2402 J. Org. Chem., Vol. 40, No. 16,1975 a value of +66O was obtained,2O but the pure trialcohol 10 h a d a value of +5g0.21 R e g i s t r y No.-1, 4205-23-6; 2, 55520-69-9; 3, 55520-70-2; 4, 55520-71-3; 5,55520-72-4; 7,55555-40-3; 8,32653-60-4; 9,524-69-6; 9 picrate, 55520-73-5; 2,2-dimethoxypropane, 77-76-9; 2,3-o-isopropylidene-5,6-di-O- methanesulfonyl-a-D-mannofuranoside, methyl, 50692-25-6.
References and Notes This work was supported by Grant CAI3802 from the National Cancer institute, National Institutesof Health. For example: M. L. Wolfrom, P. McWain, R. Pagnucco, and A. Thompson, J. Org. Chem., 29, 454 (1964): M. L. Wolfrom and P. McWain, ibid., 30, 1099 (1965); L. M. Lerner and P. Kohn. IbM., 31, 339 (1966); L. M. Lerner, B. D. Kohn. and P. Kohn, bid., 33, 1780 (1968); P. Kohn, R. H. Samaritano, and L. M. Lerner. /b& 31, 1503 (1966); and references cited in these articles. A. Bloch in "Drug Design". Voi. IV, E. J. Ariens, Ed., Academic Press, New York, N.Y., 1973, p 285. L. M. Lerner. J. Org. Chem., 37, 473 (1972). The route intended started from ~-idono-l,4-lactone. See P. Kohn, R. H. Samaritano, and L. M. Lerner, J. Am. Chem. Soc., 86, 1457 (1964). H. Pauisen, W. P. Trautwein, F. Garrido Espinosa, and K. Heyns. Chem. Ber., 100, 1183 (1967). K. iwadare, BuU. Chem. SOC.Jpn., 19, 27 (1944). E. J. Reist, R. R. Spencer, and B. R. Baker, J. Org. Chem., 23, 1958 11958). The procedure is based upon the one used for D-mannose: M. E. Evans and F. W. Parrish, Carbohydr. Res., 28, 359 (1973). L. M. Lerner, Carbohydr. Res., 36, 392 (1974), has a list of references concerned with this reactlon. 8. R. Baker, R. E. Schaub, J. P. Joseph, and J. H. Williams, J. Am. Chem. SOC.,77, 12 (1955): J. Prokop and D.,H. Murray, J. Pharm. Sci.. 54,359 (1965). J. R. Parikh. M. E. Woiff. and A. Buraer, J. Am. Chem. Soc., 79, 2778 ' (1957). M. L. Wolfrom, A. 8. Foster, P. McWain, W. von Bebenburg, and A. Thompson, J. Org. Chem., 26,3095 (1961). 0. Kjolberg. Acta Chem. Scand., 14, 1118 (1960); P. Jerkeman and B. Lindberg, ibM., 17, 1709 (1963). See Experimental Section of M. J. Robins, Y. Fouron, and R. Mengel, J. 010. Chem., 39, 1564 )1974), for an extensive list of melting points and optical rotations. in addition, A. Magnani and Y. Mikuriya. Carbohydr. Res., 28, 158 (1973), report data on a methanol solvate of 9. P. Chang and B. Lythgoe, J. Chem. Soc., 1992 (1950). Elementalanalyses were performed by the Spang MicroanalyticalLaboratory, Ann Arbor, Mich., or by the Baron Consulting Co., Orange, Conn. Melting points were determined on a Kofler micro hot state and are corrected values. ir spectra were recorded on a Perkin-Elmer Model 21 spectrophotometer and optical rotations were determined on a Rudolph polarimeter. Moist organic solutions were dried over anhydrous magnesium sulfate and evaporations were carrled out on a rotary evaporator under reduced pressure and a bath temperature of 40'. M. L. Wolfrom and A. Thompson, Methods Carbohydr. Chem., 2, 65
Notes With the exception of the Claisen rearrangement of 3allyloxy-2-cyclohexen-1-ones2that yields 2-methylated 3,5,6,7-tetrahydro-4(2H)-benzofuranones(isolated as semicarbazone derivatives), the known syntheses of 1, and of its simple alkyl derivatives, are low yielding and give, in general, impure Our new one-pot synthesis of 1 is accomplished simply by refluxing cyclohexane-1,3-dione with excess ethylene glycol in the presence of some RuC12(PPh& The method is not only extremely facile, but permits the isolation of the analytically pure bicyclic compound in a reasonable yield (64%). Similarly alkylated cyclohexane-1,3-diones can be converted to the corresponding substituted 3,5,6,7-tetrahydro-4(2H)-benzofuranones. 5,5-Dimethylcyclohexane-1,3dione (dimedone) and 5-tert-butylcyclohexane-l,3-dione8 give 2 and 3 in 40 and 27% yields, respectively. 0
R 4
/R1 I RJ s R 3 R4= H 2,RL = R2 = H;RA = R4 = CHJ 3,R' = R' R' H; R' = C(CH 4,R?= H,R1= RJ = R4 = CH, 5,R1= H;R'= RJ= R4 = CH,
j)j
The reaction of dimedone with propane-1,2-diol afforded a mixture of 2,6,6- and 3,6,6-trimethyl-3,5,6,7-tetrahydro4(2H)-benzofuranone (4 and 5, respectively) in a ratio of 3:l. Compounds 4 and 5, however, proved difficult to separate.g The catalysis is assumed to proceed by the following mechanism.
-
l l.B R 3\ , --,.
6b
6a
(19) Unpublished data of Dr. S.Angyal, reported in ref 9. (20) R. S. Wright, G. M. Tener, and H. 0. Khorana, J. Am. Chem. Soc., 80, 2004 (1958). (21) L. M. Lerner, Cerbohydr. Res., 13, 465 (1970).
0
7 6a
+
HOCH,CHO
-+
0
0
A Simple RuClZ(PPh&-Catalyzed Synthesis of the 3,5,6,7-Tetrahydro-4(2H)-benzofuranone System Pnina Albin, Jochanan Blum,* Ersa Dunkelblum, and Yoel Sasson
Department of Organic Chemistry, The Hebrew University, Jerusalem, Israel
8
Received March 21,1975
In a previous communication' we reported the selective transfer hydrogenation of one carbonyl group in cyclohexane-1,3-diones using ethylene glycol as hydrogen donor and RuC12(PPh& as catalyst. The reduction is effective under conditions in which the dehydrogenated carbinol, the glycol aldehyde, is continuously removed from the reaction mixture during the process. (See footnote 5, ref 1). When the aldehyde is allowed to accumulate these cyclic diketones undergo a remarkable catalytic reaction whereby the title system is formed.
9
+
(CH20H)j
9
-
+ 10a 0
HOCH,CHO
J.Org. C h e m . , Vol. 40, No. 16, 1975 2403
Notes
110 (loo), 80 (27), 67 (31). Anal. Calcd for C~H1002:C, 69.6; H, 7.2. Transfer hydrogenation of the starting diketone (in the Found: C, 69.2; H. 7.6. enol form) gives enough glycolaldehydelo to start a The cyclohexanone ethylene ketal: NMR (CDC13) 6 1.50 (s, R u C l ~ ( P P h 3 ) 3 - c a t a l y z e dc o n d e n s a t i o n with 6. The slow lo), 3.80 (s, 4); mass spectrum (70 eV) m / e (re1 intensity) 142 (22), rate in this step is presumably the reason for an induction 113 (621, 99 (loo), 86 (60). Anal. Calcd for CgH1402: C, 67.5; H, 9.9. period recorded in the catalysis. Further molecules of the Found: C, 67.5; H, 10.0. aldehyde are formed by transfer hydrogenation of the a$Acknowledgment. We are grateful to the Central Fund unsaturated ketone 9. The bicyclic compound 1 results of the Hebrew University for financial support. then via Ru(I1)-catalyzed ether formation from 10b.11J2 The very high ratio of 1:7 (including the transformation Registry No.-1, 42858-96-8; 2, 19225-65-1; 3, 55401-07-5; 6a, products of 7) indicate that glycol aldehyde formation in 504-02-9; RuCl~(PPh3)3,15529-49-4; ethylene glycol, 107-21-1; dimedone, 126-81-8; 3,3-dimethylcyclohexanone ethylene ketal, step 9 --* 10a is considerable faster than in 6b --* 7. 49673-64-5; 3-tert49673-67-8; 5-tert-butylcyclohexane-1,3-dione, At the elevated temperature of the catalysis the probutylcyclohexanone ethylene ketal, 49673-70-3; cyclohexanone posed reaction intemediates could not be isolated. We ethylene ketal, 177-10-6. found, however, that in the initial stages of the catalysis References and Notes (with dimedone as starting ketone) an unstable keto alcohol of mass 184 is formed. This compound may be the 5 3 (1) Y. Sasson, J. Blum, and E. Dunkelblum. Tetrahedron Lett., 3199 (1973). (2) Y. Tamura, Y. Kita, M. Shimagaki, and M. Terashima, Chem. Pharm. dimethyl analog of 10. Bull., 19, 571 (1971). Finally it should be recalled that in the presence of p i (3) J. Nickl. Chem. Ber., 91, 553 (1958). p e r i d i n e , glycol aldehyde reacts with t w o molecules of di(4) F. Korte, D. Scharf, and K. H. Buchel, Justus Liebigs Ann. Chem., 664, medone to give 3,5,6,7-tetrahydro-3-(2-hydroxy-4,4-di- 97 (1963). (5) S. Uemura, T. Nakano, and K. Ichikawa, Nippon Kagaku Zasshi, 89, methyl-6-oxo-1-cyclohexen- 1-yl)-6,6-dimethyl-4(2H)-benz203 (1968). ofuranone,14 which is not formed in our catalytic process. (6) K. Ichikawa, 0. Itoh, and T. Kawamura, Bull. Chem. SOC.Jpn., 41, 1240
Experimental Section 6,6-Dimethyl-3,5,6,7-tetrahydro-4(2H)-benzofuranone (2). In a 150-ml flask equipped with an efficient condensor, a mixture of 4.2 g of dimedone, 70 mg of RuC12(PPh3)3,15and 60 ml of ethylene glycol was refluxed for 4 hr. The clear solution was cooled to room temperature and the products were extracted (four times) with 100 ml of benzene. The benzene extract was washed with water, dried (MgS04), and concentrated and the residue (4.6 g) was analyzed by the aid of a 2-m GLC column packed with 10% SE-30 on Chromosorb W, operated at 130'. (Dimedone methyl enol ether served as internal standard.) The mixture was found to consist of 3.5% 3,3-dimethylcyclohexanone,15% 3,3-dimethylcyclohexanol,24% 3,3-dimethylcyclohexanone ethylene ketal, and 42% of the bicyclic compound 2. The first two compounds were identified by comparison with authentic ~ a m p l e s . ' ~The J~ ethylene ketal: NMR (CDC13) 6 0.98 (s, 6), 1.3-2.0 (m, 8 ) , 3.86 (s, 4); mass spectrum (70 eV) m / e (re1 intensity) 170 (3), 155 (3), 152 (lo), 127 (loo), 101 (271, 99 (94), 96 (27), 81 (25), 78 (25). Anal. Calcd for CloHl802: C, 70.6; H, 10.6. Found: 70.3; H, 10.6. The dimethyltetrahydrobenzofuranone 2: uv max (EtOH) 274 mp ( t 12,800); ir 1630 cm-'; NMR6 (CDC13) 6 1.10 (s, 61, 2.24 (s, 21, 2.30 (t, 2, J = 1.5 Hz), 2.83 (t, 2, J = 9 Hz), 4.55 (t, 2, J = 9 Hz); mass spectrum (70 e\/) m / e (re1 intensity) 166 (21), 151 (4), 123 (4), 111 ( l l ) , 110 (loo), 80 (9). Anal. Calcd for C10H1402: C, 72.3, H, 8.4. Found: C, 72.1; H, 8.4. The 2,4-dinitrophenylhydrazonederivative of 2 melted at 168-169' (lit.6 mp 167-169). The reaction mixture was distilled a t 0.9 mm. The fraction of bp 89-90' was further purified by preparative GLC to give 2.0 g (40%) of analytically pure 2. 6-tert-Butyl-3,5,6,7-tetrahydro-4(2H)-benzofuranone (3). By the same method 5.04 g of 5-tert-butylcyclohexane-1,3-diones was converted into 1.57 g (27%) of 3. The GLC analysis was accomplished by a 2-m long column packed with 10% FAAB on Chromosorb W at 160': uv max (EtOH) 269 m+ (6 11,000); ir 1635 cm-l; NMR (CDC13) 6 0.85 (s, 91, 1.3-2.3 (m, 4), 2.68 (t,2, J = 9 Hz), 3.80 (m, l), 4.50 (t, 2, J = 9 Hz); mass spectrum (70 eV) m / e (re1 intensity) 194 (161, 1'79 (61, 155 (81, 138 (20), 137 (51), 110 (loo), 57 (25). Anal. Calcd for C12HisOz: C, 74.2; H, 9.3. Found: C, 73.9; H, 9.0. The 3-tert-butylcyclohexanone18and 3-tert-butylcyclohexanoll9 were compared with authentic samples. 3-tert-Butylcyclohexanone ethylene ketal: NMR (CDC13) 6 0.89 (s, 9), 1.0-1.8 (m, 91, 3.87 (s, 4); mass spectrum (70 eV) m / e (re1 intensity) 1.98 (l), 155 (15), 141 (98), 137 (18), 99 (loo), 57 (38). Anal. Calcd for C12H2202: C, 72.6; H, 11.1. Found: C, 72.5; H, 11.0. 3,5,6,7-Tetrahydro-4(2H)-benzofuranone (1) was prepared similarly from cyclohexane-1,3-dione in 46% yield. The unsubstituted bicyclic compound 1 is less stable than 2 and 3, and therefore had to be freshly distilled [bp 100" (4 mm)] or gas chromatographed (on 15% QF-1 on Chromosorb W a t 120') prior to each spectroscopic recording and the elementary analysis: uv max (EtOH) 272 mp ( t 15,600); ir 1630 cm-';' NMR7 (CDC13) 6 1.882.58 (m, 61, 2.81 (t, 2, J = 9.5 Hz), 4.55 (t, 2, J = 9.5 Hz); mass spectrum (70 eV) m / e (re1 intensity) 138 (32), 124, (19), 111 ( l l ) ,
(1960). (7) J. M. Mcintosh and P. M. Beaumier, Can. J. Chem., 51, 843 (1973). (8) E. Dunkelblum, R. Levene, and J. Klein, Tetrahedron,28, 1009 (1972). (9) lchikawa et al. (ref 6) reported the preparation of an inseparable mixture of 4 and 5. The NMR spectrum of our mixture and the reported one proved to have exactly the same peaks. (IO) Y. Sasson, M. Cohen, and J. Blum, Synthesis, 359 (1973). (11) Y. Sasson and J. Blum. J. Chem. Soc., Chem. Commun., 309 (1974). (12) With the available evidence we cannot be certain that ether formation takes place at this stage. Thus in an alternative mechanism, e.g., 6b may react with ethylene glycol to give ether 11. intramolecular hydrogen transfer from the OH function to the double bond (to give 12) followed by internal cyclization may lead to 13. The product 1 is then formed by Ru(ll)-catalyzedmigration of the C S - C double ~~ bond.I3
&o,I:H
&()J 11
12
13
(13) Cf., e.g.. Y. Pickholtz, Y. Sasson, and J. Blum, Tetrahedron Left., 1263 (1974). (14) D. C. C. Smith, J. Chem. SOC., 1244(1956), (15) T. A. Stephenson and G. Wllkinson, J. horg. Nucl. Chem., 28, 945 (1966). (16) 0. H. Wheeler and J. Zabicky, Can. J. Chem., 36, 656 (1958). (17) E. L. Eliel and C. A. Lukach, J. Am. Chem. SOC.,79, 5986 (1957). (18) C. Djerassi, E. J. Warawa, R. E. Wolff, and E. J. Eisenbraun, J. Org. Chem., 25, 917 (1960). (19) W. Huckel and K.Thiele, Chem. Ber., 94, 2027 (1961).
Intramolecular and Intermolecular 1,3-Dipolar Cycloadditions of Nitrile Oxides Bearing an Alkenyl Substituent Luisa Garanti,* Albert0 Sala, and Gaetano Zecchi
Istituto di Chimica industriale dell'llniversita', Centro del C.N.R. per la Sintesi e sterekhimica di speciali sistemi organici, 20133 Milano, Italy Received March 21,1975
Oxidation of 2-allyloxybenzaldoxime by nitrogen dioxide has been recently reported1 to give the fused ring compound 2a, the product of a n intramolecular cycloaddition of the intermediate nitrile oxide la. The stereochemistry of the latter molecule reasonably accounts for the intramolecular process as well as for the unusual orientation, leading to 5-unsubstituted 2-iso~azoline.~ This result led us to examine whether the intramolecular reaction proceeds as the chain length between the dipole
