Anisaldehyde reduction

Hydroxybenzaldehyde has an agreeable aromatic odor, but is not itself a fragrance. It is, however, a useful intermediate in the synthesis of fragrances. The methyl ether of -hydroxybenzaldehyde, ie, -anisaldehyde, is a commercially important fragrance. Anisaldehyde can be made in a simple one-step synthesis from hydroxybenzaldehyde and methyl chloride. Another important fragrance, 4-(p-hydroxyphenyl)butanone, commonly referred to as raspberry ketone, can be prepared from the reaction of -hydroxybenzaldehyde and acetone, followed by reduction (see Flavors and spices). 

This method is an adaptation of that of Dengel. -Methoxy-phenylacetonitrile can also be prepared by the metathetical reaction of anisyl chloride with alkali cyanides in a variety of aqueous solvent mixtures by the nitration of phenylaceto-nitrile, followed by reduction, diazotization, hydrolysis, and methylation 1 by the reduction of ct-benzoxy- -methoxy-phenylacetonitrile (prepared from anisaldehyde, sodium cyanide, and benzoyl chloride) and by the reaction of acetic anhydride with the oxime of -methoxyphenylpyruvic acid. ... 

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

Fluoride ion is effective in promoting the reduction of aldehydes by organosil-icon hydrides (Eq. 161). The source of fluoride ion is important to the efficiency of reduction. Triethylsilane reduces benzaldehyde to triethylbenzyloxysilane in 36% yield within 10-12 hours in anhydrous acetonitrile solvent at room temperature when tetraethylammonium fluoride (TEAF) is used as the fluoride ion source and in 96% yield when cesium fluoride is used.83 The carbonyl functions of both p-anisaldehyde and cinnamaldehyde are reduced under similar conditions. Potassium bromide or chloride, or tetramethylammonium bromide or chloride are not effective at promoting similar behavior under these reaction conditions.83 Moderate yields of alcohols are obtained by the KF-catalyzed PMHS, (EtO SiH, or Me(EtO)2SiH reduction of aldehydes.80,83,79... 

Reduction of Other Aldehydes. We examined the reduction of anisaldehyde, p-CH30C6H4CH0 and tolualdehyde, p-CH3(C6H<,)CH0 to examine the effect of electron density on aldehyde reduction. In addition, we also investigated one ketone, acetophenone, C6H5C0CH3. The results of these experiments are given in Table 2. 

It not tertiary, the product yield is lowered by transfer of the carbinol hydride ion to the aldehyde to produce a new alkoxide and an enolate ion. Thus, propylene oxide, after reductive cleavage with LDBB and trapping with isobutyraldehyde or p-anisaldehyde, provided 5-methyl-2,4-hexanediol in 40-50% yield or 1-p-anisyl-1,3-butanediol in 44% yield, respectively (in both cases about equal mixtures of diastereoisomers were obtained). The cyclohexene oxide-derived dianion, when trapped with isobutyraldehyde, gave 2-(1-hydroxy-2-methylpropyl)cyclohexanol in 71% yield as a mixture of only partially separable isomers in the ratio 15 11 39 35. 

Regioselective reductions of the maleic anhydride derivatives (387) and (389) with lithium aluminum hydride yielded (388) and (390). Metallation of the O-methyltetronic acid (388) with lithium N- cyclohexyl-A- isopropylamide followed by treatment with, for example, p-anisaldehyde led to pulvinones such as (391) (79JCS(P1)70). 

Examples of this reaction have long been known, and several have been discussed above (pp. 99-102). Applications of the method to aldehydes of the aromatic series have been reported more recently. Nenitzescu and Gav t 89 observed that equimolal mixtures of benzalde-hyde or anisaldehyde with formaldehyde led to the formation of both possible acids and alcohols, and that if formaldehyde was present in large excess the aromatic- alcohol, and little of the corresponding acid, was formed. The procedure may therefore be looked upon as a method for reducing aromatic aldehydes. Davidson and Bogert90 have worked out experimental conditions for carrying out the reduction of aldehydes by this means to give 85-90% yields of the alcohols. 

Aniline, 4,4 -azodi-, 40,18 Aniline, reaction with hexachloroace-tone to form a,reaction with maleic anhydride, 41,94 o-Anisaldehyde, 44, 4 Anisoin, reduction to deoxyanisoin by tin and hydrochloric add, 40, 16 Anthracene, chlorination by cupric chloride, 43,15... 

It seemed desirable to point out the connection between these two phenomena— namely, autoxidation and production of ozonides, which at first glance seem to have nothing whatsoever to do with each other. This connection is of practical interest, because it is useful to know that aldehydes, such as anisaldehyde or vanillin, are already present to a considerable extent in the prefabricated state— that is, before the reductive hydrolysis to which the ozonization products are finally submitted with a view to scission of the ozonides formed. 

Rate acceleration provided by the chelate formation was further observed in a discrimination experiment between two isomeric alkoxycarbonyl compounds 36 and 37 (X = OMe R =Pr or H) as shown in Table 1-9 (entries 1-4). Thus, chelation-induced selective reduction of a-methoxyisobutyrophenone 36 (X=OMe R =Pr ) was observed to furnish o-methoxyphenyl carbinol 38 (X = OMe R =Pr R = H) preferentially with (C6F5)3B and Me3Al. The (CfiF5)3B and Me3Al-pro-moted discriminative allylation of an equimolar mixture of o- and p-anisaldehyde,... 

Hydroxyproline is abundant but hydroxylysine is not. Fortunately it can be made59 from an abundant member of the chiral pool - malic acid 34. Borane reduction gives the triol 332 and anisaldehyde gives the diequatorial acetal 333 under thermodynamic control. 

The Midland reduction has also been used in the large-scale synthesis of chiral glycines. Deuterium labeled anisaldehyde was reduced with 3 to provide deuteriated arylmethyl alcohol 21 in 82% ee.13 This alcohol was then converted in 4 steps to JV-Boc-glycine (22). 

Evans-Tishchenko reduction of ent-26 with cither p-nitrobenzaldehyde or benzaldehyde itself afforded benzoates 84 and 85, respectively, in good yield and with complete diastereoselectivity in each case. Interestingly, the same reaction, when attempted with / -anisaldehyde, gave none of the expected p-methoxybenzoate 86. Failure of this reaction may reflect the lower propensity of p-anisaldehyde to form hemiacetals owing to its poor electrophilicity. Alternatively, the in situ generation of a Sm(lll) "pinacolate" catalyst from Sml2 and p-anisaldehyde may be hampered by the relatively high reduction potential of this electron rich aldehyde. 

Fig. 9. Comparison of the spectra of transient interme(diates forme(d during alcohol oxidation (B, C) and aldehyde reduction (D) with the spectrum of the Co(II)E(NAD, triflu-oroethanol) complex (A) in the 450-700 nm region at 25°. (A) Spectra of the Co(II)E (NAD. trifluoroethanol) complex 1, pH 4.3 2, pH 6.23 3, pH 9.0. The spectra shown in (B), (C), and (D) have been selected from RSSF data sets (such as those presented in Figs. 5 and 8) to show the maximum amount of 570 nm intermediate. (B) Oxidation of benzyl alcohol 1, pH 4.8 2, pH 5.6 3, pH 6.8 4, pH 9. (C) Comparison of the transient intermediates formed during the oxidation of (1) 4-nitrobenzyl alcohol, (2) ethanol, and (3) benzyl alcohol, all at pH 9. (D) Comparison of the transient intermediates formed during the oxidation of (1) acetaldehyde, (2) anisaldehyde, (3) benzaldehyde, and (4) 4-nitrobenzaldehyde, all at pH 9. The amplitudes of the spectra have been normalized to the same concentration of Co(II)E. (From Sartorius el al. with permission.) Copyright 1987 American Chemical Society.

Barger (22) synthesized the base by reduction of p-hydroxyphenyl-acetonitrile with sodium. Barger and Walpole (33) later described two other syntheses. The p-hydroxy group was introduced into phenyl-ethylamine by nitration, reduction, diazotization etc., or anisaldehyde was converted to p-methoxyphenylpropionamide, from which, by Hofmann degradation and demethylation, tyramine was obtained. Hosen-mund (34) condensed anisaldehyde with nitromethane, and obtained tyramine by reduction followed by demethylation. Further syntheses of tyramine have been described by Kondo and Shinozaki (35), Slotta and Altner (36), Koessler and Hanke (37), Kindler and Peschke (38) and Buck (39, 40). A well known method of preparation is the thermal decarboxylation of tyrosine. Waser (41) obtained a 96% yield by heating the amino acid suspended in a high boiling solvent (fluorene). 

The impact category AP (Figure 14.5b) includes the environmental impact of acidifying pollutants. This may be, for example, fish mortality, forest decline or crumbling of building materials [16]. Nearly the same reduction in the AP (32%) was determined if the synthesis of m-anisaldehyde was conducted in the continuous microreactor mode rather than the batch mode. Here, on the one hand the supply of m-bromoanisole [42% (batch) and 62% (microreactor)] and on the other hand the supply of liquid nitrogen [34% (batch)] play the major roles. In contrast, the electric current demand (3% and 8%, respectively) and the other chemicals (except m-bromoanisole) have no outstanding effect. 

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