Sahcylaldehyde

Method 2. Dissolve 20 0 g. of sahcylaldehyde in 30 ml. of rectified spirit, add a solution of 15 g. of hydroxylamine hydrochloride in 10 ml. of water, and render the mixture just alkahne with 10 per cent, sodium carbonate solution whilst coohng in ice. Allow to stand overnight. Acidify with acetic acid, distil off the alcohol under reduced pressiu e (water pump), dilute with twice the volume of water, and extract with two 50 ml. portions of ether. Dry the ethereal extract with anhydrous sodium or magnesium sulphate, distil off most of the ether, and allow the residue to crystaUise. RecrystallLse from chloroform - hght petroleum (b.p. 40-60°). The yield of sahcylaldoxime, m.p. 57°, is 12 g. 

Reactions of the Hydroxyl Group. The hydroxyl proton of hydroxybenzaldehydes is acidic and reacts with alkahes to form salts. The lithium, sodium, potassium, and copper salts of sahcylaldehyde exist as chelates. The cobalt salt is the most simple oxygen-carrying synthetic chelate compound (33). The stabiUty constants of numerous sahcylaldehyde—metal ion coordination compounds have been measured (34). Both sahcylaldehyde and 4-hydroxybenzaldehyde are readily converted to the corresponding anisaldehyde by reaction with a methyl hahde, methyl sulfate (35—37), or methyl carbonate (38). The reaction shown produces -anisaldehyde [123-11-5] in 93.3% yield. Other ethers can also be made by the use of the appropriate reagent. 

Sulfonation andDiazonium Coupling. Like phenol, sahcylaldehyde reacts easily in these reactions (40,41), with a high para-selectivity. 

Sahcylaldehyde is readily oxidized, however, to sahcyhc acid by reaction with solutions of potassium permanganate, or aqueous silver oxide suspension. 4-Hydroxybenzaldehyde can be oxidized to 4-hydroxybenzoic acid with aqueous silver nitrate (44). Organic peracids, in basic organic solvents, can also be used for these transformations into benzoic acids (45). Another type of oxidation is the reaction of sahcylaldehyde with alkaline potassium persulfate, which yields 2,5-dihydroxybenzaldehyde (46). 

Many excellent chelating agents are piepaied by the reaction of sahcylaldehyde with 1,2- or 1,3-dianiinoalkanes and have wide use in chemistry, for... 

Primary amides condense with hydroxybenzaldehydes in a manner similar to amines. This reaction is often conducted in the presence of sodium acetate or an organic base such as pyridine. For example, the reaction of sahcylaldehyde and propionamide produces sahcyhdene propionamide (58). 

Perkin Reaction. A product of significant commercial importance, coumarin [91-64-5] is made by the reaction of sahcylaldehyde with acetic anhydride and sodium acetate, a Perkin reaction (61). 

The main processes for the manufacture of hydroxybenzaldehydes are based on phenol. The most widely used process is the saligenin process. Saligenin (2-hydroxybenzyl alcohol [90-01-7]) and 4-hydroxybenzyl alcohol [623-05-2] are produced from base-catalyzed reaction of formaldehyde with phenol (35). Air oxidation of saligenin over a suitable catalyst such as platinium or palladium produces sahcylaldehyde (62). 

Reaction of phenyl metaborate with formaldehyde, followed by catalytic oxidation, has been reported to give sahcylaldehyde selectively and directiy from phenol without isolation of any intermediate products (63). 

Although 4-hydroxybenzaldehyde can be made by the saligenin route, it has been made historically by the Reimer-Tiemann process, which also produces sahcylaldehyde (64). Treatment of phenol with chloroform and aqueous sodium hydroxide results in the formation of benzal chlorides, which are rapidly hydrolyzed by the alkaline medium into aldehydes. Acidification of the phenoxides results in the formation of the final products, sahcylaldehyde and 4-hydroxybenzaldehyde. The ratio of ortho and para isomers is flexible and can be controlled within certain limits. The overall reaction scheme is shown in Figure 1. Product separation is accomphshed by distillation, but this process leads to environmental problems because of the quantities of sodium chloride produced. 

Other routes for hydroxybenzaldehydes are the electrolytic or catalytic reduction of hydroxybenzoic acids (65,66) and the electrolytic or catalytic oxidation of cresols (67,68). (see Salicylic acid and related compounds). Sahcylaldehyde is available in drums and bulk quantities. The normal specification is a freezing point minimum of 1.4°C. 4-Hydroxybenzaldehyde is available in fiber dmms, and has a normal specification requirement of a 114°C initial melting point. More refined analytical methods are used where the appHcation requires more stringent specifications. 

Rhc ne-Poulenc (RP), producing both in Europe and the United States, is the only producer of sahcylaldehyde worldwide, for merchant sales. A large portion of it is used captively in the manufacture of coumarin. The remainder is available for the merchant market. 

Sahcylaldehyde has a moderate acute oral toxicity the LD q for rats is 0.3-2.0 g/kg of body weight. Hydroxybenzaldehyde has a low acute oral toxicity the LD q for rats is 4.0 g/kg of body weight. Neither material is likely to present a problem from ingestion incidental to its handling and industrial use. It should be recognized, however, that serious effects may result if substantial amounts are swallowed. 

The hydroxybenzaldehydes are used primarily as chemical intermediates for a variety of products. The largest single use of sahcylaldehyde is in the manufacture of coumarin. Coumarin is an important commercial chemical used in soaps, flavors and fragrances, and electroplating (see Coumarin). Other significant uses of both sahcylaldehyde and -hydroxybenzaldehyde are as follows. 

Flavors and Fragrances. SaUcylaldehyde is a starting material in the synthesis of coumatin, which finds extensive use in the soap (qv) and perfume (qv) industries and saUcylaldehyde can be used itself as a preservative in essential oils and perfumes (see Oils, essential). The antibacterial activity of sahcylaldehyde is strong enough to allow its use at very low concentrations (79). 

Petroleum Products. Condensation products of sahcylaldehyde and amines ate used in various forms for the removal or neutralization of the metallic ions that cause oxidative degradation in petroleum products. The product formed from propylenediamine and sahcylaldehyde, ie,... 

Polymer Applications. The reaction of sahcylaldehyde with poly(vinyl alcohol) to form an acetal has been used to provide dye receptor sites on poly(vinyl alcohol) fibers (89) and to improve the light stabihty of blend fibers from vinyl chloride resin and poly(vinyl alcohol) (90) (see Fibers, POLY(VINYL alcohol)). ... 

The metal coordination complexes of both sahcylaldehyde phenyhiydrazone (91) and sahcylaldoxime provide antioxidant (92) protection and uv stabihty to polyolefins (see Antioxidants). In addition, the imines resulting from the reaction of sahcylaldehyde and aromatic amines, eg, p- am in oph en o1 or a-naphthylamine, can be used at very low levels as heat stabiLizers (qv) in polyolefins (93). 

Miscellaneous. The reaction products of sahcylaldehyde with certain compounds containing active methylene groups, eg, acetylacetone, are excellent uv absorbers. Films containing these compounds can be used as uv filters to protect light-sensitive foods, wood products, paper, dyes, fibers, and plastics (95). 

The reaction product of sahcylaldehyde and hydroxylamine, sahcylaldoxime, has been found to be effective in photography in the prevention of fogging of silver hahde emulsions on copper supports (96). It also forms the basis for an electrolytic facsimile-recording paper (97) and in combination with a cationic polymer, is used in another electrolytic dry-recording process (98) (see Electrophotography). 

Reactions with Sahcylaldehydes. Tetraalkyl titanates react in benzene with sahcylaldehyde in a 1 1 or 1 2 molar ratio to give sahcylaldehydotrialkoxy and dialkoxy products, which when heated at reflux seem to undergo a Meewein-Pomidorf reaction to give an aldehyde derived from the alcohol group on the titanate and a reduced titanate complex (37) ... 

Phenyhsonitrile has a powerful characteristic odor it is used as a qualitative test (the carbylamine test) for chloroform or primary aromatic amines. Chloroform reacts with phenols in alkaline solution to give hydroxyaromatic aldehydes in the Reimer-Tiemann reaction eg, phenol gives chiefly Nhydroxyben2aldehyde and some sahcylaldehyde (11) (see Hydroxybenzaldehydes). 

Photochromism Based on Tautomerism. Several substituted anils of saHcylaldehydes are photochromic but only in the crystalline state. The photochromic mechanism involves a proton transfer and geometric isomerization (21). An example of a photochromic anil is /V-sa1icylidene-2-ch1oToani1ine [3172-42-7] C H qCINO. 

Until the late 1890s, coumarin was obtained commercially from only natural sources by extraction from tonka beans and deer tongue. Then synthetic methods of preparation and industrial manufacturing processes were discovered and developed starting principally from o-cresol, phenol, and sahcylaldehyde. Various methods can be used to obtain coumarin from each of these starting materials. 

Perkin Reaction. Perkin first syathesized coumaria ia 1868 by reactioa of the sodium salt of sahcylaldehyde with acetic anhydride (44) and it was foundlater that the reaction could be made from sahcylaldehyde [90-02-8] itself by usiag sodium acetate as a catalyst, through the iatermediary of i7j -(9-acetoxycianamic acid [50363-92-3]. 

Many compounds capable of chelation have been tested for antimicrobial properties. Those showing positive results include saHcylaldoxime [94-67-7] l-nitroso-2-naphthol [131-91-9] mercaptobenzothiazol [149-30-4], dimethylglyoxime [95-45-4], saHcylaldehyde [90-02-8], cupferron [135-20-6], phenanthroline [66-71-7], isoniazid [54-85-3], thiosemicarbazones, the sulfur analogue of oxine, and numerous antibiotics (qv) including tetracyclines. Whether these compounds function exclusively, partially, or at all by virtue of their abiHty to chelate is open to debate. 

The Michael aclcliQon of oxygen-nucleophiles followed by subsequent cyclizadon or cycloaddidon provides an important method for the preparadon of oxygen-heterocycles such as tetrahydrofurans For example, 3-nitro-2//-chromenes bearing various snbsdtnents are prepared by the reaction of snbsdtnted sahcylaldehydes with nitro ilkenes fEq 4 14 ... 

A family of interesting polycychc systems 106 related to pyrrolidines was obtained in a one-pot double intermolecular 1,3-dipolar cycloaddition, irradiating derivatives of o-allyl-sahcylaldehydes with microwaves in toluene for 10 min in presence of the TEA salt of glycine esters [71]. A very similar approach was previously proposed by Bashiardes and co-workers to obtain a one-pot multicomponent synthesis of benzopyrano-pyrrolidines 107 and pyrrole products 108 (Scheme 37). The latter cycloadducts were obtained when o-propargylic benzaldehydes were utihzed instead of o-allyhc benzalde-hydes, followed by in situ oxidation [72]. 

Figure 44.6. Conversion of phenol ( ), molar selectivity to o-cresol (O), xylenols (O) and sahcylaldehyde ( ) as functions of temperature. Catalyst Mg/Fe/0. Feed composition as in Figure 44.5.

Furthermore, the use of Ralstonia eutropha JMP134-containing sensors for the determination of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been described [118,121]. This sensor was sensitive to 2,4-D and 2,4,5-T (2,4,5-trichlorophenoxyacetic acid) with a detection Emit of 40 mg 1 with a response time of 15 s. Moreover, catechol, benzoic acid, and sahcylaldehyde caused higher signals, but no or very little signal was obtained for phenol, biphenyl, and the usual substrates such as glucose, fructose, ethanol, and acetate. 

Figure 1 The stabihty of complexes of divalent transition metal cations. 1, Triethylenetetramine, NH2C2H4NHC2H4NHC2H4NH2 2, EDTA, ethylenediaminetetraacetic acid 3, diethylenetriamine, NH2C2H4NHC2H4NH2 4, norleucine, Me(CH2)3CH(NH2)C02H 5, 1,2,3-triaminopropane, NH2CH2CH(NH2)CH2NH2 6, ethylene-diamine, NH2C2H4NH2 7, sahcylaldehyde, 2-(HO)CgH4CHO 8, oxalic acid, HO2CCO2H. For norleucine, 4, the values for log 82 are plotted...

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