Isocyanates synthesis from halides

The availability of amino-substituted furazans, both by direct synthesis from aminogly-oximes and via Hofmann degradation of the corresponding carboxamides, allows urea, thiourea, imino and acylamido derivatives, for example, to be prepared by reaction with isocyanates, isothiocyanates, aldehydes and acyl halides, respectively (73JPR791, 77JCS(P1)1616). Alkoxy and acyloxy derivatives are likewise formed from hydroxyfurazans (79JHC689). 

III. SYNTHESIS FROM KETENES, ISOCYANATES AND ACYL HALIDES A. Ketenes... 

Treatment of alkyl halides with alkali metal or silver cyanate is of no preparative value for the synthesis of cyanates. - - As cyanate ions do represent ambident nucleophiles. Holm and Wentrap tried to reach cyanates under well-defined SnI conditions (Scheme 28). But even treatment of isopropyl iodide with silver cyanate in nitromethane provided only a very low yield of a 1 1 mixture of isopropyl cyanate and the corresponding isocyanate, and from a reaction of silver cyanate with triphenylchloro-methane they isolated only triphenylmethyl isocyanate, although the cyanate may have been an intermediate in this transformation." ... 

A special problem arises in the preparation of secondary amines. These compounds are highly nucleophilic, and alkylation of an amine with alkyl halides cannot be expected to stop at any specifle stage. Secondary amides, however, can be monoalkylated and lydrolyzed or be reduced to secondary amines (p. 11 If.). In the elegant synthesis of phenyl- phrine an intermediate -hydroxy isocyanate (from a hydrazide and nitrous acid) cyclizes to pve an oxazolidinone which is monomethylated. Treatment with strong acid cleaves the cyclic irethan. 

The inherent problems of cotrimerization may be circumvented by using the reaction of inorganic cyanates with organic isocyanates to form the salt (158), which can react with an alkyl halide to give the isocyanurate (159 Scheme 96) (70JHC725). The reaction does give the symmetrical isocyanurate as a by-product but it is readily separated from the salt. The route can be applied to the synthesis of many isocyanurates. 

A facile assembly of 2,4-orthogonally-functionalised oxazoles as useful bidirectional linchpins was achieved by treatment with diazomethane of acyl isocyanates, generated in situ from acyl halides 132 oxazolones 133 were converted to the oxazole triflates 134, useful intermediates for further synthetic elaborations as highlighted by the synthesis of 135 via Wittig and Stille reactions <01SL1739>. This linchpin tactic was used in the stereocontrol led total synthesis of the potent cytostatic agent (+)-phorboxazole A <01JA10942>. 

In 1956, Hattori and co-workers estabUshed that aluminum azide adds to alkyl isocyanates or acid chlorides in tetrahydrofuran to afford l-aUcyl-A -tetrazoline-5-ones in excellent yields [ 101 ]. Three years later, Horwitz and coworkers reported on the synthesis of l-aryl-A -tetrazoline-5-ones by reaction of aryl isocyanates with a mixture of sodium azide and aluminum chloride in tetrahydrofiuan at reflux temperature [102]. The in situ produced aluminum azide adds to the N=C-bond of the corresponding isocyanate 122 and yields the 1-substituted A -tetrazoHne-5-one 124. According to this method, different 1-substituted A -tetrazoUne-5-ones 124 were synthesized by reaction of phenyl isocyanate and further 1-p-substituted phenyl isocyanates with aluminum azide. In addition, acyl halides 123, like acetyl chloride and benzoyl chloride, were converted to 1-methyl and 1-phenyl-A -tetrazoline-5-one with aluminum azide under the same conditions (Scheme 28A). It is assumed that in the initial step of the reaction, aluminum azide is able to coordinate to the aryl isocyanate by foiu pathways, forming an aluminum salt 129. The first two possibilities (Scheme 28B 125 and 126) require the separation of an azide ion from the complex, recombination at the electrophihc carbon atom followed... 

Scheme 28 A Synthesis of 1-substituted A -tetrazoiine-5-ones 124 from isocyanates 122 or acyi halides 123 by use of aluminum azide [101,102], B Four possible aluminum azide salt intermediates of aryl isocyanates and their cyclization to the alumimun salt of 1-substituted A -tetrazoline-5-ones 129 [102]...

Speranza and Peppel, reported the synthesis of polyoxazolidones from diisocyanates and diepoxides using quarternary ammonium halides as catalysts (Reaction 1). They postulated that the opening of the epoxide ring, by halide ion (Reaction 2), preceded the addition of the isocyanate reaction ... 

---