Solvent effects on the photocycloaddition and ...

Solvent effects on the photocycloaddition and photoenolisation reactio~~s of isophorone JANICEDEBORAH SHILOFF A N D NORMAN ROBERT HUNTER'

Can. J. Chem. 1979.57:3301-3303. Downloaded from www.nrcresearchpress.com by 113.240.238.6 on 10/17/15. For personal use only.

Dc,pn~.tmet~t c ~ f ' C h e ~ n i s t tUnicc>rsih y, of Manitohri, Wirltlipeg, ,Won., Crincicirr R372,\[2 Received June 18, 1979 This paper. is dedicclted to Prof. Kurel Wiesrler on the occasion o f h i s 60th birthday

J A ~ I CDEBORAH E SHILOFFand NORMAX ROBERT HUNTER. Can. J. Chem. 57,3301 (1979). The influence of solvent on two photochemical reactions of isophorone has been investigated. The photocycloaddition of isopropenyl acetate to isophorone (3,5,5-trimethylcyclohex-2-en1-one) (1) is best achieved using methanol as solvent. Photodeconjugation of isophorone (1) to the exocyclic methylene isomer 2 proceeds most efficiently in ethyl acetate.

J A ~ I C EDEBORAH SHILOFFet NORMAN ROBERTHUNTER. Can. J. Chem. 57.3301 (1979). On a CtudiC I'influence du solvant sur deux reactions photochimiques de I'isophorone. La photocycloaddition de I'acetate d'isopropenyle sur l'isophorone (trimethyl-3,5,5 cyclohexen-2one-1) (1) se produit plus facilement si on utilise le methanol colnme solvant. La photodCconjugaison de l'isophorone en l'isom6re 2 possedant un methylene exocyclique se produit avec un lneilleur rendement lorsqu'on utilise I'acktate d'ethyle comnie solvant. [Traduit par le journal]

Introduction In a recent review on the photocatalyzed enolisation process Salnmes (1) indicated that the general utility of the photoisomerisation of z,P-unsaturated ketones to their P,y-isomers is restricted by the many competing photoreactions which a, p-enones undergo. Earlier Dauben et al. (2) had reported the effects of tion of isopropenyl acetate to isophorone according alkyl substitution on the photochemistry of 2-cyclo- to the procedurc of Valenta and Liu (7) (Scheme 2). hexenones and summarized the knonn photodecon- In the literature procedure, a 0.5 M solution of jugation reactions of P-alkyl IX, P-cyclohexenones. isophorone in benzene was irradiated for four days More recently Chapman and Weiss (3) and Naka- in the presence of a 20-fold molar excess of isonishi and Sato (4) have provided short reviews on propenyl acetate to give the photoadduct 3 which photodeconjugation of enones and Tada and Miura could not be distilled because of the presence of (5) reported on the photoenolisation of four P-methyl polymeric by-products. a, P-enones. The only systematic investigation of the effect of solvent on the photodeconjugation reaction is Jennings' study of isophorone photochemistry (6). Jn that report Jennings indicated that solvent polarity played a very important role in the competition between isophorone photodimerisation and photodeconjugation. In very polar solvents the yield When we monitored this reaction by gas chromaof dimer was highest and decreased to zero in very tography, we observed that one important comnon-polar solvents. Jennings also reported that peting reaction was the photodeconju&.tion of isoirradiation of isophorone (1) in heptane at - 13°C phorone to the exomethylene compound 2. Comgave a single, unstable, product which was proven by pound 2 slowly isomerized back to 1 on standing in chemical and spectroscopic methods to be the de- the photolysis solution. It was our feeling that by a conjugated enone 3-methylidene-5,5-dimethylcyclo- judicious choice of solvent, the yield of both the hexanone (2) (Scheme 1) which probably arises via photodeconjugation and the photocycloaddition rethe transient enol. actions could be substantially improved. The results Our interest in the photodeconjugation reaction of our investigation are described below. was aroused when we repeated the photocycloaddiResults and Discussion 'To whom enquiries should be addressed. At the outset of our investigation, we laid down ooO8-4042/79/243301-03$01 .OO/O 0 1 9 7 9 National Research Council of CanadalConseil national de recherches du Canada


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several criteria to be met for the two reaction types. Firstly, both reactions must proceed with complete selectivity on the basis of solvent change only. Secondly, both reactions should be amenable to scale-up and thirdly, the products must be readily isolable in high yield and purity. The small-scale reactions which were carried out to determine appropriate solvent choices are described in the Experimental. The deconjugated enone 2 was prepared by irradiation of a 0.1 M solution of isophorone (1) in ethyl acetate. After 14 h of irradiation gc analysis indicated a greater than 9 5 x conversion of I to 2. Careful evaporation of the solvent yielded a colourless liquid which gave spectral data in agreement with that recorded by Jennings (6) for compound 2. The ethyl acetate solution of 2 obtained after photolysis could be stored at OcC for several weeks without appreciable reversion to 1.' We next turned our attention to the photocycloaddition of isopropenyl acetate to isophorone. Many of the earlier studies of photocycloaddition reactions (7-9) are characterized by the use of non-polar solvents and a large excess of alkene. In this study we have used methanol as solvent and only a four-fold excess of the alkene relative to isophorone. These modifications allow the preparation of photoadduct 3 in 7 1 z yield after distillation. In order to effect comparison of this photoproduct with that reported (7), the ketoacetate 3 was hydrolyzed to the known ketoalcohol 4 (7) in 88% yield after distillation. Our procedure provides improvement over the literature procedure in terms of reaction time, ease of purification, and increased yield. The dramatic effect of solvent in the course of isophorone photoreactions reported in this paper can be understood in terms of the reported dualistic nature of the triplets arising from enone photolysis (10) and the effect of solvent upon these triplet states (4). Our results indicate that many enone photoreactions may be profoundly affected by the appropriate choice of solvent. Infrared spectra were recorded with a Pye Unicam SPl000 infrared spectrometer using a neat film or in CCl, as solvent. Proton magnetic resonance spectra were recorded with a Varian EM-360 spectrometer using CCI4 as solvent and tetramethylsilane as internal standard. Mass spectra were measured with a Finnigan-1015 quadrupole mass spectrometer. Gas chromatographic analyses were done on a 10% SE-30 column using an Hewlett-Packard 700 chromatograph with flame ionization detection. 2This process affords,for the first time, a ready source o f 2 for further chemical studies. The results o f these studies, as well as kinetic studies o f the photodeconjugation reaction, will be reported in a future communication.

All photoreactions were carried out using a Photochemical Research Associate PRA-R400 photoreactor after purging the solvent with dry N 2 gas. Solvents were used as obtained from commercial sources. Isopropenyl acetate was used as obtained from J . T . Baker Chemical Co. and isophorone (Aldrich Chemical Co. Inc.) was distilled prior t o use. Small-scale Reactions The small-scale reactions were set up in Pyrex test-tubes in a "merry-go-round" assembly using a 0.25 M solution o f isophorone (0.35 g per 10 m L o f solvent) and a 1.0 M solution o f isopropenyl acetate (1.0 g per 10 m L o f solvent) for each o f the solvents studied. The reactions were monitored at two hour intervals by gas chromatography. All the photoadducts have longer reaction times than isophorone while the deconjugated isomer 2 had a shorter retention time. In methanol as solvent, exclusive photoadduct formation was observed. In ethyl acetate, exclusive deconjugation was observed. Benzene and hexane gave mixtures o f deconjugation and cycloaddition products as well as extensive polymeri~ation o f isopropenyl acetate.

3-Methylidene-5,5-dimet/1ylcyclo/zexatze (2) lsophorone (4.50 m L , 4.15 g, 0.03 mol) in ethyl acetate (300 m L ) was irradiated through a Pyrex filter in a PRA-R400 photoreactor for 14 h at which time gc indicated greater than 95% conversion o f isophorone into the deconjugated isomer 2 . Careful evaporation o f a 10 m L aliquot o f the ethyl acetate solution, at less than 3OGC,gave a clear colourless liquid (0.135 g, 9 8 2 o f theoretical) which had the following spectral e 138 data: mass spectrum, C,H,,O requires twle 138 ; n ~ / found: (fragmentation pattern identical t o isophorone); infrared (neat): 1720

(>c=o)and 1640 ()c=cH,)

c m - ' ; ' H m r in-

dicated that the sample contained less than 10% isophorone. The ' H m r peaks due t o 2 are 6 : 4.75 (2H, bs, >c=cH,),2.93 (2H, bs, H's on C-2), 2.15 (2H, bs), and 2.27 (2H, bs) due t o H's on C-4 and C-6, and 0.98 (6H, sharp singlet, CH,'s on C-5). T h e ' H m r spectrum was in agreement with the spectrum published in the literature (6). 7-Aceto~~y-4,4,6,7-tef~anzefhylbicyc/o [4.2.0]octcin-2-otie 13) The PRA-R400 photoreactor, equipped with a Pyrex filter system, was charged with isophorone (10.0 g, 0.072 mol, 0.24 M ) , 300 m L o f methanol, and isopropenyl acetate (30.0 g, 0.30 mol) and cooled in an ice-water bath. After 6.5 h o f irradiation gc analysis indicated essentially total consumption o f the isophorone, no deconjugation, and no polynierization o f the isopropenyl acetate. The reaction was worked up by evaporation o f the solvent and unconsumed isopropenyl acetate followed by addition o f 100 m L o f toluene and evaporation o f the toluene t o give the crude product (16.27 g, 0.068 mol, 94%). T h e crude product was distilled at 1.5 Torr in a Kugelrohr ( 1 3 0 C air bath temperature) t o yield, as the major fraction collected, 12.21 g (0.051 mol, 70.8%) o f pure 3 as a mixture o f diastereomers. Mass spectrum for C,,H,,O, requires mle 238; mle found: 238 ( M + ) , 196 (loss o f CH,=C=O), base peak 43 (CH,-C-O+). Infrared (CCI,): 1705 \

( ,C=O)

and 1730 (CH,-C-0-)

c m - ' ; ' H m r : complex ab-

I

0 sorption pattern showing acetate methyl peaks at 1.93 and 1.97 6 and saturated methyl singlets (eight peaks) in the region 0.87 t o 1.30 6 .

7-Hjdi.oxy-4,4,6,7-fetramethylbicyclo [4.2.0]octane-2-one(4) 7 - Acetoxy - 4,4,6,7 - tetramethylbicyclo[4.2.0]octan - 2 - one (11.90 g, 0.05 mol) was dissolved in methanol (125 m L ) with


SHII OFF 4 N D H U N T E R

slight warming on the steanibath. After the solution had cooled to ambient temperature, anhydrous potassium carbonate (20.7 g, 0.15 mol) was added. The resultillg mixture was stirred for 6 h and then worked up by pouring into 300 m L of H 2 0 and extracting the organic product with methylene chloride (3 x 75 mL). The organic extracts were washed with water (2 x 50 mL), dried, and evaporated. The resulting oil was distilled at 1.2 Torr in a Kugelrohr (120-140cC air bath temperature) t o give the keto alcohol 4 (8.62 g, 0.044 mol, 88%). Mass spectrum for C 1 2 H Z 0 0 2requires m/e 196; mle \

found: 196. Infrared (neat): 3450 (OH) and 1700 (,C=O) c m - I ; 'Hmr (CC14): complex pattern showing OH absorption at 3.98 6 and at least five methyl singlets in the region 0.9 to 1.23 6.

Acknowledgments The financial assistance of the Natural Sciences and Engineering Research Council of Canada and the Research Board, University of Manitoba, is gratefully acknowledged.

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I. P. G . S . A \ I \ ~ ETetrahedron. S. 32.405 (1976). 2. W. G . D A U R E N G.. W. SHAFFER, and N. D. VIETMEYER. J. Org. Chem. 33.4060 ( 1968). 3. 0. L. C H A P Z Iand A ~ D. S. Wrrss. Organic photochemistry. Vol. 3. Editecl by 0. L. Chapman. Marcel Dekker. Inc.. Nem York. NY. 1973. Chapt. 3. 4. K. N A K A ~ I Sand H I H. S A I O Natural . products chemistry. Vol. 2. Etlired hy K. Nakanishi. T. Goto. S. It6. S. Natori. and S. Noyoe. Kodanska Ltd.. Tokyo. Academic PI-ess. Inc.. New York. NY. 1975. Chapt. 12. 5 . M . TADAand K. MIURA.Bull. Chem. Soc. Jpn. 49. 713 (1976). 6. P. W . J ~ N U I N GPh.D. S . Dissertation, University of Utah. 1965; Diss. .4bstr. 26. 698 (1965). and H.-J. LIU.Org. Synth. 57, 113 (1977). 7. Z. VALENTA 8. N. R . HUNTER.G . A. MACALPINE. H.-J. LIU. and Z. VALENTA. Can. J. Chem. 48, 1436 (1970). 9. P. G . BAUSLAUGH. Synthesis. 287 (1970) and references quoted therein. 10. T . T E Z U K ATetrahedron . Lett. 5677 (1968).