4- Nitrobenzoic anhydride

A large excess of thionyl chloride is recommended in order to avoid the format tion of p-nitrobenzoic anhydride (see Note 1 to Section IV,185). 

Sc(OTf)3, AcOH, p-nitrobenzoic anhydride or Sc(OTf)3, AC2O, 66- >95% yield. The lower yields are obtained with allylic alcohols propargylic alcohols give higher yields. Phenols are effectively acylated with this catalyst, but at a much slower rate than simple aliphatic alco-hols. The method was shown to be superior to most other methods for macrolactonization with minimum diolide formation. 

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. ... 

A number of mixed anhydrides react with alcohol in a rather peculiar manner. Thus benzoic nitrobenzoic anhydride and benzoic mesitylenccarboxylic anhydride yield benzoic acid together with ethyl nitrobenzoate and ethyl mcsitylcarboxylate, respectively, whereas benzoic cuminic anhydride forms both acids and both esters in conaderable quantity. ... 

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 %). 

Aminofurans cannot be prepared by reduction of 2-nitrofurans or by hydrolysis of 2-acetamidofurans. The latter are prepared by the reduction of 2-nitrofurans in the presence of acetic anhydride. Benzofuranone (161) and not 2-aminobenzofuran is obtained from tin and hydrochloric acid reduction of 2-nitrobenzo[h]furan (160). 

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

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. 

To a vigorously stirred solution of 9.0 gm (0.062 mole) of o-nitrobenzo-nitrile in 75 ml of acetic acid and 10 ml of acetic anhydride, while maintaining the reaction temperature between 30°C and 35°C by adjusting the addition rate and wanning or cooling as needed, is gradually added 12.0 gm (0.19 gm-atom) of zinc dust over a li hr period. Then the pasty reaction mixture is diluted with 1 liter of ice water and the solid is separated by centrifugation. 

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). 

The position of the equilibrium of Eq. (13) depends markedly on the nature of R. When R = H the product is entirely the ketone, whereas when R = CH3 the product can be shown from IR and NMR spectroscopic data to be completely enolized. Whichever form predominates, Schotten-Baumann benzoylation gives the indolizine / -nitrobenzoate ester (67). Acetic anhydride instead of perchloric acid with 65 gives the 1-acetamidoindolizine which is also available from the 1-acetyl compound via the Schmidt reaction. 

A strategy for producing unsymmetrical TB derivatives is based on the Wilcox synthetic protocol (Scheme 5). The reaction of aniline 4 with the derivative of isatoic anhydride, 3,l-benzoxazine-2,4(l//)-dione 5, or 2-nitrobenzoic acid 6 affords ami-noamide 7 and nitroamide 8, respectively. The reduction of 7 or 8 followed by a final cyclization reaction of bisamine 9 yields unsymmetrical TB derivatives 10 (90JOC363). 

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...

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