Cyclization agents/cyclizations triethyl orthoformate

One laboratory has made use of triethyl orthoformate as an effective cyclizing agent as shown by the conversion of 411 to 412 (Equation 152) <2001CHC681, 2003CHC171, 2005CAR547>, although the nature of the carbohydrate moiety has been varied. 

Cyclization of 2-hydrazinocyanopyrimidinone 392 with triethyl orthoformate afforded the triazolopyrimidin-5-one 394 rather than 396, together with its A-ethylated derivative 395, whose amount increased with time. Here the orthoester acts as a novel alkylating agent. The products from reaction with N-substituted pyrimidinones (393) were the triazolopyrimidin-7-ones 146 (98UP1) (Scheme 74). 

Triethyl orthoformate has proved to be a useful cyclizing agent, especially when mixed with acetic anhydride which produces diethoxymethyl acetate (56JA1928,56JOC599, B-78MI40903, p. 995). 

Regiochemical synthesis of 1-substituted imidazole-4-carboxylates can be achieved by treatment of a (Z)-)3-dimethylamino-of-isocyanoacrylate with an alkyl or acyl halide (see Section 2.1.1 and Scheme 2.1.8), by cyclization of 3-alkylamino-2-aminopropanoic acids with triethyl orthoformate followed by dehydrogenation of the initially formed imidazoline (see Section 3.1.1 and Scheme 3.1.2), by condensation of 3-arylamino-2-nitro-2-enones with ortho esters in the presence of reducing agents (see Section 3.1.1 and Scheme 3.1.4), by reaction of an alkyl A -cyanoalkylimidate with a primary amine (see Section 3.2 and Scheme 3.2.1), the poor-yielding acid-catalysed cyclization of a 2-azabutadiene with a primary amine (see Section 3.2 and Scheme 3.2.3), the cyclocondensation of an isothiourea with the enolate form of ethyl isocyanoacetate (see Section 4.2 and Scheme 4.2.5), and from the interaction of of-aminonitrile, primary tunine and triethyl orthoformate (see Chapter 5, Scheme 5.1.5, and Tables 5.1.1 and 5.1.2). 

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