330
J. Org. Chem. 1981,46, 330-335
g, 86.1 mmol) was dissolved in anhydrous ether (500 mL) and t, 2, benzylic CH,), 6.76 (s, 1,Ar H), 7.03 ( 8 , 1,Ar H), 7.36-7.76 added dropwise to a stirred slurry of lithium aluminum hydride (m, 5, Ar H), 8.13 (s, 1, azomethine CH). (13.14 g, 346 "01) in anhydrous ether (300 mL), and the mixture Anal. Calcd for C17H1&rN02: C, 58.62; H, 5.17; Br, 22.99; N, was stirred a t 0-5 "C for 5 h, after which the mixture was hy4.02. Found C, 58.74; H, 5.37; Br, 23.15; N, 3.87. drolyzed by addition of 28 mL of water, 28 mL of 20% sodium l-Phenyl-1,2,3,4-tetwhydroisoquinoline (14a). To a solution hydroxide, and finally 70 mL of water. The precipitate was fdtered of 2.88 g (10 mmol) of 13a in a mixture of dry tetrahydrofuran (125 mL) and dry hexane (30 mL) at -100 "C was added 10 mmol off and washed with ether, and the combined Citrates were dried, of butyllithium a t such a rate as to maintain the temperature filtered, and concentrated (rotary evaporation) to yield 15.12 g below -95 "C. 'HN M R data from quenched samples showed that (88%) of dark yellow oil which was purified by column chromatography on silica gel, eluting with benzene-ethyl acetatebromine-lithium exchange was complete within 15 min. The methanol (1:2:3): IR (fii) 3370,3270,1565,1470 cm-'; 'H NMR mixture was allowed to warm to room temperature and then quenched in 200 mL of 6 N hydrochloric acid. The organic layer (CDC13) d 1.96 (br s, J = 5 Hz, 2, NH,), 2.90 (overlapping t, 4, was removed and the acid solution extracted with ether (3 X 100 CH2),6.88-7.52 (m, 4, Ar H). mL) to remove any neutral compounds. The acid layer was then Anal. Calcd for C&&rN: C, 48.02; H, 5.04; Br, 39.94; N, 7.00. made basic to litmus by addition of 30% sodium hydroxide soFound: C, 47.95; H, 4.85; Br, 40.23; N, 6.73. lution and extracted with ether (3 x 100 mL). The ether solution B. From N-(B-(2-Bromopheny1)ethyl)phthalimide(11). was dried and concentrated (rotary evaporation), affording 2.29 The purified phthalimide (83.64 g, 253 mmol) was mixed with g of a brown oil which solidified on standing. Recrystallization 250 mL of methanol and 30.43 mL (506 mmol) 85% hydrazine of the solid afforded 0.88 g (42%) of colorless needles: mp 97-98 hydrate, and the mixture was refluxed and stirred for 1h. The "C (lit.= mp 97 "C); IR (KBr) 3260 cm-'; 'H NMR (CDCld 6 1.92 mixture, now containing a white voluminous solid, was allowed (br s, 1,NH),2.94 (distortedt, 2, CHJ, 3.18 (distortedt, 2, benzylic to cool to room temperature, and the methanol was removed by CH,), 5.10 (s, 1, benzylic CH), 6.68-7.57 (m, 9, Ar H). rotary evaporation. Concentrated hydrochloric acid (120 mL) was 1-Phenyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline added to the solid and the mixture refluxed for 1.5 h with stirring. (14b). From 3.48 g (10 "01) of 13b was obtained 2.90 g of brown The mixture was cooled, the phthalimide removed by filtration, oil by following the procedure used in the preparation of 14a. and the fiitrate made basic to litmus with 2 N sodium hydroxide, When this oil was dissolved in anhydrous ether and hydrogen followed by refrigeration for 3 h at 3 "C. The aqueous solution chloride gas bubbled through it, 0.78 g of a brown precipitate was extracted with ether (4 X 200 mL), and the ethereal solution formed. Recrystallization of the precipitate from methanol-ether was dried and concentrated (rotary evaporation) to yield 41.87 afforded 0.69 g (23%) of colorless needles: mp 262-264 "C (lit.23 g (83%) of 12 as a yellow oil. Distillation afforded a colorless oil: mp 224-250 "C); IR (KBr) 2760,2625,2540,1510 cm-'; 'H NMR bp 82-86 "C (0.3 torr); 'H NMR and IR data as indicated in part (CDC13)6 3.19 (t,J = 5.5 Hz, 2, CH,), 3.46 (t, 2, benzylic CH,), A. 3.73 (s, 3, OCH3),3.92 (s, 3, OCHd,5.79 (s,l,benzylic CH), 6.23 n -Benzylidene-&(2-bromopheny1)ethy lamine (13a). The (s, 1, Ar H), 6.75 (s, 1,Ar H), 7.08-7.52 (m, 5, Ar H), 7.70 (br s, reaction of &(2-bromophenyl)ethylmine (12; 13.11 g, 66 mmol) 1, exchangeable H), 8.80 (br s, 1, exchangeable H). with benzaldehyde (6.95 g, 66 mmol) was carried out in refluxing Anal. Calcd for C17HlgN02-HCl:C, 66.78; H, 6.55; C1,11.62; benzene (250 mL), water being removed by the use of a DeanN, 4.58. Found: C, 66.59; H, 6.78; C1, 11.94; N, 4.57. Stark trap. Concentration of the benzene solution and distillation of the residue afforded 12.55 g (66%) of a yellow oil: bp 172-173 Registry No. 1, 74824-35-4; 2a, 538-51-2; 2b, 780-20-1; 2c, "C (0.25 torr); IR (film) 1620 cm-'; 'H NMR (CDC13)b 3.15 (t, 75767-88-3; 2d, 27895-67-6; 3a, 28519-59-7; 3b, 75767-89-4; 3c, J = 8 Hz, 2, CH,),3.88 (t, 2, benzylic CH,), 6.93-7.88 (m, 9, Ar 75767-90-7;3d, 75767-91-8;5,59043-57-1;7,75767-92-9; loa, 36149H), 8.17 (s, 1, azomethine CH). 34-5; lob, 75767-93-0; lod, 75767-94-1;11,75767-95-2;12,65185482; Anal. Calcd ClSHl4BrN: C, 62.50; H, 4.86; N, 4.86. Found: 138, 75780-68-6; 13b, 75767-96-3; 14a, 22990-19-8; 14b, 4118-36-9; C, 62.39; H, 4.74; N, 4.82. bromide, 1074-15-3;benzaldehyde, 100-52-7; N-Benzylidene-~-(2-bromo-4,5-dimethoxyphenyl)ethyl-/3-(2-bromophenyl)ethyl potassium phthalimide, 1074-82-4;2-bromo-&nitrostyrene,65185amine (13b). The reaction of @-(2-bromo-4,5-dimethoxy68-4; /3-(2-bromo-4,5-dimethoxyphenyl)ethylamine, 63375-81-5. phenyl)ethylminelg(11.02 g, 42 mmol) with benzaldehyde (4.49 g, 42 "01) was carried out as in the preparation of 13a, affording 9.47 g (65%) of a viscous yellow oil: bp 205-207 "C (0.5 torr); (22) Leithe, W.Monatsh. Chem. 1929, 53, 956. IR (film) 1645 cm-'; 'H NMR (CDC13)b 3.07 (t, J = 6.5 Hz, 2, (23) Paul, R.; Coppola, J. A.; Cohen, E. J.Med. Chem. 1972,15,720. (24) Sekiya, M.; Terao, Y.Chem. Pharm. Bull. 1972,20, 2128. CH2),3.72 (s, 3,0CH3),3.82 (s, 3,0CH3),3.87 (partially observed
Reaction of Aromatic Sulfonyl Azides with Dienes Rudolph A. Abramovitch,*l" Margarita Ortiz,lbPcand Samuel P. McManus*lb Departments of Chemistry, The University of Alabama in Huntsville, Huntsville, Alabama 35899, The University of Alabama, University, Alabama 35486, and Clemson University, Clemson, South Carolina 29631 Received J u l y 8, 1980
The addition of aromatic sulfonyl azides to simple acyclic and cyclic dienes in a 1:2 molar ratio was investigated.
In no case was the triazoline cycloaddition product isolated from the thermal cycloaddition. With the nonconjugated dienes 1,5-hexadiene and 1,7-octadiene, hydrogen migration occurred with nitrogen loss, affording sulfonimide products. No evidence for olefinic participation or alkyl group migration was obtained. Hydrolysis of the sulfonimidesgave the correspondinguneaturated ketones 5-hexen-2-one and 7-octen-2-one,respectively. Conjugated dienes reacted with aromatic sulfonyl azides to give enamines rather than sulfonimides. The reaction of pnitrobenzenesulfonylazide with 1,3-cyclohexadienefollowed by hydrolysis afforded only 2-cyclohexen-1-oneresulting from hydrogen migration. Addition to either cis,trans- or trans,trans-2,4-hexadienegave, after hydrolysis, trans-4-hexen-3-oneand trans-2-methyl-2-pentenal arising from competitive hydrogen and vinyl group migration, respectively.
Although the reaction of organic azides with monoolefins the addition to dienes has has been widely 0022-3263/81/1946-0330$01.00/0
received less a t t e n t i ~ n . ~Scheiner5 first suggested the addition of phenyl azide to conjugated dienes as a route 0 1981 American Chemical Society
J. Org. Chem., Vol. 46, No. 2, 1981
Reaction of Aromatic Sulfonyl Azides with Dienes
,
Scheme I
+
CH2=CH(CH2)nCH=CH 2
p 0 2 NC 6 H 4 SO 2 N 3
CH2=CH(CH
Ar :OS H
CH2=CH(CH
"SE - H-N2/L+2 2 nl* ) C
-N2
,
CH2=CH(CH
to 2-vinylaziridines by the photolysis of the isolable triazoline adduct. Recent studies have demonstrated the use of the l,&dipolar addition of cyanogen4or sulfonyl azidesM to olefins as a way of preparing ketones after hydrolysis of the intermediate imides. The addition of sulfonyl azides to cyclic olefins followed by reduction of the sulfonimide intermediates has also been reported.8 As an extension of our studies of the reactions of sulfonyl azides with olefins,8we now report the reaction of sulfonyl azides with conjugated and nonconjugated dienes and conversions of the intermediates to ketones or to N-substituted sulfonamides.
Results and Discussion Addition Reactions and Product Identification. The addition of p-nitrobenzenesulfonyl azide (PNBSA) to l,&hexadiene and 1,'l-octadiene (nonconjugated acyclic dienes), to cis-2-trans-4-hexadiene and trans-2-trans-4hexadiene (conjugated acyclic dienes), and to 1,3-cyclohexadiene (conjugated cyclic diene) was studied using a 1:2 molar ratio of azide to olefin. Benzene solutions of the two reactanb were heated in a sealed vessel at 90 "Cuntil the azide band at 2120 cm-' could not be detected by IR analysis of an aliquot. Intermediate triazolines could not be detected by IR analysis. The products initially isolated from each addition reaction were those of decomposition and rearrangement of the triazoline expected from addition of 1mol of azide to the diene. The addition products were subjected to hydrolysis, and the major products of hydrolysis were identified by comparison with authentic samples. The data on these studies are summarized in Table I. In the reaction of PNBSA with unconjugated dienes, the formation of imide 1was indicated by the strong infrared absorption of the product at 1610 cm-'. After acid hydrolysis, the expected unsaturated ketones were obtained in high purity as determined by GLC,and their structures were confirmed by isolation of their 2,4-dinitrophenylhydrazones (2,4-DNP). The reaction sequence which accounts for the products isolated with the nonconjugated dienes is thus as shown in Scheme I. (1) (a) Clemson University. (b) The University of Alabama in Huntsville. (c) Abstracted in part form the dissertation presented by M.O. in partial fulfillment of the requirements of the Ph.D. degree at the University of Alabama, May 1979. (2) (a) Abramovitch, R. A.; Kyba, E. P. "The Chemistry of the Azido Group"; Patai, S.,Ed.; Interscience: New York, 1971; p 221. (b) L'Abb6, G. Chem. Reu. 1969,69,345. (3) Huisgen, R.; Grashey, R.; Sauer, J. In "Chemistry of Alkenes"; Patai, S.Ed., Interscience: New York, 1964; p 835. (4) Hermes, M. E.; March, F. D. J . Org. Chem. 1972,37, 2969. (5) Scheiner, P. Tetrahedron 1967, 24, 349. (6) McMurry, J. E. J. Am. Chem. SOC.1969, 91, 3676. McMurry, J. E.; Coppolina, A. P. J. Org. Chem. 1973, 38, 2821. (7) Wohl, R. S. J. Org. Chem. 1973,38, 3862. (8)Abramovitch, R. A.; Knaus, G. N.; Pavlin, M.; Holcomb, W. D. J . Chem. SOC.,Perkin Trans. I 1972, 2169.
CH I 3 ) C=NS02Ar
T *
) CH-CH
2nl
n 1 2 o r 4
331
?;fi> CH
I 3
H30+ ~
2 n
CH2=CH(CH ) C - 0 2 n
Table I. Reactions of PNBSA with Dienes, Followed by Acid Hydrolysis reaction hydrolysis products after diene time,a days conditions hydrolysisb 1,5-hexadi7 2 N HCl in 5-hexen-2-one ene 95%eth- (47) anol 1,7 -0ctadi8 2 N HCl in 7-octen-2-one (52) ene 95% ethanol trans-2-trans6 2 N HCl in trans-2-methyl-24-hexadiCH,Cl,pentenal (23), ene ether trans-4-hexen-3one (16) cis-2-trans-45 2 N HC1 in trans-2-methyl-2hexadiene CH,Cl,pentenal (22), ether trans-4-hexen-3one (17) 1,3-cyclo1 2 N HC1 in 2-cyclohexen-lhexadi95% eth- one (45) ene anol a The approximate time for complete reaction based on disappearance of the azide band a t 2120-I in the IR. Yields (in percent) based on GLC analysis (see Experimental Section) are given in parentheses.
Scheme I1
L
& dL "301
4
.u
x
r/
OH?
the enol
Y
The reaction of PNBSA with the conjugated dienes gave enamine intermediates as indicated by IR absorptionsg at
332
Abramovitch, Ortiz, and McManus
J. Org. Chem., Vol. 46, No. 2, 1981
Table 11. Product Analysis of the Reaction of PNBSA Followed by Hydrolysis with trans-2-trons-4-Hexadiene % yield by % by GLC DNP (all three hydrolysis conditions 4 6 ethersa products)b 2NHC1(2mL)in 95% 21 5 14 39 ethanol ( 5 mL), 25 'C, 160 h 2NHC1(2mL)in95% 20 5 17 39 ethanol ( 5 mL), 25 "C, 160 h in the presence of hydroquinone acid alumina, MeOH23 9 12 not determined ether, 23 OC, 24 hC moist alumina-CH,Cl,, 17 12 0 not determined 25 OC, 504 h 2 N HCI, CH,Cl,23 16 0 not determined ether, 25 "C, 125 h
Scheme IV
-1 Arso*-G
3290 and 1570 cm-' (NH)and two medium-intensity bands at 1630-1610 cm-' (C=CC=C). The strong band characteristic of the C-N group which usually appears at about 1600 cm-' in such compounds was not present. The hydrolyses of the crude enamines from the acyclic dienes were initially carried out at room temperature with HC1 in aqueous ethanol. GLC analysis of the hydrolysis products indicated the formation of trans-2-methyl-2pentenal (4), trans-4-hexen-3-one(6), and a side product, tentatively identified principally on the basis of its NMR spectrum and molecular weight as a mixture of the two ethers expected from the conjugate addition of ethanol of the &unsaturated carbonyl compounds 4 and 6 formed as in Scheme 11. On the other hand, 1,3-cyclohexadiene gave only one major product, namely, 2-cyclohexen-1-one. To avoid the side products formed in the hydrolysis of the enamines from the acyclic conjugated dienes, we tried other hydrolysis conditions, and these are summarized in Table 11. Although the hydrolysis in methylene chloride-ether was very slow (5 days), it gave the highest overall yield of products 4 and 6. In most cases the yield of product 4 was higher than that of 6, but since both products are quite unstable, it is difficult to ascertain which product is the major one in the reaction. Hydroquinone was added to one reaction of PNBSA and trans-2-trans4-hexadiene to see if the presence of a free-radical inhibitor changed the product ratios; there seemed to be no effect. In another set of reactions, the products of addition of either 0- or p-nitrobenzenesulfonyl azide with the 2,4-
hexadienes were reduced with sodium borohydride (presumably via the imine tautomers subsequently formed) to give four isomeric products which were shown by GLC/MS analysis to have the composition N0&J-I4SO2NHC6HI1. These products may have the structures 7-10 as indicated in Scheme 111. Relative Reactivity of Dienes. There are some noticeable differences in reactivity among the dienes studied (Table I). With 1,3-cyclohexadiene, PNBSA is completely consumed in 1day while 1,5-hexadieneand 1,7-octadiene require a week or more for complete reaction. The acyclic conjugated dienes are definitely slower reacting than 1,3cyclohexadiene and appear to be slightly more reactive than the nonconjugated dienes. While there may be some electronic contribution to the differences in reactivity observed, the relative rate differences noted between acyclic and cyclic conjugated dienes may perhaps best be attributed to steric factors. Mechanism of Addition Product Formation. In the classical view,2B 1,3-dipolar addition of organic azides to electron-rich olefins, although concerted, takes place by a weak dipolar transition state. The bond between the terminal nitrogen of the azide and the olefin has progressed to a greater extent than the other C-N bond, generating the most stable carbocation on the olefinic part (Schemes I and 11). This type of transition state is supported by the observed orientation of the p r o d ~ c t s . Although ~~~ the triazoline intermediate has not been isolated in the case of sulfonyl azides, the regiospecificity of the reaction8 suggests a similar pathway. In recent years, the regiospecificity of 1,3-dipolar additions has been successfully predicted by a consideration of perturbational molecular orbital (PMO) theoryelo For example, consideration of the orbital energies and atomic orbital Coefficients for phenyl azide and l,&butadiene or for phenyl azide and 1-hexene allows one to predict correctly the regioselectivity observed for the reactions by S~heiner.~ Application of PMO theory to a quantitative prediction of the regiochemistry of the addition reactions of sulfonyl azides awaits reliable methods for calculation of the orbital energies and coefficients. To explain the observed products, we propose that the labile triazoline forms and decomposes to the betaine zwitterion intermediate which eliminates nitrogen with concerted hydrogen, alkyl, or vinyl migration to form the corresponding enamines 2 and 3 (Scheme 11). These are undoubtedly in equilibrium with the corresponding imines as suggested by the NaBH4 reduction of 3. It is interesting that products from double bond participation were not major products in the reactions of
(9) Bellamy, L. J. "The Infrared Spectra and Complex Moldea", 2nd ed.; Wiley: New York, 1966. This was used as the reference for the IR assignments.
(IO) Huisgen, R. J. Org. Chem. 1976,41,403. Houk, K. N. Acc. Chem. Res. 1975,8, 361. Caramella, P.; Cellerino, G.; Houk, K. N.; Albini, F. M.; Santiago, C. J . Org. Chem. 1978, 43, 3006 and references therein.
Product of addition of alcohol solvent to 4 and 6. The yield based on DNP may include some high-boiling ketonic or aldehydic side products. After 48 h and 72 h, GLC analysis indicated no increase in the percentages of 4 and 6. Scheme I11 NaBH4 ' I
7
v .
ArS0,NH
3 x
I
ArS02rH
NaBH4
a
Iv
ArSO. NH 9
rl
2
10
)Y
J. Org. Chem., Vol. 46, No.2, 1981 333
Reaction of Aromatic Sulfonyl Azides with Dienes
olefin 11. In contrast, 12 reacts with preferential alkyl migration.
Scheme V ACH..-N,L
I /
12.
ArS02N
P+ L
I
G CH2=CH(CH ) CHO 2 3
1,5-hexadiene and 1,7-octadiene.’l There are many literature examples of participation of olefinic bonds which suggest the possibility of the pathway shown in Scheme IV for the reaction of 1,5-hexadiene and an arylsulfonyl azide. Studies of ?r participation in deamination reactions do not allow for generalizations but suggest that this participation is not as important as ?r participation in solvolysis rea~tions.’~Since N2loss in amine deaminations occurs with little nucleophilic as~istance,’~ the amount of nucleophilic assistance to N2 loss from the betaine may also be small. Regardless of when nucleophilic attack occurs, hydride shift to form the observed products (Scheme I) has a more favorable entropy term13J6than ?r participation, thus ?r participation may be entirely excluded in the case of nonconjugated dienes. Hydrogen migration in these reactions also occurs to the apparent exclusion” of alkyl group migration (Scheme V). The latter mode of reaction, which would give aldehydic products, is not observed apparently owing to the greater migratory aptitude of hydrogen as compared to alkyl groups.16 In the additions of PNBSA to the isomeric 2,4-hexadienes, both hydrogen and vinyl migration occur (Scheme 11). However, the addition of PNBSA to the structurally constrained cyclohexadiene proceeds with hydride migration occurring to the exclusion of vinyl group migration. In solvolytic reactions, vinyl group migratiod7has been shown to be more facile than that of alkyl groups and has a driving force similar to that of the phenyl g r ~ u p . ’ ~ J ~ thus, the migratory aptitude for the vinyl group in solvolysis reactions may be superior to that of hydrogen. In azide additions, studies involving vinyl group migration are rare, and the trend of migratory aptitudes of vinyl vs. hydrogen is not established. McMurrf observed preferential vinyl migration over alkyl migration in conjugated (11) Other than tarry products, minor unidentified components amounted to leas than 5% in the reaction of 1,Shexadiene. A high-boiling unidentified component, amounting to 2.3% of the reaction mixture, appeared in the gas chromatogram of the 1,’l-octadiene produde. These unidentified fractions could be produde of intramolecular T participation or alkyl group migration. (12) (a) Johnson, W. S.; Bailey, D. M.; Owyang, R.;Bell, R. A,; Jaques, B.; Crandall, J. K. J. Am. Chem. SOC. 1964,86,1959. (b) Van Tamelen, E. E.; Padlar, A. D.; Li, E.; James, D. R. Ibid. 1977,99,6778. (c) Stork, G.; Grieco, P. A. Ibid. 1969,91, 2407. (d) Peterson, P. E.; Kamut, R. J. Ibid. 1969,91,4521. (e) Park, H.; King, P. F., Paquette, L. A. Ibid. 1979, 101, 4773. Johnson, W. S. Bioorg. Chem. 1976,5,51. (13) Wnuk, T. A.; Tonnis, J. A.; D o h , M. J.; Padegimae, S. J.; Kcvacic, P. J. Org. Chem. 1975, 40, 444. (14) Keating, J. T.; Skell, P. S. “Carbonium Ions”; Olah, G. A., Schleyer, P. v. R., Eds.; Wiley-Interscience: New York, 1970; Vol. 11, pp 573-653. (15) Capon, B.; McManus, S. P. “Neighboring Group Participation”; Plenum: New York, 1976; Vol. 1, pp 43-70. (16) McManus, S. P.; Pittman, C. U., Jr. In “Organic Reactive Intermediates”;McManus, S. P., Ed.; Academic Press: New York, 1973; pp 292-294. March, J. “Advanced Organic Chemistry”, 2nd ed.; McGraw-Hill: New York, 1977; p 969. (17) Wiberg, K. B.; Hess, B. A., Jr.; Ashe, A. J., I11 In “Carbonium
Ions”; Olah, G. Schlyer, P. v. R., Eds.; Wiley-Interscience: New York, 1972; Vol. 111, pp 1335-1341. (18)Bly, R. S.; Swindell, R. T. J. Org. Chem. 1965, 30, 10. (19) Wilt, J. W.; Niineamae, R. J. Org. Chem. 1979, 44, 2533.
c13, ::;:::+ a+ ’
R
0
R
r--btio
uVinvl
of Products 7 -Alkyl
12,R
= H
70
30
12
= CH3
13
87
R
Abramovitch and co-workers8 found that hydrogen migrates in preference to phenyl in the addition of PNBSA to stilbene. However, it is difficult to establish clearly that electronic factors are dominant in rearrangements involving nitrogen loss. Thus, Henery-Logan and Clarkm found that the adducts from alkenes and phenyl azide lost nitrogen preferentially from the more stable conformation of the intermediate zwitterion, probably owing to the relatively high energy of the particular intermediates. Our results and those discussed above agree with studies of other cationic rearrangementsI6 in suggesting that the inherent electronic migratory aptitudes may be overridden by steric factors and by secondary electronic factors, and hence, generalizations cannot be drawn. Interestingly, cyclopropylcarbinyl products, which have been found in allylcarbinylamine deaminationz1 and in solvolytic studies of allylcarbinyl to~ylates,’~ are absent here. On the other hand, in the 2,4-hexadiene reactions, simple vinyl migration should lead to the imine 3i and thus to the aldehyde 5. Although it is conceivable that 5 could be converted to 6 under hydrolysis conditions, the absence of 5 as a product suggests that 3i is not formed initially. Instead, a cyclopropylcarbinyl intermediate results which gives the enamine 3 directly (Scheme 11). Alternatively, if 3i is formed, it too may result from the cyclopropylcarbinyl intermediate, e.g., 13. Finally, the strain at-
A ..
tending formation of the bicyclic cyclopropylcarbinyl intermediate from the cyclohexadiene adduct may account for the absence of vinyl migration product in that case. In summary, sulfonyl azides react with simple acyclic and cyclic conjugated dienes to give enamines with predictable regiochemistry. The unstable triazolines then decompose to the betaine intermediate which may undergo rearrangement by hydride or, in the case of open-chain conjugated dienes, vinyl migration with concerted elimination of nitrogen.
Experimental Section General Methods. Melting points are uncorrected. The IR spectra were recorded on a Perkin-Elmer 257 or on a Beckman Acculab 3. The NMR spectra were obtained with a Varian EM360 or a Brucker HFX-10SOMHz spectrometer using CDCla as solvent, unless otherwise specified. Chemical shifts (6)are expressed in parts per million relative to internal tetramethylsilane. Gas chromatographic (GLC) analyses of reaction products were accomplished on a in. X 6 ft column packed with 5% FFAP on Chromosorb W by using an Aerograph Model 1520 instrument equipped with a flame-ionization detector. All of the addition reactions were sampled daily and examined by IR spectroscopy (20) Henery-Logan, K. R.; Clark, R. A. Tetrahedron Lett. 1968,801. 1951, 73,2609. (21) Roberts, J. D.; Mazur, R. H. J. Am. Chem. SOC.
334 J. Org. Chem., Vol. 46, No. 2, 1981 for disappearance of the strong azide band at 2120 cm-'. Gas chromatographic/mass spectroscopic analyses were carried out with a Hewlett-Packard Model 5830A gas chromatograph interfaced with a UTI lOOOZ quadrapole mass spectrometer operating at 70 eV. Reagent grade benzene and acetonitrile were dried over d u m wire and calcium hydride, respectively, distilled, and collected over molecular sieves (Fisher, type 4A, 8-12 mesh) where they were stored prior to use. The olefiis were supplied by Chemical Samples Co. and Aldrich Chemical Co., distilled prior to use, and stored over molecular sieves in a refrigerator. Neutral alumina (Baker; Brockmann Activity I) and silica gel (E. Merck; 30-70 mesh) were used for chromatography. Reaction of PNBSA with tran6-2-trams-4-Hexadiene.(a) Followed by Reduction with Sodium Borohydride. A benzene (30 mL) solution of PNBSAzZ(1.61 g, 7.1 mmol) and trans-2trans-4-hexadiene(10 g, 121.7 mmol) in a Fisher-Porter tube was heated in an oil bath at 90 "C while being protected from light until IR analysis indicated that all the azide had reacted (3 days): IR (neat) 3270 (w, NH), 3110 (C=CH), 1635, 1620 (m, C=C), 1570 (s, C=CNH), no band at 2120 cm-'. Sodium borohydride (1.0 g) and acetonitrile (10 mL) were added sequentially. Immediately after the acetonitrile was added, the solution turned reddish, and the color slowly faded. After b e i i stirred overnight, the solution was hydrolyzed by the addition of 5% aqueous acetic acid, and the mixture was washed with distilled water to pH 7. The aqueous phase was extracted with ethyl acetate, the combied organic layers were dried (Na&304),and the solvent was removed in vacuo to give the crude proproduct as a thick dark yellow oil. Chromatography on silica gel (50 X 3.0 cm) and elution with benzene gave 0.44 g of an oil which was further separated by TLC to give 0.02 g of an unidentified addition produd: IR (neat) 3100 (w, C=CH), 2960,2940,2880 (8, CH), 1660 (m, CH=CH), 1610 (m, C==C),1580 (w), 1535 (8, NOz), 1450,1405 (w, CHI, 1355 (s, NOz), 1320 (8, SOz), 1180 (8, SOz), 1095 (m), 1005 (m), 975 (m, CH=CH), 934 (w), 915 (w), 860,745 (vs), 690 (vs); NMR 6 8.38 and 8.0 (AzB2,4 H), 5.67-5.06 (m, CH=CH, 2 H), 4.28-4.03 (m, 1H), 2.6-2.2 (m, 2 H), 1.71 (d, CH,CH=C, 3 H), 0.96 (m, CH3, 6 H). On the basis of the absence of NH and C=N absorptions in the IR spectrum, this fraction is not an expected addition product.a The remaining oil (-0.42 g) had no SOz, NOz, or NH absorption (IR) and was tentatively thought to be an oligomer of the diene. Further elution with benzene of the original chromatogram gave 0.836 g of a light yellow oil identified by IR as addition product. Purification by TLC and vacuum distillation gave 0.547 g of product, bp 180-190 "C (0.1 mm). Gas chromatography/mass spectroscopy of the distilled oil indicated the presence of four compounds (retention times 1.8,3.1,4.3 and 4.7 min, respectively); the molecular ion for compounds of retention times 3.1 and 4.7 min was at m / e 284; however, for the other two compounds, small unexplained signals at m / e 309 and 432 were present in addition to the m / e 284 peak Assuming the four compounds to be isomers of formula p-N0zC6H~OS0zNHC6H,l, the yield based on crude product was 39.2%. (b) Followed by Acid Hydrolysis in Ethanol. With an azide to olefin ratio of 1:2, the reaction was repeated in benzene (0.31 M solution of azide). the reaction was completed after 6 days at 90 i 4°C. The solvent and excess olefin were removed, and the yellow syrup was hydrolyzed by stirring at 25 "C for 160 h in 95% ethanol (5 mL) and 2 N hydrochloric acid (2 mL). The sulfonamide which formed was filtered and washed with 50% ethanol, and the filtrate was neutralized with saturated sodium bicarbonate and extracted with ether (5 X 25 mL). The combined extract was dried (MgSOJ, the ether was distilled, and the residue was transferred to a volumetric flask and diluted with ethanol. GLC analysis of the ethanolic solution indicated the presence of three major reaction products of retention times 2.66,3.04, and 4.28 min, respectively (column temperature 85 "C, injector 194 O C , detector 265 "C, He flow 20 mL m i d ) . By comparison with (22) Reagan, M. T.; Nickon, A. J . Am. Chem. SOC.1968, 90,4096. (23) An aziridine product is a possibility, but aziridines are not nor-
mally isolated as intermediates in addition of aromatic sulfonyl azides to simple alkenes (cf. ref 8). There are, however, some examples where aziridines are formed (cf. ref 2a).
Abramovitch, Ortiz, and McManus authentic samples, the first two peaks were identified as trans2-methyl-2-pentenalu-27(21.1%) and trans-4-hexen-3-0ne~~~ (5.5%). The yields were calculated by using the intemal standard method with authentic samplm and cycloheptanone as the intemal standard. The third peak was tentatively identified (as described below) as a mixture of the addition products of ethanol to the a,@-unsaturated carbonyl compounds. The yield was 14.3% based on peak area. Also detected by GLC were several other peaks of higher retention times, possible mixtures of oligomers of the olefin, or condensation products of the carbonyl-containing products. The reaction mixture gave 2,4-DNP derivatives (56.1% crude). Purification of this mixture by column chromatography on silica gel (25 X 40 cm) and elution with benzene-hexane (1:l v/v) gave a mixture of three compounds as indicated by the TLC components. Comparison with authentic samples of the 2,4-DNP derivatives of 4 and 6 indicated these components to be present in the mixture. Indeed, recrystallization from ethanol afforded a 23.1% yield of the 2,4-DNP derivative of trans-2-methyl-2-pentenal (6): mp 161-162.5 "C (lit.24mp 161-163.5 "C). The mass, IR, and NMR spectral properties of the 2,4-DNP derivative were identical with those of the authentic sample. (c) With Hydroquinone as Radical Inhibitor Followed by Acid Hydrolysis in Ethanol. The reaction was carried out by following the same procedure as above but with a small amount of hydroquinone added to inhibit radical polymerization of the diene. Hydrolysis in EtOH-HCl gave the crude products, which were analyzed by GLC. This indicated that 20.4% of trans-2methyl-2-pentenal, 4.9% of trans-4-hexen-3-one,and 17.2% of the ethanol adducts were present. Again, high-retention-time products were observed, indicating that they were likely condensation products of the aldehydes and ketones. The isolation of a higher yield of crude DNP derivativethan of products found by GLC is also indicative of higher molecular weight carbonyl components. With a column of 15% FFAP on Chromosorb W (20 ft X 3/s in. at 100 "C, injector 175 "C, detector 200 "C, helium flow 20 cm3min-'), three major components were separated from the reaction mixture. By use of internal addition of authentic samples and two separate GLC columns, trans-2-methyl-2-pentend and trans-4-hexen-3-one were identified. By preparative GLC on the same column as above, trans-2-methyl-2-pentenal and the ethanol adducts were isolated. The structure of the unsaturated aldehyde was confirmed by its IR, NMR, and mass spectra and by ita 2,4-DNP which proved to be identical with that of an authentic sample. The adduct was tentatively identified from its NMR spectrum as a mixture of two saturated products containing the ethoxy group, probably formed by the addition of ethanol to the two a,@-unsaturatedcarbonyl products. The DNP derivative of this fraction gave an oily crystalline derivative that by gas-liquid chromatography/mass spectroscopy was separated into four isomeric compounds, mol wt 278 (M+- CzH50H), tentatively identified as a mixture of syn- and anti-2,l-DNP derivatives of CH3CHzCOCH2CH(OC2H5)CH3 and CH3CH2CH(OC2Hb)CH(CH3)CHO. The total yield of carbonyl products in the reaction mixture based on the 2,4-DNP derivatives was determined as 35.3%. The DNP derivative of trans-2-methyl-2-pentenal could again be isolated from the crude product; mp 160-161 "C. (24) Doebner, 0.;Weissenborn, A. Chem. Ber. 1902,35,1143. Astle, M. J.; Pinns, M. L. J. Org. Chem. 1959, 24, 56. (25) This compound was identified by Chan et al.= as the trans E isomer; they stated that any cis isomer formed in the reaction isomerized to the more stable trans isomer. They prepared the cis isomer and found that it was 35% isomerized after 48 h. They also observed that both these aldehydes are very unstable, even under nitrogen at 3 OC. However, our sample, stored in the refrigerator, was completely transparent after a long period of time. GLC analysis indicated a high purity of the stored compound. (26) Chan, K. C.; Jewell, R. A.; Nutting, W. H.; Rapoport, H. J. Org. Chem. 1968,33, 3382. (27) Gerson, K.; Flynn,E. H.; Segal, M. V., Jr.; Wiley, P. F.; Monaham, R.; Quarck, H. C. J . Am. Chem. SOC.1956, 78,6396. (28) Young,W. G.; McKennis, A. G.; Webb, I. D.; Roberts,J. D. J.Am. Chem. Soe. 1946,58, 295. (29) Favorskaya, I. A.; Auvinen, E. M. Zh. Obshch. Khim. 1963, 32, 1373. (30) Tarbell, S. D.; Lovett, W. E. J. Am. Chem. SOC.1956, 78, 2259.
Reaction of Aromatic Sulfonyl Azides with Dienes (d) Followed by Acid Hydrolysis in Methanol-Ether. The crude product from the reaction of PNBSA with the diene was hydrolyzed by being stirred at room temperature with wet acidwashed alumina (2 g of HzO, 10 g of acid alumina) in methanol-ether solution (15 mL, 1:2 v/v) while product formation was monitored by GLC. After 3 days neither the product yield nor the product ratio changed; quantitative analysis gave trans-2methyl-2-pentenal (22.6%), trans-4-hexen-3-one (9.3%), and a third product which had a slightly shorter retention time than the adduct assigned as the ethanol addition product above. By analogy with the results discwed above, the adduct here should be a mixture of the methanol adducts of the unsaturated aldehyde and ketone. (e) Followed by Hydrolysis with Moist Alumina in Methylene Chloride. Hydrolysis of the addition product by stirring it at room temperature with moist neutral alumina (2 g of H20, 10 g of alumina) in CH2C12(25 mL) gave, after 3 weeks, 16.7% of trans-2-methyl-2-pentenal and 11.7% of trans-4-hexen-3-one. No product correspondingto the above alcohol adduct was detected by GLC. (f) Followed by Acid Hydrolysis in CH2Clz-Ether. Hydrolysis of the crude product (10 mmol) by stirring at room temperature for 5 days in a CHzCl-ether solution (5 mL, 1:l v/v) and 2 N hydrochloric acid (5 mL) gave, after neutralization (NaHC03) and extraction (ether), 22.5% of trans-2-methyl-2pentenal and 16.0% of trans-4-hexen-3-one by GLC analysis. Reaction of PNBSA with cis-%trans-4-Hexadiene. (a) Followed by Acid Hydrolysis in Ethanol. The reaction of PNBSA with this diene in a 1:2 molar ratio in the presence of hydroquinone (0.3% in benzene for 5 days at 90 OC, protected from light) gave the enamine intermediate addition products as determined by IR absorptiona at 3290 (NH), 1632,1610,and 1570 cm-' (C=CC=C and C=CNH). Hydrolysis of the crude product was accomplished by stirring it for 1week with 2 N hydrochloric acid (2 mL) in ethanol (5 mL) solution. The solution was steam distilled, and the distillate was extracted with ether. The ether extract was dried (MgSOJ, concentrated, and subjected to GLC analysis, giving 12.0% of transs-2-methyl-2-pentenal, 10.0% trans-4-hexen-3-one,and 8.2% of the ethanol adducts. A 2,4-DNP formed from the reaction products (36.2% yield baed on PNBSA) was identified as the same mixture of 2,4DNP's as that formed from the trans,trans isomer by TLC. From the mixture, the DNP or trans-2-methyl-2-pentenal was isolated by crystallization as before. (b) Followed by Acid Hydrolysis in CHzClz-Ether. Hydrolysis of the crude product (10 mmol) by stirring it for 5 days in 2 N hydrochloric acid (5 mL) in CHzClz-ethersolution (5 mL, 1:l v/v) gave the following analysis by GLC: 22.3% trans-2methyl-2-pentenal and 17.3% trans-4-hexen-3-one. Reaction of PNBSA with 1,3-Cyclohexadiene Followed by Acid Hydrolysis. A benzene solution (15 mL) of the azide (1.14 g, 5.0 mmol) and 1,3-cyclohexadiene (0.801 g, 10 mmol) containing hydroquinone (10 mg) was heated a t 90 "C until no azide could be detected by IR analysis (21 h). Evaporation of the solvent and excess olefin left an orange syrup containing the enamine: IR (neat) 3290 (w, NH), 3100 (w, C=CH), 3020 (w, C=CH), 1610 (m, C=N), 1568 cm-' (8, C=CN). The crude product was hydrolyzed with 2 N HCl(5 mL) and ethanol (5 mL) for 3 days. The workup procedure described for similar experiments above was followed. GLC analysis was carried out at 120 OC and a He flow of 20 mL min-'. The major product (retention time 2.72 min) was identified by comparison with an authentic sample as 2-cyclohexen-1-one. An unidentified second product (retention time 5.58 min) was estimated to be less than 5% of the major peak,on the basis of relative areas. Quantitative analysis was accomplished by using the internal standard method with cycloheptanone as the internal standard. The yield of 2-cyclohexen-1-one in the addition reaction was determined to be 44.6%. When an aliquot from the reaction solution was allowed to react with 2,4-DNP reagent, an orange precipitate formed: 0.175 g (63.3%), mp 125-126 "C. Recrystallization from ethanol gave an orange powder, mp 158-163 "C. Further purification by column chromatography on silica gel gave orange plates of the 2,4-DNP of 2-cyclohexen-1-one (mp 162-163 OC) identical with an authentic sample.31
J. Org. Chem., Vol. 46, No. 2, 1981 335 Reaction of PNBSA with l$-Hexadiene Followed by Acid hydrolysis. A benzene solution (15 mL) of pnitrobenzenesulfonyl azide (1.14 g, 5 mmol), 1,bhexadiene (0.82 g, 10 mmol), and hydroquinone (10 mg)w a heated ~ (90 "C) in a Fisher-Porter tube in the dark until the azide band in the IR disappeared (7 days). Formation of the imine product was indicated by the strong IR absorption a t 1610 cm-'. A large amount of tars was observed on the walls of the tube. The solution was filtered under dry nitrogen (drybox),and the flask was rinsed with dry benzene (15 mL). The solvent and excess olefii were removed under reduced pressure, leaving a brown oil. Hydrolysis of the imine according to procedure b for trans-2trans-Chexadiene (2 N HCl in 95% aqueous ethanol for 24 h a t room temperature) and a workup as described in that same procedure yielded the ethanolic solution of the reaction products which was chromatographed on a FFAP column a t 65 "C with a 12 mL min-l He flow. Only one large peak was observed in the chromatogram. The product was tentatively identified as 5hexen-2-one (46.6% based on PNBSA) by comparison of its retention time with that of an authentic sample. Other components amounted to less than 5% by peak integration using a known standard. Reaction of an aliquot of the reaction solution with 2,4-DNP reagent for 10 min gave a brown precipitate (50.3% yield based on PNBSA). Two recrystallizations from ethanol gave orange plates (mp 107-108 "C) identical with an authentic sample of the DNP of 5-hexen-2-0ne.~~ Reaction of PNBSA with 1,7-Octadiene and Subsequent Acid Hydrolysis. A benzene solution (15 mL) of PNBSA (1.14 g, 5 mmol), 1,7-octadiene(1.1g 10 mmol), and hydroquinone (10 mg) was heated a t 90 "C for 8 days in the dark. No azide was left as determined by IR spectroscopy, and a strong band for an imine product was o b r v e d at 1610 cm-'. After removal of solvent under reduced pressure, the crude product was hydrolyzed by being stirred for 24 h at room temperature with HC1-EtOH as described above. A workup procedure similar to that used for 1,5-hexadiene was followed. GLC analysis of the ethanol solution containing the reaction product indicated only one major product with traces of a second compound. Owing to the unavailability of an authentic sample of the assumed product, 7-hexen-2-one,the concentration of the main product was determined by direct comparison with a known concentration of cyclopentanone used as an internal standard. The yield of the major product from the reaction was estimated to be 51.6% and that of an unidentified higher molecular weight product to be 2.3%, assuming the same molar response as cyclopentanone. Reacting an aliquot (1 mL) of the solution containing the reaction products with DNP reagent for 10 min produced a brown oil that solidified in the refrigerator (0.172 g, 56.2%) as a brown gum. Crystallization attempts failed. Chromatography of the crude material on a neutral alumina column (20 X 2.5 cm) gave an orange waxy compound (benzene-pentane, 1:1 v/v). Two recrystallizatonsfrom 95% ethanol gave the DNP of 7-octen-2-one as orange plates, mp 64-65 "C (lit.33mp 65-65.5 "C).
Acknowledgment. This work was supported by granta from the National Science Foundation (to R.A.A.) and the donors of the Petroleum Research Fund, administered by t h e America1 Chemical Society (to S.P.M.), for which we are grateful. Registry No. 4,50396-87-7; 4 DNP, 75600-11-2;6,14250-96-5;6 DNP, 75600-12-3; 1,5-hexadiene,592-42-7;5-hexen-2-one,109-49-9; l,7-octadiene,3710-30-3; 7-octen-2-one,3664-60-6; trans,trans-2,4hexadiene, 5194-51-4;trans-2-methyl-2-pentenal, 14250-96-5;trans4-hexen-3-one, 50396-87-7; cis,tram-2,4-hexadiene, 5194-50-3; tra~-2-methyl-2-pentenal,14250-96-5;trans-4-hexen-3-one,5039687-7; 1,3-cyclohexadiene, 592-57-4; 2-cyclohexen-l-one, 930-68-7; PNBSA, 73901-01-6;5-hexen-2-oneDNP, 2057-91-2;7-octen-2-one DNP, 3664-65-1. (31) Bartlett, P. D.; Woods, G. F.J. Am. Chem. SOC.1940,62,2933. (32) Bailey, W. J.; Daly, J. J., Jr. J. Org. Chem. 1957, 22, 1189. (33) Crombie, L.; Harper, S. H. J. Chem. SOC.1952, 869.
