Synthesis of Cyanamide

Synthesis of a cyanide from a carbonate was actually the earliest means of fixing atmospheric Ni by a chemical reaction in a laboratory in 1860 F. Margueritte and A. de Sourdeval heated a mixture of barium carbonate, nitrogen, and carbon to 1,200 °C and produced barium cyanide  

At lower temperatures and in the presence of water vapor the compound broke down, producing ammonia and barium hydroxide, which could be reused in the synthesis. 

In 1895 Adolf Frank (1834-1916) and Nikodemus Caro (1871-1935) substituted barium carbide for the carbonate and reported that the reaction proceeded better with addition of water vapor. In contrast, shortly afterward F. Rothe, employed by Beringer Sohne in Charlottenburg found that the reaction proceeds best with very pure Nz and in the driest possible conditions. In 1898, after Rothe began working for Frank and Caro in Hamburg, he discovered that cyanamide, rather than cyanide, was the main product. Once it was shown that a much cheaper calcium carbide reacts in much the same way at temperatures between 1,000 and 1,100 °C, it was possible to contemplate a commercial venture based on the reaction 

An agreement signed in July 1899 in Frankfurt between Frank and Caro and Siemens 8c Halske established the Cyanid-Gesellschaft. The first field experiments with the product as a nitrogenous fertilizer began in 1901, and in the same year F. E. 

Polzenius discovered that addition of calcium chloride (CaC ) enabled the reaction temperature to be lowered by more than 300 °C. But it produced a highly hygroscopic product that was difficult to store. 

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Kaupp et al. also exploited heterogeneous reactions with CICN and BrCN in the quantitative synthesis of cyanamides, cyanates, thiocyanates and derivatives [26]. Gaseous acids were shown to form salts with strong and weak solid nitrogen bases. Solid hydrohalides are formed quantitatively by reaction with vapours of HCl, HBr and HI the same applies to di-bases such as o-phenylen-diamines. The products are much more easily handled than when they are formed in solution. The solid products can in turn be used in reactions with gaseous acetone to form the corresponding dihydrohalides of 1,5-benzodi-azepines [27]. 

Kaupp, G., Schmeyers, J., and Boy, J. 1998. Quantitative gas-solid reactions with CICN and BrCN synthesis of cyanamides, cyanates, thiocyanates, and their derivatives. European Journal of Chemistry, 4 2467-2474. 

The synthesis of these disubstituied thioureas takes place in three steps. First the alkyl bromide is prepared by the action of hydrobromic acid on the corresponding alcohol (518). Then the dialkylcyanamide is obtained by treatment at 25°C with calcium cyanamide. The yields are of the order of 30 to 60%. Thioureas are obtained in a third step from the cyanamide by reaction at 40 C with HjS in the presence of pyridine. Yields ranged from 57 to 90% (518),... 

Synthesis of l-guanyl-3-methylpyrazole (29) (86% yield) from pyrazole 13 and aqueous cyanamide has been claimed (94GEP4237687). 

Like the Haber process for the synthesis of ammonia, this reaction represents a way of converting elemental nitrogen into a compound (nitrogen fixation). Moreover, calcium cyanamide reacts with steam at high temperature to yield ammonia,... 

A synthesis of variously substituted imidazo[l,2- ]imidazol-2-ones 448 was described. These compounds were prepared by cyclocondensation of ct-amino acid derivatives 447 with cyanamide (Equation 210) <1995JHC141>. 

An efficient synthesis of 2-amino derivatives 256 is depicted in Scheme 70 2-halopyridines are first Ar-alkylated with various halides under microwave activation and next reacted with cyanamide under basic conditions <1999T2317>. A rapid parallel synthesis of derivatives bearing a benzoyl substituent at C-3 based on this reaction has been described <2002SL1544>. 

The synthesis of the oligomers involved the known reaction of isocyanates and cyanamide (Nl CN). For example, N-cyano-N -phenyl urea has been synthesized from phenyl isocyanate and an aqueous alkaline solution of cyanamide in high yield.(3) Recently, similar reactions were used to prepare various di-N-cyanourea compounds from diisocyanates. ( 1) These monomers were also synthesized directly by reacting diisocyanates with cyanamide at melt temperatures. 

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]. 

The discovery of the imidazolinotte herbicides had its beginnings in a random screening test some 12 years ago. The phthalimide 1 prepared originally as an anticonvulsant at Cyanamid s Lederle Laboratories had sufficient herbicidal activity to warrant the synthesis of additional members of this series. One of these, the chloro analog was essentially devoid of herbicidal activity but had instead a pronounced... 

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>. 

Cyanamide can also be used as a source of the C(2)-N(3) unit, to give 2-aminoquinazolines, and good results can be achieved in condensations with 2-aminoketones <2000BML1317, 2005JOC8764>, as shown by the 97% yield achieved in the synthesis of the 2-amino -piperidinyl derivative 845 from the aminoketone 844 <2000BML1317>. 

The dimethylaminooxazolidone derivative thozalinone (40-3) is described as an antidepressant. The synthesis of this agent again uses a cyanamide, provided in this case as a preformed reagent. Thus, reaction of alkoxide from ethyl mandelate (40-1) with A,A-dimethylcyanamide leads to the amidine (40-2) by addition to the nitrile. Internal displacement of the ester ethoxide group closes the ring to an oxazo-lidinone, forming the product (40-3) [42]. 

One other synthesis of a A3-oxadiazoline was obtained unintentionally. Hull and Farrand114 refluxed cyanamide and phenylhydroxyl-amine in acetone expecting to obtain the disubstituted hydroxylamine (23). Instead, the solvent acetone had condensed with the hypothetical... 

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