J. Org. Chem. 1991,56,3192-3194
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the Mass Spectrometry Facility, University of California-San Francisco, supported by the NIH Division of Research Resources. Supplementary Material Available: ‘H and 13C NMR spectra for each entry of Table I and for 3 and 5 (22 pages). Ordering information is given on any current masthead page.
Solid Superacid Catalyzed Organic Synthesis. 6.’ Perfluorinated Resinsufonic Acid (Nafion-H) Catalyzed Ring Closure Reaction of 2%’-Dihydroxybiphenyls. A Preparative Route to Dibenzofurans Takehiko Yamato,*pt Chieko Hideshima,’ G. K. Surya Prakash,*and George A. Olah* Department of Industrial Chemistry, Faculty of Science and Technology, Saga University, Honjo-machi, Saga 840, Japan, and Donald P. and Katherine B. Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, University Park, Los Angeles, California 90089-1661 Received September 4, 1990
Introduction The acid-catalyzed ring closure of 2,2’-dihydroxybiphenyls to corresponding dibenzofurans has been studied using various acid catalysts.” However, these methods require elevated temperatures (>350 “C), long reaction times, and an excess of protic and Lewis acids. Furthermore, some of these reactions were plagued with undesirable side products during cyclization.’ Therefore, the scope and selectivity for the preparation of dibenzofuran derivatives have been limited. Now we wish to report an efficient and mild procedure for the ring closure of 2,2’-dihydroxybiphenyls in the presence of the solid superacid, Nafion-H (a solid perfluorinated resinsulfonic acid) to afford dibenzofuran derivatives in good to moderate yields.
Results and Discussion The preparative route for 2,2’-dihydroxy3,3‘-dimethyldiphenyl (lb) is shown in Scheme I, and the preparation of other dihydroxybiaryls la, Id, and le using the tert-butyl group as a positional protective group6 was described in a previous paper. Compound IC was prepared according to the literature.s The attempted ring closure reaction of 2,2’-dihydroxybiphenyl (la),carried out under benzene reflux for 36 h in the presence of Ndion-H, only led to recovery of starting material. However, under toluene or o-xylene reflux the desired dibenzofuran 2a was obtained (see Table I). In the case of toluene reflux, it takes more than 36 h to complete the reaction, but under o-xylene reflux only 1 2 h are required. Products (2) were simply isolated by filtration of the hot reaction mixture and evaporation of the solvent. The reactions are very clean, with water the only byproduct formed during the reaction. Optimum yield of dibenzofuran 2 was obtained with 50% of the catalyst, whereas 30% gave only slightly lower yield. The Nafon-H-catalyzed ring closure was further applied to the methyl-substituted 2,2’-dihydroxybiphenyls lb and IC to afford 4,6-dimethyl- (2b) and 2,8-dimethyldibenzofuran (24 in 40% and 90% yield, respectively. However, Saga 840, Japan.
8 California.
0022-3263/91/1956-3192$02.50/0
R
R2
C Nafion-H
+
___c
Ar-H
2
1
- -
a :R’ H b : R’ = H, R2 Me c : R’ = Ma. R2- H d : R’ = 1-Bu, R2 = H e : R’ = = t-Bu
10
-- -
a:R’=R2=H b : R‘ H, R2 Me c : R’ Me, R2 = H d : R’ = 1-Bu. R2 IH
in the case of tert-butyl-substituted 2,2’-dihydroxybiphenyls Id and le, it was found that the trans-tert-butylation occured along with the ring closure reaction to afford mixture of 2a and 2,8-di-tert-butyldibenzofuran(2d). From the above results, it might be assumed that the compound 2d would be intermediate for the formation of 2a from Id and le under the condition used. Although attempts to separate these reaction products failed by chromatography,further treatment of the reaction mixture with excess Nafon-H catalyst (100 wt 70)carried out under o-xylene reflux for 24 h did not result in complete removal of tert-butyl groups. Again mixtures were obtained. Based on the above results, one might conclude that initially de-tert-butylation occurs to give 2,2’-dihydroxybiphenyl la from Id and/or le and followed by cyclization of la to afford compound 2a. However, formation of compound 2d indicates direct ring closure of Id. It has been previously reported by us7 that treatment (le) in of 3,3’,5,5’-tetra-tert-butyl-2,2’-dihydroxybiphenyl the presence of Nafion-H under toluene reflux gives trans-tert-butylated product, 2,2‘-dihydroxybiphenyl, in high yield without the formation of dibenzofuran. Utilizing this reaction we have developed a one-pot procedure to convert di-tert-butyl-2,2’-dihydroxybiphenyls Id and 8 directly to dibenzofurans 2a and 2b much more conveniently. Thus, heating of compounds la and 8 with Nafion-H catalyst in o-xylene at 120 “C for 2 h followed by heating at o-xylene reflux gives the desired dibenzofurans 2a and 2b in 98% and 50% yield, respectively. It was also found that this ring closure reaction was also applicable to the corresponding 2,2’-dimethoxybiphenyls under mild reaction conditions. When 5,5’-dimethyl2,2’-dimethoxybiphenyl (12) was treated in refluxing oxylene for 36 h in the presence of Nation-H (50 wt %), the desired product 2c was obtained in 60% yield. In this reaction, intermediate formation of 5,5‘-dimethyL2,2’-dihydroxybiphenyl (IC) was observed only by GLC analysis without isolation. The present method provides excellent yields, easy isolation of the products, and ready regeneration of the catalyst without the loss of catalytic activity.
Experimental Section All melting and boiling points are uncorrected. NMR spectra
were recorded at 270 MHz with a Nippon Denshi JEOL FT-270 NMR spectrometer with MelSi as an internal reference. IR (1) Solid Superacid Catalyzed Organic Synthesis. 6. Part 5 Yamato, T.; Hideahima, C.; Prnkd, G. K. S.;O W , G.A. J. Org.Chem.,in press. Also considered ae Catalyie by Solid Superacide part 31 a t University of Southern California. (2) Kruber, 0. Ber. 1932,65, 1413. (3) Gilman, H.; Swiss, J.; Cheney, L. C. J. Am. Chem. SOC.1940,62, 1963. (4) Gray, A. P.; Dipinto, V. M.; Solomon, I. J. J. Org. Chem. 1976,41, 2428. ( 5 ) Taahiro, M.; Watanabe, H.;Tsuge, 0. Org. Prep. Proced. Znt. 1974, 6, 117. (6) Kaeding, W. W. J. Org. Chem. 1963,28, 1063. (7) Olah,G. A.; Prakash, G. K. S.; Iyer, P. S.; Tashiro, M.; Yamato, T. J . Org. Chem. 1987,52, 1881.
0 1991 American Chemical Society
J. Org. Chem., Vol. 56, No. 9, 1991 3193
Notes Scheme Io OMe
OMe
OMe
e*$Y1* 3
C I ClCHp
111
__L
(65%)
4
COMeH
5
pOM0 u CHpCI
C CH3 H
3
U
C
H
3
V
(80%)
t
(90%)
+
t
+ 7
6 OH
OH
CHI
CHI
VI
CH3
CHI
(72%)
t
+
Ib
9
0
“i) 12/HI04/H2S04/AcOH/H20,60-65 “C for 3 h; (ii) Cu, 260-280 “C for 3 h; (5)(HCHO),/H,P04/HC1, W 9 5 O C for 36 h; (iv) LiAlH4/THF, reflux for 3 h; (v) BBr3/CHzC12,0 O C for 2 h; (vi) AlCl3-CH3NO2/benzene,50 “C for 2 h. Scheme IP OMe
OMe
I (60%)
CHI
*
2c
CH3
12 O
(i) Nafion-H (50 w t %), o-xylene, reflux for 36 h.
Table I. Nafion-H-Catalyzed Condensation of 2.2’-Dihrdroxvbi~henvls(1)‘ substrate reaction (1) Ar-H time, h products yield! % la benzene 36 l a (1001, 2a (0) toluene 36 la (61, 2a (80) 12 la (2), 2a (96) o-xylene 12 lb (9,2b (40) lb o-xylene 12 IC (2), 2c (90) IC o-xylene 12 Id (O),2d (12), 2a ( 7 9 , 10 (82) Id o-xylene 12 le (O), 2d (16), 2a (70), 10 (80) le o-xylene OCatalyst 50 w t %. *Yields were determined by GLC analyses. spectra were measured on KBr pellets or a liquid film on NaCl plates in a Nippon Denshi JIR-AQ2OM spectrometer. Mass spectra were obtained on a Nippon Denshi JMS-OlSA-2 spectrometer at 75 eV using a direct inlet system. Generation of Superacidic Nafion-H from Nafion-K Resin? Commercial (Du Pont) Nafion-K is treated in boiling deionized water for 2 h and then filtered. The resin is then stirred in 20-25% HN03 for 4-5 h at room temperature and filtered. This acid treatment is repeated three to four times to obtain maximum exchange of potassium ion with protons in the polymer. The resin is finally washed several times with water until a neutral filtrate is obtained followed by drying under vacuum at 105 “C for at least 24 h. It is advisable to use deionized water throughout this process. Preparation of 2-Iodo-4-tert-butylanisole (4). A mixture of 64.8 g (0.396 mol) of :3 9.24 g of HI04.2H20, 20.2 g of Iz, 102 mL of AcOH, 18 mL of H20, and 3.6 mL of concentrated H2S04 was warmed at 60-65 “C for 3 h. The reaction mixture was cooled to room temperature and extracted with benzene. The benzene solution was washed with Naa208solution and water, dried over
-
( 8 ) Olah,G. A.; Iyer, P. S.; Prakash, G. K. S . Synthesis 1986,513and references therein.
(9) Tashiro, M.;Fukata, G.; Yamato, T. Org. Prep. Proced. Znt. 1976,
8, 263.
Na#04, and evaporated in vacuo. The reaidue was distilled under reduced pressure to give 78.1 g (68%)of 4 as a colorless liquid bp 92-94 “C (2 mm); NMR (CDC13) b 1.28 (9 H, s), 3.84 (3 H, s), 6.75 (1H, d, J = 8.46 Hz), 7.30 (1H, dd, J = 2.42 Hz, J = 8.46 Hz),7.76 (1H, d, J = 2.42 Hz);mass ( m / e )290 (M+). Anal. Calcd for Cl1HlSOI: C, 45.53; H,5.21. Found C, 44.96; H, 5.17. Preparation of 4.4‘-Di- tert-butyl-2,2’-dimethoxybiphenyl (5). A mixture of 20 g (68.9 mmol) of 4 and 20 g of Cu powder (100 mesh) was heated at 260-280 OC with stirring for 3 h. After the reaction, the mixture was cooled to room temperature and dissolved in benzene. Unreacted Cu powder and insoluble materials were filtered off, and the benzene solution was evaporated in vacuo to leav a residue, which was recrystallized from ethanol to give 9.8 g (87%) of 5 colorless prisms (EtOH); mp 132-134 “C;IR (KBr) 2950,1600,1500,1455,1390,1350,1280,1270,1255, 1240,1180,1140,1105,1045,1020,880,820,790,670 cm-’; NMR (CDC13) 6 1.30 (18 H, s), 3.72 (6 H, s), 6.86 (2 H, dd, J = 2.5 Hz, J = 7.0 Hz), 7.30 (2 H, d, J = 7.0 Hz), 7.31 (2 H, d, J = 2.5 Hz); mass ( m / e )326 (M+). Anal. Calcd for CZ2HmO2:C, 80.93; H, 9.26. Found: C, 80.96; H, 9.32. P r e p a r a t i o n of 4,4’-Di-tert-butyl-3,3’-bis(chloromethyl)-2,2’-dimethoxybiphenyl(6). A mixture of 10 g (30.6 mmol) of 5,20 g of paraformaldehyde, 80 mL of H3P04,80 mL of concentrated HC1(36%), and 80 mL of acetic acid was heated at 90-95 OC under vigorous stirring for 36 h, cooled to room temperature, and extracted with benzene. The benzene solution was washed with Na2CO3solution and water, dried over Na2S04, and evaporated in vacuo. The residue was recrystallized from hexane to give 8.45 g (65%) of 6: colorless prisms (hexane); mp 172-174 OC; IR (KBr) 2960,1904,1868,2831,1484,1466,1432, 1364,1271,1265,1215,1110,1013,1003,695,644,636cm-’; N M R (CDCl3) 6 1.34 (18 H, s), 3.46 (6 H, s), 4.74 (4 H, s), 7.43 (4 H, 8 ) ; mass ( m / e ) 422,424,426 (M+). Anal. Calcd for CuHs202C12: C, 68.08; H, 7.62. Found: C, 68.24; H, 7.66. Preparation of 4,4’-Di-tert-butyl-3,3’-dimethyl-2,2’-dimethoxybiphenyl (7). To a suspension of 2 g (53.7 mmol) of LiAH4 and 25 mL of THF was added gradually a solution of 8.52 of 6 in 50 mL of THF over 20 min. The mixture was g (20 “01) refluxed for 3 h and cooled to 10 OC. To the mixture, kept below 20 OC, was added THF-water (25 mL; 6040 v/v), and the whole solution was poured into dilute H2S04(25 mL; 1:l)and extracted with ether. The ether solution was washed with water, dried over Na2S04,and evaporated in vacuo to leave a residue, which was column chromatographed over silica gel using hexane as an eluent to give 5.7 g (80%)of 7 colorless oil; IR (NaC1) 3036,2962,2905, 2867,1362,1221,1160,1116,1016,875cm-’; NMR (CDC13)6 1.32 (18 H, s), 2.35 (6 H, s), 3.40 (6 H, s), 7.18 (2 H, d, J = 2.45 Hz), 7.24 (2 H, d, J = 2.45 Hz). Anal. Calcd for C%HsO2: C, 81.31; H, 9.67. Found: C, 81.63; H, 9.20. Preparation of 4,4’-Di-tert-butyl-3,3’-dimethyl-2,2’-dihydroxybiphenyl(8). To a solution of 3 g (8.47 mmol) of 7 in 150 mL of CHzC12was added gradually a solution of 2 mL of BBr3 in 20 mL of CHzC12at 0 “C. After the mixture was stirred for 2 h at room temperature, it was poured into a large amount of ice-water and extracted with CHICll. The dichloromethane solution was washed with water, dried over Na2S04,and evaporated in vacuo to give 2.5 g (90%) of 8 as colorless glassy solid! Preparation of 3,3’-Dimethyl-2,2’-dihydroxybiphenyl (lb). To a solution of 1.63 g (5 mmol) of 8 in 60 mL of benzene was added gradually 2.93 g (22 mmol) of AlC13 at 0 “C. After the reaction mixture was stirred for 2 h at room temperature, the mixture was poured into a large amount of ice-water and extracted with benzene. The benzene solution was washed with water, dried over Na2S04,and evaporated in vacuo to obtain a residue, which was recrystallized from hexane to give 772 mg (72%) of lb: colorless prisms (hexane);mp 85-86 OC; IR (KBr) 3030,2922,1453, 1241, 1214, 1200, 1124 cm-l; NMR (CDCl,) b 2.32 (6 H, s), 5.22 (2 H, s), 6.90-7.20 (6 H, m). Anal. Calcd for C14H1402: C, 78.48; H, 6.59. Found: C, 78.73; H, 6.61. Preparation of 5,5’-Dimethyl-2,2’-diethoxybiphenyl(l2). A mixture of 20 g (80.2 mmol) of 2-iodo-4-methylanisole(11) and 20 g of Cu powder (100 mesh) was heated at 260-280 “C with stirring for 3 h After the mixture was cooled to room temperature, it was dissolved in benzene. Unreacted Cu powder and insoluble materials were filtered off, and the benzene solution was evaporated in vacuo to leave a residue, which was recrystallized from
J. Org. Chem. 1991,56,3194-3197
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pentane to give 9.7 g (85%) of 1 2 colorless prisms; mp 62-64 O C (lit.lo mp 63-64 "C). General Procedure for the Ring Closure of 2,2'-Dihydroxybiphenyla (1) in the Pmwnce of Nafion-H. A mixture of 500 mg of I and 250 mg (50 wt 46) of Ndion-H in 5 mL of o-xylene was refluxed until completion of the reaction as monitored by GLC analysis (Silicone OV-1, 2 m). The solid resin sulfonic acid was then filtered off, and the filtrate was analyzed by GLC. The filtrate was evaporated under vacuum to leave a residue, which was recrystallized from MeOH to give corresponding dibenzofurans (2). The reaction conditions and the yields are summarized in Table 1. Dibenzofuran (fa): colorless prisms (MeOH);mp 83-85 "C (lit." mp 83-85 "C). 4,6-Dimethyldibenzofuran(2b): colorless prisms (MeOH); mp 75-81 O C ; IR (KBr)3052,2923,2851,1190,771,761,738an-'; NMR (CDC13)6 2.59 (6 H, 81, 7.15-7.25 (4 H, m), 7.70-7.75 (2 H, m). Anal. Calcd for C14H12O C, 85.68; H, 6.16. Found C, 85.82; H, 6.49. 2,bDimethyldibenzofuran (2c): colorless prisms (MeOH); mp 59-62 "C (lit.12mp 64 "C); IR (KBr)3018,2915,2856,1485, 1458,1213,1187,1115,809,800cm-'; NMR (CDC13)Q 2.49 (6 H, s), 7.31 (2 H, dd, J = 8.3 Hz, J = 1.0 Hz), 7.40 (2 H, d, J = 8.3 Hz), 7.68 (2 H, 8). Anal. Calcd for C14H12O: C, 85.68 H, 6.16. Found: C, 85.61; H, 6.39. Regeneration of NaPion-H Catalyst. The used catalyst was washed five times with acetone and deionized water, followed by drying at 105 O C for 10 h. The catalytic activity of regenerated catalyst was as good as that of fresh catalyst. (10) Koenig, K. E.;bin, G. M.; Stuckler, P.; Kaneda, T.; Cram, D. J. J. Am. Chem. SOC.1979,101,3553. (11) Dictionary of Organic Compounds, 4th ed.; Oxford University: New York, 1978. (12) Sugi, Y.; Shindo, H. J. Pharm. SOC.Jpn. 1933, 53, 97.
Prototropic Tautomerism of 2-(Phenylimino) tetrahydro-1,3-thiazine and 2-Anilino-4H-5,6-dihydro-1,3-thiazine Aiko Nabeya* and Tadatoshi Endo
Tsurumi University, School of Dental Medicine, 2-1 -3 Tsurumi, Tsurumi-ku, Yokohama, Japan Received August 27, 1990
Introduction In the tautomeric equilibrium la e lb, the identity of the predominant tautomer has been a subject of controversy ever since Tigler obtained l by the isomerization of N-(thiocarbamoy1)azetidine and assigned it the structure la.' This assignment of structure was based on a comH Ph-N-C5 1P
lb
parison of the IR spectrum of 1 with those of what were presumed to be the 3-methyl and 3-phenyl derivatives of 1. However, what Tigler believed to be the 3-methyl derivative of l was later shown to be 3, not 2, by Najer et al.2 (1) TiBler, M. Tetrahedron Lett. 1959, 12, 12.
0022-3263/91/1956-3194$02.50/0
2
3
They prepared both 2 and 3 in an unequivocal way and concluded that lb was the predominant structure after comparing the UV spectrum and the pK, value3 of 1 with those of the model compounds 2 and 3 and the 3-phenyl derivative of 1. Since then, a number of workers have become interested in this subject. lH NMR'a mass! and U V spectroscopy were used to determine the structure of 1. It was claimed that la was the predominant structure because the spectra of 1 were similar to those of 2. However, none of the arguments presented seemed sufficiently convincing. Years later, an extensive study of tautomerism in this sort of system was published by Jackman and Jen! They concluded that la predominated because the respective 13C NMR spectra indicated that the ortho and para carbon atonhs of the phenyl group of both 1 and 2 were abnormally magnetically shielded compared to those of 3. They also showed that the IH NMR spectrum of 1 and those of a variety of model compounds possessing an exocyclic carbon-nitrogen double bond were similar. At thispoint, what was the predominant structure of 1 seemed to have been established. More recently, however, T6th and AlmLy! in a study of the la e l b equilibrium by 'H, 13C,and 15N NMR spectroscopy, concluded that la and lb were rapidly interconverted and calculated the tautomeric ratio, na/nb,from the I5N chemical shifts of 1 , 2 , and 3. It was assumed that the chemical shifts of the endo and exo nitrogens of la would be very close to those of 2, and that the corresponding chemical shifts of l b would be very close to those of 3. The na/nbratio was reported to be 75:25 (calculated from the chemical shifts of the endo nitrogens) or 73:27 (calculated from the chemical shifts of the exo nitrogens). Furthermore, they suggested a nearly planar geometry for N(3) based on the relatively high and JN(3w(4), despite the predominance values of Jc(2)-N(3) of l a . It had been shown earlier'O that the reaction of isocyanates with 1 occurred exclusively at N(3) and that the carbamoyl group then migrated to the exo nitrogen intramolecularly. It was not clear if reaction at N(3) exclusively was due to a higher reactivity of an endo-NH compared to that of an exo-NH, or because 1 existed in solution only in the la form. The large difference in the 16Nchemical shifts of N(3) in 1 and 2 (44.7ppm), reported by T6th and AlmLy? cannot be explained without assuming the existence of an equilibrium between la and lb. In CDC1, solution, the 15Nchemical shift differences between NH and NMe of pyrrole-type nitrogen atoms were reported to be within 1.8 ppm,ll and within 5 ppm for the nitrogen atoms of other heterocycle^.^ The difference in the values of the I6N chemical shift of the amide nitrogen (2) Najer, H.; Giudicelli, R.; Menin, J. Bull SOC.Chim. Fr. 1966,2120. (3) Najer, H.; Armand, J.; Menin, J.; Voronine, N. C. R. Acad. Sci. 1965,4343. (4) Rabinowitz, J. Hela Chim. Acta 1969,52, 255. (5) Toldy, L.; S o b , P.;Faragb, K.;Tbth, I.; Bartalita, L. Tetrahdron Lett. 1970,-25, 2167. (6) Tamb, J.; Toldy, L. Tetrahedron Lett. 1970, 25, 2173. (7) Toldy, L.; LiptAk, J. Tetrahedron Lett. 1970,49, 4319. (8) Jackman, L. M.; Jen, T. J. Am. Chem. SOC.1975,97, 2811. (9) Tbth, G.; Almby, A. Org. Magn. Reson. 1982, 19, 219. (10) Nabeva. A.: Endo. T.: Saito,. J.:. Mitauishi.. T.:. Inahara, M. J. Heterocycl. &m.'1990,27, 903. (11) Wofford, D. S.; Forkey, D. M.; Rueeell, J. G. J. Org. Chem. 1982, 47, 5132.
0 1991 American Chemical Society
