2-Ethyl-4-hydroxybenzaldehyde

In recent years there has been some interest in monastrol (62), a potentially important chemotherapeutic for cancer which acts as an inhibitor of mitotic kinesin Kappe and coworkers successfully synthesized racemic monastrol (62) using microwave-mediation in 60% yield from ethyl acetoacetate (6), 3-hydroxybenzaldehyde (63), and thiourea (3b) in the presence of PPE." ... 

Ethoxy-3-hydroxybenzaldehyde (isobourbonal) has been prepared in good yield (84%) by ethylation of 3,4-dihydroxybenzaldehyde [Benzaldehyde, 3,4-dihydroxy-] with diethyl sulfate [Sulfuric acid, diethyl ester] in dimethylformamide.2... 

Cyclocondensation of 2-amino-5-nitro-3-pyridinecarboxamide with 4-hydroxybenzaldehyde in the presence of ZnCl2 in refluxing diethylene glycol dimethyl ether gave the pyridopyrimidine 351 <1994MIP2056742>. Reaction of ethyl 2-(l-ethoxyethylidene)amino-4,5,6-trisubstituted-3-pyridinecarboxylate with A -(2-aminoethyl)morpholine in the presence of HCl gave the polysubstituted pyridopyrimidin-4(3/7)-one 352 <1997W09719946>. 

Di-ter2-butylphenol 2,4,5-Trichlorophenol Phenyl salicylate Methyl 4-hydroxybenzoate 4-Hydroxyacetophenone Ethyl 4-hydroxybenzoate 4-Hydroxybenzaldehyde Pentachlorophenol 4-Chloro-2-nitrophenol 4-Nitrophenol... 

A solution of 7.3 g of 3-ethoxy-5-hydroxy-4-methoxybenzaldehyde in 100 mL acetone was treated with 5 mL methyl iodide and 8.0 g finely powdered anhydrous K2CO, and held at reflux on a steam bath for 6 h. The solvent was removed under vacuum, and the residue was suspended in H20. After making this strongly basic, it was extracted with 3x50 mLCH,CL, the extracts were pooled, and the solvent removed under vacuum. The residual amber oil was distilled at 110-120 °C at 0.4 mm/Hg to yield 7.3 g of a white oil. This spontaneously set to white crystals of 3,4-dimethoxy-5-ethoxybenzaldehyde which had a mp of 49-49.5 °C. Anal. (CmHi (04) C,H. This same aldehyde can be obtained, but in a less satisfactory yield, by the ethylation of 3,4-dimethoxy-5-hydroxybenzaldehyde described under the preparation of metaproscaline (MP). 

SYNTHESIS A solution of 83 g bourbonal (also called ethyl vanillin, or vanillal, or simply 3-ethoxy-4-hydroxybenzaldehyde) in 500 mL MeOH was treated with a solution of 31.5 g KOH pellets (85% material) dissolved in 250 mL H,0. There was then added 71 g methyl iodide, and the mixture was held under reflux conditions for 3 h. All was added to 3 volumes of H20, and this was made basic with the addition... 

Keywords hydroxybenzaldehyde, ethyl acetate, Knoevenagel condensation, microwave irradiation, coumarin... 

The Schiff base obtained by (5)-(—)-tyrosine ethyl ester hydrochloride with 2-hydroxybenzaldehyde has been reported to be transformed, via Staudinger... 

The reaction of nitriles with aldehydes in the presence of the catalyst 9 proceeds under neutral conditions to give the corresponding a,/3-unsaturated nitriles [8]. It is noteworthy that even acidic substrates tolerate the reaction. Thus, the reaction of ethyl cyanoacetate with 4-hydroxybenzaldehyde gave ethyl ( )-2-cyano-3-(4-hy-droxyphenyl)-2-propenoate (10) in 98% yield [7, 8]. 

A mixture of ethyl cyanoacetate (0.113 g, 2.00 mmol), p-hydroxybenzaldehyde (0.249g, 2.20 mmol), and RuH2(PPh3)4 catalyst (0.06 mmol) in dry THF (0.5 mL) was stirred at room temperature for 24 h under argon. After removal of the solvent, the residue was purified by Kugelrohr distillation and chromatography on silica gel to give the product 10 in 98 % yield m.p. 176.2-177.2 °C. 

Sulfonation. The direct sulfonation of alkylaminotriphenylmethane dyes gives mixtures of substituted products. Although dyes containing anilino or benzylamino groups give more selective substitution, a sulfonated intermediate such as 3[(N-ethyl-N-phenylamino)methyl]benzenesulfonic acid (ethylbenzylanilinesulfonic acid) is the preferred starting material. However, Patent Blue V [354649-0], Cl Acid Blue 3, was made from 3-hydroxybenzaldehyde and two moles of diethyl aniline, followed by sulfonation of the leuco base and oxidation to the dye. FD C Green 2 [5141 -20-8/,... 

Di-f-butyl-4-hydroxybenzaldehyde (0.411 mol) and 300 ml acetic anhydride were mixed, then treated with 0.6 ml 70% perchloric acid, and stirred overnight at ambient temperature. The solution was then cooled in an ice bath and treated with the portionwise addition of 2000 ml ice water. An oil was formed, which solidified into brown lumps, and was washed with water and acetic acid, then dried under vacuum. The solid was boiled 10 minutes with 250ml ethyl alcohol containing 25ml 12M HC1, then cooled, and resolidified by pouring into 2000 ml water. The solid was washed with 1000 ml water and the product isolated in 99.4% yield as a light brown solid, mp = 65.2-74.5°C... 

Figure 2a. Chromatogram from lOul of a standard mixture. Peaks 1 = 2.5ug of 4-hydroxybenzyl alcohol 2 = 2.5ug of vanlllyl alcohol 3 = 2.5ug of 4-hydroxybenzo1c acid 4 = 0.5ug of 4-hydroxybenzaldehyde 5 = 2.5ug of vanillin 6 = 2.5ug of ethyl vanillin 7 = 0.5ug of coumarin.

SYNS BOURBONAL ETHAVAN ETHOVAN 3-ETHOXY-4-HYDROXYBENZALDEHYDE ETHYL-PROTAL FEMA No. 2464 4-HYDROXY-3-ETHOXY-BENZALDEHYDE PROTOCATECHLTC ALDEHYDE ETHYL ETHER QUANTROVANIL VANILLAL VANIROM... 

C15H17N306 (2R)-2-[(4-ethyl-2,3-dioxopiperazinyl)carbon 62893-24-7 25.00 1.3389 2 28673 C15H2202 3,5-di-tert-butyl-4-hydroxybenzaldehyde 1620-98-0 25.00 0.9856 2... 

The traditional intermolecular three-component version of the Biginelli reaction was utilized for the improved synthesis of racemic monastrol by A. Dondoni and co-workers. The one-pot Yb(OTf)3 catalyzed reaction took place between 3-hydroxybenzaldehyde, ethyl acetoacetate, and thiourea. Racemic monastrol was isolated in 95% yield and was resolved on a preparative scale using diastereomeric A/-3-ribofuranosyl amides. 

The activity of the ethanolic extract of both the pods and the seeds of M. oleifera is equivalent at the dose of 30 mg/kg. The ethyl acetate phase of the ethanolic extract of pods has more hypotensive potency at the same dose. The bioassay-directed fractionation ethyl acetate phase of the ethanohc extract of pods led to the isolation of thiocaibamate and isothiocyanate glycosides which are also the hypotensive compounds observed in M. oleifera leaves. Two new compounds, 0-[2 -hydroxy-3 -(2 heptei5rloxy)]-propyl undecanoate and O-ethyl-4-[(a-Z-rhamnosyloxy)-benzyl] carbamate along with methyl p-hydroxybenzoate and p-sitosterol are also isolated from the pods. The latter two compounds and /7-hydroxybenzaldehyde shows promising hypotensive activity (89). 

The moisture- and air-stable ionic liquids, l-butyl-3-methylimidazolium tetra-lluoroborate [bmim]BF and l-butyl-3-methylimidazolium hexafluorophosphate [bmim]PFg, were used as green recyclable alternatives to volatile organic solvents for the ethylenediaimnonium diacetate-catalyzed Knoevenagel condensation between aldehydes or ketones with active methylene compounds. As described by Su et al. [57], the ionic hquids containing a catalyst were recycled several times without decrease in yields and reaction rates. In the case of 2-hydroxybenzaldehyde, the reactions led to the formation of 3-substituted coumarin derivatives in high yields of up to 95% (Scheme 17.11). When ethyl cyanoacetate was used, 2-imino-27f-l-benzopyran-3-carboxyhc acid ethyl ester was formed. 

Enaminones react with 2-hydroxybenzaldehydes on prolonged heating under Dean and Stark conditions to give chromenes. / m -cyclization of aldehyde and hydroxy groups by reaction with ethyl chloroacetate in an alkaline medium produces a pyrano derivative in high yield. T erf-annulated naphthalenes and similar compounds are discussed in a review [390S]. 

Ortho and para hydroxybenzaldehydes, vanillin, ethyl vanillin, protocatechu-aldehyde, veratraldehyde and piperonal are the most important products. 

The more interesting challenge is the regiospecific preparation of para substitution products for the manufacture of 4-hydroxybenzaldehyde, vanillin and ethyl vanillin. 

Phenols can also be converted into ethers by the procedures described above. As example, the preparation of / -nitrophenyl ethers recorded by Weygand and Gabler751 is reproduced below—it can be carried out smoothly if ketones are used that boil higher than cyclopentanone. Other solvents used for such reactions are acetone, ethyl methyl ketone, dioxan,752 toluene, xylene, and chlorobenzene. Similar methods can be used for etherification of /7-hydroxybenzaldehyde with higher alcohols. 

This category comprises essentially Claisen or Knoevenagel reactions followed invariably by cyclisation. For example, a stirred mixture of 2-hydroxybenzaldehyde and ethyl cyanoacetate was treated at ambient temperarure with a 3 1 mixture of aluminium phosphate /alumina during 1 hour to give ethyl, 3-ethoxycarbonyl-2-iminobenzopyran, hydrolysis of which with dilute hydrochloric acid at 60°C afforded 3-ethoxycarbonylcoumarin (ref. 68). 

In the synthesis of coumarins by the von Pechmann reaction, a spiro-compound (251) was simultaneously formed from 4-chloro-2-methylphenol (and from 2,3,5-trimethylphenol). A possible mechanism for this reaction involves the formation of the lactone (252), which reacts with another molecule of the phenol. The condensation of the dicyano-ester (253) [obtained from malononitrile and ethyl cyanoacetate] with substituted o-hydroxybenzaldehydes yields substituted coumarinimines, e.g. (254).A series of 4,6,7-substituted coumarins have been prepared and assessed for their suitability in fluorescence labelling of polymers. Esters of the type PhCH CRCOaAr react with AICI3 to give coumarins, which are probably formed via dihydrocoumarins (255) by dearylation. ... 

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