Cyanates synthesis

Mono-substituted and unsymmetrical di-substituted ureas may be prepared by a modification of Wohler s urea synthesis, salts of primary or secondary amines being used instead of the ammonium salt for interaction with potassium cyanate. Thus when an aqueous solution containing both aniline hydrochloride and potassium cyanate is heated, aniline cyanate is first formed, and then C,HjNH,HCl -h KCNO = C,H6NHj,HCNO -h KCl C,HsNH HCNO = C.H NHCONH, by the usual molecular rearrangement is converted into monophenyburea. 

Wohler s classical synthesis of urea from ammonium cyanate may be carried out by evaporating solutions of sodium cyanate and ammonium sulphate ... 

Aryl, heteroaryl, and alkenyl cyanides are prepared by the reaction of halides[656-658] or triflates[659,660] with KCN or LiCN in DMF, HMPA, and THF. Addition of crown ethers[661] and alumina[662] promotes efficient aryl and alkenyl cyanation. lodobenzene is converted into benzonitrile (794) by the reaction of trimethylsiiyl cyanide in EtiN as a solvent. No reaction takes place with aryl bromides and chlorides[663]. The reaction was employed in an estradiol synthesis. The 3-hydroxy group in 796 was derived from the iodide 795 by converting it into a cyano group[664]. 

Synthesis from OC-Amino Acids and Related Compounds. Addition of cyanates, isocyanates, and uiea derivatives to a-amino acids yields hydantoin piecuisois. This method is called the Read synthesis (2), and can be considered as the reverse of hydantoin hydrolysis. Thus the reaction of a-amino acids with alkaline cyanates affords hydantoic acids, which cyclize to hydantoins in an acidic medium. 

A one-step synthesis o( mtnles from carbonyls by a reductive cyanation with tosylmethyl isocyanide (TosMIC), also synthesis of 1,3-azole or of ketones... 

The hydroxyl derivative of X-CN is cyanic acid HO-CN it cannot be prepared pure due to rapid decomposition but it is probably present to the extent of about 3% when its tautomer, isocyanic acid (HNCO) is prepared from sodium cyanate and HCI. HNCO rapidly trimerizes to cyanuric acid (Fig. 8.25) from which it can be regenerated by pyrolysis. It is a fairly strong acid (Ka 1.2 x 10 at 0°) freezing at —86.8° and boiling at 23.5°C. Thermolysis of urea is an alternative route to HNCO and (HNCO)3 the reverse reaction, involving the isomerization of ammonium cyanate, is the clas.sic synthesis of urea by F. Wohler (1828) ... 

The 6-methyl derivative (98, R = Me) was an important intermediate in the synthesis of analogs (e.g., 183) of folic acid. Korte has shown that 2-aminopyrido[3,2-guanidine carbonate with 3-aminopicolinic acid and that treatment of the same acid with ammonium thiocyanate or potassium cyanate yields the thioureido and ureido derivatives (100, X = S and X = 0). In contrast to the pyrido[2,3-d]pyrimidine system bsoth of these compounds could be cyclized by heat and the latter (100, X = O) is a likely intermediate in the synthesis of the dione (98) by the fusion with urea. 

Faneti/ole (122) is a biological response modifier with significant immunosuppressant activity It can be synthesized by conversion of 2 phen> lethylamine (120) with ammonium thio cyanate to the corresponding thiourea analogue 121 The synthesis of faneli/ole (122) concludes by thiazole nng formation of 121 by reaction with phenacylbromide Thus its synthesis involves use of the classic Hantzsch procedure in which a bromoacetone analogue and an appropriate thio urea denvative are reacted 143]... 

The naturally occurring compound urea, CO(NH,), was first synthesized by Friedrich Wohler in Germany in 1828 by heating ammonium cyanate. This synthesis was a significant event because it was the first time that an organic compound had been produced from an inorganic substance. Urea may also be made by the reaction of carbon dioxide and ammonia ... 

These major routes to quinoxalmecarbonitriles have been covered already by primary synthesis (Chapter 1), by cyanalysis of halogenoquinoxalines (Section 3.2.5), by deoxidative cyanation of quinoxaline N-oxides (Section 4.6.2.2), by cyanolysis of nitroquinoxalines (Section 6.1.2.2), from primary quinoxalina-mines by a Sandmeyer-type reaction (Section 6.3.2.3), from quaternary ammonio-quinoxalines with cyanide ion (Section 6.3.2.4), and by dehydration of quinoxalinecarboxamides (Section 7.4.2). Those remaining preparative routes that have been used recently are illustrated in the following examples. 

The synthesis of (hetero)aryl cyanides from (hetero)aryl halides via transition-metal catalysis is a very valuable reaction since a nitrile can be easily transformed into several other functional groups. Not until 2000 were the first examples on microwave-assisted cyanation reported in the literature. Alter-man and Hallberg found that 3-bromopyridine and 3-bromothiophene were... 

In 2004, Alterman et al. apphed their cyanation protocol to the synthesis of N-(t-butyl)-3-(4-cyanobenzyl)-5-isobutylthiophene-2-sulfonamide [61]. Deprotection of the sulfonamide followed by carbamate formation via reaction with butyl chloroformate finally gave the target compoimd for biological evaluation as a selective angiotensin 11 AT2 receptor agonist (Scheme 65). The cyano derivative, however, showed only a low affinity for the AT2 receptor (Ki value >10 p,M). 

A short synthesis of 6-cyano-l,2,3,4-tetrahydroisoquinoline used an improved method of aryl triflate cyanation that employs zincfll) cyanide as the cyanide source <95SC(25)3255>. 

The term organic chemistry was first used by the Swedish chemist Berzelius in 1807 (Larsson, 1981). He coined the name to describe the chemistry of substances derived from living matter. Berzelius was a staunch believer in the vis vitalis theory, which held that such substances were endowed with a mystical vital force that precluded their synthesis in the laboratory from materials of mineral origin. Ironically, it was a student of Berzelius, Wohler, who heralded the demise of vitalism with his synthesis of urea from ammonium cyanate (Wohler, 1928). In a letter to Berzelius in 1828, Wohler wrote I must tell you that I can make urea without requiring kidneys, or even an animal, whether a human being or a dog . 

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