2-Methyl-6-nitrobenzoic anhydride

SCHEME 14.9 Synthesis of lipid A from Helicobacter pylori. Alloc, allyloxycarbonyl CbzOBt, l-(benzyloxycarbonyl)benzotriazole CPME, cyclopentylmethyl etliel CSA, cam-phorsulfonic acid DMDO, dimethyldioxirane MNBA, 2-methyl-6-nitrobenzoic anhydride PMB, />-methoxybenzyl. 

A variation of the mixed-anhydride lactonization process was developed for the synthesis of lactone 107, an intermediate in the synthesis of octalactin B. In this case, 2-methyl-6-nitrobenzoic anhydride (MNBA) and a catalytic amount of DMAP are used and the reaction occurs at room temperature (Scheme 22) <2004TL543, 2005SL2851>. The yield of this transformation was increased to 90% by conducting the reaction in DCM and using 4-dimethylaminopyridine 1-oxide (DMAPO) instead of DMAP <2005CEJ6601>. 

RCO2H, R OH, 2-methyl-6-nitrobenzoic anhydride, TEA, DMAP, CH2CI2, rt, 72-100% yield. Other aryl anhydrides are also effective. ... 

Following developments of lactonization methodology, Shiina et al. proposed a novel mixed-anhydride method for the preparation of lactones including mediumsized ring compounds, and they applied this new technology to the preparation of several macrocyclic molecules (Scheme 5.8 and Scheme 5.9). This reaction could be promoted by Lewis acid catalysts, or nucleophilic catalysts, such as DMAP and DMAPO(4-dimethylaminopyridine N-oxide). For example, ricinoleic acid lactone (20) was first synthesized by combination of 4-trifluoromethylbenzoic anhydride (TFBA) with Lewis acid catalysts (Scheme 5.8) [34, 35], whereas aleuritic acid lactone (21) was alternatively synthesized using 2-methyl-6-nitrobenzoic anhydride (MNBA) with nucleophilic catalysts (Scheme 5.9) [36-38]. 

Yonemitsu et al. [46] modified the Yamaguchi conditions in which the mixed anhydride is not isolated and DMAP is directly introduced at room temperature from the beginning. Shiina et al. [47] described the use of 2-methyl-6-nitrobenzoic anhydride (MNBA) as an alternative to 2,4,6-trichlorobenzoyl chloride. Pivaloyl chloride [48], trifluoroacetic anhydride [49], AC2O [50], and B0C2O [51] are also employed for the lactonization via mixed anhydride under basic conditions. Furthermore, Yamamoto et al. [52] described the use of Sc(OTf)3 as a Lewis acid. 

To a solution of 2-methyl-6-nitrobenzoic anhydride (MNBA, 8.1 mg, 0.0234 mmol) and DMAP (7.1 mg, 0.0585 mmol) in toluene (10 mL) was slowly added hydroxy carboxylic acid (17.1 mg, 0.0195 mmol) in toluene (10 mL) at 80 °C by syringe pump over a 4-h period. After stirring for additional 6 h at the same temperature, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes/EtOAc, 8/1) to afford macrolactone 2.332 (13.5 mg, 81 %). 

The configuration of the products was established by periodate oxidation of the D compound, and reduction of the resulting dialdehyde to an optically active diol whose sign and magnitude of optical rotation ([a] ° +2.5° in water) correspond to that of the diol ([a]n° 46.8° in water) obtained by similar treatment of methyl a-L-arabinopyrano-side. The bis(p-nitrobenzoates) of the two diols exhibited similar relationships. Hence, it appears likely that the configuration at C-2 of the anhydride is the same as that at C-l of the L-arabinoside. The cis relationship of the hydroxyl groups was retained from the arabinal started with. 

Mononitration of benzo[6]thiophene gives a complex mixture in which the 3-isomer predominates (73% in acetic anhydride at 25 °C) and can be separated from other isomers, which may include 4-, 5-, 6- and 7-nitro derivatives. However, benzo[6]thiophenes with electron-donating groups at the 3-position, e.g. 3-methyl-, 3-acetamido- or 3-bromo-benzo[6]thiophene, are nitrated almost exclusively in the 2-position. 2-Nitro-benzo[6] thiophene may be prepared by debromination of 3-bromo-2-nitro-benzo[6 ]thiophene, or by decarboxylation of 2-nitrobenzo[6]thiophene-3-carboxylic acid (70AHC(11)177). 

Scheme 8. Step-by-step and simultaneous preparation of bis-TB derivatives. Reaction conditions (i) 6-nitroisatoic anhydride, THF (ii) 5-methyl-2-nitrobenzoic acid, DCC, DMF (iii) Pd/C, H2, CHCl3/EtOH (iv) BH3-THF, reflux (v) CH20, HC1, EtOH (vi) 5-methyl-2-aminobenzoic acid, DCC, DMF...

The following are some further examples. Acetomesitylene is obtained from mesitylene and glacial acetic acid in the presence of phosphoric oxide and kieselguhr, yields reaching 82.5%.525,566 (o-Nitrobenzoyl)mesitylene is obtained (75%) from mesitylene and a-nitrobenzoic acid in the presence of boron trifluoride and trifluoroacetic anhydride.567 Toluene and benzoic acid in the presence of molybdenum pentafluoride give a 70% yield of 4-methylbenzo-phenone, but with aluminum chloride give a mixture of the 2- and the 4-methyl derivative.568... 

Dimethylaminopyridine 4,6-Dinitro-o-cresol Diphenylamine Disodium octaborate tetrahydrate Endosulfan Ethiofencarb 6-Ethoxy-1,2-dihydro-2,2,4-trimethylquinoline 2-Ethylhexanal Ethyl hexanediol 2-Ethylhexenal 2-Ethyl-2-hexenal Ethyl-p-nitrobenzoate Etrimfos Fenamiphos Fenpropathrin Fenthion Fluometuron Furfural Glyoxalic, acid Hexachloro-1,3-butadiene Hexachloroethane Hydramethyinon 2-Hydroxy-2-methylpropanenitrile 2-Imidazolidinone lodofenphos Isofenphos Isooctyl thioglycolate Isopropanolamine Kojic acid Laurie acid Lead acetate Lead acetate trihydrate Lead naphthenate 2,6-Lutidine Mecarbam Mercury chloride (ic) Metam-sodium P-Methylnaphthalene Naphthalene Nicotine Oxamyl Parathion-methyl Pentaerythritol Perchloropentacyclodecane Permethrin Phenothiazine Phenylmercuric acetate Phorate Phosalone Phoxim Phthalic anhydride a-Pinene Pine (Pinus palustris) tar oil Piperazine Piperazine dihydrochloride... 

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