Generation and Diels-Alder Trapping of 4,5-Bis(bromomethylene)-4,5-dihydrothiazole

Abstract

Treatment of 4,5‐bis(dibromomethyl)thiazole (1a) with sodium iodide in DMF led to 4,5‐bis(bromomethylene)‐4,5‐dihydrothiazole (2a). Trapping the latter in situ with dienophiles afforded directly the aromatized cycloadducts. Starting with 5‐hydroxynaphthoquinone or its 2‐ and 3‐bromo derivatives 6 gave a mixture of the tetracyclic quinones 10 + 11 from which the 1,6‐regioisomer 10 predominates. Using acrylate dienophiles gave 6‐substituted benzothiazoles 13 as the major products. The regiochemistry of the cycloadditions between 2a and naphthoquinones 6 agrees with the predictions of the frontier molecular orbital theory. In contrast, the regioselectivity observed from 2a and acrylate dienophiles 12, similar to that previously obtained with 5‐bromomethylene‐4‐methylene‐4,5‐dihydrothiazole (2b), is opposite to that predicted and could be better accomodated by a competitive Michael addition followed by a cyclization‐elimination step.

Synthesis and antiproliferative activity of thiazole-fused anthraquinones

“…The published preparation of thiazole-fused anthraquinones is based on cycloaddition reactions. [14][15][16][17] However, this general approach has limitations for the synthesis of substituted derivatives, especially for the linear anthrathiazoles with modifications at peri-positions. Thus, the schemes for the synthesis of benzothiazoles (Scheme 1) [18][19][20][21] were analyzed and adopted for the preparation of desired thiazole-fused anthraquinones considering the availability of anthraquinone derivatives.…”

o-Quinodimethanes: Efficient Intermediates in Organic Synthesis

“…Inter- or intramolecular cycloaddition reactions involving heterocyclic oQDMs provide an attractive route to heteropolycyclic compounds, and an increasing number of examples of such processes are to be found in recent review articles where the literature of the generation of heterocyclic oQDMs until 1993 is thoroughly reviewed . Thus, during the past decade a great deal of effort has been devoted to the syntheses of heteroanalogues of oQDM and furan ( 87 ), − pyrrole ( 88 ), thiophene ( 89 ), , oxazole ( 90 ), isoxazole ( 91 ), , pyrazole ( 92 ), , imidazole ( 93 ),116c thiazole ( 94 ), , isothiazole ( 95 ), triazole ( 96 ), pyridine ( 97 and 98 ), , pyridazine ( 99 ), pyrimidine ( 100 ), , pyrazine ( 101 ), pyrimidinone ( 102 ), benzofurano ( 103 ), , indolo ( 104 ), benzothieno ( 105 ), quinoline ( 106 and 107 ), quinoxaline ( 108 ), , quinolinone ( 109 ), coumarin ( 110 ), phenanthroline ( 111 ), and carbazole ( 112 ) based oQDMs (Scheme ). ,

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“…1,4-Exocyclic eliminations are also largely employed to generate oQDMs since they are carried out under very mild conditions. Indeed, oQDM heteroanalogues have been synthesized (i) by fluoride-induced expulsion of the silicon and leaving groups (L = OAc or NR 3 + ) from substrates 124 , , based on the original Ito−Saegusa idea for the generation of o -quinodimethanes from the corresponding benzenoid derivatives, (ii) by treatment of a tributylstannylfuryl derivatives ( 125 ) with boron trifluoride−diethyl ether, or (iii) by the well-known reductive debromination of vicinal halomethyl derivatives 126 (Figure ). 109b,,,,131a,132a,

3 Precursors of oQDM heteroanalogues by 1,4-exocyclic elimination.

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