Cyclopropylcarboxylic acids

Some cyclopropylcarboxylic acids, namely 14 [125] and 15 [46] could be coupled to bicyclopropyl compounds, others led to allylic compounds via ring opening of an intermediate carbenium ion (see chap. 7). Tertiary alkanoates yield predominantly non-Kolbe products (see chap. 8). 

Aluminum trichloride is able to convert ethyl cyclopropanecarboxylate (8) into a bifunctional electrophile that undergoes Friedel-Crafts reactions. When this reaction was carried out in boiling benzene, 2-methyl-l-indanone (9, R = H) was obtained in excellent yield.The aluminum trichloride catalyzed reaction of cyclopropylcarboxylic acid chloride with benzene led to a mixture of 2- and 3-methylindanones. ... 

An effort was made to prepare a butyl analogue containing a ring, but it was never completed. This was the cyclopropylmethyl isomer, 2,5-dimethoxy-4-cyclo-propylmethylamphetamine hydrochloride, DOCPM. Only the first step of its synthesis was complete (the reaction of cyclopropylcarboxylic acid chloride with p-dimethoxybenzene) and even it went badly. The desired ketone (2,5-dimethoxyphenyl cyclopropyl ketone) was most difficult to separate from the recovered starting ether. A promising approach would be the isolation of the phenol (2-hydroxy-5-methoxyphenyl cyclopropyl ketone) which is a beautiful yellow solid with a melting point of 99-100 °C from methanol. Anal. (Cl 1 HI203) C,H. It then could be methylated to the wanted intermediate. It is the major product when the reaction is conducted with anhydrous aluminum chloride in methylene chloride. 

Cyclohexanone added in one portion at 25 under Ng to a suspension of di-methylthetin anion (a stable S-ylid prepared from dimethylthetin and NaH-dispersion in dimethyl sulfoxide), stirred 3 hrs. at room temp., and the ethereal soln. of the resulting crude glycidic acid treated with diazomethane glycidic ester. Y 60%. F. e., also cyclopropylcarboxylic acid esters, s. J. Adams, L. Hoffman, and B. M. Trost, J. Org. Chem. 35, 1600 (1970). 

According to Kaneko (2010), the major metabohc reaction is ester hydrolysis followed by hydroxylation of the alcohol moiety and its subsequent oxidation to an acid. The cyano group of the alcohol, benzeneacetonitrile, a-hydroxy-3-phenoxy (CAS no. 39515-47-4) is converted to an SCN ion. The major metabolites of the acid moiety are cyclopropylcarboxylic acid and its glucuronide, while the alcohol moiety is converted to PB acid (benzoic acid, 3-phenoxy) (CAS no. 3739-38-6), 4 -OH PB acid (benzoic acid, 3-(4-hydroxyphenoxy)) (CAS no. 35065-12-4), and the sulfate of 4 -OH-PB acid (benzoic acid, 3-[4-(sulfooxy)phenoxy]) (CAS no. 58218-91-0). 

The novel ylide (125) reacts with alkenes to give cyclopropanes and with ketones to give epoxides, but yields are variable. In a similar way Me2S=CHC02 Na has been used to synthesize a cyclopropylcarboxylic acid by addition to the C=C bond of cyclopent-2-enone and this has been useful for synthesis of prostaglandin derivatives. ... 

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