Benzocyclobutenone

BENZOCYCLOBUTENONE BY FLASH VACUUM PYROLYSIS (Bicycfo[4.2.0Jocta-i,3,5-trien-7-one)... 

This corresponds to a yield of benzocyclobutenone, >99% homogeneous by VPC, of 32% with respect to the 2-toluic acid chloride subjected-to pyrolysis, and of 63% with respect to the 2-toluic acid chloride consumed in the reaction. 

Benzocyclobutenone was first prepared from 1 -bromobenzocyclobutene by hydrolysis followed by chromium trioxide oxidation.3 More recent procedures involve hydrolysis of 1,1-dichloro- or 1,1-dimethoxybenzocyclobutene which in turn have been obtained through cycloaddition of the appropriate 1,1-disubstituted ethylenes to benzyne generated either from anthranilic acid through diazotization5 6 or from bromobenzene through sodium amide treatment.7.3 Benzocyclobutenone has... 

BENZOCYCLOBUTENONES PREPARED THROUGH FLASH VACUUM PYROLYSIS OF... 

The next three procedures provide useful synthetic intermediates. A stereospecific synthesis of ETHYL (Z)-3-BROMO-2-PROPENOATE affords an alternative vinyl bromide partner for the coupling chemistry in the preceding procedure. A very simple but elegant illustration of the flash vacuum pyrolysis technique is used to prepare BENZOCYCLOBUTENONE from o-toluoyl chloride. Another member of the functionalized indole family of synthetic intermediates is presented in a four-step procedure for 5-METHOXYINDOLE-2-ACETIC ACID METHYL ESTER. 

P. Sohiess, P. V. Barve, F. E. Dussy, and A. Pfiffner 116 BENZOCYCLOBUTENONE BY FLASH VACUUM PYROLYSIS... 

The pyrolysis temperature and the rate of addition are chosen such that about 50% of the acid chloride is recovered as 2-toluic acid after hydrolysis. Under these conditions only a small amount of benzyl chloride and polymeric material is formed in addition to benzocyclobutenone. The percentage of reactant conversion depends not only on the pyrolysis temperature, but also on the pressure in the reactor and on the rate of reactant addition. It is advisable, therefore, to optimize the pyrolysis temperature in trial runs keeping the other variables constant. 

In the runs carried out by the checkers, conversion of reactant was slightly lower than 50% as shown by the recovery of 2-toluic acid in 63-74% yield. In these runs benzocyclobutenone was obtained in 17-20% yield only. However, the yield calculated with respect to reactant consumed and not recovered as 2-toluic acid amounted to 56-64% and thus did not differ significanlty from the value given in the procedure. 

Benzocyclobutenone Bicyclo[4.2.0]octa-1,3,5-trien-7-one (8,9) (3469-06-5) 2-Toluic acid chloride o-Toluoyl chloride (8) Benzoyl chloride, 2-methyl- (9) (933-88-0)... 

By analogy, benzocyclopropene (1) is formed in low yield via biradical cycliza-tion upon irradiation of benzocyclobutenone (79), upon its flash vacuum pyrolysis, or upon pyrolysis of indan-2,3-dione (80). Reaction of phthalide 81 in a RF plasma leads also to However, these latter extrusion methods are of no preparative interest. 

Other approaches to alkylidenecycloproparenes have been attempted without success. Aromatization of appropriate alkylidenecyclopropanes or their precursors could not be realized, and flash vacuum pyrolysis of methylene phthalide and 3-methylene-2-coumaranone afforded rearrangement products rather than alkylidenecycloproparenes via extrusion of 002. The photochemical or thermal decomposition of the sodium salt of benzocyclobutenone p-toluenesulfonyl hydrazone led to products derived from dimerization of the intermediate benzocy-clobutenylidene, or from its reaction with the solvent, but no ring-contracted products were observed. When the adduct of methylene-l,6-methano[10]annulene to dicyanoacetylene (249) was subjected to Alder-Rickert cleavage, phenylacety-lene (250) was formed, which derives reasonably from the parent 234. ... 

The characteristic pyrolytic process for acid chlorides is loss of HC1 and this occurs for the bicyclic example 235 on FVP at 800 °C to give cyclohexa-1,2-diene 238 by way of the ketene 236 and carbene 237 as shown113. The product can be directly observed by low-temperature IR and forms a [2 + 2] dimer on warming up. FVP of >-toluoyl chloride 239 at 630 °C also results in loss of HC1 to provide a dependable large-scale synthesis of benzocyclobutenone 240 in excellent yield114. Pyrolysis of trichloroacetyl chloride, CI3C—COC1, over a bed of zinc at 420 °C results in dechlorination... 

Benzocyclobutenone and derivatives have been shown to react with diazomethylene anions to give 2,3-benzodiazepines under very mild conditions. A mechanism has been proposed which involves four-electron electrocyclic ring opening of the initial alkoxide, with important acceleration by the alkoxide anion. Torquoselectivity to set up an eight-electron electrocyclic ring closure to the benzodiazepine enolate has been attributed to the strong preference of the alkoxide anion for outward rotation. This mechanism has been supported by isolation of one of the /S-diazo alcohols, and its conversion to a benzodiazepine on LDA treatment.84... 

Lithium diisopropylphosphide (LDP) mediated distal ring opening of rac-(benzocyclobutenone)tricarbonylchro-mium 1139 forms the acylphosphane intermediate 1140, which reacts diastereoselectively with benzaldehyde to furnish the 3-phenyl-iscochroman-l-one chromium complex 1141 in moderate yield (Scheme 283) <2003EJO4363>. 

Benzocyclobutenones 1164 undergo heterolytic C( 1)—G(4) bond fission and reaction with aldehydes to provide a route to isochroman-3-ones 1165 (Equation 453, Table 55) <1997TL8985>. 

When diphenylbromoborane was used as electrophile, an acylborane 116 was obtained in 80% yield109. In the case of using (benzocyclobutenone)tricarbonylchromrum(O) as electrophile, a diastereoselective addition of compound 84 took place yielding the product... 

Similar flash vacuum pyrolysis of o-toluic acid chloride (561) lends itself to the easy preparation of benzocyclobutenone (563) (76% at a laboratory scale of 250 g). Variations of the aromatic nucleus are easy, as demonstrated by the preparation of derivatives (564)- 567) (Scheme 130). 

Stevens and Bisacchi have carefully examined the trailing of benzynes, generated fiom a number of aryl bromides and sodium amide in THF, with 1,1-dimethylethylene and report procedures which afford 6 6% yields of 1,1-dimethoxycyclobutenes, e.g. (131). These compounds are hydrolyzed quantitatively to the corresponding benzocyclobutenones (132). Excellent regioselectivity was obtained with unsym-metrical benzynes derived from methoxy substituted bromobenzenes due to the polarized nature of the benzyne intermediate. Steric effects also influence regioselectivity o-bromotoluene afforded a 3 1 mixture of 3-methyl- and 6-methyl-benzocyclobutene. 

The diazotization of anthranilic acid, a classic route to benzyne, when carried out in the presence of vinyl acetate, vinyl ethers or 1,1-dichloroethylene gives the expected benzocyclobutenes in about 40% yield. Despite the rather moderate yields this method represents a convenient route to multigram quantities of the parent compounds, benzocyclobutenol and benzocyclobutenone. The latter is easily converted to benzocyclobutene-1,2-dione. The diazotization sequence applied to 2-amino-3,6-dimeth-oxybenzoic acid and 1,1-dichloroethylene results in a 80% yield of 3, imethoxycyclobuten-l-one. Trapping of benzynes with other ethylene derivatives, and especially more substituted alkenes, has given generally poorer, variable results. ... 

In 1,2-disubstituted series such as cis- and frans-2-alkyl-l-alkoxybenzocyclobutenok, the traits isomer is more likely to lead to a high yield of cycloaddition product than the cis since the 1,5-hydrogen shift is precluded, llie forced inward rotation of an aryl substituent in 1-methoxy-l-phenylbenzocyclobutene is potentially advantageous and leads to anthracene derivatives." See also the anthraquinone synthesis fiom the corresponding benzocyclobutenones (Section 6.1.5). 

Isochroman-3-ones. A regioselective incorporation of an aromatic aldehyde unit accompanying opening of benzocyclobutenones to give l-arylisochroman-3-ones is promoted by LTMP. 

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