Heterocyclic acylating agents

The synthetic approaches described thus far for 191 resemble quite closely those reported for similar heterocycles. The system has been prepared for the first time by Tamura and co-workers (79CPB2521). 2-Aminothiadiazole can be aminated with O-mesitylsulfonylhydroxylamine, giving an N-3-aminated product that on treatment with acylating agents (benzoyl chloride, acetic acid anhydride, 200°C) yields the desired compounds (192, R = Me, Ph). Yields are low (15-26%). 

It is known that certain Friedel-Crafts acylations of reactive aromatics may proceed with a small amount of catalyst or even, to some extent, with no catalyst at all.41 Effective catalysts are Fe, FeCl3, ZnCl2, iodine, and hydroiodic acid. However, satisfactory yields are usually obtained with activated and polynuclear aromatics, and heterocycles. The mixed anhydrides acyl triflates are also powerful acylating agents without catalyst.34... 

Reaction of an amino-substituted heterocyclic thiol such as (81) with acylating agents gives compounds (82), which are cyclized by POCl3 to form, for example, imidazo[2, l -b [l,3,4]thiadiazoles... 

These compounds are easily prepared from the appropriate 2-aminothiazole and acyl chloride (see Section III.2.D) or by general heterocyclization methods. Acyl chlorides may be replaced by the corresponding anhydrides (471). Adds themselves may be used as acylating agents provided that the imidazole-triphenyl phosphine mixture is used as a catalyst (472). The Curtius degradation of 247 yields 2-acetamido-4-phenylthiazole (248) (Scheme 149) (473). 

The reaction of a-mercapto-A-amino heterocycles with acylating agents leads to fused 1,3,4-thiadiazoles. In general, the dehydration step is carried out with phosphorus oxychloride. The method has been used to prepare imidazo[2,l-6][l,3,4]thiadiazoles (63LA(663)113) and s-triazolo[3,4-6][l,3,4]thiadiazoles (64CI(L)1919> (equation 29). 

Covalent compounds, which are strong alkylating or acylating agents may initiate the cationic polymerization of heterocycles. Again, as in the case of acids, classification of these agents is relative for example, alkyl bromide will efficiently alkylate strongly nucleophilic monomers like cyclic amines or oxazolines and thus initiate their polymerization whereas it will be uneffective in the polymerization of cyclic ethers. 

Acyclic nonpeptide acylating agents Heterocyclic inhibitors/inactivators Lactone and coumarin based inhibitors 4H-3,1 - Benzoxazin-4-ones Saccharin derivatives fi-Lactams... 

A-Acylation is one of the most important synthetic methods in the chemistry of A -aminoazoles, and is widely used in various heterocyclizations as well to protect the amino group. There are numerous papers devoted to acylation of practically all types of N-aminoazoles, with the exception of A-aminopyrazole. As acylating agents, carboxylic acids... 

In aromatic acylation, present industrial practice involves stoichiometric amounts of metal halides as "catalysts" and of acylating agents. Aromatic heterocycles present exceptions. For example, catalytic amounts of SnCU promote the reaction of benzofuran with acetic anhydride to give 4()% 2-acetyl-benzofuran [1]. 

Acylation of imidazole produces A-acylimidazoles via loss of proton from the initially-formed A-3-acyIimidazolium salt. A device which has been employed frequently for the synthesis of 1-acylimidazoles is to use two mol equivalents of the heterocycle for one of the acylating agent, the second mole of imidazole serving to deprotonate the first-formed A-acylimidazolium salt. 

Chiral oligotriazoles catalyze the reaction of quinohnes with acylating agents and nucleophiles to form dearomatized heterocycles in moderate... 

The A-heterocyclic carbene precursor 49 is a photo-switchable catalyst for amidation reactions. The synthesis of this catalyst begins with two Friedel-Crafts reactions firstly, 2-melhyl-5-phenylthiophene was 3-acetylated with acetic anhydride using SnCLj, then product ketone oxidised to a glyoxal by SeOa- The glyoxal itself was used as acylating agent to react with 2-methyl-5-phenylthiophene with the assistance of SnCLj. After several further steps, the salt 49 was obtained (Scheme 51) [69]. 

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