Bromocyclobutanones

Paquette has used the chloroketal derivatives of thietane 1,1-dioxide as an especially well-suited model for the theoretical study of the thermally induced intramolecular six-electron ring contraction rearrangement, which is pointed out in Eq. (54) for the ketals of 2-bromocyclobutanone that give cyclopropylcarboxylates. Desulfurization of thietanes to cyclopropane did not prove too successful. ... 

Bromocyclobutanone and o-phenylenediamine condense to give the strained ring system cyclobuta[6]quinoxaline,33 and the cyclopenta[6]-quinoxaline ring system is similarly synthesized from suitable cyclo-pentanedione derivatives.34... 

Bromocyclobutanone acetals (249) are quantitatively converted to cyclopropane-carboxylic esters (250) and alkyl bromides, or to bromoesters in the case of cyclic acetals, upon simple heating in a sealed tube at 200°C (equation 168) . 

The rearrangement could also be affected by the action of NaNa-INs on 2-iodocyclobutyl azides (254) in acetonitrile . The reaction of o-phenylenediamine with 2-bromocyclobutanone does not afford a fused dihydroquinoxaline derivative (257) as first claimed , but 2-cyclopropylbenzimidazole (258) is formed by way of a similar ring contraction (equation 175) . 

The simplest system that can react according to this scheme is a cyclobutanol a-substituted with a leaving group. 2-Bromocyclobutanol, prepared by lithium aluminum hydride reduction of 2-bromocyclobutanone (obtained by bromination of cyclobutanone, readily available from methylenecyclopropane ), and 2-tosyloxycyclobutanol, also prepared by lithium aluminum hydride reduction of 2-tosyloxycyclobutanone (available from 2-hydroxycyclobutanone ), undergo quantitative ring contraction to cyclopropanecarbaldehyde (1), on simple treatment with aqueous sodium hydroxide. 

To a solution of NaOH (6g, 0.15 mol) in EtOH (25 mL) was added dropwise at 0°C with stirring a solution of 2-bromocyclobutanone (2.5 g, 17 mmol) in EtOH (10 mL). The solution turned yellow-orange while formation of NaBr occurred. The mixture was stirred at 20 °C for 1 h, then HjO (35 mL) was added. The solution was concentrated by distillation of EtOH until the boiling point reached 100°C. The aqueous phase was cooled to 20°C, washed with Et20, acidified to pH 1 by 0.5 M HCl and extracted with EtjO (4x20mL). The EtjO layer was dried (Na2S04) and concentrated under reduced pressure. The residue was fractionated under vacuum yield 1.3 g (91%) bp 84 C/ll Torr mp 12-14 C (ref 42 bp 182.5°C/760 Torr) mp 16-17°C). 

A mixture of 2-bromocyclobutanone (0.5 g, 3.4 mmol) in HjO (10 mL) was heated at 100°C until complete dissolution of the a-bromo ketone (30 min). The pH of the solution was close to 1 then the cooled solution was extracted with EtjO (4 x 10 mL). The organic phase was dried (Na2S04) and EtjO was removed on a rotary evaporator yield 0.22 g (82%). 

To 2-bromocyclobutanone (1 g, 6.8 mmol) was added liquid ammonia (10 mL) and the solution was allowed to evaporate. The residue was then extracted with boiling CHCI3 (25 mL) to remove insoluble NH4Br. Evaporation of CHCI3 gave 0.4 g of residue which was recrystallized from CHCl, yield 0.3 g (53%) mp 124-125°C ° (ref 42 mp 125°C). 

To anhyd EtOH (50 mL) was added sodium (0.35 g, 15 mmol) and the EtOH was removed under vacuum then anhyd Et20 (50 mL) was added. To this suspension of NaOEt in Et20 was added dropwise at 20°C a solution of 2-bromocyclobutanone (2 g, 13.5 mmol) in anhyd EtjO (10 mL). The mixture was stirred for 15 min and HjO (20 mL) was added. The aqueous layer was extracted with EtjO (10 mL) and the organic layer was dried (Na2S04). Evaporation of EtjO gave a residue which was fractionated under vacuum yield 1.03 g (67%) bp 43-48°C/30 Torr. 

In order to distinguish between a mechanism proceeding via a symmetrical cyclopropanone intermediate (Favorskii reaction) and a mechanism closely related to the benzilic acid rearrangement and called semibenzilic (or quasi-Favorskii) rearrangement, the ring contraction of 2-bromocyclobutanone was studied in deuterium oxide using sodium carbonate as base (50 C) or in boiling deuterium oxide only. 

In the ring contraction of 2-bromocyclobutanone, the nature of the solvent does not seem important thus, traM-2-bromo-3-methylcydobutanone underwent stereospecific ring contraction to form tran -2-methylcyclopropane derivatives 23 exclusively, either using ammonia, aqueous sodium carbonate (basic medium) or water (acidic medium). ... 

One other argument to discard the mechanism with a symmetrical intermediate was provided by the fact that no a -hydrogen is required to obtain the ring contraction thus, 2-bromo-4,4-dimethylcyclobutanone (24) underwent ring contraction at the same rate as 2-bromo-3,3-dimethylcyclobutanone (25) and 2-bromocyclobutanone itself. ... 

On simple heating in a sealed tube at 200°C 2-bromocyclobutanone acetals undergo quantitative ring contraction to cyclopropanecarboxylic esters 1 and alkyl bromides 2. ... 

The ambivalent nature of the acetal function must be underlined effectively it can act equally either as an electron-withdrawing substituent (Section 4.1.2.2.4. the ring contraction of 2-hydroxycyclobutanone acetals) or as an electron-donating substituent in these rearrangements of 2-bromocyclobutanone acetals. ... 

A 2-bromocyclobutylamine has been postulated as the intermediate in the reaction of 1,2-phenylenediamine with 2-bromocyclobutanone. The reaction did not afford a fused di-hydroquinoxaline derivative 7 as first reported,but was shown to give 2-cyclopropyl-benzimidazole (8), exclusively. This imidazole was unequivocally prepared on heating molecular equivalents of 1,2-phenylenediamine and cyclopropanecarboxylic acid at 180 °C for 30 minutes. 

As the reaction of 2-bromocyclobutanone with 1,2-phenylenediamine was carried out in 80% acidic aqueous methanol, ring contraction of a 2-bromocyclobutanone hydrate, hemiacetal or dimethyl acetal to cyclopropanecarboxylic acid (Section 4.1.2.2.4), followed by a Philipps-type benzimidazole synthesis could explain the formation of the 2-cyclopropylbenzimidazole (8). However, the reaction proceeded equally well in an aprotic solvent such as chloroform. Therefore, direct ring contraction of a 2-bromo-l,l-(l,2-phenylenediamino)-... 

Cyclopropanecarboxylic acid esters from 2-bromocyclobutanone ketals... 

Hydroxycoumarin treated with K- er -butoxide in terf-butanol, evaporated in vacuo, then treated in dimethyl sulfoxide with 2-bromocyclobutanone in benzene cyclopropyl 4-hydroxy-3-coumaryl ketone. Y 98%. F. e. s. V. S. Velezheva, I. V. Madiinskaya, and V. A. Barkhash, Zh. Vses. Khim. Obsdichest. 14, 467 (1969) C. A. 71, 112747. 

Bromocyclobutanone shaken with at least 2 moles of satd. aq. Na-carbonate soln. until the startg. m. is dissolved cyclopropanecarboxylic acid. Y ca. 90%. Also amide and ethyl ester s. J.-M. Conia and J.-L. Ripoll, C. r. 251, 1071 (1960). 

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