Nitromethane reaction with benzaldehyde

Trioxymethylene, condensation with nitromethane, 41, 67 Triphenyldnnamylphosphonium chloride, from triphenylphosphine and cinnamyl chloride, 40, 36 reaction with benzaldehyde and lithium ethoxide to yield... 

The addition of nitromethane to cyclohexanone was completed in 1 h at 0 °C, affording product 32 in 82% yield as expected the reaction with benzaldehyde afforded the corresponding product 33 in 95% yield in only 5 min at the same temperature. However, the reaction was not generally applicable as other aliphatic ketones and acetophenone did not react. 

Alternatively, compound 54 was converted to the corresponding benzylidene acetal, upon reaction with benzaldehyde dimethylacetal, whose dithioacetal was hydrolyzed to give 58, which was reacted with nitromethane to afford 59 in 83% yield and >99 1 diastereose-lectivity. Treatment of 59 with ethanethiol and stannous chloride effected removal of the benzylidene acetal, without dehydration of the 3-hydroxynitro functionality, to afford the corresponding triol in 82% yield. Protection of the triol with excess TBSOTf afforded a 91% yield of the corresponding TBS ether. Selective removal of the phenolic TBS group was effected by treatment with CSA in methanol to afford 56 in 88% yield, which upon similar sequence of reactions as shown above afforded 60 as the sole cyclization product in 90% yield. 

As in the case of other groups which activate adjacent CH6, the nitro group in aliphatic nitro compounds soon acquired importance in preparative organic chemistry, particularly for condensation reactions. The condensing agents are normally bases. Thus nitromethane will react with benzaldehyde to give first a nitro-alcohol and then a nitro-olefin (Priebs, 188425) ... 

Various nitro compounds have been condensed with carbonyl compounds in reactions catalyzed by alkaline earth metal oxides and hydroxides 145). It was found that the reactivities of the nitro compounds were in the order nitro-ethane > nitromethane > 2-nitropropane, and those of carbonyl compounds were propionaldehyde > isobutyraldehyde > pivalaldehyde > acetone > benzaldehyde > methyl propionate. Among the catalysts examined, MgO, CaO, Ba(OH)2, and Sr(OH)2, exhibited high activity for nitroaldol reaction of nitromethane with propionaldehyde. In reactions with these catalysts, the yields were between 60% (for MgO) and 26% (for Sr(OH)2) at 313 K after 1 h in a batch reactor. On Mg(OH)2, Ca(OH)2, and BaO, the yields were in the range of 3.8% (for BaO) and 17.5% (for Mg(OH)2). Investigation of the influence of the pre-treatment... 

Application of Accelerating Rate Calorimetry (ARC) in Evaluating a Reaction with a Potentially Explosive Nitro Compound. One of our process development projects required the preparation of 2-hydroxy-l-nitro-2-phenylethane via the addition of sodium methoxide to a mixture of one mole of benzaldehyde and one mole of nitromethane in methanol (Scheme 1). 

Condensation of A-rerf-butoxycarbonylpelletierine (12) with benzaldehyde proceeded smoothly in aqueous methanolic sodium hydroxide to afford the enone 14 in 90% yield. Deprotection with either hydrogen chloride in nitromethane or trifluoroacetic acid in methylene chloride furnished 9 (Ar = C6H5), which had been considered as an intermediate in pathway a (Scheme 1). The cyclization of 9 (Ar = C6H5) in CDC13 without base, monitored by H-NMR, revealed that the reaction was completed after 3 days to give the cis isomer 15 as a sole product. None of the trans isomer 16 was formed under these conditions even after 2 weeks. 

Nitrostyrene has been obtained in small yields by a number of methods, but the only practical methods of preparation start with benzaldehyde and nitromethane. The condensation was first accomplished by heating nitromethane and benzaldehyde in sealed tubes with anhydrous zinc chloride.1 Good results are obtained by adding small amounts of a primary aliphatic amine to a mixture of nitromethane and benzaldehyde,2 but it takes a number of days for the reaction to go to completion. Undoubtedly the best method is the use of alkali to condense benzaldehyde and nitromethane, as first discovered by Thiele.3... 

Reaction of [Cu(en)2]2+ with benzaldehyde and nitroethane forms the 5,7,12,14-tetrabenzyl-6,13-dinitro-6,13-dimcthyl-cyclam80 and reaction with ethanal and nitromethane forms the 5,7,12,14-tetramethyl-6,13-dinitro-cyclam compound (87).81... 

In the presence of piperidine in benzene, benzaldehyde reacts with diethyl (nitromethyl)-phosphonate to afford at 67% yield of diethyl (2-hydroxy-l-nitro-2-phenylethyl)phos-phonate, presumably as a mixture of diastereoisomers. However, a similar reaction with 4-nitrobenzaldehyde leads to phosphorus-carbon bond cleavage and the formation of 1-nitro-2-(4-nitrophenyl)ethane. The converse procedure, i.e. a reaction which involves a nitroalkane and an (oxoalkyl)phosphonic diester, is also subject to certain restrictions. The base-catalysed nucleophilic additions of nitromethane to dialkyl acetylphosphonates (Scheme 7 R = Me) to give dialkyl [(1-hydroxy-l-nitromethyl)alkyl]phosphonates have... 

The condensation of aromatic aldehydes with nitroalkanes over alkaline-ion exchanged zeolites affords nitroalkenes directly (88). Thus, in the reaction of benzaldehyde and 4-chlorobenaldehyde with nitromethane, CsNaX gave the corresponding nitroalkenes in 68 and 80% yields, respectively at 413 K. 

Table 1.8 Nitroaldol reactions of nitromethane with benzaldehyde using various catalysts."...

The title Diels-Alder (DA) addition reaction shown in equation 81195 has been reinvestigated recently196 by labelling 223 with 14C successively at C(i) and at C(2). The [2-14C]-l-nitro-2-phenylethene has been obtained in the reaction of [7-14C]benzaldehyde with nitromethane (equation 82). 

In the Mukaiyama aldol additions of trimethyl-(l-phenyl-propenyloxy)-silane to give benzaldehyde and cinnamaldehyde catalyzed by 7 mol% supported scandium catalyst, a 1 1 mixture of diastereomers was obtained. Again, the dendritic catalyst could be recycled easily without any loss in performance. The scandium cross-linked dendritic material appeared to be an efficient catalyst for the Diels-Alder reaction between methyl vinyl ketone and cyclopentadiene. The Diels-Alder adduct was formed in dichloromethane at 0°C in 79% yield with an endo/exo ratio of 85 15. The material was also used as a Friedel-Crafts acylation catalyst (contain-ing7mol% scandium) for the formation of / -methoxyacetophenone (in a 73% yield) from anisole, acetic acid anhydride, and lithium perchlorate at 50°C in nitromethane. 

Examples are the formation of diacetone alcohol from acetone [reaction type (A)] catalysed by barium or strontium hydroxide at 20—30°C [368] or by anion exchange resin at 12.5—37.5°C [387], condensation of benzaldehyde with acetophenone [type (C)] catalysed by anion exchangers at 25—-45°C [370] and condensation of furfural with nitromethane [type (D)] over the same type of catalyst [384]. The vapour phase self-condensation of acetaldehyde over sodium carbonate or acetate at 50°C [388], however, was found to be first order with respect to the reactant. 

A mixture of 22 g 2,5-dimethoxypropylbenzene, 23 g POCl3 and 22 g N-methylformanilide was heated on the steam bath for 1.5 h. The hot, dark reaction mass was poured into 1 L H20, which allowed the eventual separation of 2,5-dimethoxy-4-(n)-propylbenzaldehyde as a clear yellow oil weighting 14 g. Although the homologous 4-ethyl and 4-butyl benzaldehydes were clean crystalline solids, this propyl homologue remained an oil. Gas chromatographic analysis showed it to be about 90% pure, and it was used as obtained in the nitrostyrene steps with either nitromethane (here) or nitroethane (under DOPR). 

The last compound was prepared as follows the hydroxyl groups of 3,4-dihydroxy-benzaldehyde was protected using t-butyldimethylsilylchloride (1). 100 mg (0.26 mmol) of 3,4-di(t-butyl-methylsiloxy)benzaldehyde was dissolved in 1 ml tetrahydrofurane under atmosphere of argon at -40°C, and 0.30 ml of metal complex from (S)-6,6 -bis(triethylsilylethynyl)-l,l-dihydroxy-2,2 -binaphtalene (2) mixed with a solution of n-butyllitium in hexane.After stirring for 30 minutes, 79.4 mg (1.3 mmol) of nitromethane was added dropwise to the mixture. After 67 hour reaction time, 2 ml of 1 N aqueous solution of hydrochloric acid added to stop the reaction. Product was extracted with 50 ml ethyl acetate, dehydrated with anhydrous sodium sulfate and concentrated within evaporator followed by silica gel chromatography (n-hexane/acetone = 10/1), after which (R)-l-(3,4-di(t-butyldimethylsiloxy) phenyl)-2-nitroethanol with an optical purity of 92% e.e. was obtained in a yield of 93%. 

The lanthanoid and group 3 metals, the so-called rare earth elements, are generally regarded as a group of 17 elements with similar properties, especially with respect to their chemical reactivity. However, in the above-mentioned catalytic asymmetric nitroaldol reactions, pronounced differences were observed both in the reactivity and in the enantioselectivity of the various rare earth metals used.29 For example, when benzaldehyde (54) and nitromethane (12) were used as starting materials, the EuLB complex gave 55 in 72% ee (91% yield) compared to 37% ee (81% yield) in the case of LLB (-40 °C, 40 h). The unique relationship... 

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. 

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). 

Benzyl chloride can be converted into benzaldehyde by treatment with nitromethane and base. The reaction involves initial conversion of nitromethane into its anion, followed by Sn2 reaction of the anion with benzyl chloride and subsequent E2 reaction. Write the mechanism in detail using curved arrows to indicate the electron flow in each step. 

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