CYCLOBUTANECARBOXYLIC

V,32. CYCI.OBUTANE-1 1-DICARBOXYLIC ACID AND CYCLOBUTANECARBOXYLIC ACID... 

In a short path distilling apparatus is placed 3-5 g of 1,1-cyclohexanedicarboxylic acid. The flask is heated in an oil, sand, or metal bath to 160-170° until all the effervescence stops then the temperature of the bath is raised to 210°. Cyclobutanecarboxylic acid distills over at 191 -197°. It may be purified by redistillation at atmospheric pressure, bp 195-196°. 

To a slurry of 110.5 g of lA-hydroxydlhydronormorphinone in 2.5 liters of methylene chloride and 280 ml of triethylamine was added a solution of 106 g of cyclobutanecarboxylic acid chloride in 500 ml of methylene chloride. The temperature of the reaction mixture was maintained at 20°C to 25°C during the addition. After 5 minutes the reaction mixture was brought to reflux and heated for 5 hours. 

In a 1-1. three-nccked, round-bottomed flask equipped with a mechanical stirrer, reflux condenser, and powder funnel are placed 180 ml. of reagent grade chloroform, 16.0 g. (0.16 mole) of cyclobutanecarboxylic acid (Note 1), and 48 ml. of concentrated sulfuric acid. The flask is heated in an oil bath to 45-50°, and 20.0 g. (0.31 mole) of sodium azide (Note 2) is added over a period of 1.5 hours (Note 3). After the addition of sodium azide is complete, the reaction mixture is heated at 50° for 1.5 hours. The flask is cooled in an ice bath, and approximately 200 g. of crushed ice is added slowly. A solution of 100 g. of sodium hydroxide in 200 ml. of water is prepared, cooled to room temperature, and then added slowly to the reaction mixture until the pH of the mixture is approximately 12—13. The mixture is poured into a 2-1. three-necked, round-bottomed flask, the... 

Cyclobutanecarboxylic acid was purchased from the Aldrich Chemical Co., Milwaukee, Wisconsin. A synthesis of the acid is described in Org. Syntheses, Coll. Vol. 3, 213 (1955). 

This procedure permits the synthesis of cyclobutylamine from cyclobutanecarboxylic acid in one step and in high yield. The procedures involving the Hofmann rearrangement require the preparation of the amide from the acid and afford lower yields of the amine. 

A1( -octalone, 45, 80 N-nitioso-N-phenylglycine to N-phenylsydnone, 45, 96 Cyclobutanecarboxylic acid, reaction with hydrazoic acid, 47, 28 Cyclobutene, 1,2,3,4-tetrasiethyl-3,-4-dichloro-, 46, 34 reactions of, 46, 36 Cyclobutylamine, 47, 28 Cyclobutyl isocyanide, 46, 77 Cycloheptanone, 45, 31... 

Methyl 2-butenoate 3-Methyl- 1-butyne 2-Methylbutyl acetate Methyl chloroacetate Methyl cyanoacetate Methyl cyclobutanecarboxylate Methylcyclohexane 6.75... 

Cyclobutylcyclopropanol [133] To a well-stirred solution of ethyl cyclobutanecarboxylate [134] (56.47 g, 0.441 mol) and titanium tetraisopropoxide (26.3 mL, 88.2 mmol, 20 mol%) in anhydrous diethyl ether (200 mL), ethylmagnesium bromide (0.980 mol, 276 mL of a 3.55 m solution in Et20) was added over a period of 3 h. The temperature was maintained at between 20 and 25 °C with a water bath. After the addition was complete, the mixture was stirred for an additional 0.5 h at the same temperature, then cooled to —5 °C, whereupon the reaction was quenched by the careful addition of ice-cold 10 % aqueous sulfuric acid (500 mL) while the temperature was maintained between —5 and 0°C with an acetone/dry ice bath. The mixture was stirred at 0°C for an additional 1 h and then the aqueous phase was extracted with Et20 (100 mL). The combined ethereal phases were washed with saturated aq. NaHC03 solution (2 X 200 mL) and brine (200 mL), dried, and concentrated at water-pump pressure at 20 °C to give 48.92 g (99%) of 1-cyclo-butylcyclopropanol. The spectroscopic data of the product were identical to those reported in the literature [135]. 

Cyclobutanecarboxylic Acids. Techn. Rep. Calif. Inst, of Technol. 1953. 

Silver Cyclobutanecarboxylate with Iodine. J. Amer. chem. Soc. 73, 5487 (1951). 

Cyclobutanecarbonyl chloride was obtained from Aldrich Chemical Company, Inc. It was distilled prior to use. The acid chloride can be prepared by the reaction of thionyl chloride with the corresponding acid (available from Aldrich) by the general procedure of Helferich and Schaefer.3 The preparation of cyclobutanecarboxylic acid has been described in Organic. Syntheses4 and elsewhere.r>... 

Some variations of the method have been used to prepare cyclopropyl and cyclobutyl halides. Simultaneous addition of bromine and 3-bromocyclobutanecarboxylic acid to the suspension of mercuric oxide gives 1,3-dibromocyclobutane in good yield.7 Similarly, cyclopropanecarboxylic acid gives bromo-cyclopropane,9 and 3-(bromomethyl)cyclobutanecarboxylic acid gives 3-(bromomethyl)cyclobutyl bromide.10 In the latter reaction, it was found desirable to remove the water from the reaction as it is formed in order to obtain high yields. Another variation is the addition of a mixture of the acid and mercuric oxide to excess bromine in bromotrichloromethane.6... 

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