Toluates synthesis

It now became of interest to determine the biological activity of the individual isomers in AC 222,293 and this required an alternate regio-selective synthesis The synthesis for the m-toluate is shown in Scheme II. 

The present procedure4 is an especially effective method for the synthesis of esters of aromatic acids and hindered tertiary alcohols or of acid-labile alcohols such as 2,2-diphenylethanol. The yields are excellent, and the reaction procedure is simple. The method is illustrated by the preparation of /-butyl p-toluate, a compound that could not be prepared by a conventional method0 of esterification involving the acid chloride and /-butanol in the presence of dimothylaniline. Examples of esters prepared by this method are illustrated in Table I. 

The Dynamit Nobel-Hercules process995 produces dimethyl terephthalate in a more complex synthesis (Scheme 9.25). To overcome the difficulty in the oxidation of the second methyl group, p-xylene and recycled methyl p-toluate formed after... 

In the aromatic series, acetophenone and methyl iodide, for example, yield phenyldimethylcarbinol. An important step in the synthesis of i-terpineol is the preparation of ethyl-S-hydroxy-hexahydro-p-toluate from ethyl-S-ketohexahydrobenzoate and magnesium methyl iodide. 

Lateral lithiation of (d )-4-isopropyl-2-(o-tolyl)oxazoline and reaction with aldehydes provides the addition products 1148 with moderate to good diastereoselectivity. The addition of TMEDA is vital for any diastereoselectivity to be observed. The major (,S,A)-products lactonize faster under acidic conditions providing dihydroisocoumarins 1149 in up to ee 97% (Scheme 286, Table 53) <2005T3289>. Similarly, the addition of laterally metallated o-toluates to chiral aldehydes provides a key dihydroisocoumarin during a total synthesis of AI-77-B <1999J(P1)1083>. 

Enantiopure l,2-cis-dihydroxycyclohexa-3,5-diene carboxylic acids have considerable synthetic potential as building blocks in chiral synthesis. Such cis-diols can be produced from benzoic acid derivatives by the action of toluate- 1,2-dioxygenase of Pseudomonas putida mt-2125 or homologous enzymes of a different origin (Fig. 16.6-... 

Cresylol. See Cresylic acid m-Cresyl phenylacetate CAS 122-27-0 EINECS/ELINCS 204-531-0 Synonyms Acetic acid, phenyl-, m-tolyl ester Benzeneacetic acid, 3-methyl phenyl ester m-Cresyl a-toluate Phenylacetic acid, m-tolyl ester m-Tolyl phenylacetate Empirical C15H14O2 Toxicology TSCA listed Uses Fragrance in cosmetics Manuf/Distrib. Advanced Synthesis Tech. http //www.advancedsynthesis.com, Aldrich http //www.sigma-aldrich. com... 

The synthesis pathway started with the lithiation of ethylbenzene 121 at the benzylic position, followed by acylation of the toluate anirni intermediate at low temperature. It is noteworthy that a potentially competing orf/io-lithiati(Mi of the type championed by Snieckus 85) i.e. between the two stabilizing methoxyl radicals) was not reported under these conditions. Subsequent reduction of benzyUcetone 122 provided smooth access to the t/irco-dimethyl-substituted bicy-clic intermediate 123 via lactonization. DIBAL reduction (—> 124) and reductive debenzylation with palladium on charcoal gave the ring-opened alcohol 125, which was further demethylated to provide a 1,3-diphenol, and then carboxylated under buffered conditions to yield acid 117, also known as phenol B . This compound was formylated with trimethyl orthoformate and acid, then cyclized to give the quinone structure and natural product, 116 (Scheme 3.1). 

Barber JA, Staunton J, Wilkinson MR (1986) A Diastereoselective Synthesis of the Polyke-tide Antibiotic Citrinin Using Toluate Anion Chemistry. J Chem Soc Perkin Trans 1 2101... 

Regan AC, Staunton J (1987) Asymmetiie Synthesis of (-t)-Citiinm Using an Ortho-toluate Carbanion Generated by a Chiral Base. J Chem Soe Chem Commun 520... 

Regan, A.C., and J. Staunton Asymmetric Synthesis of Mellein Methyl Ether Use of or//zo-Toluate Carbanions Generated by Chiral Bases. Chem. Commun. 1983, 764. 

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