Salicylaldehyde, reactions

Salicylaldehyde, reaction with chloro-acetic acid, 46, 28... 

Many preparative methods have been used, with variable success oxidative decarbonylation of Cr(CO)6 by the ligand,1093,1094 reaction of the appropriate amine with [Cr(sal)3J (salH is salicylaldehyde), reaction of the ligand, either produced in the reaction mixture or preformed,1095 with hydrated or anhydrous CrCl3, hydrated Cr111 acetate,1096 or [CrCU(THF)3],1097-1099 and aerial oxidation of the chromium(II) cpmplex produced in sifu.1099-1101 No well-established chromium(II) complexes, except of a few /3-keto amines (Section 35.3.9.1), have been isolated. 

Salicylaldehyde gives a yellow coloration and forms salicylic acid very slowly. Cannizzaro s reaction is also given by formaldehyde but, owing to the difficulty in isolating the products, is not used as a test. 

Action of sodium hydroxide. Does not undergo the Cannizzaro reaction. It dissolves in dil. NaOH solution, giving a yellow solution from which the aldehyde is precipitated unchanged on acidification. If heated with cone. NaOH solution, salicylaldehyde slowly undergoes atmospheric oxidation to salicylic acid. 

In the strongly basic medium, the reactant is the phenoxide ion high nucleophilic activity at the ortho and para positions is provided through the electromeric shifts indicated. The above scheme indicates theorpara substitution is similar. The intermediate o-hydroxybenzal chloride anion (I) may react either with a hydroxide ion or with water to give the anion of salicyl-aldehyde (II), or with phenoxide ion or with phenol to give the anion of the diphenylacetal of salicylaldehyde (III). Both these anions are stable in basic solution. Upon acidification (III) is hydrolysed to salicylaldehyde and phenol this probably accounts for the recovery of much unreacted phenol from the reaction. 

Basic catalysts other than alkali acetates have been employed in the Perkin reaction thus salicylaldehyde condenses with acetic anhydride in the presence of triethylamine to yield coumarin (tlie lactone of the cis form of o-hydroxy-cinnamio acid) together with some of the acetyl derivative of the trans form (o-acetoxycoumaric acid) ... 

Coumarin. In a 250 ml. round-bottomed flask, provided with a small reflux condenser and a calcium chloride drying tube at the top, place 2 1 g, of salicylaldehyde, 2 0 ml. of anhydrous triethylamine and 5 0 ml. of acetic anhydride, and reflux the mixture gently for 12 hours. Steam distil the mixture from the reaction flask and discard the distillate. Render the residue in the flask basic to litmus with solid sodium bicarbonate, cool, filter the precipitated crude coumarin at the pump and wash it with a little cold water. Acidify the filtrate to Congo red with... 

Both carbonyl groups of terephthaldehyde are reported to react with the exocyclic nitrogen of 2-aminothiazole yielding 1.4-phenylene bis(2-methyleneamino)thiazole. The same report describes the reactions of 2-amino-4-phenylthiazole with terephth aldehyde and salicylaldehyde as yielding 64 and 65, respectively (Scheme 45) (215), whose structures are based on ultraviolet and infrared spectra. 

The reaction product of salicylaldehyde and a secondary aniline is the benzyUc alcohol, with total para-selectivity (57). The yield is 93%... 

The DOOB reagent, which is formed by reaction of diphenylboric anhydride with salicylaldehyde, yields fluorescent reaction products with primary amines [1]. 

Salicylaldehyde, 188 Salicylic acid, 190 Sa tdnieycr s reaction, 165, 167 Saponification of ethyl acetate, 82 palm oil, 104 Sthlff s azotometer, 14 reaction, 67... 

The synthesis of a large number of y-pyrones and y-pyranols from enamines has been brought about through the use of a wide variety of bifunctional molecules. These molecules include phenolic aldehydes (126,127), phenolic Mannich bases (128), ketal esters (129), and diketene (120-132). All of these molecules have an electrophilic carbonyl group and a nucleophilic oxygen center in relative 1,4 positions. This is illustrated by the reaction between salicylaldehyde (101) and the morpholine enamine of cyclohexanone to give pyranol 102 in a quantitative yield (127). 

Comforth has reviewed literature reports and independently studied the special cases of reaction of 1 with salicylaldehyde and with 2-acetoxybenzaldehyde. Coumarins (10) are afforded in the condensation of 1 with salicylaldehyde or its imine, whereas when 2-acetoxybenzaldehyde is used, acetoxy oxazolone 12 is the major product. The initial aldol condensation product between the oxazolone and 2-acetoxybenzaldehyde is the 4-(a-hydroxybenzyl)oxazolone 11, in which base-catalyzed intramolecular transacetylation is envisioned. The product 9 (R = Ac) can either be acetylated on the phenolic hydroxy group, before or after loss of acetic acid, to yield the oxazolone 12, or it can rearrange, by a second intramolecular process catalyzed by base and acid, to the hydrocoumarin, which loses acetic acid to yield 10. When salicylaldehyde is the starting material, aldol intermediate 9 (R = H) can rearrange directly to a hydrocoumarin. Comforth also accessed pure 4-(2 -hydroxyphenylmethylene)-2-phenyloxazol-5(4//)-one (13) through hydrolysis of 12 with 88% sulfuric acid. 

The importance of the solvent, in many cases an excess of the quatemizing reagent, in the formation of heterocyclic salts was recognized early. The function of dielectric constants and other more detailed influences on quatemization are dealt with in Section VI, but a consideration of the subject from a preparative standpoint is presented here. Methanol and ethanol are used frequently as solvents, and acetone,chloroform, acetonitrile, nitrobenzene, and dimethyl-formamide have been used successfully. The last two solvents were among those considered by Coleman and Fuoss in their search for a suitable solvent for kinetic experiments both solvents gave rise to side reactions when used for the reaction of pyridine with i-butyl bromide. Their observation with nitrobenzene is unexpected, and no other workers have reported difficulties. However, tetramethylene sulfone, 2,4-dimethylsulfolane, ethylene and propylene carbonates, and salicylaldehyde were satisfactory, giving relatively rapid reactions and clean products. Ethylene dichloride, used quite frequently for Friedel-Crafts reactions, would be expected to be a useful solvent but has only recently been used for quatemization reactions. ... 

Reaction of the potassium salt of salicylaldehyde with chlo-roacetone affords first the corresponding phenolic ether aldol cyclization of the aldehyde with the ketonic side chain affords the benzofuran (1). Reduction of the carbonyl group by means of the Wolf-Kischner reaction affords 2-ethyl-benzofuran. Friedel-Crafts acylation with anisoyl chloride proceeds on the remaining unsubstituted position on the furan ring (2). The methyl ether is then cleaved by means of pyridine hydrochloride (3). lodina-tion of the phenol is accomplished by means of an alkaline solution of iodine and potassium iodide. There is thus obtained benziodarone (4)... 

Another CNS active agent in this structural class is the tranquilizer-antidepressant caroxazone (52). Its published synthesis begins by reductive aminatiwi of salicylaldehyde and glycinamide to give The synthesis is completed by reaction with phosgene and sodium bicarbonate. ... 

Demailly and coworkers195 found that the asymmetric induction increased markedly when optically active methyl pyridyl sulfoxide was treated with an aldehyde. They also synthesized (S)-chroman-2-carboxylaldehyde 152, which is the cyclic ring part of a-tocopherol, by aldol-type condensation of the optically active lithium salt of a,/3-unsaturated sulfoxide. Although the diastereomeric ratio of allylic alcohol 151 formed from lithium salt 149 and 150 was not determined, the reaction of 149 with salicylaldehyde gave the diastereomeric alcohol in a ratio of 28 72196. 

An improved route to fluorinated 4-hydroxycoumarins has been reported, based on a facile decarboxylation-deacetylation of their 3-(3-oxopropanoic acid) derivatives <96TL15S1>. The reaction of methyl salicylates with triphenylphosphoranylidene ketene, Ph3P=C=C=0, affords 4-methoxycoumarins <96JCS(P1)2799> and the formation of coumarin 3-phosphonates from salicylaldehydes and phosphonoacetates, Et02CCH2P(0)(0R)2, has been investigated <96T12597>. 

A further example of the utility of the cyclobuta[ >]chroman system in synthesis (see 6.4.1.3) is provided by the conversion of the cyclobutenedione derivatives (19) into substituted xanthones. Compounds (19) are obtained in high yield from salicylaldehydes and squarate esters and their reaction with alkenyl, aryl and heteroaryl li compounds is both facile and high yielding <96JA12473>. 

Rap-Stoermer reactions are useful for the preparation of 2-benzoylbenzofuran derivatives (91) by a base-assisted condensation of salicylaldehydes (89) with phenacyl bromides (90) (Scheme 15). However, these reactions are not very... 

The first asymmetric intramolecular Stetter reactions were reported by Enders and co-workers utilising triazolium salt pre-catalyst 125. Treatment of substrate 123 generated 1,4-dicarbonyl compound 124 in good yield and enantioselectivity [56]. These salicylaldehyde-derived substrates 123 have since become the standard test substrates for the development of new catalysts for the asymmetric intramolecular Stetter reaction. Bach and co-workers have achieved moderate enantioselectivities using axially-chiral thiazolium pre-catalyst 126 [41], whilst Miller and co-workers have developed peptidic thiazolium pre-catalyst 127 [57]. In 2005, Rovis and coworkers showed that the NHCs derived from triazolium salts 128-130 were excellent catalysts for the asymmetric intramolecular Stetter reaction of a wide range of substrates, giving typically excellent yields and enantioselectivities [58]. The iV-pentafluorophenyl catalyst 129 currently represents the state of the art in asymmetric Stetter reactions (Scheme 12.24) [59]. 

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