Methoxybenzaldehyde benzylation

R B Woodward was one of the leading organic chemists of the middle part of the twenti eth century Known pnmanly for his achievements in the synthesis of complex natural products he was awarded the Nobel Pnze in chemistry in 1965 He entered Massachusetts Institute of Tech nology as a 16 year old freshman in 1933 and four years later was awarded the Ph D While a student there he earned out a synthesis of estrone a female sex hormone The early stages of Woodward s estrone synthesis required the conversion of m methoxybenzaldehyde to m methoxy benzyl cyanide which was accomplished in three steps... 

Phenylcoumarins are conveniently prepared by the Knoevenagel condensation of salicylaldehyde with a benzyl cyanide, in the presence of base such as sodium hydroxide or piperidine, followed by acid hydrolysis of the resultant imine. A second convenient synthesis is via condensation of 2-methoxybenzaldehyde with benzyl cyanide and cyclization of the 2-methoxy-a-phenylcinnamic nitrile in pyridine (Scheme 12). 

The overhydrogenation of aromatic aldehydes beyond benzylic alcohols is rarely important with copper-chromium oxide and Raney nickel unless the reaction conditions are too vigorous. Thus, over copper-chromium oxide o- and p-methoxybenzaldehydes were hydrogenated to the corresponding methoxybenzyl alcohols in high yields in methanol at 110-125°C and 22-24 MPa H2 (eq. 5.18).42 At 185°C, however, / -methoxybenzyl alcohol was hydrogenolyzed to give p-cre-sol methyl ether (eq. 5.18). 

Creation of the 8-membered ring 3 3 of IhxoL by an intramolecular directed aldol reaction failed when the thionium ion intermediate 3 2 underwent intramolecular hydride transfer from a neighbouring p-methoxy benzyl ether instead [Scheme 1.38]. Loss of p-methoxybenzaldehyde and hydrolysis of the enol silane occurred on workup to give the hemiacetal 38,5 in 48% yield. Benzyl ethers can also transfer hydride to proximate carbocationic intermediates.71... 

Raney Nickel W2 or W4, EtOH, 85-100% yield. - Mono- and dimethoxy-substituted benzyl ethers, benzaldehyde and 4-methoxybenzaldehyde acetals are not cleaved under these conditions, and trisubstituted alkenes are not reduced. 

After precomplexation with ji-CD, a variety of alcohols, including aromatic alcohols, were oxidized to their corresponding carbonyl compounds in good yields with NaOCl-KBr in aqueous solution. A substrate-selective and transition metal-free oxidation of benzoic and allylic alcohols with NaOCl oxidant mediated by j8-CD in water was developed. In the presence of one molar equivalent of jS-CD, benzyl alcohol, 4-methoxybenzyl alcohol and some primary aromatic alcohols were oxidated to form benzaldehyde, 4-methoxybenzaldehyde and aromatic aldehydes, respectively, at 50 °C for 1-4 h. When 20% of acetone was added to the reaction system, the yield of aldehyde was dramatically decreased. 

Electrooxidation of aromatic compounds has been intensively investigated, and many useful fine chemicals have been prepared by both side-chain and aromatic nucleus oxidation. Side-chain oxidation of alkylbenzenes may furnish benzyl alcohols, benzyl acetates, benzyl methyl ethers, Af-benzyl acetamides, benzaldehydes, benzoic acids, and so on. For instance, electrooxidation of p-methoxytoluene affords p-methoxybenzyl methyl ether, p-methoxybenzaldehyde, and/or its dimethylacetal depending on the choice of electrolysis media [3]. Many examples of electrooxidation of aromatic nucleus have been also reported. p-Quinones and their methyl acetals and semiquinones are prepared by electrooxidation of phenol derivatives and hydroquinones [3]. Nucleus-nucleus coupling of methoxybenzene derivatives... 

Hexamethyldisilane can also act as an oxidant in the conversion of benzyl alcohols to carbonyl cort5)ounds. Under alkaline conditions, reaction of a-cyclopropylbenzyl alcohol or 3-methoxybenzyl alcohol with hexamethyldisilane generates (y-trimethylsilyl)butyrophenone or 3-methoxybenzaldehyde, respectively. 

A soln. of benzyl 2-amino-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside and p-methoxybenzaldehyde in methanolic 0.15 N Na-methoxide refluxed 10 min. 

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