Azides, carbamoyl synthesis

The formation of carbamoyl azides from isocyanates is the best known application of this method of synthesis. The reaction v/as discovered in 1901 by Hantzsch and Vagt who prepared carbamoyl azide itself from isocyanic acid and hydrazoic acid °. Alkyl and aryl carbamoyl azides are usually obtained in good yields from low temperature reactions between hydrazoic acid and the corresponding isocyanate in non-aqueous (equation 89)... 

Other types of carbonyl azides, such as azidoformates and carbamoyl azides, previously believed not to undergo the rearrangement, can also be induced to rearrange by photolysis in alcohols . Diaryl-carbamoyl azides have been found to rearrange even upon heating in /-butanol and this reaction was used for the synthesis of 1,1-diaryl-hydrazines, thus JV-aminocarbazole (41) was prepared in 80% yield from 40 . 

Staudinger, who discovered the reaction applied it to the synthesis of numerous aryl and alkyl iminophosphoranes and to benzoyl-iminophosphoranes . The scope of the reaction has been widened to include sulphonyl azides and carbamoyl azides... 

Aldehydes can also be precursors for the Curtius acyl azide rearrangement tScheme 4.24) Aliphatic and aromatic aldehydes can be converted to the corresponding acyl azides by treatment with iodine azide. Subsequent heating gave various carbamoyl azides in high yields. A radical pathway, proceeding by homolysis of the iodine-azide bond, was proposed. The resulting carbamoyl azides 65 are relevant precursors for the synthesis of amines or ureas, for example. 

Moreover, Bols et al. developed another methodology for the synthesis of carbamoyl azides from aldehydes by treatment with iodine azide at reflux in acetonitrile [41]. The carbamoyl azides are obtained in 70-97 % yield from the aliphatic and aromatic aldehydes (Scheme 5.4). When the reaction of phenyl-propanal with IN3 at 25 °C was performed in the presence of the radical trap, no acyl azide was observed, which was taken as support for a radical reaction mechanism. The mechanism shown in Scheme 5.6 is proposed for the reaction. Iodine radicals are formed by homolysis of the weak iodine-azide bond, abstracting the aldehyde hydrogen atom. The resulting carbon-centered radical reacts with iodine azide to produce an acyl azide. The following Cuitius rearrangement provides carbamoyl azides. 

Futhermore, Bols et al. provides an alternative safe and convenient synthetic strategy for the synthesis of carbamoyl azides from aldehydes by treatment with polymer supported iodine azide in MeCN at 83 °C (Scheme 5.4) [42]. Considering the drawback of its potentially explosive nature, IN3 as a reagent cannot be... 

Scheme 5.8 Synthesis of carbamoyl azides from ketones...

Ali A, Reddy GSKK, Nalam MNL, Anjum SG, Gao H, Schiffer CA, Rana TM (2010) Structure-based design, synthesis, and structure-activity relationship studies of HIV-1 protease inhibitors incorporating phenyloxazolidinones. J Med Chem 53(21) 7699-7708 Lieber E, Minnis RLJ, Rao CNR (1965) Carbamoyl azides. Chem Rev 65(3) 377-384 Doyle AG, Jacobsen EN (2007) Small-molecule H-bond donors in asymmetric catalysis. Chem Rev 107(12) 5713-5743... 

Feng P, Zou M, Jiao N, Kl/TBHP catalyzed nitrogenation of aldehydes or alcohols the direct synthesis of carbamoyl azides and ureas. Unpublished work... 

In 2003, Bols and co-workers described that the reagent IN3 can easily transform the aldehydes into the acyl azides under mild conditions (Scheme 6.22a) [76]. Furthermore, they demonstrated that the synthesis of carbamoyl azides could be realized at reflux by combining the aldehyde C-H bond azidation and flie Cuilius rearrangement in a one-pot protocol (Scheme 6.22b). A possible radical mechanism were proposed for this transformation (Scheme 6.22c). The weak I-N3 bond homolysis can initiate the chain reaction. The generated iodine radical abstracts an aldehyde hydrogen atom from the substrates to produce the acyl radical A. The acyl radical A reacts with IN3 to afford the acyl azides and iodine radical, thereby sustaining the radical chain. 

Brandt and Wirth performed the synthesis of carbamoyl azides in the presence of in situ prepared E 3 3 (Scheme 6.2), whereby subsequent thermal rearrangement of the isocyanate 4 in the presence of excess E 3 3 afforded the carbamoyl azide 5. To quench any residual E 3 3 or organic azides formed safely, the reaction products were collected in an aqueous solution of sodium thiosulfate and the products were extracted into dichloromethane. Using... 

The 1,3-dipolar cycloaddition of azides to alkynes is a versatile route to 1,2,3-tri-azoles. Different combinations of substituents on the azide and on the alkyne allow the preparation of diverse N-substitutcd 1,2,3-triazoles. Katritzky and Singh have described the synthesis of C-carbamoyl-1,2,3-triazoles by microwave-induced cydoaddition of benzyl azides to acetylenic amides (Scheme 6.220) [393]. Employing equimolar mixtures of the azide and alkyne under solvent-free conditions, the authors were able to achieve good to excellent isolated product yields by microwave heating at 55-85 °C for 30 min. In general, the triazole products were obtained as mixtures of regioisomers. Control experiments carried out under thermal (oil bath)... 

Katritzky, A.R. and Singh, S.K., Synthesis of C-carbamoyl- 1,2,3-triazoles by microwave-induced 1,3-dipolar cycloaddition of organic azides to acetylenic amides, ]. Org. Chem., 2002,67, 9077-9079. 

A range of densely functionalized five- and six-membered nitrones were formed in this way, and the method is proposed as suitable for the synthesis of the alkaloid laccarin. Under the influence of nucleophilic fluoride sources, including TBAT, a carbamoyl silane undergoes addition to ketones and aldehydes to give a-silyloxyamide products. TBAT can be used in combination with Mc3SiN3 to effect glycosyl azide formation, and finally it can be used to effect self-condensation of some unsaturated carbonyl compounds, a process in which fluoride presumably acts as a base. ... 

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