Nitromethane, condensation with aldehydes

Nitro alcohols ate usually isolated (method 102) but are sometimes dehydrated directly to olefinic nitro compounds as in the preparation of co-nitro-2-vinylthiophene from nitromethane, thiophenecarboxaldehyde, and sodium hydroxide (78% yield). Many substituted /3-nitrostyrenes have been obtained by condensation of nitromethane or nitroethane with substituted benzaldehydes. A methyl group on the benzene ring is sufficiently activated by nitro groups in the orlio or para position to cause condensation with aldehydes. A series of nitrostilbenes has been made in this way from substituted benzaldehydes. ... 

Aliphatic nitro compounds show a number of reactions which parallel those of carbonyl chemistry. Primary and secondary nitro compounds exhibit tautomerism paralleling keto-enol tautomerism (Scheme 3.94a). Aliphatic nitro compounds dissolve in aqueous sodium hydroxide with the formation of sodium salts. The resultant anions behave as carban-ions and will condense with aldehydes. An example involves the formation of m-nitrostyrene from nitromethane and benzaldehyde (Scheme 3.94b). 

Condensation with carbonyl compounds. Nitromethane condenses with benz-aldehyde in methanol-aqueous sodium hydroxide at 10-15° to give a sodium enolate. 

Nitroalkanes RCH2N02also condense with aldehydes and ketones and both double bond and nitro group in the products (11) can be reduced in one step to give amines (12), The condensation is unambiguous as nitromethane forms an anion so easily and does not react with itself. The reduction can be carried out catalytically or with Red-Al , NaAlH2(OCH2CHiOMe)2... 

Aldehyde (4) can be made by chloromethylation (P 9), the condensation with nitromethane with mild base gives an excellent yield of crystalline (3) and LiAlH can be used for the reduction. 

The condensation of aldehydes and ketones with aminoacetonitriles, although it requires more vigorous soliddiquid catalytic conditions to produce the cyano-enamines, is preferable in many respects to the traditional Wittig-Horner or Peterson procedures [45]. Hydroxyalkylphosphonates are obtained from the catalysed aldol condensation of nitromethane with acylphosphonates [46]. 

Henry reactions have been extensively exploited for the synthesis of nitrate ester explosives. The condensation of nitroalkanes with aldehydes, followed by esterification of the hydroxy groups with nitric acid, leads to a number of nitrate ester explosives (see Chapter 3). The two examples given above (166 and 167) are synthesized from the C-nitration of the polyols obtained from the condensation of formaldehyde with nitromethane and nitroethane respectively. 

This reactivity pattern is rather rare but is seen in the condensation of carbon nucleophiles such as nitromethane with arylidene isocyanides (equation 74) (79JHC(S)lll). The isocyanides are obtained by condensing aromatic aldehydes with tosylmethyl isocyanide. 

Nitroalkanols are intermediate compounds of /1-amino alcohols that are used extensively in many important syntheses. They are obtained by Henry s reaction through the condensation of nitroalkanes with aldehydes. Different nitro compounds have been reacted with carbonyl compounds in reactions catalysed by alkaline earth metal oxides and hydroxides/621 Among the catalysts examined, MgO, CaO, Ba(OH)2, and Sr(OH)2, exhibited high activity for the reaction of nitromethane with propionaldehyde. The yields were between 60 % (for MgO) and 26 % [for Sr(OH)2] at 313 K after 1 h in a batch reactor. The study of the influence of the pretreatment temperature of the solid showed that for MgO and CaO a... 

Even when a five-molar excess of nitromethane is employed the yield of 2-nitroethanol by this reaction is only about 40 percent. With homologs of either nitromethane or formaldehyde the tendency for more than one molecule of aldehyde to condense with one molecule of nitro-paraffin decreases sharply with increasing molecular weight or complexity of either component. 

When aromatic aldehydes are condensed with nitroalkanes in the presence of a base, a, p-unsaturated nitro compounds are produced directly. For example, benzaldehyde and nitromethane in the presence of a base give a,p-unsaturated compound nitrostyrene (3.25). Similarly, the reaction of nitrobutane with furfural in the presence of a base followed by hydrolysis gives 82% yield of 2-substituted furan derivative 3.26. 

The yields of nitro alcohols from simple nitroparaffins and aliphatic aldehydes or benzaldehyde are usually above 60%. The condensations are generally carried out with aqueous ethanolic sodium hydroxide, although weaker bases are sometimes desirable to prevent polymerization of the aldehyde. Sodium bisulfite addition compounds of the aldehydes are sometimes used. Better results are obtained with sodium methoxide than with alkali hydroxides in the condensation of nitroethane with formaldehyde. Sodium alkoxides are also used to effect the condensation of nitroethane with acetone and cyclohexanone. Condensation proceeds to the nitroalkanediol stage in certain cases with both nitromethane and with formaldehyde. ... 

When aliphatic nitro compounds are used instead of aldehydes or ketones, no reduction occurs, and the reaction has been referred to as a Tollens reaction (see 16-43). However, the classical condensation of an aliphatic nitro compound with an aldehyde or ketone is usually called the Henry reaction or the Kamlet reaction, and is essentially a nitro aldol reaction. A variety of conditions have been reported, including the use of a silica catalyst, Mg—A1 hydrotalcite, a tetraalkylam-monium hydroxide,proazaphosphatranes, " or an ionic liquid.A solvent free Henry reaction was reported in which a nitroalkane and an aldehyde were reacted on KOH powder. Potassium phosphate has been used with nitromethane and aryl aldehydes. The Henry reaction has been done using ZnEt2 and 20%... 

An intriguing synthesis of chiral cyclopentenone [100] from D-glucose has recently been described (53). The readily available diacetone glucose [94] was benzylated, selectively deprotected, and oxidatively cleaved to the aldehyde, which was condensed with nitromethane to adduct [95]. Acidic hydrolysis of the product gave hemiacetal [96], cleaved with periodate in methanol to aldehyde [97], Aldol-type cyclization was effected with triethylamine subsequent dehydration to [98] was induced by mesyl-ation. The nitro olefin [98], upon treatment with activated lead in an acidic media, was converted to ketone [99], Mesylation in the presence of triethylamine then led directly to cyclopentenone [100],... 

The nitroaldol condensation with nitromethane (Henry s reaction), followed by Nef decomposition of the resultant nitronate under strongly acidic conditions, has been used to elongate aldehydes. For instance, A-acetyl-D-mannosamine has been converted into A-acetylneuraminic acid applying this method iteratively [69]. Chikashita and coworkers [70] have reported good levels of anti diastereoselectivity better than 99% in an iterative homologation sequence using 2-lithio-l,3-dithiane [71] with 2,3-O-cyclohexylidene-D-glyceraldehyde R)-62. In the case of the BOM-protected tetrose derivative, the addition of 2-lithio-l,3-dithiane was syn selective (synlanti 82 18) (Scheme 13.30). 

The nitroaldol condensation with nitromethane (Henry s reaction), followed by Nef decomposition of the resultant nitronate under strongly acidic conditions has been used to elongate aldehydes. For instance, A-acetyl-D-mannosamine has been converted into A-acetylneu-... 

The base-catalysed condensation of nitromethane with aldehydes to give nitroalkenes -13 (the Henry reaction). One example -14 was used in a Corey prostaglandin synthesis.2... 

The reactivity of pyridazine-3- and 4-carbaldehydes towards active methylene reagents under the conditions of Knoevenagel, Wittig, and Hantzsch-type reactions has been examined. The 4-aldehyde reacts readily with malononitrile and methyl cyanoacetate, and less readily with triethyl phos-phonoacetate, indane-l,3-dione and alkyl acetoacetates/ammonia (e.g.. Scheme 52). Condensation with nitroethane is successful, but nitromethane gives an unstable intermediate which decomposes. The 3-aldehyde has similar reactivity to the 4-aldehyde, but some reactions are unsuccessful due to reduced reactivity, or instability of the products <90JHC1313>. 

Nef reaction. Optically active /3-hydroxy nitroalkanes are obtained in the condensation of nitromethane with aldehydes using a BINOL-lanthanum complex as catalyst. 

The irregularity mentioned was confirmed by Spath (3) who, guided by biogenetical considerations, arrived at the correct structure, in spite of the confusing analytical evidence. In Spath s mescaline synthesis 3 4 5-trimethoxybenzoyl chloride was reduced by the Rosenmund method (108) to the corresponding aldehyde, wihich when condensed with nitromethane yielded w-nitro-3 4 5-trimethoxystyrene. This was reduced with zinc dust and acetic acid to the corresponding oxime and the latter was further reduced, by sodium amalgam, to j3-3 4 5-tri-methoxyphenethylamine, i.e., mescaline. Subsequently a number of improved syntheses have been reported. 

In an attempt to increase the water solubility of carborane - antibody complexes, the dialdehyde (23) and several other sugar aldehydes were treated with lithiated dicarba c/r o-dodecaboranes (29). The reactions were reasonably stereoselective, giving erythro- and tAreo-products, e.g., compounds (30) in ca. 4 1 ratios. From the same starting compound (23) the 1,6-C-linked disaccharide (33) was prepared by fluoride ion mediated condensation with peracetylated -C-glucopyranosyl nitromethane (31) followed elaboration of the... 

A synthesis of sinefungin (22) proceeded from a condensation of N -benzoyl-2, 3 -0-isopropylidene-adenosine 5 -aldehyde with nitromethane, the nitroaldol then being reduced to the corresponding 5, 6 -dideoxy-6 -nitro derivative, which was further condensed with an L-aspartic acid derivative leading to (22) and its 75... 

Fluorinated tryptamine 183 was prepared by Rh-catalyzed reduction of the corresponding nitrile 177 by hydrogen [58c]. Alternatively, the compound 183 was synthesized by hthium aluminum hydride reduction of nitroaUcene 182, which was obtained by condensation of aldehyde 175 with nitromethane [54],... 

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