Isocyanates as reagent

W. Konig, I. Benecke, et al., Isocyanates as reagents for enantiomer separation application to amino acids, N-methylamino acids and 3-hydroxy acids, J. Chromatogr., 279 555-562 (1983). 

Both dimethyl carbonate [616-38-6] and diphenyl carbonate [102-09-0] have been used, in place of carbon monoxide, as reagents for the conversion of amines into isocyanates via this route (28,29). Alternatively, aniline [62-53-3] toluene diamines (I JJA), and methylene dianilines (MDA) have also been used as starting materials in the carbonylations to provide a wide variety of isocyanate monomers. 

Oxadiazoles are obtained by reaction of aromatic isocyanates or CS2 with N-acylaminoiminophosphoranes (151), as shown in Scheme 60. Upon treatment with isocyanate, an unstable carbodiimide 152 is generated, which cyclizes spontaneously in 80-84% yield. With CS2 as reagent, the corresponding isocyanate cyclizes without isolation of any intermediates to 2-mercapto-l,3,4-oxadiazole 154 in 72-90% yield [91PS(57)11]. 

There are several types of chiral derivatizing reagents commonly used depending on the functional group involved. For amines, the formation of an amide from reaction with an acyl halide [147,148], chloroformate reaction to form a carbamate [149], and reaction with isocyanate to form the corresponding urea are common reactions [150]. Carboxyl groups can be effectively esterified with chiral alcohols [151-153]. Isocynates have been used as reagents for enantiomer separation of amino acids, iV-methylamino acids, and 3-hydroxy acids [154]. In addition to the above-mentioned reactions, many others have been used in the formation of derivatives for use on a variety of packed and capillary columns. For a more comprehensive list, refer to References 155-159. 

Pereira [38] separated enantiomers of sec.-alcohols on Carbowax 20M after their conversion into carbamates by treatment with optically pure / -(+)-N-l -phenylethyl isocyanate. This reagent is prepared from commercially available R-(+)-1 -phenylethylamine and phosgene. 3(3-Acetoxy-As-etienic acid esters [39] were used for the same purpose. 

Treatment of the sodium salt of 2-cyanocyclododecanone (VII/109) with a>-haloisocyanates yields the 14-membered imide VII/U2. Two cyclization products of VII/112 were obtained in the presence of potassium carbonate as base. In the C-alkylated bicycle, VII/113, the central bridge bond is solvolyzed to form the 16-membered amide VII/114. The O-alkylated bicycle, VII/US, which is the minor product, was not investigated further. When 2-chloroethyl isocyanate was used as reagent, the analogue of VII/115 was formed directly. Because of its multistepcharacter the reaction resembles MIMIRC (Scheme VII/9) [59] [60]. 

Both reagents have proved to be useful substitutes for phosgene in all its main applications. Indeed, they are sold commercially as the efficient equivalents of 2 and 3 phosgene molecules respectively in processes yielding chloro-formates, carbonates, carbamates, ureas and isocyanates, as well as in chlorinations, carboxylations and dehydrations (For a recent review of Triphosgene use in organic synthesis, see Ref. 33). 

A. Dondoni, A. Marra, and A. Massi, Hybrid solution/solid-phase synthesis of oligosaccharides by using trichloroacetyl isocyanate as sequestration-enabling reagent of sugar alcohols, Angew. Chem. Int. Ed., 44 (2005) 1672-1676. 

Zhang and coworkers have developed the use of fluorous-tagged isocyanate as well as isatoic anhydride and acid chloride for the scavenging of amines for use in combinatorial as well as conventional chemistry (Figure 8.3) [30]. All reagents were readily prepared from commercially available sources, and the F-isatoic anhydride was prepared via a simple NaH-mediated alkylation of isatoic anhydride with per-fluoroalkyl halide. 

A variety of ion exchange resins with strong and weak acid, weak base, and quaternary ammonium ion functionality are available in bead form well suited for filtration from reaction mixtures and for use in continuous flow processes. They have been used for >30 years in flow systems for water deionization. Sulfonic acid resins are already used on a large scale as catalysts for the addition of methanol to isobutylene to form methyl terr-butyl ether, for the hydration of propene to isopropyl alcohol, and for a variety of smaller scale processes. Tertiary amine resins have been used as catalysts for the addition of alcohols to isocyanates to form urethanes. The quaternary ammonium ion resins could be used as reagents with any of a large number of counter ions, and as catalysts in two and three phase reaction mixtures, although the author is not aware of any commercial process of this sort at present. 

Alkoxybenzene compounds have been utilized as endquenching reagents in the quasiliving polymerization of IB. A variety of functionalized alkoxybenzene compounds have been utilized to prepare functionalized polymers including alkyl halides, amines, azides, and isocyanates as shown in Scheme 39. 

Formation of Isocyanates. The Pd-catalyzed reaction of PhI=NS02Ar in the presence of CO generates the isocyanates ArS02NC0. Thus bis(benzonitrile)dichloropalladium(II) catalyzes the formation of the isocyanate TsNCO (which can be isolated as the urea 6 in 60% 3deld after reaction with 2-chloroaniline) with PhI=NTs (eq 18). This reaction has been reported for several arylsulfonylimino iodinanes. Similar results can be achieved, however, by emplo3dng the less expensive chloramine-T and its derivatives as reagents. ... 

Carbamates are also formed by one-stage, two-step processes involving isocyanates as intermediates and precursors. Thus, carbamates are prepared under modified Hofmann rearrangement conditions, using NBS/NaOMe as the reagent [443], by Curtius rearrangement of the acyl azide if the reaction is carried out in alcohol, by the reaction of amides with lead tetraacetate [444], or by the Lossen rearrangement, if the carbamates are not sensitive to the presence of base. 

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