Acylating Agents and Isocyanates

Benzoyl, acyl (i) or carbamoyl halides (ii) (including fluoride), dihalocarbonyl compounds (iii) (e.g., phosgene), and anhydrides (iv) are potent acylating agents 

Critical position/factor Effect on carcinogenic potential Rationale 

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For highly reactive compounds that can readily hydrolyze upon contact with aqueous solutions, volatility can be an important factor. For example, bis(chloromethyl) ether, one of the most potent human respiratory carcinogens, can only be shown to be carcinogenic in animal tests by the inhalational route (Figure 14.3). The chemical readily hydrolyzes when dissolved in aqueous solution. Other notable examples include acylating agents and isocyanates. 

These plates allowed the reaction of resin aliquots with reagents in solution by sealing the filter bottom and to discard the solution and wash the resin by filtering the solutions after removal of the seal. The samples 6.33 were then acylated (step d, monomer set M3, 16 acylating agents, including isocyanates, isothiocyanates, and acid chlorides) to produce 384 resin-bound intermediates 6.34, each as a discrete distributed into 22 different wells. Final cleavage from the support was performed (step e, monomer set... 

Acyl aminimides have proved useful as surface-active and antimicrobial agents and as an intermediate for isocyanate preparation (50). 

Nitroalkanes are easily functionalized with a variety of acylating agents such as phenyl isocyanate, acetic anhydride, and ethyl chloroformate in the presence of a... 

While metallocenes are usually acetylated with acid halides, acid anhydrides, or carboxylic acids, a number of other acylating agents have been reported. The reaction of ferrocene with various isocyanates and aluminum chlorides leads to N-substituted ferrocenecarboxamides (IX) (89). Use of ruthenocene in place of ferrocene leads to analogous results (88). The preparation of V-phenyl-ferrocenecarboxamide from phenyl isocyanate in this manner has been used as a proof of structure for the product obtained from the Beckmann rearrangement of benzoylferrocene oxime (124). 

Scheme 6.27 Metal-assisted synthesis of isocyanates from C02, amines, and an acylating agent.

N-l and 0. Other acylating agents used have been arylsulfonyl chlorides1199 and alkylchloroformates.61 Isocyanates react with N-l of 2-pyrazolin-5-ones having no 1-substituent to form 5-oxo-2-pyrazolin-1-carboxanilides. Treatment of l-acyl-5-acyloxypyrazoles with piperidine in ethanol removes the 0-acyl to give l-acyl-2-pyrazolin-5-ones.1898... 

Acyloxaziridines are easily obtained from compounds unsubstituted at nitrogen by reaction with acid chlorides or isocyanates. Acylation proceeds so smoothly that, in the amination of carbonyl compounds, oxaziridine compounds are obtained in better yields on addition of acid chlorides than in the absence of the acylating agent. With aliphatic aldehydes, amination does not succeed at all except in the presence of benzoyl chloride. Proof of structure comes from reduction by iodide to give the acid amide and carbonyl compound. 

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