Dehydration nitroaldols

The Henry (nitroaldol) reaction was reported under very mild reaction conditions, in aqueous media using a stoichiometric amount of a nitroalkane and an aldehyde, in NaOH 0.025 M and in the presence of cetyltrimethylammonium chloride (CTAC1) as cationic surfactant (Eq. 8.94) 240 Good to excellent yields of (i-nitroalkanol are obtained. Under these conditions several functionalities are preserved, and side-reactions such as retro-aldol reaction or dehydration of 2-nitroalcohols are avoided. 

Nitroalkanols are intermediate compounds that are used extensively in many important syntheses 142). They can be converted by hydrogenation into / -aminoalcohols, which are intermediates for pharmacologically important chemicals such as chloroamphenicol and ephedrine. They are obtained by Henry s reaction by the condensation of nitroalkanes with aldehydes. The classical method for this transformation involves the use of bases such as alkali metal hydroxides, alkoxides, Ba(OH)2, amines, etc. 142-144). However, these catalysts give predominantly dehydrated products—nitroalkenes— which are susceptible to polymerization (Scheme 16). The reaction proceeds by the nucleophilic addition of the carbanion formed by the abstraction of a proton from the nitro compound to the carbon atom of the carbonyl group, finally forming the nitroaldol by abstraction of a proton from the catalyst. 

The nitroaldol may be dehydrated to a nitroalkene in the case of nitroaldols arising from aromatic aldehydes this dehydration reaction occurs spontaneously as is illustrated in the preparation of co-nitrostyrene (Expt 6.136). The nitroalkenes are important dienophiles in the Diels-Alder reaction (Section 7.6, p. 1117). An example of the Michael addition reaction is illustrated in the syn-... 

Nitroalkenes. Nitroaldols are dehydrated to nitroalkenes by reaction with DCC and a catalytic amount of CuCl in ether at 20° (equation I).1... 

The ,/J-LinsaUirated-o -nitrosulfone intermediate, 113, in the tandem nitroaldol/ dehydration reactions was successfully intercepted with various thiols, 117, added to the reaction mixture prior to the addition of aldehyde, 118. In four cases examined, little if any of 112 was formed. The initial products 119-122 were a mixture of diastereomers, although after crystallization, a single diastereomer was obtained in each case with good yields (Scheme 39). 

The preparation of 2-nitro alcohols was also achieved by reaction of equimolar amounts of nitroal-kanes and aldehydes in the presence of alumina-supported potassium fluoride without solvent (equation 12). A peculiar feature of diis method were reactions performed with aromatic aldehydes, such as benz-aldehyde and furaldehyde, which allowed preparation of the corresponding 2-nitro alcohols without dehydration of these into nitroalkenes, as observed when nitroaldol reactions were performed with organic bases in homogeneous medium or with alumina alone. 

The most recent entry to bicyclic P-lactam compounds through this approach, has been introduced by Barrett and his coworkers [120] by using an intramolecular Michael type reaction of a Af-silyl p-lactam to a nitroalkene induced by fluoride ion (Scheme 45). Namely, the known P-lactam 299 [32a] readily prepared from CSI addition to 1,5-hexadiene, was protected by using TBDMSCI and DIPEA to produce the p-lactam 300. Subsequent ozonolysis, gave the aldehyde 301. Henry reaction of the aldehyde 301 with (phenylthio)-nitromethane furnished, after dehydration of the resulting nitroaldol, the nitroalkene 302 which smoothly cyclized to the carbapenam 303 in the presence of... 

A more traditional reaction is the condensation of nitroalkanes with carbonyl compounds (Henry reaction). Nitroaldol products can be isolated but are more commonly oxidised or dehydrated. The nitroaldol products formed from methyl-8-nitrooctanoate and aldehydes, in the presence of Amberlyst A21 resin, were oxidised with... 

Similar Henry-type condensations were utilised in syntheses of heterocyclic derivatives from o-hydroxy-benzaldehydes. Condensations with bromonitromethane afforded 2-nitrobenzoC ]furans after dehydration of intermediate nitroaldols in refluxing acetic anhydride,whilst Michael additions to nitroalkenes prior to... 

Nitroaldol Reaction (The Henry Reaction). The nitroaldol reactions (or Henry reaction) is an aldol type reaction between a nitro compound and a carbonyl compound. The primary aldol products may be dehydrated to the corresponding alkenes. 

CJNitromethane is a versatile building block. It is most useful as a nucleophilic labeled Ci-building block for major homologation processes, such as nitroaldol reactions and Michael additions, and there exist several valuable methods for the subsequent transformation of the nitro group into further interesting functionalities. In addition, nitroolefins resulting from the nitroaldol reaction and subsequent dehydration are excellent Michael acceptor molecules and Diels-Alder dienophiles. 

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