Cyclobutanecarboxylic acids

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... 

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

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... 

Cyclobutanecarboxylic acid, 98%, is from Aldrich Chemical Company, Inc., and is vacuum distilled before use. Tetrahydrofuran is freshly distilled from sodium-benzophenone under nitrogen. N-Methyiraorpholine, 99%, is from Aldrich Chemical Company, Inc., and is pre-dried over barium oxide, distilled from ninhydrin, and stored over sodium hydroxide pellets. Ethyl chloroformate, 97%, is from Aldrich Chemical Company, Inc., and is freshly distilled prior to use under a nitrogen atmosphere. Anhydrous ammonia (99.99% min) is from a Matheson lecture bottle. The silica gel used for flash chromatography is... 

Cyclobutanecarboxylic acid, 98%, is from Aldrich Chemical Company, Inc., and is vacuum distilled before use. Tetrahydrofuran is freshly distilled from... 

Table 1. Cyclobutanecarboxylic Acid Derivatives by Wolff Rearrangement of a-Diazocyclopentanones...

Decarboxylation reactions of cyclobutanecarboxylic acids appear to pose no particular problems. Cyclobutane-1,1-dicarboxylic acids can usually be decarboxylated thermally at temperatures up to 200 C.1 5> n 340 For example, cyclobutane-1,1,3,3-tetracarboxylic acid was heated to 185 °C at reduced pressure to give a mixture of cis- and frani-cyclobutane-l,3-dicarboxylic acid (l).1 Noteworthy in this reaction is the stereocontrof obtained in the product due to the formation of the anhydride. Generally, decarboxylation will give a mixture of cis- and transacids. The decarboxylation has sometimes been performed in a distillation step.4,5... 

Decarboxylation can be accompanied by hydrolysis in a one-pot reaction as in the formation of cyclobutanecarboxylic acid from diethyl cyclobutane-1,1-dicarboxylate.4... 

Acid treatment of cyclobutanecarboxylic acids with an external /(-carbonyl group was reported to give good yields of decarboxylated compounds. For example, dimethyl 3-oxo-l,2,2a,3,8,8a-hexahydrocyclobuta[/j]naphthalene-2a,8a-dicarboxylate was treated with acetic acid, water and sulfuric acid at 100°C to give 8-oxo-l,2,2a,3,8,8a-hexahydrocyclobuta[6]naphthalene-2a-car-boxylic acid (5) after in situ hydrolysis in 91 % yield.8... 

Other cyclobutanecarboxylic acid derivatives have also been converted to nitrogen-substituted cyclobutanes.37 43 47,339 For example, ran.s-2-(cyanomethyl)cyclobutanecarbohydrazide reacted with sodium nitrite/hydrochloric acid in methanol to give methyl traw-2-(cyanomethyl)-cyclobutylcarbamate (3).43... 

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