Chemistry and Chemical Biology ETDs

Publication Date

1-10-1979

Abstract

The ketone, 3, 4-dihydrobenz[a]anthracen-1(2H)-one (1), was prepared in three steps from anthracene. Condensation of the lithioenolate of ethyl acetate with the ketone(1) in tetrahydrofuran at -78°C afforded ethyl (1-hydroxy-1, 2, 3, 4-tetrahydrobenz[a]anthracen-1-yl)acetate (2). Dehydration and dehydrogenation over palladium/charcoal provided ethyl (benz[a]anthracen-1-yl)acetate (3). Reduction of the ester (3) with diisobutylaluminum hydride in toluene at -75°C gave benz[a]anthracen-1-ylacetaldehyde (4) which was cyclized with methanesulfonic acid to benzo[a]pyrene (5). Saponification of the ester (3) gave benz[a]anthracen-1-ylacetic acid (6) which was cyclized with methanesulfonic acid to benzo[a]pyren-11-o1 (7). Oxidation of the phenol (7) with Fremy's salt afforded the quinone, 11, 12-dihydrobenzo[a]pyrene-11, 12-dione (8). Reduction of the quinone (8) with potassium borohydride in 2-propanol afforded trans-11, 12-dihydrobenzo[a]pyrene-11, 12-diol (9). Preparation of the dipotassium salt of the trans-diol (9) followed by addition of tosyl chloride presumably provided 11, 12-dihydrobenzo[a]pyrene-11, 12-oxide (10) which could not be isolated before rearranging to benzo[a]- pyren-12-o1 (11). The use of ethyl acetate-1-13C and ethyl acetate-2-13C where appropriate led to the 11- and 12-labelled benzo[a]pyrenes and appropriately labelled 11, 12-quinones. Allowing the dilithioenolate of the acid (6) to react with acetyl chloride in tetrahydrofuran at -78°C gave 2-(benz[a]anthracen-1-y1)-3-oxobutanoic acid which was decarboxylated and cyclized with methane­sulfonic acid to 11-methylbenzo[a]pyrene (12). In similar fashion, chrysen-4-ylacetic acid (13) was converted to 5-methylbenzo[a]pyrene (14). Condensation of the lithioenolate of ethyl acetate with 1, 2, 7, 11btetrahydro-3H-benz[de]anthracen-3-one (15) in tetrahydrofuran at -78°C afforded ethyl (3-hydroxy-1, 2, 7 11b-tetrahydro-3H-benz[de]anthracen-3-y1)­acetate (16). Dehydration of the crude hydroxyester (16) with anhydrous formic acid followed by hydrogenation over palladium/charcoal gave ethyl (1, 2, 7, 11b-tetrahydro-3H-benz[de]anthracen-3-y1)acetate (17). The ester (17) was reduced with lithium aluminum hydride and converted with thionyl chloride to 2-(1, 2, 7, 11b-tetrahydro-3H-benz[de]anthracen-3-yl)chloroethane (18). Treatment of the chloride (18) with potassium cyanide in acetonitrile and benzene containing 18-Crown-6 and subsequent hydrolysis afforded 3-(1, 2, 7, 11b-tetrahydro-3H-benz[de]anthracen-3-y1)­propanoic acid (19) which was cyclized with anhydrous hydrofluoric acid to 1, 6, 10b, 11, 12, 12a-hexahydrobenzo[a]pyren-3(2HO-one (20). Reduction of the ketone (20) with lithium aluminum hydride followed by dehydration and dehydrogenation over palladium/charcoal gave benzo[a]pyrene (5). Dehydrogenation of the ketone (20) over palladium black gave benzo[a]­pyren-3-o1 (21). Oxidation of the phenol (21) with Fremy's salt didnot give 2, 3-dihydrobenzo[a]pyrene-2, 3-dione (22) as expected but gave instead an unknown quinone of benzo[a]pyrene. The use of ethyl acetate-1-13C, ethyl acetate-2-13C and potassium cyanide-13C where appropriate in this sequence afforded the 1-, 2- and 3-labelled benzo[a]pyrenes. The 13CNMR spectra of the labelled benzo[a]pyrenes and derivatives were determined. The previous assignment of 13CNMR chemical shifts by Buchanan and Ozubko for benzo[a]pyrene was correct for carbons 3 and 11 but incorrect for carbons 1, 2 and 12.

Project Sponsors

Grant No. CA-16871 awarded by the National Cancer Institute, DHEW

Language

English

Document Type

Dissertation

Degree Name

Chemistry

Level of Degree

Doctoral

Department Name

Department of Chemistry and Chemical Biology

First Committee Member (Chair)

Guido Herman Daub

Second Committee Member

David Lee Vanderjagt

Third Committee Member

Cary Jacks Morrow

Fourth Committee Member

Illegible

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