Henry condensation

A two-step synthesis of indoles from o-nitrobenzaldehydes proceeds by condensation with nitromcthanc followed by reductive cyclization. Like the Leim-gruber Batcho method, the principal application of the reaction is to indoles with only carbocyclic substituents. The forniation of the o,p-dinitrostyrenes is usually done under classical Henry condensation conditions but KF/18-crown-6 in propanol was found to be an advantageous reaction medium for acetoxy-substituted compounds[1]. The o,p-dinitrostyrenes can also be obtained by nitration of p-nitrostyrenes[2]. 

Another approach is based on the Henry condensation of activated primary AN... 

Yet another approach to the synthesis of five-membered cyclic nitronates (5) is based on the Henry condensation of a-halo-substituted aldehydes (9) with primary AN followed by cyclization of nitroaldols (Scheme 3.14, Eq. 4) to give five-membered nitronates containing the hydroxy group at the C-4 atom. 

Many of the nitronate salts of polynitroaliphatic compounds, particularly salts of gem-nitronitronates, exhibit properties similar to known primary explosives. Consequently, the storage of such salts is highly dangerous. Treatment of these nitronate salts with formaldehyde yields the corresponding methylol derivative via the Henry condensation. These methylol... 

The Henry condensation of nitroform and terminal dinitromethyl compounds with formaldehyde and other aldehydes, followed by nitration of the resulting alcohol functionality, has been used to synthesize numerous explosives. The nitrate esters (104), (105), (106) " and (107)155 ij yg ijggjj synthesized from the action of absolute nitric acid on the parent alcohols. In a similar manner, NMHP (109) is synthesized from the condensation of TNHP (108) with formaldehyde, followed by O-nitration with absolute nitric acid. ... 

Table 6 a,a-Difluoroalkyl Ketones Synthesized by Henry Condensation 12-27 ... 

Drew, K N, Gross, P H, C-glycoside syntheses. II. Henry condensations of 4,6-0-alkylidene pyranoses with a 1,3-proton transfer catalyst — a route to blocked aminomethyl-C-glycosides, Tetrahedron, Al, 6113-6126, 1991. 

Since silica is such a common support for immobilization, the effect of the weakly acidic silanol groups has been studied. A cooperative silanol effect is thought to improve the catalytic activity of mesoporous silica-supported amines in base-catalyzed reactions such as the nitroaldol (Henry) condensation [6, 7], Knoevenagel condensation [6, 8,9], and Michael addition [6]. Thus immobilizing amines onto supports with stronger acid groups could be expected to further increase the catalytic activity. 

A general route for the regiospecific synthesis of 3-alkylbenzopyran-l-ones, which occur in natural products, is based upon the formation of nitroalkyl-susbtituted isobenzofuranones from Henry condensation of nitroalkanes with phthalaldehydic acids. 

Phiasivongsa, P., Samoshin, V. V., Gross, P. H. Henry condensations with 4,6-O-benzylidenylated and non-protected D-glucose and L-fucose via DBU-catalysis. Tetrahedron Lett. 2003,44, 5495-5498. 

The formation of trisubstituted cyclohexenecarbaldehyde is a result of subsequent Michael addition, Henry condensation, Michael addition, and aldol condensation. Under classical conditions, at room temperature, the product was obtained in 25% of yield and >99% ee after 7 days. In comparison, when the reaction was performed with microwave irradiation at 60 °C for 5h the yield increased to 45% and the ee was still very high (>99% ee). Other aromatic nitroalkenes were also tested under the MW conditions, giving 25-40% yields and high enantioselectivi-ties (89-99% ee). 

A similar organocatalytic quadruple domino Friedel-Crafts/Michael/Michael/ aldol condensation reaction initiated by Friedel-Crafts reaction of indole to acrolein was also developed by Enders et al. [48], as well as a microwave-assisted qnadruple cascade organocatalytic Michael/Henry condensation/Michael/aldol condensation anploying acetaldehyde and nitroalkenes as substrates [49]. 

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