Keto ethers. IV.' Products formed on reaction of dihydro-2,2,5,5-tetramethyl-3(2H)-furanone with strong acids

PETER YATES AND PATRICK MICHAEL BURKE:!

Lash Miller Chemical Laboratories, University of Toronto, Toronto, Ont., Canada M5S IAI

Received August 20, 1986

This paper is dedicated to Professor John T. Edward

PETER YATES and PATRICK MICHAEL BURKE. Can. J. Chem. 65, 1695 (1987). Reaction of tetrahydro-2,2,5,5-tetramethyl-3(2H)-furanone (1) with 96 or ca. 100% sulfuric acid or hot polyphosphoric acid

followed by aqueous quenching gave the following products: 2-hydroxy-2,5-dimethyl-4-hexen-3-one (3), 2,4,4-trimethyl-2- cyclopenten-1-one (7), 3,5,5-trimethyl-2-cyclopenten-1-one (8), tetrahydro-3,4,5,5-tetramethylfuran-2,3-diol ( l l ) , 2,5- dihydro-3,5,5-trimethyl-2-methylenefuran (17) and its dimer 20, 2,5-dihydro-2,3,5,5-tetramethyl-2-furanol (IS), 4-hydroxy- 2,4-dimethyl-2-pentenoic acid y-lactone (22), 2,3,5-trimethyl-2-cyclopenten-1-one (23), and tetramethylfuran (25). In 96% sulfuric acid the products arise by ring opening, ring opening followed by reclosure to carbocyclic products, methyl migration from C-2 to C-3 to give rearranged furan derivatives, and oxidation. Inca. 100% sulfuric acid or hot polyphosphoric acid further methyl migrations can occur to give 23 and 25.

PETER YATES et PATRICK MICHAEL BURKE. Can. J . Chem. 65, 1695 (1987). La reaction de la tetrahydro tCtramCthyl-2,2,5,5 2H-furannone-3 (1) avec de I'acide sufurique a 96 ou ti environ 100% ou avec

de l'acide polyphosphorique chaud, suivie par un piCgeage avec de l'eau, conduit aux produits suivants : l'hydroxy-2 dimethyl-2,5 hexkne-4 one-3 (3), la trimithyl-2,4,4 cyclopentkne-2 one-1 (7), la trimethyl-3,5,5 cyclopentkne-2 one- 1 (8), le tetrahydro tCtramCthy1-3,4,5,5 furannediol-2,3 (11), le dihydro-2,5 trimethyl-3,5,5 mCthyl6ne-2 furanne (17) et son dimere 20, le dihydro-2,5 tetramethyl-2,3,5,5 furannol-2 (18), la y-lactone de l'acide hydroxy-4 dimethyl-2.4 pentkne-2 olque (22), la trimethyl-2,3,5 cyclopentkne-2 one- 1 (23) et le tktramethylfuranne (25). Dans l'acide sulfurique a 9610, les produits proviennent d'ouvertures de cycle, d'ouvertures de cycle suivies d'une recyclisation conduisant a des produits carbocycliques, de transpositions de groupements mtthyles de la position C-2 a la position C-3 conduisant a des dCrivCs furanniques transposCs et d'oxydations. Dans I'acide sulfurique a environ 100% ou dans l'acide polyphosphorique a chaud, il se produit d'autres migrations de groupernents mkthyles qui conduisent aux composCs 23 et 25.

[Traduit par la revue]

There have been many investigations of the reactions of organic compounds with strong acids (3, 4). Several of these have concerned substrates with saturated or unsaturated car- bony1 functions. Less attention has been paid to carbonyl compounds containing other functional groups. We report on an investigation of the variety of reactions undergone by the keto ether 1 in strongly acidic media.3 We describe here the isolation and determination of the structures of the products formed in such reactions and plan, in a subsequent publication, to discuss the formation of these products in terms of the site(s) of protonation of 1 and the nature of the cationic intermediates.

Compound 1 is readily available from the ynediol 2 (6). Reactions in strongly acidic media followed by aqueous quenching gave mixtures of products whose composition was dependent on both the nature of the medium and the time of reaction. These products were isolated by standard procedures and identified by their spectra (Tables 1 and 2) and by comparison in most cases with independently synthesized samples.

Vapor phase chromatographic (vpc) analyses of product mixtures from 96% sulfuric acid showed that one compound was formed rapidly and that the amount of this product reached a maximum after 2 h and then fell to zero after several days. This compound was shown to be 3 by comparison with an authentic

'This series of papers was originally designated as a-Keto Ethers (1); to avoid ambiguity we now use the term Keto Ethers. Reference 2 is considered to be paper 111 in this series.

2~resent address: E. I. du Pont de Nernours and Co., Petrochemicals De artment, Wilmington, DE 19898, U.S.A.

'Part of this work was carried out some years ago (5); where other workers have in the meantime reported related results we give only a cursory account of our own observations.

TABLE 1. The ir and uv spectra of the products from the reactions of compound 1 with sulfuric acid and of related compounds

3 5.87, 5.96 (s), 6.19 240 (12 600) 7 5.85 (s), 6.10 229 (1 2 000) 8 5.85 (s), 6.15 229 ( 12 600) 9 5.84(~) ,5.90(sh) ,6.15 229(12000)

11 2.75, 2.78, 2.85-2.95 - 17 6.04, 6.12 254 (7000) 18 2.75, 2.85, 2.95, 6.05 End absorption 20 6.04, 6.09 261 (7200) 23 5.87 (s), 6.04 236 (1 3 200) 25 6.05, 6.25 222 (7000)

"For structures, see Table 2. CCI,; s = strong, sh = shoulder.

'In 95% EtOH; only n-n* bands recorded.

sample prepared as in Scheme 1 (2,7). It has been reported that 3 fails to form a 2,4-dinitrophenylhydrazone (7); our attempts to form such a derivative in ethanol gave the 2,4-dinitrophenyl- hydrazone of the 0-ethyl analogue of 3.

A second product that was detected by vpc analysis increased in amount gradually to a maximum of about 5% after 6 h and then remained essentially constant in amount. This compound was shown to be 7 by comparison with an authentic sample (Scheme 1). Treatment of 2 with hot 50% sulfuric acid gave the dienyne 4 (8) in 45-50% yield, accompanied by a complex mixture of otherproducts, three of which were identified as 1 ,3 , and 5; the structural assignment 5 is based on spectroscopic data (see Experimental). Cuprous ion-catalyzed addition of hydrogen chloride to 4 gave a product whose ' H nmr spectrum

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TABLE 2. The 'H and I3c nrnr spectra of the products from the reactions of compound 1 with sulfuric acid and of related compounds

Compound H6" ' t i b

1.27 CHI-2

fiO 1.96 (d, J 1.5) CHI-5z 2.18 (d, J 1.5) c H 1 - 5 ~

E zHO 3.75 (br s) 3

OH 6.20 (m)

1.18 CHI-4 a0 1.68(d,J1.5) CHI-2 2.13 H-5

7 6.92 (q, J 1.5) H-3

1.05 CHI-5 2.09 (d, J 1) CHI-3 2.48 (br s) H-4

8 5.78 (m) H-2

1.22 CHI-4 2.01 (d, J 1.5) CHI-3 2.17 H-5

9 5.68 (q, J 1.5) H-2

11 1.95 (AB, J 12) H-4 2.70 (br s) OH

1.29 CHI-5 \::; r, J 2) CHI-3 H- l

17 3.99 5.80 (q, J 2) H-4

5.42 (q, J 2) H-4

1.28 I 1.45 CH3-2'

2oC 1.71 l . M ( d , J 2 ) } (d, J 2 ) {CHI-3' CHI-3

4.15 H- 1 5.13(q, J 2 ) H-4' 5.72 (q, J 2) H-4

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TABLE 2. (concluded)

Compound " 8 a '8'

1.27 1.57 (br s)

2IC

2.30 5.17 (q, J 2)

1.08 (d, J 7) v0 1.61 2.01

23 2.0-3.0 (rn)

"In CCI,; signals are singlets unless otherwise specified, and have relative intensities in accord with assignments; J values are in hertz.

b ~ n CDC13; multiplicities in SFORD spectra are in accord with assignments. 'For numbering see structure below:

0

Hg(oAc11 1. Hg(OAc)?, Ac20 P (CH3)2CC-CC(CH3)2

I1 t (CH3)2C=CHCC(CH3)2

aq.HIS04 I I 2. OH-

1 OH OH O H

HCI, NH4CL Cu20, Cu I C

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1698 CAN. J. CHEM. VOL. 65, 1987

showed it to be 3,4-dichloro-23-dimethyl-2,4-hexadiene (6) and not the corresponding 1,3-dichloro compound as earlier considered (8).4 Treatment of 6 with hot 85% sulfuric acid gave 7.

A second cyclopentenone was detected among the reaction products from treatment of 1 with 96% sulfuric acid; it was present in only trace amounts, but was formed in greater, albeit still small, amounts from 1 on treatment with ca. 100% sulfuric acid (vide infra). This product was shown to be 3,5,5-trimethyl- 2-cyclopenten-1-one (8) by comparison with an authentic sample (lo), obtained as a 2:3 mixture with 3,4,4-trimethyl-2- cyclopenten-1-one (9). The individual structural assignments

are based on an alternative, unambiguous synthesis of 9 (1 1) and are confirmed by comparison of the 'H nmr spectra of these compounds and 7 (Table 2).

Work-up of the reaction mixture of 1 and 96% sulfuric acid after short reaction times gave, in addition to compounds 3, 7 , and 8, a crystalline, highly water-soluble compound, C8Hl6O3, which could only be isolated by continuous extraction. The yield of this product increased in the first two hours and decreased to zero after 12 days. It is assigned the gross structure 11 on the following basis. Its ir spectrum shows the presence of one or more hydroxyl groups and the absence of a carbonyl group. Oxidation with lead tetraacetate followed by basic hydrolysis gave diacetone alcohol (14) (Scheme 2). It was independently synthesized by treatment of the hydroxy lactone 10 (12) with methylmagnesium iodide. This reaction also gave 12, identified by comparison with an authentic sample prepared by treatment of 1 with methylmagnesium iodide (13), and a high-melting crystalline product 13. The structure of the latter was not established, but it may be related to 2,3,5-trimethyl- 2,3,5-hexanetriol since it gave 12 on treatment with 50% sulfuric acid. While 11 was obtained as a crystalline solid with a 2" melting range, its 'H and 13c nmr spectra exhibit a complex series of peaks in the methyl proton region, indicating that in solution it exists as a mixture of diastereomers (the 'H nmr data given in Table 2 are the signals assigned to the major tautomer). These diastereomers should be readily interconvertible via ring-chain tautomerization, although none of the ketonic tautomer could be observed spectroscopically.

Two interesting reactions of the diol11 were observed. When injected onto a vpc column (see Experimental) at 140°C it underwent pinacol rearrangement to give 1; this reaction appears to be catalyzed by acid sites on the column, since no reaction was observed on heating 11 alone at 150°C. When a solution of 11 in benzene was boiled in the presence of a catalytic amount of p-toluenesulfonic acid, bimolecular dehydration occurred to give a high-melting crystalline product lacking hydroxyl or carbonyl groups. This is assigned the gross structure 15, the head-to-tail isomer being preferred on mecha- nistic grounds and because both 15 and 11 dissolve in 96% sulfuric acid to give rapidly and quantitatively the same cationic species, as shown by 'H nmr spectroscopy.

After long reaction times (5- 12 days) the 'H nmr spectrum of

4~oewenthal (9) has reached the same conclusion regarding the structure of this intermediate.

the reaction mixture of 1 and 96% sulfuric acid indicated that only one major cationic species was present. However, the usual work-up conditions (quenching in water) gave rise to a complex mixture of "infinity" products. It soon became evident that this was because the product initially formed on quenching was extremely sensitive both to acids and to atmospheric oxygen. When the reaction mixture was quenched in aqueous base and precautions were taken during work-up to avoid contact of the product with adventitious acid and to minimize contact with air, a volatile product was obtained. This was shown to be 17 by comparison with an authentic sample prepared by treatment of the enynol 16 (14, 15) with aqueous mercuric acetate (Scheme 3).5

When the base-quenched reaction mixture of 1 and 96% sulfuric acid was worked up without precautions to avoid contact with adventitious acid the major product isolated was not 17, but a compound that decomposed to give 17. This compound is assigned structure 18 on the basis of its conversion on standing to 17 and the fact that the latter in the presence of water is converted to the former. On longer standing both 17 and 18 formed the same bimolecular product, 17 via dimerization and 18 via dehydration and dimerization. This product was also isolated from the mixture of infinity products from 1 and 96% sulfuric acid on quenching with water (vide s~ipra). It is assigned structure 20 on spectroscopic grounds and because of its conversion on hydrogenation to a dihydro derivative considered to be 21 (Scheme 3). The ir spectrum of 20 shows ethylenic stretching bands analogous to those of 17 and its uv spectrum shows a maximum at 261 nm ( E 7100) with a small bathochromic shift as expected in relation to the maximum of 17 at 254 nm. Its 'H nmr spectrum shows the presence of five CH3-c(sp3) and two CH3-C(sp2) groups, the latter each being allylically coupled to a vinyl proton; in addition, a one-proton singlet at 6 4.15 ppm is attributable to the HC=C-0 proton of 20, analogous to the H2C=C-0 proton signals of 17 at 6 3.67 and 3.99 ppm. The relationship of the I3C spectra of 20 and 17 (Table 2) confirms the structural assignment.

The hydrogenation of 20 is considered to occur in 1,4 fashion giving 21, whose 'H nmr spectrum shows the presence of five CH3-C(sp3) groups, two CH~-C(S~') groups, and a single vinyl proton, coupled to one of the latter CH3 groups. It is considered that the conversion of 17 and 18 to 20 is effected by traces of adventitious acids, involving reversible protonation of 17 to give the cation 19 and attack of this on 17 followed by loss of a proton. The ease of conversion of 17 to 20 is shown by the fact that treatment of 16 with mercuric acetate in 2% sulfuric acid gives 20 rather than 17 (Scheme 3).

It was noted above that the nature of the product mixture from 1 and 96% sulfuric acid is affected by the presence of atmospheric oxygen. This led to the formation of an additional product, whose relative amount was increased when the reaction mixture was exposed to air after quenching and work-up. This product was identified as the lactone 22 by comparison with an authentic sample obtained by dehydration of 10 (Scheme 2) (12). It is clear that this product arises by autoxidation of either 17 or its cationic precursor.

When 1 was treated with 99.5-100.3s sulfuric acid, the

his synthesis is based on that of 2,5-dialkylfurans (16). Arens and Brandesma and co-workers have prepared 17 by base-catalyzed cyclization of 16 (17) and rearrangement of 4,s-epoxy-3,5-dimethyl- 1-hexyne (18).

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I . MeMgI d' 2, aq, NH4Cl ' a'' + dH + l 3

I . MeMgI

aq. KOH 2. aq. NH4CI

OH

16

2% aq.

product distribution after quenching was markedly different from that observed on treatment with 96% sulfuric acid. The amount of the diene 17 was greatly reduced and the product mixture consisted largely of the cyclopentenones 7 and 8, together with a new product, which in the case of 100.3% sulfuric acid was the preponderant product. This was isomeric with 7 and 8 and was identified as the cyclopentenone 23 on the following basis. Its spectra indicated that it is either 2,3,5- trimethyl-2-cyclopenten- 1-one (23) or 2,3,4-trimethyl-2-cyclo- penten- 1 -one. The latter compound has been prepared pre- viously (19) and the melting point of its semicarbazone does not correspond with that of the semicarbazone prepared from the product obtained in the present work. Furthermore, ozonolysis of this product followed by oxidative work-up gave a mixture of a-methyllevulinic acid (24) (20) and its tautomeric lactol. Thus the product from 1 and 99.5- 100.3% sulfuric acid has structure 23.6

When 1 was heated with polyphosphoric acid for 2 h at 100°C the diene 17 and the cyclopentenone 7 were observed after quenching, together with a major additional product. When the reaction mixture was heated for 6 h at 120"C, this new product was formed almost exclusively. It was identified as tetramethyl- furan (25) by comparison of it and its exo adduct with maleic anhydride with authentic samples (22, 23).

In summary, 1 on treatment with 96% sulfuric acid followed

he fact that the ir carbonyl stretching band of 9 has a shoulder while those of 7 , 8, and 23 do not is in accord with expectation, based on our studies of Fermi resonance in the spectra of 2-cyclo- penten-1-ones (21).

by quenching gives the products shown in Scheme 4. The hydroxy enone 3 and the diol11 are isolated only after relatively short reaction times, while the diene 17 is the major product after long reaction times. The cyclopentenones 7 and 8 are formed in relatively small amounts but persist after long reaction times. Autoxidation gives the lactone 22. Reaction of 1 with 99.5- 100.3% sulfuric acid followed by quenching gives increased amounts of the cyclopentenones 7 and 8 together with the diene 17 and the cyclopentenone 23. In hot polyphosphoric acid 1 gives, after quenching, tetramethylfuran (25) together

with cyclopentenone products. Thus in 96% sulfuric acid the products arise by (i) ring opening,' (ii) ring opening followed by reclosure to carbocyclic products, (iii) methyl migration to give rearranged furan derivatives, and (iv) autoxidation. In 99.5-100.35% sulfuric acid or hot polyphosphoric acid solu- tions further methyl migrations can occur to give 23 and 25.

Experimental Melting points were determined on a Fisher-Jones micro hot stage

and are uncorrected. Infrared spectra were recorded in CC14, unless otherwise indicated; ultraviolet spectra were recorded in 95% EtOH.

'We.have shown that cleavage of 1 to 3 is reversible (2).

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The 'H and '3Cnmr spectra were recorded in CC14 and CDC13, respectively.

Vapor phase chromatographic (vpc) analyses were canied out on an F and M Model 500 gas chromatograph. Helium was used as carrier gas and the flow rate was adjusted to 35-45 mL/min. The columns used were commercially available (F and M Scientific Corporation) and consisted of coiled stainless steel tubes with 0.25-in. od containing one of the following packings (10% substrate in each case): diisodecyl phthalate (DIDP) on 60-80 mesh Chromsorb P (6 ft); neopentylglycol sebacate (NPGS) on 60-80 mesh Chromsorb P (8 ft); fluorosilicone on 60-80 mesh Diatoport S (6 ft); Carbowax 1500 on 60-80 mesh Chromsorb P (6 ft). Preparative vapor phase chromatographic separa- tions were performed on an F and M Model 770 automatic preparative gas chromatograph with helium at a rate of 1.5-2.0 L/min as camer gas. The column consisted of two 4-ft, 0.75-in. od stainless steel tubes connected at the bottom with a 0.25-in. jumper tube. The column packing consisted of NPGS supported on 60-80 mesh Chromsorb W (10% substrate). Dry Ice - acetone was used in the cooling bath.

The 96% H2SO4 used in this work was C.P. reagent grade concentrated H2S04, specified to contain a minimum of 95.5% by weight &So4. The 100.3% H2S04 was made by addition of 30% oleum (Fisher reagent grade fuming H2SO4 specified to contain 30-33% free SO3; 80 g) to 96% H2SO4 (120 g). Its strength was determined by titration. The 99.5% H2SO4 was made in similar fashion.

Dihydro-2,2-5,5-tetramethyl-3(2H)-furanone (1) Compound 1 was prepared from 2,5-dimethyl-3-hexyne-2,5-diol by

the method of Leonard et al. (6). The product was distilled to give a colorless liquid, bp 54-55°C (22 Tom; 1 Torr = 133.3 Pa); ni3 1.4192 (lit. (6) bp 150-151°C; n',O 1.4211); ir, A,,,: 5.68, 8.67 Fm; uv, A,,: 295 ( E 32), 245 nm (sh, E 88). The 2,4-dinitrophenylhydrazone of 1 was prepared by the method of Shriner, Fuson, and Curtin (24); recrystallization from 95% EtOH gave yellow plates, mp 179.5- 180.5"C (lit. (6) mp 178-179°C).

Reactions of compound 1 in 92-96% sulfuric acid (i) Isolation of products formed after 10 rnin - 25 h Solutions of 1 in 96% &So4 were allowed to stand for the following

periods: lOmin, 2 h, 6 h, 12 h, 18 h, 25 h, and 12 days. The following procedure was used in carrying out the reactions and working up the reaction mixtures.

Compound 1 (2.00 g) was added dropwise with gentle swirling to 96% H2SO4 (20g), which was cooled in ice-water. The reaction mixture was allowed to stand at room temperature in a stoppered flask.

The initially light yellow solution slowly darkened on standing for some hours and finally became black after ca. 2 days. After being allowed to stand for a specified time, the solution was poured in a thin stream into a rapidly stirred ice-water mixture (200 g). The aqueous solution was extracted with ether (2 x 100 mL) and the extract was dried over a mixture of anhydrous MgS04 (10 g) and K2C03 (2 g). Removal of the solvent gave an oil (Extract I). The remaining aqueous solution was contiguously extracted with ether for 2 days. The extract was dried over MgS04-K2C03 and the solvent was evaporated. The residue (Extract 11) generally crystallized on standing in petroleum ether or cyclohexane.

Extract I was analyzed by vpc on a DIDP column at 150°C. The products were isolated by allowing the effluent carrier gas stream from the exit port to pass through U-tubes cooled in Dry Ice - acetone as each peak appeared on the chromatogram.

The following results for a reaction time of 6 h exemplify those obtained with the procedure described above. Extract I consisted of a pale yellow oil (0.72 g) that slowly turned dark red on being exposed to air. Its ir spectrum showed bands at 2.75, 2.8-2.9, 5.68, 5.84, 5.95, and 6.0-6.17 pm. Vapor phase chromatography on a DIDP column at 150°C showed the presence of three components.8 These were (with retention times given in parentheses) residual compound 1 (3.7 rnin), 2,4,4-trimethyl-2-cyclopenten-1 -one (5)"6.8 min), and 2-hydroxy- 2,5-dimethyl-4-hexen-3-one (3)' (1 1.1 min). Quantitative comparison of the vpc peak area produced by a known volume of compound 1 with that produced by the same volume of Extract I indicated that ca. 54% of the latter was retained on the column.

Extract I1 consisted of a viscous yellow oil (0.66 g). Its ir spectrum showed prominent bands at 2.75, 2.8-2.9,9.15, and 10.5-1.07 Fm. On standing alone or in petroleum ether, the oil deposited long, needle-like crystals of tetrahydro-2,3,5,5-tetramethylfuran-2,3-diol (111.9

Analysis by vpc of Extract I from the 12-, 18-, and 25-h reactions revealed the presence of an additional product with longer retention time (13.8 min), which was found to be 4-hydroxy-2,4-dimethyl-2- pentenoic acid y-lactone (22).' These analyses were carried out on samples that had stood in air for several days. It was subsequently found that the relative amount of this component in the mixtures increased with time of standing. Moreover, reexamination of a sample

'~hin-layer chromatography on silica gel with chloroform - 10% methanol as eluent and iodine vapor as developer indicated the presence of at least four components in the mixture; it was subsequently found that trace amounts of compound 8 (vide infra) were present.

'~dentified by comparison with an authentic sample (vide infra).

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of Extract I from the 6-h reaction that had stood for 2 weeks now indicated the presence of ca. 5% of 22.

The composition of Extract I, as indicated by the vpc and spectroscopic analyses, varied with the reaction time as follows: the amount of compound 3 increased to a maximum at 2 h and then decreased gradually to zero after 12 days; that of compound 7 increased in the first 6 h and then remained constant. The amount of product retained on the vpc column increased with time, becoming ca. 94% of Extract I after 12 days. The composition of Extract 11, as indicated by spectroscopic analysis, remained essentially constant for the different reaction times. The yield of 11 increased during the first 2 h, then remained approximately constant up to a reaction time of 25 h and decreased to zero after 12 days.

Each of compounds 3 , 7 , and 11 was isolated in pure form by vpc of a sample of Extract I in which it appeared in optimum concentration. With the use of temperatures 10-20°C lower than those used for the analytical runs, it was found that sample sizes up to 100 pL could be separated on the analytical columns without serious loss of resolution.

(ii) Isolation of injinity products (a ) Work-up under acidic conditions. A solution of 1 (10.0 g) in 92%

~ 2 ~ 0 4 " (100 g) was allowed to stand at room temperature for 5 days in a loosely stoppered flask. The solution was then poured in a thin stream into rapidly stirred ice-water (1 kg). A black scum that formed on the surface of the aqueous solution was filtered and the brown filtrate was extracted with ether (500 mL; 2 x 250 mL). The extract was washed with saturated aqueous NaHC03, 250 mL) and water (250 mL) and dried over MgS04. Evaporation of the solvent gave a pale yellow liquid (6.2 g); ir, A,,: 5.84, 6.02-6.10, 10.5 p m Vapor phase chromatographic analysis on an NPGS column at 120°C indicated the presence of three components with low retention times (3.2,4.2, and 7.6 min) and one component that gave rise to a broad peak with a very long retention time (54.2 min; ca. 65% of total). Distillation of the product mixture gave a colorless liquid (1.25 g), bp 85-87°C (0.65 Torr). This slowly turned red on exposure to air. Two further distzations gave pure compound 20,9 bp 73-74°C (0.35 Torr).

( b ) Work-up under basic conditions. A solution of 1 (50 g) in 94% H,SO~" (1 kg) was allowed to stand at room temperature for 3 weeks. Part of this solution (200 g) was added through a capillary to the periphery of a rapidly stirred solution of NaOH (200 g) in water (1 L) cooled to ca. 5°C and surrounded by an ice bath. When the addition was complete the alkaline solution was steam distilled. The distillate (250 mL) was saturated with NaCl and extracted with ether (200 mL; 2 x 150 mL). The extract was dried over K2C03 and the solvent was evaporated to give 2 ,5 -dihydro-2,3,5,5 - tetramethyl-2 -furan01 (18) as a pale yellow, mobile liquid (6.82 g). Distillation, which was accompanied by much decomposition, gave 18 as a colorless liquid (1.6g), bp 80-81°C (27 Torr).

When compound 18 was allowed to stand in a tightly stoppered flask for 2 weeks globules of water were formed. The H nmr spectrum of the resulting organic product was identical with that of compound 20.

In a second experiment all glassware with which the extract from the basified reaction mixture was to come into contact was soaked in aqueous 10% NaOH before use. Under these conditions the product (15.7 g) from 400 g of a similar acid reaction solution to that above showed much reduced absorption in the 2.75-2.9 p m region of its ir spectrum. Distillation gave two well-~e~arated'fractions: (i) bp 46-48°C (30 Torr) (5.3 g) and ( i i ) bp 103°C (2 Torr) (3.7 g). The latter was shown to be compound 20. Fraction ( i ) was a clear, colorless liquid with a strong mint-like odor; ir, A,,,: 5.85, 6.05-6.10, 10.45 pm; uv (EtOH), A,,,: 254 nm. Analysis by vpc (NPGS, 85°C) and collection of fractions showed the presence of compound 7 and 2,5-dihydro-3,5,5-trimethyl-2-methylenefran (17),~ the latter being the major product.

at such a rate that the temperature did not rise above 20°C. The solution rapidly developed a deep red color, which darkened slowly on standing. The reaction mixture was allowed to stand for 4 h and was then added through a capillary to rapidly stirred ice-water (2 kg). The aqueous acid solution was extracted with ether (3 X 300 mL) and the extract was washed with saturated aqueous NaHC03 (100 mL) and dried over MgS04. Removal of the solvent gave a light yellow, sweet-smelling liquid (4.1 g); ir, A,,,: 5.84,6.10 pm. Analysis by vpc (NPGS, 130°C) showed the presence of three compounds (retention times and relative yields are in parentheses): compound 1 (6.0 min; 44%), 3,5,5-trimethyl-2-cyclopenten-I-one (8)"12.0 min; 1.7%), and 2,3,5-trimethyl-2-cyclopenten-I-one (23)9 (12.0 min; 54%). These were separated by preparative vpc (NPGS, 120°C).

(b ) Work-up under basic conditions. The reaction of 1 (10.0 g) with 100.3% H2S04 (200 g) was allowed to proceed as above for 5 h. The reaction mixture was then added through a capillary to aqueous 10% NaOH (2 L) and cooled to 5°C in an ice bath. Steam distillation and extraction with ether gave a yellow liquid (6.0 g); ir, A,,,: 5.84, 6.10 p m Analysis by vpc (NPGS, 130°C) indicated the presence of the same three components, in the same relative yields, as above. These were separated by preparative vpc.

(ii) 99.5% H2S04 The following results exemplify those obtained. Compound 1

(20.0 g) was added dropwise with swirling to 99.5% H2S04 (200 g), which was cooled to S°C in an ice bath. The deep red mixture was allowed to stand at 5°C for 24 h and then at room temperature for a further week. Work-up under basic conditions as described above gave a yellowish liquid (14.9 g); ir, A,,,: 2.75,2.90,5.84, 6.05-6.10 pm. Analysis by vpc (NPGS, 110°C) indicated the presence of four compounds: 7 (65%), 8 (1.4%), 17 (25%), and 23 (8.4%).

Reactions of compound I in polyphosphoric acid A mixture of 1 (2.00 g) and polyphosphoric acid (PPA; Victor

Chemical Co.; 25 g) was heated at 100°C for 7 h in a 3-necked flask fitted with a condenser, thermometer, and CaC12 drying tube. The reddish-brown reaction mixture was allowed to cool to room tempera- ture and poured into water (100 mL), and the flask was washed out with further water (100 mL). The combined aqueous solutions were extracted with ether (2 X 200 mL) and the extract was washed with saturated aqueous NaHC03 (100 mL) and water (2 X 200 mL) and dried over Na2S04. Evaporation of the ether gave a pale yellow liquid (1.45 g); ir, A,,,: 2.85-2.95, 5.84, 6.09 pm. Its ' H nmr spectrum showed strong signals at 6 1.75 and 2.08. Vapor phase chromato- graphic analysis (NPGS, 110°C) indicated the following composition (retention times and relative yields in parentheses): compound 17 (4.5 min; 8%)," compound 1 (7.0 min; 5%), tetramethylfuran (2519 (87.7 min; 81%), compound 7 (14.3 min; 6%).

Compounds 1 , 7 , and 17 were collected from the analytical column. Compound 25 was isolated by preparative vpc (NPGS, 100°C) as a colorless liquid (0.54 g).

The yields of the three products when 1 was heated with PPA under different conditions are given in Table 3.

2-Hydroxy-2,5-dimethyl-4-hexen-3-one (3) 2-Acetoxy-2,5-dimethyl-4-hexen-3-one was prepared from 2,s-

dimethyl-3-hexyne-2,s-diol(2) and hydrolyzed to give 3, as previously described (2, 7).

2-Ethoxy-2,5-dimethyl-4-hexen-3-one-2,4-dinitrophenylhydrazone To a solution of 3 (200 mg) in 95% EtOH (2 mL) was added

2,4-dinitrophenylhydrazine reagent (24) (8 mL). The mixture was allowed to stand for 24 h and filtered to give orange-yellow crystals (340 mg), mp 93-98°C. Four recrystallizations from aqueous 70% EtOH gave orange needles, m 108- 1 10°C; ir, A,,,: 3.02, 6.18 pm; P uv, A,,,: 360 nm ( E 22 600); H nmr, 6: 1.18 (t, J = 7 Hz, 3H), 1.48

Reactions of compound I in 99.5-100.3% sulfuric acid (s, 6H), 1.67 (s, 3H), 2.08 (s, 3H), 3.40 (q, J = 7 Hz, 2H), 5.8 1 ( i ) 100.3% sulfuric acid (s, lH),7.9-8.4(m,2H),9.08(d, J = 3 H z , lH), 11.20(s, lH) .Ana l . (a) Work-up under acidic conditions. Compound 1 (10.0 g) was calcd. for C I ~ H Z Z N ~ O ~ : C 54.84, H 6.33, N 15.99; found: C 54.99,

added slowly with stirring to 100.3% H2S04 (200 g) cooled to 10°C H 6.28, N 16.04.

'O~imilar results were obtained in 96% H2S04. "Variable amounts of 17 were retained on the vpc column.

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TABLE 3. Yields of products from the reactions of compound 1 with PPA

Reaction time (h): 4 7 8.5 6 Temperature ("C): 100 100 110 120

Combined yield (%): 77 80 82 8 1 Relative yield (%): 7 13 6.6 6.0 1 .O

17" 14.5 8.4 0 0 25 72.5 85 94 99

"See footnote 10.

2,4,4-Trimethyl-2-cyclopenten-1 -one (7) A mixture of 2,s-dimethyl-3-hexyne-2,s-diol (2) (71 g; 0.50 mol)

and 50% H2S04 (90 g) was stirred rapidly and heated at 50°C for 2 h under nitrogen. The organic layer (53.0 g) was removed, dried, and distilled. The major fraction was 2,5-dimethyl-1,5-hexadien-3-yne (4), obtained as a pale yellow liquid (27.0 g), bp 40°C (28 Torr); ir, A,,,: 6.20(w), 1 1 . 2 0 p m ; ' ~ n m r , 6 : 1.90(t, J = 2Hz,6H),5.25(m,4H). On standing for 2 days this product polymerized to a viscous yellow oil. Subsequent distillation fractions were shown by vpc analysis (Carbowax, 120°C) to contain five components. The major component was isolated by vpc and is considered to be tetrahydro-2,2,5-trimethyl- 4-pyrone (5); ir, A,,,: 5.81 pm; 'H nmr, 6: 0.92 (d, J = 7 Hz, 3H), 1.14 (s, 3H), 2.28 (br s, 2H), 2.50 (m, lH), 3.2-4.2 (m, 2H). The 2,4-dinitrophenylhydrazone of 5 was prepared in the usual manner (24); after five recrystallizations from 95% EtOH it was obtained as yellow needles, mp 15 1.5- 153°C. Anal. calcd. for Cl4HI8N4o5: C52.17,H5.61, N 17.38;found:C51.85,H5.67,N 17.47.

Two of the other products from the higher-boiling fractions from the original reaction mixture were identified by vpc and IH nmr analysis as compounds 1 and 3.

A mixture of 4 (19.2 g), concentrated hydrochloric acid (150 mL), cuprous oxide (0.5 g), ammonium chloride (1.0 g), and copper bronze (0.50 g) was heated at 60-65OC for 4.5 h under nitrogen. The reaction mixture was cooled to room temperature, diluted with water (100 mL), and extracted with ether (3 X 60 mL). The combined extracts were washed with saturated aqueous NaHC03 (2 X 30 mL) and water (50 mL), and dried. Distillation of the residue after removal of solvent gave 3,4-dichloro-2,5-dimethyl-2,4-hexadiene (6) ( 12.8 g), bp 29- 31°C (0.65Torr); niO 1.4940); ' ~ n m r , 6: 1.73 (s, 6H), 1.88 (s, 6H).

Compound 6 (12.0 g) was stirred rapidly with 85% H2S04 (100 g) at 60°C for 2 h. The mixture was cooled, diluted with water (50 mL), and extracted with ether (2 x 100 mL). The extract was washed with saturated aqueous NaHC03 (50 mL) and dried. Distillation of the residue after removal of the solvent gave a colorless liquid (5.5 g), bp 42-52°C (3 Torr), which was shown by 'H nmr spectroscopic analysis to be a mixture of 6 and 2,4,4-trimethyl-2-cyclopenten-1-one (7). The latter was separated by the use of Guard's Reagent T (25) and obtained as a colorless liquid, bp 52°C (10 Torr); n? 1.4606 (lit. (19a) bp 66°C (20 Torr); ni5 1.4573). The 2,4-dinitrophenylhydrazone of 7 was prepared in the usual manner (24); after recrystallization from EtOAc-EtOH it was obtained as orange crystals, mp 21 1.5-223°C. Anal. calcd. for Cl4HI6N4o4: C 55.25, H 5.30, N 18.41; found: C 55.33, H 5.43, H 18.14.

3,5,5-Trimethyl-2-cyclopenten-I-one (8) and3,4,4-trimethyl-2-cyclo- penten-1 -one (9)

A solution of redistilled 2-methyl-2-butene (47 g) in CHC13 (140 mL) was cooled in an ice bath and rapidly stirred. Nitrosyl chloride was slowly bubbled through this solution until a permanent green color was produced (ca. 2 h). Removal of the solvent gave crude 3-chloro-3-methyl-2-butanone oxime as a bright blue viscous liquid (85 g; 95%); ir (CHC13), A,,,: 2.80,2.90-3.10 pm; 'H nmr, 6: 1.75 (s, 6H), 2.01 (s, 3H), 9.6 (s, 1H).

Sodium (15.0 g, 0.65 mol) was dissolved in dry EtOH (250 mL) and freshly distilled ethyl acetoacetate (81 g, 0.7 mol) was added to the solution. The mixture was cooled in ice-water and the crude oxime

(85 g, 0.63 mol) in dry EtOH (50 rnL) was added slowly over 25 min. The mixture was allowed to stand overnight and the precipitated NaCl was filtered. Removal of the EtOH from the filtrate gave a pale brown crystalline mess. This was heated with boiling 50% aqueous KOH (1200 g) under reflux for 4 h. The resulting solution was steam distilled and the steam distillate was extracted with ether (2 X 200 mL). Evaporation of the ether gave a pale brown liquid (20.5 g), which on distillation gave a colorless liquid (9.5 g), bp 6 2 4 5 ° C (10 Torr), consisting of the cyclopentenones 8 and 9 (2:3 by vpc analysis); these were readily separated by preparative vpc (NPGS, 120°C).

3,5,5-Trimethyl-2-cyclopenten-1 -one (8) (2.04 g), n;O 1.4670, the component with the lower retention time, was obtained as a colorless liquid. The 2,4-dinitrophenylhydrazone of 8 was prepared in the usual manner (24). Two recrystallizations from EtOAc-EtOH gave orange needles, mp 227.5-228.S0C. Anal. calcd. for CI4Hl6N4O2: C 55.25, H 5.30, N 18.41; found: C 55.27, H 5.32, N 18.51.

3,4,4-Trimethyl-2-cyclopenten-1-one (9) was obtained as a colorless liquid, niO 1.4737. The semicarbazone of 9 was prepared in the usual manner (24); on recrystallization from EtOH it was obtained as white platelets, mp 20 1-202°C (dec.) (lit. (10) mp 199-200°C).

Tetrahydro-2,3,5,5-tetramethyl-2,3-furandiol(ll) To a solution of 2,4-diydroxy-2,4-dimethylpentanoic acid y-lactone

(10; 7.2 g, 0.050 mol) (26) in dry ether (100 mL) was added 1.24 M ethereal methylmagnesium iodide (1 10 mL, 0.15 mol). The mixture was allowed to stand overnight and worked up with aqueous NH4CI. The clear supernatant layer was separated, and the inorganic cake was washed with ether (2 x 50 mL). The ethereal solutions were combined, dried, and freed of solvent to give 11 as an oil (2.9 g , 36%). This slowly crystallized on standing in petroleum ether - cyclohexane. Two recrystallizations from this solvent mixture gave 11 as colorless crystals, mp 72-74°C. Anal. calcd. for C8HI6o3: C 59.98, H 10.07; found: C 60.11, H 10.17.

Extraction of the inorganic cake with hot CHC13 (3 X 30 mL) and evaporation of the combined extracts gave compound 13 as a white solid (3.9 g), which was insoluble in ether, CH2C12, and CHC13. It was recrystallized from acetone-EtOAc to give white prisms, mp 227-229°C (dec.); ir (Nujol), A,,,: 3.02 (m) pm. Compound 13 was converted to 12 (vide infra) on treatment with 50% H2S04.

The inorganic cake remaining after the above extraction was dissolved in 50% H2SO4, and the solution was extracted with CHC13 (3 x I00 mL). A pale brown crystalline product (1.03 g) was obtained on removal of the solvent. Purification by vpc (fluorosilicone, 100°C) gave tetrahydro-2,2,3,5,5-pentamethyl-3-furanol (12) as a white crystalline solid, mp 75-76°C (lit. (13) mp 76-77°C); ir, A,,,: 2.75 (w), 2.90 (m) pm. This was shown to be identical with an authentic sample of 12 prepared by treatment of 1 with methylmagnesium iodide (13).

Lead tetraacetate cleavage of 14. Formation of diacetone alcohol (14) To a solution of 11 (100 mg) in water (3 mL) was added a suspension

of lead tetraacetate (346 mg) in glacial acetic acid (3 mL). After 2 h the mixture was filtered, and the filtrate was made strongly alkaline with aqueous KOH and allowed to stand for a further 90 min. The solution acquired a strong odor of diacetone alcohol (14). 2,4-Dinitrophenyl- hydrazine reagent (24) was added and the solution was allowed to stand for 2 days, giving orange-yellow crystals, mp 198-202°C. Recrystal- lization from 80% EtOH gave diacetone alcohol, 2,4-dinitrophenyl- hydrazone as yellow needles, mp 202-204°C (lit. (24) mp 203°C).

Rearrangement of 11 to 1 on vapor phase chromatography When a 10% solution of 11 in CHC13 was injected on a vpc column

(DIDP or NPGS) at 140°C a peak with retention time equal to that of 1 was produced. Collection from the column gave a colorless liquid, the ir spectrum of which was identical with that of authentic 1. Peak area measurements indicated a yield of ca. 30%. No change was observed when 1 was heated alone at 1 50°C.

Acid-catalyzed self-condensation of 11. Formation of 15 A solution of 11 (0.60 g) in benzene (50 mL) containing a crystal of

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p-toluenesulfonic acid was boiled under reflux for 30 min. The solution was washed with water (30 mL) and dried. Evaporation of the solvent gave a crystalline product that showed no hydroxyl or carbonyl absorption in its ir spectrum. Three recrystallizations from hexane gave compound 15 as colorless crystals, m 190.5-191.5"C (sealed cap); ir, A,,,: 8.5-8.6, 8.85, 10.55 pm; 'H nmr, 8: 1.25 (s, 6H), 1.32 (s, 6H), 1.39 (s, 6H), 1.47 (s, 6H), 1.90 ( J = 13 Hz, H), 2.00 (d, J = 13 Hz, 2H). Anal. calcd. for C16H2804: C 67.57, H 9.93, Mol. Wt . 284; found: C 67.66, H 9.93. Mol. Wt . (Rast) 284.

2,5-Dihydro-3,5,5-trimethyl-2-methylenefuran (17 ) A solution of lithium acetylide was prepared from acetylene and

lithium wire (1.73 g, 0.25 mol) in liquid ammonia (250 mL) in the presence of hydrated ferric nitrate (50 mg). Mesityl oxide (24.5 g, 0.25 mol) in dry ether (25 mL) was added with stirring and cooling. A slow stream of acetylene was passed continuously through the solution, which was stirred and cooled for a further 2.5 h. Ammonium chloride (20 g) was cautiously added and the ammonia was allowed to evaporate overnight. Extraction with ether and evaporation of the solvent gave a mixture (1.76 g) consisting only of 3J-dimethyl-4- hexen-1-yn-3-01 and unconsumed mesityl oxide (28.5% conversion from vpc analysis). A pure sample of the product was collected from a vpc column (NPGS, 85°C); ir, A,,,: 2.78, 3.02, 4.75, 6.0-6.1, 10.9 pm; 'H nmr, 6: 1.51 (s, 3H), 1.71 (s, 3H), 1.87 (s, 3H), 2.33 (s, lH), 2.38 (s, lH), 5.32 (s, 1H).

The mixture (15 g) of the above ynol and mesityl oxide from a larger scale run was dissolved in ether (150 mL) and the solution was shaken for 30 min with 50% H2S04 (150 mL). The ethereal layer was separated and the aqueous solution was extracted with ether (150 mL). The combined ethereal solutions were washed with water (2 X 50 mL), dried over CaC12, and concentrated. Fractional distillation with a spin- ning band column gave 2,4-dimethy1-3-hexen-5-yn-3-01 (16) (1.2 g), bp 59-61°C (15 Torr) (lit. (14) bp 65-66°C (20Torr)); ir, A,,,: 2.78, 3.02,4.78,6.17, 10.5pm; 'Hnmr,6: 1.34(s,6H), 1.86(s,3H),2.71 (s, IH), 3.25 (s, lH), 5.89 (s, 1H).

A solution of 16 (180 mg) in ether (5 mL) was shaken for 3 min with a solution of mercuric acetate (30 mg) in water (5 mL). The organic layer was separated and the aqueous layer was washed with ether (10 mL). The combined ethereal solutions were dried over K2C03 and the solvent was removed. The residue (120 mg) exhibited a single peak on vpc analysis (NPGS, 75°C). Collection of the product from the vpc column gave 2,5-dihydro-3,5,5-trirnethyl-2-methylenefura (17). Anal. calcd. for C8H,20: C 77.37, H 9.74; found: C 76.5 1, H 9.94.

Shaking an ethereal solution of 16 with mercuric sulfate in 2% w/v sulfuric acid gave 20, the dimer of 17 (vide infra).

Dimerization of 17 . Formation of 20 On standing, compound 17 neat or in solution in CC14 underwent

dimerization to give 20, which was also formed via spontaneous dehydration of 18 on standing. Repeated distillation, with precautions to minimize contact with air, gave 20 as a colorless liquid, bp 73-74°C (0.35 Torr). An analytical sample was prepared by vpc on an NPGS column at 150°C. Exact Mass calcd. for C15H2102 (M - CH3): 233.1542; found: 233.1542. Anal. calcd. for C16H2402: C 77.37, H 9.74; found: C 76.90, H 9.58.

Hydrogenation of 20. Formation of 21 A solution of 20 (3.07 g) in EtOH (50 mL) containing reduced

platinum oxide (120 mg) was stirred under hydrogen at a slight positive pressure. One molar equivalent of hydrogen was adsorbed in 100 min. Further uptake of hydrogen was extremely slow (0.28 molar equiv. after 12 h). The solution was filtered and the solvent was removed. Distillation of the residue gave 21 as a colorless liquid, bp 66-70°C (0.7 Torr). Exact Mass calcd. for C16H2602 (M), CI5H23o2 (M - H): 250.1983, 249.1854; found: 250.1900, 249.1862.

4-Hydroxy-2,4-dimethyl-2-pentenoic acid y-lactone (22 ) 2,4-Dihydroxy-2,4-dimethylpentanoic acid y-lactone (10) (26) was

heated for 14 h with boiling 47% hydrobromic acid under reflux (12) to give 22 in almost quantitative yield. Recrystallization from heptane gave white needles, mp 54.5-55°C (lit. (12) mp 55-56°C).

Ozonolysis of 23 . l or mat ion of a-methyllevulinic acid (24 ) A stream of ozonized oxygen (ca. 20% 0 3 ; 15 L/h) was passed

into a solution of 23 (0.47 g) in CH2C12 (100 mL) cooled in a Dry Ice - acetone bath, until the solution had turned deep blue (45 min). The excess ozone was removed by passing a stream of nitrogen through the solution for 5 min. The solution was added dropwise to water (30 mL) and the mixture was shaken vigorously and allowed to stand overnight. Aqueous 40% NaOH (10 mL) and aqueous 6% H202 (15 mL) were added. The mixture was shaken for 5 rnin and allowed to stand at room temperature for 20 h. The organic layer was separated and the aqueous solution was acidified with 10% H2SO4. Extraction of the acid solution with ether (4 X 50 mL) and removal of the solvent gave a mixture of 24 and its tautomeric lactol as an oil (0.59 g); ir, A,,,: 2.75-2.80, 3-4.1, 5.62-5.70, 5.80 pm. The remainder of the acidic product from the ozonolysis (ca. 0.5 g) was mixed with a solution of semicarbazide hydrochloride (400 mg) and sodium acetate (300 mg) in water (0.3 mL) and the solution was allowed to stand overnight. The resulting solid (147 mg) was filtered and twice recrystallized from 70% aqueous EtOH to give the semicarbazone of24 as colorless prisms, mp 178-178S°C, undepressed when mixed with an authentic sample prepared from ethyl 2-bromoproprionate and ethyl acetoacetate (20).

Maleic anhydride adducts of tetramethylfuran (25) The mixture of adducts (22, 23) was repeatedly crystallized from

heptane to give the exo adduct as long needles, m 96.5-97.S0C P (lit. (22) mp 95-96°C); ir, A,,,: 5.37,5.62,9.24 pm; H nmr, 6: 1.60 (s, 6H), 1.64 (s, 7.3H), 1.69 (s, 1.3H), 3.01 (s, 2H), 3.48 (s, 0.42H). Anal. calcd. for Cl2HI4o4: C 64.85, H 6.35; found: C 64.76, H 6.39.

Equimolar solutions of maleic anhydride and tetramethylfuran in CHC13 were mixed and the 'H nmr spectrum of the resulting solution was recorded after approximately 1, 3, and 6 min. The ratios of the peak heights at 6 3.01 and 3.48 were 2.05,2.95, and 4.6, respectively. This ratio remained constant after 6 min and was the same as that observed when the pure exo isomer was dissolved in CHC13.

Acknowledgments We thank Mr. Baldev Gambhir for technical assistance and

the Natural Sciences and Engineering Research Council of Canada for support of this work.

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26. K. KOHN. Monatsch. 30, 401 (1909).

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