylate (79CB1585), respectively. Reaction of 2-cyano-3-methyl-lH,6//-pyridol[l,2-a][3,l]benzoxazine-l,6-dione with ammonium acetate and hydroxylamine, hydrazines, primary aliphatic or aromatic amines, and (thio)ureas gave 5-unsubstituted and 5-substituted 2-cyano-3-methyl-l//,6H-pyrido[l,2-a]quinazoline-l,6-diones (93CCC1953). 

The reaction has been shown to be of very broad scope with a multitude of nucleophiles Nu such as imides.23,24,29,32,33,36,37,42 amines,10,32 cyanide,25,32 hydroxide,10,32 alkox-ide,10,26,32 electron-rich isocyclic or heterocyclic aromatic compounds,28 carboxamides,31 lactams,31 ureas,31 sulfonamides,31 cyanate,31 formate (to give products with Nu = H),34 C-H acidic compounds,35 hydrazines and hydrazides,38 and sulfinates.38 The amino group NR R2 of cyclopropane-1,1-diamines and the nucleophile Nu in bicycles 8, 9 or 12, respectively, can be easily replaced with other nucleophiles Nu, such as water,10,32,33 alkoxide,10,32-34,42 Grignard compounds,27,42 amines,29,30,36,37,42,43 cyanide,29,33,42,44 hydride,34,42,44 and C-H acidic compounds39-41,43,44 (see Section 5.2.1.). Therefore, it is currently the most important method for the preparation of substituted bicyclic cyclopropylamines. The toxic and costly reagent methyl fluorosulfate can be avoided in a modified synthetic route, which instead of the fluorosulfate 5 proceeds via the corresponding tetraphenylborate, hexafluorophosphate, or (most conveniently) via the tosylate.23 The different steps of the method can often be combined in a one-pot procedure. Results are summarized in Table 3. 

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