2.4- Dinitroimidazole, reaction with

Analogous reactions of 2,4-dinitroimidazole 38 with oxiranes gave mixtures of the major opened products 39 and minor 2,3-dihydroimidazo[2,l-Z ]oxazoles 40 (79JHC1499, 79JMC583, 84IJC(B)363). Similar behavior was also described... 

Sodium isopropoxide replaces the 2-bromo atom of 1-substituted 2,4,5-tribromoimidazole by an isopropoxy group <87JCS(P1)1437>. In 1,4-dinitroimidazole (81) reaction with methanol leads to c/ne -substitution, the reaction being first order with respect to both reactants and also to hydroxide ions. The yield is not affected by increasing the concentration of methanol from 10 to 40%, and only slightly by raising the pH from 8 to 10. Above that level the product is not formed (Equation (27)) <84PJC311>. 

Lewis acid SnCLj-assisted reaction between the l,3-thiazole-5-thione 434 and /ra r-2,3-dimethyloxirane led to the m 4,5-dimethyl-l,3-oxathiolane 435 The same Lewis acid enabled a second addition of /ra/ -2,3-dimcthyloxirane onto the C—N bond of the 1,3-thiazole ting of 434, leading to the formation of the tetrahydro-2//-thiazolo[2,3- ]-oxazole adduct 436 (Equation 200) <2000HCA3163>. Condensation of 2,4-dinitroimidazole, 8-bromotheophylline, and 8-bromoadenine with substituted methyloxiranes involved sequential A -alkylation-r/wo-substitution and furnished a series of 2,3-dihydro-imidazo[2,l- ]oxazole derivatives 437, 438, and 439 (Equations 201-203) <2000CCC1126, 2000EJ03489, 2005TL3561, 2004JHC51>. 

Reaction of 1,4-dinitroimidazole with 1,1-disubstituted hydrazine, i.e., A-aminomorpholine, appeared to be more successful it yields 1-(A-... 

Reaction of 1,4-dinitroimidazole with methanol leads to (743) also via cme -substitution, the reaction being first order with respect to both reactants and also to hydroxide ions. 

The reaction of 5-bromo-3-nitro-l,2,4-triazole and 3,5-dinitro-l,2,4-triazole with a variety of oxiranes yielded the expected 1-substituted imidazoles, and also resulted in the formation of 5,6-dihydrooxazolo[3,2-6]-s-triazoles upon treatment with base (75CHE612). The proposed pathway involves proton abstraction from the imidazole and subsequent attack of the oxirane on the N-anion followed by cyclization in a concerted fashion (equation 56). 2,4(5)-Dinitroimidazole reacts analogously with oxiranes to give isomeric nitro-imidazo[2,1 -f>]oxazoles in good overall yield (8UMC601). 

For many years it was not possible to introduce two nitro groups into the imidazole ring [159], By the use of a somewhat unusual nitration condition (by heating the substrate first with nitric add and then with the sulfuric-nitric acid mixture) it was possible to obtain 4,5-dinitroimidazole [79], The method has now also been used for the production of 4,5-dinitroimidazoles [84, 93, 160], It was also shown that C-polynitrobisimidazoles [79] and not /V-nitroimidazolcs, as considered earlier [161], are formed during the nitration of 2,2 -bisimidazole and its bromine derivatives. As already mentioned earlier, during the nitration of ethyl l-methylimidazole-2-carboxylate the 4,5-dinitro derivative was also isolated together with the other nitration products [128], Increase in the reaction time increases the amount of the dinitro derivative. 

In view of the importance of 2-nitroimidazoles as antibiotics e.g. 2-nitroimidazoIe azomycin ) and the problems involved in their synthesis (usually via the 2-aminoimidazole) it seemed worthwhile to attempt to prepare these compounds by thermal rearrangement of the (V-nitro compounds (by analogy with the well-known reactions of 1-nitro-pyrazoles and -indazoles) (Chapter 4.04). Thus, when 1,4-dinitroimidazole (16) is heated at 140 °C in chlorobenzene, benzonitrile or anisole there is conversion into 2,4- and 4,5-dinitroimidazoles, but considerable denitration can also occur, giving 4-nitroimidazole (Scheme 6). 2-Methyl-l,4-dinitroimidazole rearranges smoothly to 2-methyl-4,5-dinitroimidazole, but 5-methyl-l,4-dinitroimidazole appears to denitrate in preference to any other reaction. Further study of these reactions is indicated. 

Ozone-mediated nitration (Kyodai nitration) of imidazole under neutral condition gave poor yields of 4-nitroimi-dazole. However, the yield improved dramatically with the addition of methanesulfonic acid. The combination NO2-O3 is a much more reactive electrophilic reagent since a reaction temperature of 0°C was sufficient (Scheme 56), <1996JCM244>. The 4-nitro product 238 could also be converted into 1,4-dinitroimidazole 239 over a long period. 

The reaction of 2-methyl-1,4-dinitroimidazole with hydrazine results in the formation of the ring expanded bicycle 3-methyl-1,2,4-triazin-5(2//)-one [3-methyl-l,2,4-triazin-5(2//)-ylidene]hydrazone toluenesulfonate 9 <96T14905>. 

Acid-sensitive systems represent a particularly useful application for desilylative nitration with nitronium salts. Mononitration of imidazoles and triazoles is difficult because acid formed in the reactions even with NO2 BF4 tends to catalyze denitration. However, the nitration of tri-methylsilyl derivatives with NO2 BF overcomes this difficulty. It has been shown for 2-isopropyl-1-trimethyl-silylimidazole that it is possible to obtain its nitro compounds which could not be obtained previously (c.g., 2-isopropyl-1,4-dinitroimidazole) [149], Desilylative N-nitration is involved in the reaction. 

SnAr reactions like nitration (with HNO3/H2SO4) or sulfonation (with H2SO4 or oleum) proceed very slowly, since in strongly acidic medium imidazolium ions are the participants in the SnAr processes. Thus, nitration of imidazole leads to 4-nitroimidazole (11), and under more drastic conditions to 4,5-dinitroimidazole (12). Sulfonation of imidazole in oleum at 160 °C yields imidazole-4-sulfonic acid ... 

A number of -acyl- and thioureido-derivatives of 3 -amino-3 -deoxythymidine have been prepared. 1 0 Michael addition of phthalimide to enal (81) was used in the synthesis of the 3 -amino-2 ,3 -dideoxyhexo-furanose nucleosides (82) (all four isomers, R=H, Me, halogen),191 and a similar enal prepared by mercuric-ion catalysed hydrolysis of L-rhamnal was used in the same way to make the L-acosaminyl nucleoside (83) and its -anomer, and the L-ristosaminyl systems (epimers at C-3 ). 2 Michael addition of 1,2,4-triazole to (81) led, after base-sugar condensation, to the triazolyl-substituted nucleosides (84, B=T, U), together with the analogous hexopyranose systems. 93 xhe imidazolyl nucleosides (85) can be made by reaction of 3 -amino-3 -deoxythymidine with l,4-dinitroimidazoles, 9 whilst the unsaturated imidazole nucleoside (87) was made by treating the phenylselenone (86) (see Section 6) with imidazole. 195... 

Synthesis of l -Linked Oligoimidazoles and Similar Compounds. Suwinski, Jerzy Wagner, Pawel (Pol.). Zesz. Nauk. Politech. Slask., Chem. 1997, (135), 73-80 (Pol.), Wydawnictwo Politech-niki Slaskiej. Anrorc type reaction of 1,4-dinitroimidazole with 4-amino-arylimidazoles (prepd. by redn. of l-aryl-4-nitroimidazoles) afforded derivs. of 1,4 -biimidazole and triimidazole. In similar manner l,3-bis(4 -nitro-l -imidazolyl)benzenes were prepd. 

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