OrtHo-hydroxybenzaldehyde

A carbonyl group is strongly electron withdrawing and acid strengthening espe cially when ortho or para to the hydroxyl group p-Hydroxybenzaldehyde is a stronger acid than phenol... 

The location of the hydroxyl and aldehyde groups ortho to one another in saUcylaldehyde permits intramolecular hydrogen bonding, and this results in the lower melting point and boiling point and the higher acid dissociation constant observed relative to -hydroxybenzaldehyde. 

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. 

The Dakin reaction proceeds by a mechanism analogous to that of the Baeyer-Villiger reaction. An aromatic aldehyde or ketone that is activated by a hydroxy group in the ortho or para position, e.g. salicylic aldehyde 12 (2-hydroxybenzaldehyde), reacts with hydroperoxides or alkaline hydrogen peroxide. Upon hydrolysis of the rearrangement product 13 a dihydroxybenzene, e.g. catechol 14, is obtained ... 

A convenient method for the introduction of a formyl group, specifically in the ortho position of a phenol, involves reaction with tin(iv) chloride in the presence of tributylamine followed by treatment with paraformaldehyde.46 It is applicable to phenols with other electron-donating or -withdrawing substituents, and is illustrated by the conversion of p-cresol into 5-methyl-2-hydroxybenzaldehyde (Expt 6.112). The reaction is thought to proceed via two successive six-membered coordinated tin complexes. 

In the case of phenol the main product is o-hydroxybenzaldehyde (salicylalde-hyde, Expt 6.116), but some of the para isomer is also formed. The isomers are separated by steam distillation in which only the ortho isomer is steam volatile owing to intramolecular hydrogen bonding. In the cognate preparation (2-hydroxy-l-naphthaldehyde) the preferential reaction at the 1-position should be noted. 

We can, in a qualitative way, combine the directing effects of two or more substituents. In some cases the substituents both direct to the same positions, as in the syntheses of bromoxynil and ioxynil, contact herbicides especially used in spring cereals to control weeds resistant to other weedkillers. They are both synthesized from p-hydroxybenzaldehyde by halogenation. The aldehyde directs meta and the OH group directs ortho so they both direct to the same position. The aldehyde is deactivating but the OH is activating. 

The spectral nature for the transients formed in the OH reaction with -hydroxybenzaldehyde (Fig. 8) was found to be different from those recorded with its ortho- and meta-isomcrs. In addition to a single peak around 370-410 nm observed with the latter, a more intense peak at 325 nm by four folds was seen. Furthermore, this peak decayed faster with a first-order rate constant k = 5.5 x 10 s"h This decay was found to be acid-catalyzed. In the reaction of OH radical with hydroxybenzaldehydes, the time resolved spectral changes are interpreted in terms of the formation of phenoxyl radical via intermediate radical cation in the case of ortho- and /rm-isomers whereas phenoxyl radical formation by dehydration seems to be the predominant reaction pathway for the w/Jt/r-isomer. 

A general feature of this analysis is that the electron density at the carbon attached to -CHO group is significant whereas it is minimum at the exocyclic carbon. The order of the charge distribution at the carbon attached to -CHO, among the three isomers, is ortho > para > meta. The absorption maxima of transients formed with o-, m- and -hydroxyacetophenones were reported to be similar to those obtained with the corresponding isomers of hydroxybenzaldehydes. 

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

Since the Reimer-Tiemann reaction always yields a mixture of ortho- and para-substituted phenols whenever the two positions are unsubstituted (and sometimes even when the positions are substituted, see carboxy-substituted phenols), it is not surprising that attempts have been made to increase the regioselectivity. Earlier attempts (for details, see reviews) emphasized the nature of the cation, the solvent, or used phase-transfer catalysis. Recent studies have concentrated on the use of cyclodextrins as base-stable host compounds, permitting exclusive para substitution. Attaching the cyclodextrins to a solid support has also been attempted, a natural step in view of the high cost of the cyclodextrins and the need for cheap product i.e. p-hydroxybenzaldehyde). p-Hydroxybenzaldehyde has been prepared in 59-65% yield using P-cyclodextrin that has been immobilized with epichlorohydrin. TTie catalyst is easily recovered and can be reused without appreciable loss of activity. 

Intriguing but confusing information is available in two Chemical Abstracts references to Chinese publications. A 1988 abstract d reports the behavior of phenol under Reimer-Tiemann reaction conditions with the addition of tertiary amines. The authors claim that the para. ortho ratio is reversed from that normally observed and 60% yield of p-hydroxybenzaldehyde, 7% yield of o-hydroxybenzaldehyde and only 1% tars are obtained when phenol is subjected to the new conditions. One year later a report appeared in which it is claimed that the use of tertiary amines under phase-transfer conditions increases the yield of ortho product. The authors report a yield of 79% of salicylaldehyde from phenol using 0.37% catalyst (the nature of the catalyst is not mentioned in the abstract and the Chinese publication is not available to this author), and 35% sodium hydroxide at 55-60 °C for 90 min. Surely, these results (or the translation) warrant checking. 

The condensation is effected by adding chloroform to a warm solution of phenol in an excess of potassium hydroxide. In the first reaction represented above, a hydrogen atom of the benzene ring is replaced by the group CHCI2 as the result of the elimination of hydrochloric acid. The hydrogen atoms which enter into reaction are those in the positions ortho and para to the hydroxyl group. When phenol is used, a mixture of o-hydroxy-and p-hydroxybenzaldehyde is obtained. As in other cases,... 

Aromatic aldehydes having hydroxyl group in ortho or para position to the formyl groups can be oxidised with alkaline (Dakin reaction) in low yields. This reaction has been recently carried out in high yields using sodium percarbonate (SPC Na COj, 1.5 H O ) in H, 0-THF under ultrasonic irradiation. Using this procedure following aldehydes have been oxidised in 85-95% yields o-hydroxybenzaldehyde p-hydroxybenzaldehyde 2-hydroxy-4-methoxybenzaldehyde, 2-hydroxy-3-methoxybenzaldehyde and 3-methoxy-4-hydroxybenzaldehyde. 

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