Synthetic Hypoglycemic Agents. I¹

Abstract

Ethyl N-tt-Hexylthioureidomethylenecyanoacetate.-N-«-Hexylthiourea (16 g. or 0.1 mole), ethyl orthoformate (17 g. or 0.115 mole) and ethyl cyanoacetate (11.3 g. or 0.1 mole) were mixed together and heated to refluxing temperature for 30 minutes. The mixture was concentrated under reduced pressure to obtain the solid product. This was recrystallized from ethyl acetate; yield 11.5 g. or 41%, m.p.

Syntheses of Some 4‐Anilinoquinazoline Derivatives.

“…2-Methyl-4-N-phenylaminoquinazoline (6) and its interesting intermediates 2-5 were synthesized through the method of Tomisek and Christensen 14 and alternative approaches, [15][16][17][18] as shown in Scheme 1.…”

“…Subsequent heating of compound 3 with NaOH solution led to a cyclodehydration giving the quinazolinone 4. 16 3H-2-Methyl-4-thioxoquinazoline (5) was synthesized from anthranilonitrile (7) and thiolacetic acid (Scheme 2), 17 since the described method from 3H-2-methyl-4-quinazolinone (4) and phosphorus pentasulfide did not result in the desired product (Scheme 1, step d). The last step of the synthetic pathway (Scheme 1, step e) for 2methyl-4-N-phenylaminoquinazoline (6), through the reaction of compound 5 with aniline, did not lead to satisfactory results, as observed from the NMR spectrum of the crude reaction product.…”

“…7 In conclusion, twenty two quinazoline derivatives were prepared by three synthetic pathways (Experimental section). 7,14,[17][18][19] Two synthetic routes were used for preparation of compounds 5 (Scheme 2) and 6 (Scheme 1, step f) as the pathways suggested by Tomisek and Christensen 14 did not lead to satisfactory results.…”

Synthesis of new acylhydrazones as iron-chelating compounds

“…phenyl, m-fluorophenyl) were synthesized by the general method of Sah (5). All had the melting points (5)(6)(7)(8)(9)(10)(11) and physical properties reported in the literature. The condensation of the acylhydrazides with the aldehydes I, IV, and VI gave the acylhydrazones II, V, and VII, usually in yields of 80-95%.…”

“…One of the most general methods for the preparation of various isoxazole and 2-isoxazoline derivatives is the cyclo-addition reaction of nitrile oxide with substituted acetylenes (3)(4)(5)(6)(7) and substituted ethylenes (8)(9)(10), respectively. In connection with our continuing interest in the synthesis of polyfunctional heterocyclic compounds such as isoxazole and 2-isoxazolines (1, 2), we have examined herein the cycloaddition reactions of 2,4,6-trimethoxybenzonitrile oxide (1) with disubstituted acetylenes which provide polyfunctional Isoxazoles as shown in Scheme I.…”