Methyl nitroacetate

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. 

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. ... 

B. Methyl Nitroacetate. A 2-1., three-necked, round-bottomed flask equipped with a sealed mechanical stirrer, a pressure-equalizing dropping funnel fitted with a calcium chloride drying tube, and a thermometer is charged with 70 g. (0.387 mole) of finely powdered dipotassium salt of nitroacetic acid (Note 4) and 465 ml. (11.6 moles) of methanol. 

The reaction mixture is cooled to —15° 3° and 116 g. (1.16 moles) of concentrated sulfuric acid is added with vigorous stirring over approximately 1 hour at such a rate that the reaction temperature is maintained at —15°. The reaction mixture is allowed to warm to room temperature over a 4-hour period and to stir for another 4 hours at room temperature. The precipitate is removed by suction filtration and the filtrate is concentrated on a rotary evaporator under reduced pressure at 30-40°. The residual oil is dissolved in benzene and washed with water, The benzene layer is dried over anhydrous sodium sulfate and the benzene is removed by distillation. Further distillation under reduced pressure yields 30-32 g. (66-70%) of methyl nitroacetate, b.p. 80-82° (8 mm.). 111-113° (25 mm.) (Note 5). 

Methyl nitroacetate has been prepared from nitromethane through the dipotassium salt of nitroacetic acid by the classical Steinkopf method3 but in lower yield. The dipotassium salt was obtained in 45% yield. The method has been improved by Matthews and Kubler4 but the salt must be recrystallized prior to esterification. 

Reactions of methyl nitroacetate with aldehydes are induced by TiCl4 in pyridine. They afford nitroalkenyl-esters,64 which are used in the preparation of various nonnatural amino acids (Eq. 3.39).65... 

The nitroaldol reaction of methyl nitroacetate (199, Scheme 38) with 1,2 3,4-di-0-isopropylidene-a-D-ga/acfo-hexodialdo-l,5-pyranose (200) and 2,3-O-isopropyli-dene-D-glyceraldehyde (202) catalyzed by silica gel proceeded in almost quantitative yield, with high selectivity for attack on the aldehyde carbonyl group, giving derivatives 201 and 203, respectively. Two of the four possible diastereomers were detected as main products, and were obtained as a mixture. For the nitroaldol reaction with 200 gave similar results in either the presence or absence of silica gel, whereas the reaction with 202 did not proceed in its absence, showing that catalytic action of silica is mandatory in this case.176... 

SCHEME 38. Nitroaldol reaction of methyl nitroacetate with hexodialdo-l,5-pyranose 200 and 2,3-0-isopropylidene-D-glyceraldehyde (202) catalyzed by silica gel. 

P. Borrachero, M. J. Dianez, M. D. Estrada, M. Gomez-Guillen, A. Gomez-Sanchez, A. Lopez-Castro, and S. Perez-Garrido, Silica gel-catalysed addition of methyl nitroacetate to 1, 2 3, 4-di-O-isopropylidene-a-D-ga/acto-hexodialdo-... 

The first application of microwave irradiation in conjunction with dry media in the generation of nitrile oxide intermediates was reported by Hamelin [29]. In this example, methyl nitroacetate (170) was mixed with a dipolarophile in the presence of catalytic amounts of toluene-p-sulfonic acid (PTSA) (10% weight). Subsequent microwave irradiation led to the formation of the corresponding heterocyclic adducts (Scheme 9.52). Reactions were performed in an open vessel from which water was continuously removed [103], Likewise, irradiation in a domestic oven of a mixture of ethyl chloro(hydroxyimino)acetate (173) and a dipolarophile over alumina led to the same results in only a few minutes (Scheme 9.52) [103]. 

In the synthesis of nitronates (5), longer reaction sequences can also be successfully used. For example, Scheme 3.15 presents the synthesis of trisubsti-tuted nitronates (5) from functionalized primary AN (11) (exemplified by methyl nitroacetate) and alkyl iodides RCH2I (56). 

A similar process can be performed with the use of cerium ammonium nitrate (CAN) for generation of radicals from another CH acid, viz., methyl nitroacetate (72b) (Scheme 3.22, Eq. 2). 

However, certain facts contradict this interpretation. For example, the silylation of AN with BSA was accelerated after addition of triethylamine, which facilitates AN ionization (185). Besides, the addition of 1,1-dinitroethane leads to an increase in the rate of silylation of methyl nitroacetate with a deficient amount of DPSU. At the same time, the silylation of 1,1-dinitroethane by itself, taken separately with DPSU, occurs faster than silylation of MeC>2CCH2NC>2 (204). Apparently, this is accounted for by the higher nucleophilicity of methyl nitroacetate compared to that of 1,1-dinitroethane. (A separate experiment demonstrated that silyl aci-dinitroethane does not react with methyl nitroacetate.)... 

Analogous data on O-methyl derivatives of methyl nitroacetate were reported in the study (338b). 

There are also several variations on this procedure. The use of trimethylsilyl triflate (TMSOTQ provides the silyl nitronate of methyl nitroacetate in good yield. However, for primary nitroalkanes, a second silylation occurs at the a-position of the nitronate (Eq. 2.5) (102). The use of TMSCl in the presence of lithium sulfide provides good yields of silyl nitronates from secondary nitroalkanes (103,104). Unfortunately, the number of examples is limited and this procedure is not applicable to primary nitroalkanes. 

Methyl nitroacetate, 57, 60 10-Methyl-A1 (9)-2-octalone, 57, 69 1O-Methyl-A1 (9 )-2-octalone,Ar,iV-dimethyl hydrazone, 57, 69... 

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