Nitroacetates

Nitromethane, CH3NO2, the first member of the homologous series, can, however, be readily prepared by a special reaction. When equimolecular amounts of sodium nitrite and sodium monochloroacetate are heated together in aqueous solution, the chlorine in the monochloroacetate is replaced by the nitro group, and the sodium nitroacetate thus formed undergoes hydrolysis follow ed by decarboxylation ... 

Nitromethane is more easily prepared by heating together equimolecular amounts of sodium monochloroacetate and sodium nitrite in aqueous solution sodium nitroacetate is intermediately formed and is decomposed to nitromethane and sodium bicarbonate. The latter yields sodium carbonate and carbon dioxide at the temperature of the reaction. 

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

Substitutedisoxazole-3,5-dicarboxylic acids have been prepared from ethyl nitroacetate and an aldehyde (63BCJii50). A related reaction leads to diethyl 4-hydroxyisoxazole-3,5-dicarboxylate (334) and involves the reaction of acetonedicarboxylic acid ester (333) with nitrosyl chloride (78JHC1519). 

Attempted alkylation of methyl nitroacetate in base produced an isoxazoline Af-oxide (Scheme 140) (74CPB477), and the enamine (497) gave an isoxazoline A-oxide when reacted with methyl nitroacetate (74IZV845, 74MI41605). 

Dicarbonylimidazole reacted with the anthranilic acid derivative (498) to produce the fused isoxazolone IV-oxide (499) (77ZOR462). Methyl nitroacetate reacted with indole-3-carbaldehyde to produce (500) (70KGS1505). Treatment of (501) with base gave 3,4,5-triphenyl-2-isoxazoline IV-oxide (Scheme 142) (69JOC984). The reaction was reported to be a direct displacement as (502) did not give a product and no incorporation of deuterium was found using DOMe. 

This series of compounds was also discussed briefly by Quilico in 1962 and only a limited number of new representatives have been reported 62HC(17)l,p. 3). The pressure reaction of ethylene and nitric acid in the presence of Ni, Zn or Cu produced 3,3 -bis(isoxazoline) 70FRP94493), and the isoxazoline IV-oxide (515) was prepared by the reaction of /3-dimethylaminoacrylaldehyde and methyl nitroacetate (74IZV845). 

In a 1-1, three-necked, round-bottomed flask equipped with a calcium chloride drying tube, a mechanical stirrer, and a ground-glass stopper are placed 28.2 g. (0.184 mole) of freshly distilled methyl bromoacetate, 500 ml. of anhydrous iV,iV-dimethy]acetamide (Note 1), and 20.0 g, (0.168 mole) of methyl nitroacetate (Note 2). The solution is stirred vigorously while 146 ml. (0.168 mole) of 1.15N sodium methoxide in... 

Methyl nitroacetate was prepared by the method of Zen and co-workers. It should be distilled before use. 

Gas chromatographic analysis of the crude mixture (SE-30 on Chromosorb W, 1 m., 150°) showed the presence of some low-boiling materials (including unreacted methyl nitroacetate) and a significant amount of the doubly alkylated by-product, trimethyl 2-nitro-l,2,3-propanetricarboxylate. 

According to the Friedlander method, the condensation of the readily available 2-aminoiiicotinic aldehyde (20a) (74JOC726) or its 6-phenyl derivative (20b) [66JCS(C)315] with nitroacetic acid (21) in boiling ethanol with piperidine as catalyst is another example of this method, which affords in fair yields the corresponding 3-nitro-l,8-naphthyridin-2(lFI)-ones (22a, 74%) and (22b, 47%), respectively [66JCS(C)315]. 

It was reported that the Niemeiitowski synthesis of 4-hydroxy-3-iiitro-7-pheiiyl-l,8-iiaphthyridiii-2(lH)-oiie (25) from ethyl 2-amiiio-6-pheiiyhii-cotiiiate (23) and ethyl nitroacetate (24) in the presence of sodium was unsuccessful, producing only traces of (25), while condensation of ethyl 2-amino-6-phenylnicotinate (23) with the less reactive ethyl acetate resulted in the formation of 4-hydroxy-7-phenyl-l,8-naphthyridin-2(lH)-one in good yield [66JCS(C)315]. It seems that the more reactive nitroacetate tends to precipitate rapidly from the reaction mixture as its sodio derivative, which explains the low yield of (25). 

A great number of N-substituted 4-hydroxy-3-nitro-l,8-naphthyridin-2 (IH)-ones are obtained by reaction of N-substituted azaisatoic anhydrides with ethyl nitroacetate carbanion (Section II,A,4,a). A very specific method, more recently developed, is that of the inverse Diels-Alder method, involving the reactions of enamines with 5-nitropyrimidine (Section II,A,4,b). 

C-Alkyldtkin takes place in the reaction of methyl nitroacetate with ilkyl h ilicles the products are useful intermediates for preparing amino acids fEq. 5.1 /The requisite nitro acetate is prepared by seif condensadon of nitromethane. ... 

The present tandem nitro aldol-cyclizadon process is used for the preparadon of the enandomerically pure 4-hydroxy-3-isoxa2olme-3-ones They are prepared starting from chiral ct-mesyloxy aldehydes and ethyl nitroacetate under rruld reacdon conthdons fEq 8 85 ... 

Aluminum oxide catalyzed addition of ethyl nitroacetate to racemic 2,3-cpoxy aldehydes 7 affords substituted 4,5-dihydroisoxazole 2-oxides through a regio- and stereospecific tandem nitroaldol cyclization process. High diastereoselectivities are observed in the reaction of cis-epoxyaldehydes to yield the ethyl, vi7 -4.5-dihydro-4-hydroxy-5-( I -hydroxyalkyl)-3-isoxazole-carboxylate 2-oxides, with tram configuration at the ring positions, whereas reactions of trans-and 3,3-disubstituted 2,3-epoxyaldehydes proceed with lower selectivities28. 

Na hydroxide first forms the Na salt of NMe, then the Na salt of methazonic acid, and finally the Na salt of nitroacetic acid (Ref 10). 5) With Hg(ll) chloride is formed first the Hg salt of NMe which rearranges and dehydrates to MF (Ref 10). 

Cklorodifluoronitrosomethane. ClCF2NO, mw 115.47 N 8.24% a dark blue liq or gas bp ca -35° (Refs 1, 2 6) CA Registry No 421-13-6 Preparation. It has been prepd by reactions analogous to those for prepn of trifluoronitrosomethane (Refs 2 5). It has also been prepd by the action of 33% aq nitric acid on chloro-difluorosulfenyl chloride (C1CF2SC1) (Ref 3), and by the action of hot coned HC1 on difluoro-nitroacetic acid (Ref 4). Its props and reactions are similar to trifluoronitrosomethane Refs 1) Beil 1, <99) 2) R.N. Hazeldine, JCS... 

Methylamine Salt of Ethyl Nitroacetate, MeNH2.02NCH2C00Et, mw... 

Nitroacetic Acid. See Vol 1, A27-R under Acetic Acid and Derivatives. Its dipotassium salt, which is expl is briefly described, whereas its other expl salts, such as Pb, Ag and Hg are only mentioned. All of these salts are described by W. Steinkopf in Ber 42, 2026-31 (1909) CA 3,1438(1909)... 

Nitroacid. A compd containing both the radicals —COOH and —N02. Some of these are expl, eg, Nitroacetic Acid, 02N.CH2.COOH Dinitro-benzoic acid, (02N)2.C6H3.COOH Triiutro-benzoic acid, (02N)3.C6H2.COOH etc Ref Hackh s (1972), 457-R... 

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