2-Hydroxy-substituted benzaldehydes, reaction

The synthesis of functionalized 8-hydroxy-l,2,3,4-tetrahydroquinolines 77 has been reported by Dai and co-workers [119] in moderate to good yields via an aza-Diels-Alder reaction of an 2-aminophenol, a substituted benzaldehyde and a cyclic alkene catalyzed by TFA under controlled microwave irradiation in acetonitrile. In general, when electron deficient aromatic aldehydes were used, the adducts could be isolated in 39-59% yields with a predominance of the trans isomer (Scheme 58). 

Lrthreonine aldolase (L-threonine acetaldehyde-lyase) catalyzes the reversible condensation of acetaldehyde and glycine to form L-threonine. The enzyme has been shown to be an activity distinct from serine hydroxy-methyltransferase that also catalyzes the above reaction (85,86). The substrate specifically of the adolase has been demonstrated to be flexible with respect to the aldehyde involved. The enzyme has been shown to form phenylserine derivatives from substituted benzaldehydes and glycine (86). 

The methodology has been successfully apphed to the synthesis of diphenyl a-chloro-4-pyridylmethylphosphonate, which was obtained in 80% yield from diphenyl a-hydroxy-4-pyridyl-methylphosphonate with POCI3 and catalytic quantities of diethylaniline. The a-chlorophosphonate products react with various 4-substituted benzaldehydes in the presence of t-BuOK (2 eq) to produce, by the Homer-Wadsworth-Emmons reaction, 4-pyridylacetylenes showing interesting nonlinear optical properties (Scheme 3.16). °... 

The Cs+-exchanged zeolites, which are the most basic, have been shown to catalyse the Claisen Schmidt condensation between substituted 2-hydroxy-acetophenones and substituted benzaldehyde to give the 2 -hydroxychalcone structure (Reaction 3).30... 

Hydroxy- and cpoxyalkyl-phosphonic and phosphinic acids, and related sulphur or selenium co/npou/jt/s-Conventional reactions between 1,2-propadienylphosphinic acid and substituted benzaldehydes yield [(a-hydroxybenzyl)( 1,2-propadienyl)]phosphinic acids. Reactions between (1-oxoalkyl)pho.sphonic esters and nitromethane in the pre.sence of a base (K2CO3) yield the esters (281). The compounds (282 n = 1 or 2), and (283) are obtainable conventionally from the cyclic ketone and dimethyl... 

A one-pot two-step synthesis of hydroxystilbenes with trans selectivity was developed through a modified Perkin reaction between benzaldehydes and phenylacetic acids bearing 4- or 2-hydroxy substitution at the aromatic ring [67]. The reaction was performed under mild conditions in the presence of piperidine-methylimidazole and polyethylene glycol under microwave irradiation. As a result, 71% yield of ( )-4-chloro-4 -hydroxy-3 -methoxystilbene from 4-hydroxy-3-methoxybenzaldehyde and 4-chlorophenylacetic acid was obtained. A microwave-induced one-pot process for the preparation of arylethenes has been patented [118]. For the preparation of a series of arylethenes (I R -R = H, OH, OMe, AcO, halo, NO2 R, R, R = OH, AcO R= H, substituted aryl), reaction of 2- or 4-hydroxy substituted cinnamic adds or derivatives in the presence of a base, under reflux or microwave irradiation, has been used. For example, a mixture of a-phenyl-4-hydroxy-3-methoxycinnamic acid, NaHC03, methylimidazole, and polyethylene glycol was microwaved at 200 W and 180 °C for 10 min to give 96% 4-hydroxy-3-methoxystilbene. 

The Keglevich group has continued to deal with environmentally friendly and P-heterocyclic chemistry. The solid liquid phase alkylation of P=0-functionalised CH acidic compounds was accomplished under phase transfer catalytic and microwave (MW) conditions." a-Hydroxy-benzylphosphine oxides were synthesized by the addition of diphenylphosphine oxide to the carbonyl group of substituted benzaldehydes under MW conditions." The double Kabachnik-Fields (phospha-Mannich) reaction was utilized in the preparation of bis(phosphinoxidomethyl)amines. The Diels Alder cycloadditions of 1,2-dihydrophosphinine oxides and subsequent... 

Photodecarboxylation of the dissociated form of a-hydroxy-substituted arylacetic acids and related substrates occurs from the singlet excited state (SJ and leads to the corresponding benzyl alcohols with high quantum yields (O = 0.2 to 0.7) via a heterolytic mechanism (Scheme 2). Photodecarboxylation of some diarylacetic acids (Scheme 2) also proceeds from Sj via heterolytic mechanism. It is remarkable that these compounds show dramatic differences in their relative photodecarboxylation efhciency (O = 0.04 to 0.6). The reaction is enhanced when a cyclic delocalized carbanion with 4n electrons is formed. By contrast, photodecarboxylation of m- and p-nitrophenylacetic acids in aqueous solutions occurs via a heterolytic mechanism from Tj." The photodecarboxylation of pyruvic and benzoylformic acids takes place with high quantum yields ( 5 > 0.6) in aqueous solutions, to give acetaldehyde and benzaldehyde, respectively as the primary photoproducts. On the other hand, 2-, 3-, and 4-pyridinylacetic acids undergo photodecarboxylation in aqueous solutions via a heterolytic mechanism from their zwitterionic forms. 

By condensing carbon oxysulfide with o-aminOnitriles the corresponding 2-hydroxy-5-aminothiazoles can be obtained. In the presence of benzaldehyde or its substituted derivatives the reaction leads to 5-benzy-lideneaminothiazole derivatives (218) in good yields (Scheme 114 and Table 11.35) (393, 442). However, the reaction fails with or-amino acetonitrile (206), R = H (317). The 2-alkoxy analogs (220), R = Me, Et, Pr, Bu, vinyl, were similarly obtained from 219 and benzylideneamino acetonitrile (Scheme 115a) (393). 

The stereoselective synthesis of c/.v-fused pyrano and furanobenzopyran can be achieved through the one-pot three-component reaction of o-hydroxy benzaldehyde, aromatic amines, and cyclic enolethers in the presence of catalytic amounts of Bi(OTf)3 (10 mol%) in air and the moisture-stable ionic liquid [bmim]PF6 [116]. The reaction of salicilaldehyde, aniline and 2,3-dihydrofuran furnishes the c/.v-fused furanochroman. In a similar fashion, various substituted salicilaldehydes and... 

Of course, aziridines can also be synthesized by the ring-closing reactions of appropriately substituted amines. For example, halohydrins of type 142 are converted to iV-hydroxy-aziridines 144 by treatment with hydroxylamine derivatives, followed by base-catalyzed intramolecular Sn2 reaction of the intermediate p-haloaminoesters 143 under phase-transfer conditions <03TL3259>. A -Bromoethylimines 146, formed from the reaction of benzaldehyde derivatives (e.g., 145) and 2-bromo-2-methylpropylamine hydrobromide, undergo nucleophilic attack by methoxide, followed by intramolecular displacement of bromide to form A -(a-methoxybenzyl)aziridines 147 <03TL1137>. 

The reaction of the formally dipole-stabilized carboanions with a variety of electrophiles gives 2,3-substituted thiiranes (Scheme 74). Ethyl jV,7V-dimethylthiocarbamate (209) undergoes lithiation to give (210), which readily reacts with benzaldehyde to give the thiirane (212) in 81% yield by way of the i -hydroxy adduct (211). The synthesis of thiirane (214) from n-pentyl-jV,jV-dimethyl-thiocarbamate (213) is shown in Equation (33) <82JOC3855>. 

On the synthetic side, single diastereomers of P-keto phosphine oxides have been generated from intermolecular acylation of phosphine oxides using either chiral esters or chiral phosphine oxides. In most cases, reduction of the ketone products was not affected by the presence of extra chiral centres. Addition of metallated phosphine oxides to proline-derived ketoaminals provides a new route to optically active P-hydroxy phosphine oxides. The P-hydroxy phosphine oxide 97 has been prepared by the caesium fluoride mediated reaction of silyl-substituted phosphine oxide 98 and benzaldehyde." The synthesis of two (E)-(6-hydroxy-2-hexen-l-yl)diphenylphosphine oxides (99) has been reported. The Horner-Wittig reactions of these compounds with various carbonyl compounds... 

The a proton of a substituted cyclopropane is also rendered acidic if the substituent is attached to the ring by C-P bonds. A few reports have appeared on a-substitution in such compounds.(Cyclopropyl)triphenylphosphonium bromide was converted to a (1-ethoxy-carbonylcyclopropyl)triphenylphosphonium salt 18 in 80% yield by sequential treatment with lithium diisopropylamide and ethyl chloroformate. Furthermore, some diethyl cyclopropyl-phosphonates were converted, in some cases in excellent yield, to diethyl (1-hydroxymethyl-cyclopropyl)phosphonates by treatment with lithium diisopropylamide followed by addition of an aldehyde." Thus, typically, diethyl 2-hexylcyclopropylphosphonate gave diethyl 2-hexyl-l-[hydroxy(phenyl)methyl] cyclopropylphosphonate (19b) in 90% yield on reaction with benzaldehyde. ° Other electrophiles such as acetone, acetyl chloride, acetic anhydride, and ethyl acetate, were not sufficiently reactive to undergo addition to the anion. 

Several routes to benz[c]acridines involve electrophilic aromatic substitution to form the heterocyclic ring. Thus, 9-nitrobenz[c]acridine results from the cyclisation of the 2-(l-naphtlylamino)benzaldehyde derived from 1-naphthylamine and 2-fluoro-5-nitrobenzaldehyde (J. Rosevear and J.F.K. Wilshire, Austral. J. Qiem., 1981, 34, 839). The reaction between a ff-aryl-l-naphthylamine and acetic anhydride has been used to synthesise 9- and ll-hydroxy-7-methylbenz[c]acridines and cyclisation of partially reduced 2-(l-naphtltylamino)benzoic acid by phosphorus oxychloride affords the 7-chloro-l,2,3,4-tetralydro derivative (B.V. Lap et ai,y J. heterocyclic Chem., 1983, 20, 281). 

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