Cyclobutanecarboxylic acid, reaction

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... 

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... 

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... 

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... 

Cyclobutanecarboxylic acid azides react in a similar manner. The azides were either made from the acid chloride and sodium azide44,45 or directly from the acid by reaction with diphenylphos-phoryl azide.37,46,47 The carboxylic acid azides rearrange via the isocyanates. An example is the reaction of (+ )-ra-2-acetoxycyclobutanecarboxylic acid with diphenylphosphoryl azide to give 4 in quantitative yield.37... 

Another widely used decarboxylation procedure involves the use of lead tetraacetate. Depending on the nature of the substrate and the reaction conditions, this reagent may transform a carboxylic acid into an alkane or alkene, or into the respective acetoxy derivative (Scheme 2.144). The most favorable conditions for alkane formation utilize a good hydrogen donor as the solvent. Usually this transformation is carried out as a photochemically induced oxidative decarboxylation in chloroform solution, as is exemplified in the conversion of cyclobutanecarboxylic acid in cyclobutane.In contrast, the predominant formation of alkenes occurs in the presence of co-oxidants such as copper acetate. ... 

Keating and Skell" and later Laurent and Thomalla" have found that a similar mixture of products was obtained in the anodic oxidation of either cyclobutanecarboxylic acid, allylacetic or cyclopropaneacetic acid. They accounted for these results by a rapid equilibria among the carbocations initially formed. A similar observation is that in the anodic oxidation of the corresponding iodo reactants in acetonitrile N-(cyclopropylmethyl)acetamide was found in each product mixture". It is noteworthy that the same identity in products also holds for the chemical reactions of solvolysis and... 

Schmidt reaction. By the Schmidt reaction cyclobutanecarboxylic acid (Aldrich Chem. Co.) can be converted into cyclobutylamine in one step in high yield.12 On addition of powdered sodium azide to a stirred mixture of chloroform, cyclobutanecarboxylic acid, and concentrated sulfuric acid and heating at 50° for 1.5 hrs., the... 

In a second variation, one molar equivalent of sodiomalonic ester is allowed to react with one molar equivalent of a dihaloalkane. This reaction gives a haloalkylmalonic ester, which, when treated with sodium ethoxide, undergoes an internal alkylation reaction. This method has been used to prepare three-, four-, five-, and six-membered rings. An example is the synthesis of cyclobutanecarboxylic acid ... 

The synthesis of cyclobutanecarboxylic acid given in Section 18.7 was first carried out by William Perkin, Jr., in 1883, and it represented one of the first syntheses of an organic compound with a ring smaller than six carbon atoms. (There was a general feeling at the time that such compounds would be too unstable to exist.) Earlier in 1883, Perkin reported what he mistakenly believed to be a cyclobutane derivative obtained from the reaction of acetoacetic ester and 1,3-dibromopropane. The reaction that Perkin had expected to take place was the following ... 

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]. 

An acid-catalyzed lactonization of 8-hydroxy esters has been used in the diastereoselective synthesis of cA-4,5-substituted 8-lactones by Saigo et al. [48] (Scheme 11). The ring-opening aldol-type reaction of 2-methoxy-2-(trimethylsiloxy)cyclobutanecarboxylic ester 58 with aldehydes 59 in the presence of Lewis acid afforded the corresponding adducts 60 and 61. Subsequent treatment of these products with a catalytic amount of p-TsOH gave cis- and (rans-4,5-substituted lactones in favor of the c/r-isomer 62. 

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