Benzylidene compounds

Substitution of a phenyl residue in the 4-position of the selenazole ring causes only a minor alteration in the position of the absorption maximum. By contrast, the benzylidene compounds are markedly bathochromically shifted compared to the isopropylidene derivatives. Thus the absorption is caused by the whole of the conjugated system, which can be compared to that found in amino derivatives of... 

Scheme 7 shows formation of a new fused ring described by Mohan and Kataria <1998IJB819>. These authors reported that treatment of the benzylidene compound 19 with hydrazine hydrate in acetic acid in the presence of sodium acetate gave the tricyclic fused pyrazoline derivative 20 in acceptable yield (61%). The two hydrogen atoms at the site of the ring closure were found to be as. 

Aromatic aldehydes react very easily with tetramic acid under acidic conditions to give 3-benzylidene compounds (41). The yields are moderate, because often there are subsequent reactions. As a,/3-unsaturated carbonyl compounds, (41) react in a Michael addition with excess tetramic acid to form (67), but it can also react with other acyclic and cyclic 1,3-dicarbonyl compounds. In these reactions the aryl substituents may vary over a wide range. Thus, (67) and (68) can be cyclized with ammonium acetate to afford pharmacologically interesting compounds (70) and (71) (90TH1). The latter are dihydropyridines. Curiously, (69) does not cyclize under these conditions. (See Fig. 32.)... 

With aromatic and heteroaromatic aldehydes,193 4-oxo-6,7,8,9-tetra-hydro-4T/-pyrido[l,2-a]pyrimidines yielded the 9-arylmethylene derivatives,133,266 whereas with glyoxylic acid the 9-carboxymethylene derivative was formed.266,267 The primary addition product (237) could be isolated from the reaction mixture of ethyl 6-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrimidine-3-carboxylate and benzaldehyde. On dehydration the addition product (237) gave the 9-benzylidene compound.266 The 9-carboxymethylene derivatives may be transformed by catalytic hydrogenation to the 9-acetic acids, which can be esterified.266,267... 

Keywords aromatic aldehyde, active methylene compound, Knoevenagel condensation, microwave irradiation, benzylidene compound... 

In this section, consideration will be given to the actual processes of acetal- or ketal-formation and not to the more indirect methods by which acetals and ketals of the polyhydric alcohols may be synthesized from compounds (e.g. derivatives of the monosaccharides) containing preformed alkylidene or arylidene groupings. The condensation of a carbonyl compound with a glycol is facilitated by acidic catalysts, and, since the reaction is reversible, by dehydration. The catalysts most frequently employed are concentrated sulfuric, hydrochloric and hydro-bromic acids, gaseous hydrogen chloride, zinc chloride and cupric sulfate others are phosphorus pentoxide, sulfosalicylic acid, and anhydrous sodium sulfate. The formation of benzylidene compounds is promoted less efficiently by phosphorus pentoxide than by either concentrated sulfuric acid or concentrated hydrochloric acid 1" the reaction is assisted by chloro- and nitro-substituents on the aromatic nucleus, but hindered by methyl- and methoxy-groups.18... 

Notable progress in the structural analysis of methylene derivatives of the polyhydric alcohols resulted from the investigations of Hann, Hudson and their co-workers26 80,40-4 into the behavior of these compounds during acetolysis. It was found that a mixture of acetic anhydride, acetic acid and 1-2% sulfuric acid ruptures preferentially any methylene bridge which spans a primary and a secondary position, giving the acetate ester of the primary hydroxyl and the acetoxymethyl ether of the secondary hydroxyl subsequent treatment with sodium methoxide removes each of these substituents. Under similar conditions, the acetolysis of a benzylidene compound results in the replacement of the arylidene residue, wherever it is located in the molecule, by two acetyl groups.16 29 47 48... 

All the glucopyranosides substituted to restrict complex formation to the 2,3 position showed marked evidence of reaction with cuprammonium. This behavior would be compatible with ring conformations Cl, B2, and 3B except that three of the substances, the 4,6-ethylidene and 4,6-benzylidene compounds, could not exist in either the B2 or 3B conformations for steric reasons because of the spatial requirements of the second ring hence, these three substances must exist in the Cl conformation. 

The (h and m.-mirohmzoic, dm, on electrolysis, deja themselves like the free acids Jatfermann). The latter mv tigutor,3 by preparing the benzylidene compound by the mm method, proved the intermediate formation of the hydros amine phase in the reduction of the m-arid. 

Methylation with dimethyl sulfate in alkali gave the methyl derivatives 28 and 29. Although formaldehyde attacks at N-2, aldol condensation of 10 with benzaldehyde gave the 3a-hydroxybenzyl compound (30) which is dehydrated to the 2-acetyl-3-benzylidene compound (31) with acetic anhydride.27 With acid anhydrides the2-acyl derivatives are obtained however, with acid chlorides in pyridine or dimethylaniline the bicyclic ketone (32) is formed.31 Despite the occurrence of the bicyclic product (32) and the bicyclic intermediate (13) there is no evidence for the existence of a bicyclic tautomer of 10.37... 

For the hydrolysis, the benzylidene compound is dissolved in 300 cc of a warm 2 per cent soda ash solution, and the solution is filtered to remove a residue of iron carbonate. The solution is then treated with 5 cc. concentrated sodium hydroxide solution (40° B6) and heated with stirring for 1 hour on a water bath. The solution becomes cloudy and the aldehyde separates in oily drops which solidify on cooling. It is dissolved in 1 1 hydrochloric acid and reprecipitated with 2 N soda solution. The yield is 13.2 grams of dry aldehyde melting at 81° (72 per cent calculated on die base used, or 94 per cent calculated on the unrecovered base). The aldehyde can be recrystallized from ligroin. It is used, for example, in the preparation of wool blue 5B (see page 305). 

The spectra characteristically display a single band at relatively low field (7.9-8.4 ppm). For the benzylidene compounds the band is a sharp singlet, for the cinnamylide compounds the band ap-pears as a sharp triplet or doublet of doublets. 

Pyrazolones (154) and isoxazolones (155) can also be used in the Knoevenagel reaction. Thus condensations with aliphatic aldehydes, aromatic aldehydes and ketones in the presence of ethylenediammon-ium diacetate or other typical catalysts provide the corresponding alkylidene and benzylidene compounds in good yields (for stereochemistry see Section 1.1A new method involves the use of dicyclohexylcarbodiimide at 20 C without an additional catalyst. ... 

In addition to natural products, a multitude of biologically active unnatural compounds have also been synthesized using the Knoevenagel condensation. A few recent examples are given here. In an attempt to obtain enantiomerically pure 1,4-dihydropyridines as calcium channel antagonists, (/ )-sulfmylpropan-one (320) was condensed with 2-chlorobenzaldehyde in acetonitrile with piperidine as catalyst to provide exclusively the ( )-benzylidene compound (321). Formation of the (5)-l,4-dihydropyridine (323) as a... 

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