Nitromethane, aldol condensation

Secondary nitro compounds can be converted into carbanions in similar fashion. Interesting highly functionalized adducts (46) were prepared by addition to levoglucosene (45) (equation 17)59. Mixtures of diastereomeric adducts were generally formed60. The adduct from nitromethane undergoes double Michael addition followed by aldol condensation to afford the novel adduct 47. 

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]. 

Vapor-phase nitration of paraffin hydrocarbons, particularly propane, can be brought about by uncatalyzed contact between a large excess of hydrocarbon and nitric acid vapor at around 400°C, followed by quenching. A multiplicity of nitrated and oxidized products results from nitrating propane nitromethane, nitroethane, nitropropanes, and carbon dioxide all appear, but yields of useful products are fair. Materials of construction must be very oxidation-resistant and are usually of ceramic-lined steel. The nitroparaffins have found limited use as fuels for race cars, submarines, and model airplanes. Their reduction products, the amines, and other hydroxyl compounds resulting from aldol condensations have made a great many new aliphatic syntheses possible because of their ready reactivity. 

The 2,4,6-triphenylpyrylium ion reacts with nitromethane to give the dienone 39. This is followed by an intramolecular nitro-aldol condensation forming 2,4,6-triphenylnitrobenzene 40. By way of the ring-opened phosphorane 41, action of phosphorylidene produces the 2-substituted 1,3,5-triphenyl-benzene 42 ... 

Interestingly, nitromethane (CH3NO2) undergoes aldol condensation with meth-anal (formaldehyde, H2CO) in the presence of base to produce the nitrotriol, 2-hydroxymethyl-2-nitro-l,3-propanediol (Problem 9.15). The process by which it forms is presumed to be analogous to that seen in the formation of pentaerythritol (2,2-dihydroxymethyl-l,3-propanediol), Scheme 9.44, from the reaction between ethanal (acetaldehyde, CH3CHO) and methanal (formaldehyde, H2CO). 

The lactone (6), prepared by a stereocontrolled aldol condensation followed by resolution of the enantiomers, has been converted into methyl cladinoside (7). Some branched 5-amino-2,5,6-trideoxy-hexose derivatives (eg (8)) have been prepared from a l,5-dideo3ty-pent 2-ulose derivative. Treatment of levoglucosenone with a basic excess of nitromethane has afforded products (9) and (10), whereas... 

From Achiral Non-carbohydrates. - Racemic methyl 2-acetamido-2-deoxy-threofuranoside 69 was the major epimer formed as indicated in Scheme 19 from the dihydroisoxazole 68, prepared by condensation of nitromethane and chloroacetaldehyde. 2-Amino-2-deoxy-L-erythrono-1,4-lactone 73 was synthesized by enzymatic aldol condensation of 70 and 71 to give a 92 8 mixture of erythro- and rAreo-adducts, from which 72 was obtained by crystallization (Scheme 20). The lactone 74, an intermediate in previous syntheses of A -trifluoroacetyl-L-acosamine and -L-daunosamine (Vol.l4, p.72, ref. 14), was prepared from methyl sorbate as before, but by a rather inefficient route. 

The general mechanism is believed to involve iminium ions as the active electrophiles, rather than the amine simply acting as a base for the aldol condensation. Kinetic evidence in support of this mechanism has been developed in the case of condensation of aromatic aldehydes with nitromethane." Knoevenagel condensation conditions frequently involve both an amine and a weak acid. The reactive electrophile is probably the protonated form of the imine, since this is a more reactive electrophile than the corresponding carbonyl compound. 

Aldol condensation of 39 with nitromethane afforded the nitrovinylindole 4 0, which was then reduced with sodium borohydride in methanol followed by acid treatment (41) in a one-pot procedure to bring about the stereospeciHc cyclization to the tricyclic trans isomer 41. This irons isomer 41 was readily isomeiized to the cis isomer 42 by treatment with sodium methoxide in methanol, while the reverse isomerization of cis 4 2 to trans 41 was achieved by treatment with triethylamine in benzene (37). 

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). 

MISCELLANEOUS BENZOHETEROCYCLES Partial reduction of lactone 166 (using for example diisobutylaluminum hydride in the cold) affords lactol 167. Condensation with nitromethane leads to the corresponding alkylated tetrahydrobenzopyran 170. The sequence probably starts by aldol reaction of the hydroxylactone form of the lactol (168) with nitrome thane to give the vinyl nitro intermediate 169 ... 

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 penultimate item in Table 9.5 is illustrative of the more general aldol-type condensation process. The addition of nitromethane (CH3NO2) to benzenecarboxy-aldehyde (benzaldehyde, CeHsCHO) demonstrates that addition to the carbonyl group of an aldehyde only requires a sufficiently nucleophilic addend. 

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