Nitration of 2-methylthiazole

Asato, Goro

doi:10.1021/jo01270a094

Cited by 11 publications

(3 citation statements)

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“…l-(5-Nitro-2-thiazolyl)-2-imidazolidinone (Niridazole, la). 2-Bromo-5-nitrothiazole (7, 1.045 g, 5 mmol) and compound 9 (1 g, 10 mmol) were dissolved in DMF (15 ml) and the solution was stirred at room temperature for 8 hr. DMF was removed under reduced pressure and the residue was chromatographed on silica gel (EtOAc eluent), giving starting material 7 (115 mg) and then compound la (162 mg, 17%).…”

Section: Methodsmentioning

confidence: 99%

“…We then took advantage of the known7 nucleophilicity of 2-methoxy-2-imidazoline (9) and found that 2-bromo-5-nitrofuran (8) when treated with 2 molar equiv of 9 in DMF at 80°for 4 hr gave lb in 16% yield. The yield was not improved by changing solvents (DMSO, MeOH) or by varying the molar quantity of 9.…”

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confidence: 99%

“…At lower temperature (<60°), a thermally unstable product, tentatively formulated as 2-methoxy-l-(5-nitro-2-furyl)-2-imidazoline, was also obtained, whereas at 80°or higher temperature only lb was isolated. This type of reaction between a bromonitro heterocyclic compound and 2-methoxy-2-imidazoline (9) may offer a general route to imidazolidone-substituted nitro heterocyclic products. Indeed, when the readily available 2-bromo-5-nitrothiazole (7) was treated with 9 in DMF at room temperature, niridazole la was readily obtained in 17% yield (no attempt was made to optimize the yield).…”

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Structure and antischistosomal activity in the nitrofurylvinyl and the niridazole series. Noninterchangeability of the nitroheterocyclic rings

Lin¹,

Hulbert²,

Bueding³

et al. 1974

J. Med. Chem.

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Good antischistosomal activity is shown by nitrofurylvinyl derivatives such as amides of 3-(5-nitro-2-furyl)acrylic acid (4b and 5b), as well as by nitrothiazole derivatives such as niridazole (la). The effects of interchanging the nitroheterocyclic groupings have been studied by the synthesis and biological comparison of five pairs of exact analogs. Replacement of nitrofuran by nitrothiazole in the nitrofurylacrylic acid amides (4b and 5b) gave 4a and 5a and resulted in complete loss of antischistosomal activity. Substitution of nitrothiazole by nitrofuran in niridazole (la) and two new active analogs 2a and 3a gave the exact analogs lb, 2b, and 3b, respectively, with essentially complete loss of activity. These findings are surprising in view of the close similarity of biochemical and morphological effects produced by compounds of the nitrofurylvinyl and of the niridazole series. Comparisons of partition coefficients and of nitro group oxidation potentials suggest that these factors alone cannot explain all the data, and it is suggested that subtle structural differences as well as differences in metabolism are also involved.In previous s t u d i e~~,~ we have determined structural features which appear to be essential for antischistosomal activity of 5-nitro-2-fury1 derivatives. These features comprise a nitrofuran linked via an olefinic bond to a terminal nitrogen substituent of low basicity. However, a nitrothiazole derivative (niridazole, la) is also prominent among the relatively few nitroheterocyclic derivatives which show good schistosomicidal activity. We have already pointed out2 that nitrofuran derivatives, such as trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-1,2,4-oxadiazole (6, SQ 18,506) and amides of 3-(5-nitro-Z-furyl)acrylic acid (e.g., 4b and 5b), as well as the nitrothiazole la exhibit the same time course and pattern of biochemical and morphological changes in schistosomes, suggesting a common mode of action. Furthermore, in spite of the dissimilar side chains borne by the nitroheterocyclic rings, comparison of models revealed striking similarities. Specifically, superimposition of the nitroheterocyclic moieties of 6 or 4b us. la resulted in reasonable overlap not only of the respective terminal side-chain nitrogen substituents b u t also of the vinyl group of 6 or 4b with the N 1 -c~ bond of la.4 These conclusions rested on assumptions about the preferred conformations of the compounds under discussion. These assumptions have recently been supported by X-ray crystallographic studies3 3 3 with la and 6. T h e question now arose as t o the possible interchangeability of the nitroheterocyclic groupings in the nitrofuryl-vinyl and niridazole series. It is already known t h a t in the nitrofurylvinyl series replacement of nitrofuran by nitrophenyl results in complete loss of a~t i v i t y ,~ while replacement by nitrothienyl has an adverse e f f e~t .~ Furthermore, in the niridazole series, replacement of nitrothiazole by b, A = 0; B = CH; X = S 4% A = S B =-N X = CONHCH(CHJ2 5a, A = S; B = N; X = ...

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Structure and antischistosomal activity in the nitrofurylvinyl and the niridazole series. Noninterchangeability of the nitroheterocyclic rings

Lin¹,

Hulbert²,

Bueding³

et al. 1974

J. Med. Chem.

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Arylation of Unsaturated Compounds by Diazonium Salts (The M eerwein Arylation Reaction)

Rondestvedt

2011

Organic Reactions

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The arylation of unsaturated compounds by diazonium salts with copper salt catalysis was first disclosed by Meerwein. Meerwein arylation proceeds best when the double bond is activated by an electron attracting groups such as carbonyl, cyano, aryl, vinyl, ethynyl or chloro. The net result is the union of the aryl group with the carbon atom beta to the activating group, either by substitution of a beta‐hydrogen atom of by addition of Ar and Cl to the double bond. The generally accepted mechanism of the reaction involves the aryl radical from the diazonium salt, though the manner of its formation and subsequent reaction is still controversial

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