Nitromethane synthesis

In the mannose series, crystalline B-erythro-ir-manno-octose (52) has been prepared from v-glycero-D-galacto-heptose by both the cyanohydrin and nitromethane syntheses on reduction, the octose gave (inactive)... 

This second approach70 was based on the nitromethane synthesis,71 and involved, as the key intermediate, l-C-nitro-l-hexene-D-n6o-3,4,5,6-tetrol tetraacetate (66), previously reported by Sowden and Fischer.77 In re-studying their conversion of D-ribose (64) into the hexenetetrol (66), it was possible70 to secure 2,3,4,5,6-penta-O-acetyl-l-deoxy-l-nitro-D- altritol (65) as crystalline material. When (65) was subjected to the Schmidt-... 

The nitromethane synthesis, in this instance, employs reagents that... 

Approximately twice as much l-C14-D-mannose as l-C14-D-glucose is obtainable from D-arabinose by the nitromethane synthesis when no excess of CM-nitromethane is employed in the initial condensation reaction. 

In a reapplication of the cyanohydrin synthesis to L-rhamnose, the crystalline T-deoxy-L-jfZj/cero-L-gfalacto-heptose was further characterized as the pentaacetates and methyl glycosides. The heptoses derived from D-galactose and n-mannose have been prepared by the nitromethane synthesis, and this can be the method of choice for sugars which are not preferred epimers in cyanohydrin synthesis. 

Preparation. L-Mannose can be prepared by chain elongation methods, starting from L-arabinose. Both L-glucose and L-mannose are obtained. The nitromethane synthesis leads to a mixture of the nitroalditols that are separated by fractional crystallization and converted individually into the L-monosaccharides.130... 

Das B, Bhunia N, Lingaiah MA (2011) Simple and elficient metal-free synthesis of tetra-substituted pyrroles by iodine-catalyzed four-component coupling reaction of aldehydes, amines, dialkyl acetylenedicarboxylates, and nitromethane. Synthesis 2011 3471-3474 Khan AT, Ghosh A, Khan MM (2012) One-pot four-component domino reaction for the synthesis of substituted dihydro-2-oxypyrrole catalyzed by molecular iodine. Tetrahedron Lett 53 2622-2626... 

Preparation (4, 4S). D-Ribose may be synthesized from D-arabinose by alkaline isomerization, by the glycal synthesis, or through the pyridine-catalyzed epimerization of D-arabonic acid followed by reduction. The sugar also has been prepared by the oxidative degradation of calcium D-altronate (44) and by the nitromethane synthesis from D-erythrose (4 ). 

The nitromethane synthesis of higher-carbon aldose sugars utilizes two well-known general reactions of the nitroparaflBns. These are the base-catalyzed condensation of nitromethane with an aldehyde to produce a C-ni-troalcohol (146), and the decomposition of the sodium salt of the latter with cold, moderately concentrated mineral acid to produce an aldehyde (147) containing one more carbon atom than the original aldehyde. 

Under the conditions explored so far for conducting this synthesis in the sugar series (148), it is not as widely applicable, with regard to starting sugar, as is the cyanohydrin synthesis. However, for certain selected syntheses the nitromethane synthesis has the advantage of simplicity combined with satisfactory yields. 

The nitromethane synthesis is illustrated by the preparation of L-glucose and L-mannose from L-arabinose (149),... 

In addition to L-glucose and L-mannose, other sugars that have been prepared conveniently by the nitromethane synthesis include L-gulose (150), the aldoheptoses from D-mannose (151), and D-erythro-h-manno-octose (152),... 

Amino-2,6-dideoxy-D-allose and -altrose hydrochlorides have been prepared by application of the Kuhn modification of the cyanohydrin synthesis to 5-deoxy-D-ribose, the overall yields of the two amino-sugars being roughly the same as those obtained using the nitromethane synthesis. ... 

There exist a number of d -synthons, which are stabilized by the delocalization of the electron pair into orbitals of hetero atoms, although the nucleophilic centre remains at the carbon atom. From nitroalkanes anions may be formed in aqueous solutions (e.g. CHjNOj pK, = 10.2). Nitromethane and -ethane anions are particularly useful in synthesis. The cyanide anion is also a classical d -synthon (HCN pK = 9.1). 

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

Nitromethane. The nitroparaffins are used widely as raw materials for synthesis. Nitromethane is used to produce the nitro alcohol (qv) 2-(hydroxymethyl)-2-nitro-l,3-propanediol, which is a registered biocide useful for control of bacteria in a number of industrial processes. This nitro alcohol also serves as the raw material for the production of the alkanolamine (qv) 2-amino-2-(hydroxymethyl)-l,3-propanediol, which is an important buffering agent useful in a number of pharmaceutical appHcations. 

Nitromethane also is used in the synthesis of the antiulcer dmg, ranitidine [66357-35-5]. A two-step process utilizing nitromethane, carbon disulfide, potassium hydroxide, and dimethyl sulfate yields l,l-bis(methylthio)-2-nitroethene [13623-94 ] which reacts further to produce ranitidine. 

This class was first reported in 1924 and was formed 62HC(17)l) by cyclization of a-bromo-/3-aryl-y-nitroketones. The direct synthesis by oxygenation of 2-isoxazolines has not been reported. To date only 3-substituted derivatives have been prepared. Aryl-nitromethanes react with nitrostilbene to form isoxazoline A-oxide by a nitrile ion displacement (Scheme 138) <62HC(17)1, 68TL3375). 

Recently, elegant synthesis of ruin -MRS carbapenum has been reported. Sequential reaction of nitromethane via conjugate addition-elimination to a,fi-unsanirated esters followed by Pd-catalyzed subsdnidon of the residdng allyl nitro compound with the naphthosultam affords the allyladon product which is an and fEq. 7.20. ... 

Although the base-catalyzed addition of nitroalkanes to electron-deficient olefins has been extensively used in organic synthesis fsee Michael addition Chapter 4, it is only recently that the reaction has been extended to the cyclopropanadon reaction. In 1978, it was reported that the anion of nitromethane reacts with certain highly electron-deficient olefins to produce cycloptopanesingoodyieldrEq. 7.36. More recently, this reaction has been extended to more general cyclopropanadons, as shown in Eqs. 7.37 and 7.38, in which potassittm salts of nitroalkanes are employed in DMSO as alkylidene transfer reagents." ... 

An elegant example of sequence of reactions involving the Henry reaction, the Michael reaction, and elimination of HNO is demonstrated in a short synthesis of anthracyclmones. Nitromethane is used to introduce the ClO-gronp simultaneously v/irh the C9-hydroxy group fEq. 7,136. ... 

The condensation of nitro compounds and imines, the so-called aza-Henry or nitro-Mannich reaction, has recently emerged as a powerful tool for the enantioselective synthesis of 1,2-diamines through the intermediate /3-amino nitro compounds. The method is based on the addition of a nitronate ion (a-nitro carbanion), generated from nitroalkanes, to an imine. The addition of a nitronate ion to an imine is thermodynamically disfavored, so that the presence of a protic species or a Lewis acid is required, to activate the imine and/or to quench the adduct. The acidic medium is compatible with the existence of the nitronate anion, as acetic acid and nitromethane have comparable acidities. Moreover, the products are often unstable, either for the reversibility of the addition or for the possible /3-elimination of the nitro group, and the crude products are generally reduced, avoiding purification to give the desired 1,2-diamines. Hence, the nitronate ion is an equivalent of an a-amino carbanion. 

The reaction of a carboxylic acid with N,Af -carbonyldiimidazolellH33 (abbreviated as CDI), forming an imidazolide as the first step followed by alcoholysis or phenolysis of the imidazolide (second step), constitutes a synthesis of esters that differs from most other methods by virtue of its particularly mild reaction conditions.t41,[5] It may be conducted in two separate steps with isolation of the carboxylic acid imidazolide, but more frequently the synthesis is carried out as a one-pot reaction without isolation of the intermediate. Equimolar amounts of carboxylic acid, alcohol, and CDI are allowed to react in anhydrous tetrahydrofuran, benzene, trichloromethane, dichloromethane, dimethylformamide, or nitromethane to give the ester in high yield. The solvents should be anhydrous because of the moisture sensitivity of CDI (see Chapter 2). Even such unusual solvent as supercritical carbon dioxide at a pressure of 3000 psi and a temperature of 36-68 °C has been used for esterification with azolides.[6]... 

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

The Michael addition of nitromethane to cyclopentenone derivatives is used for synthesis of prostaglandins (Scheme 4.20).158 Here, the anion of nitromethane is used as a formyl anion synthon. 

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