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J. Org. Chem. 1984, 49, 3659-3660 7.6), 7.35 (m, 5). Anal. Calcd for CmHBN04Si: C, 63.28; H, 8.76; N, 3.83. Found: C, 63.04; H, 8.85; N, 3.59. Diethyl 3 4 (tert -Butyldimethylsilyl)oxy]pentanedioate (12). Under a nitrogen atmosphere, into a 100-mL round-bottomed flask equipped with a rubber septum and a magnetic stirring bar was placed 4.08 g (60.0 mmol) of imidazole in 35 mL of CH2C12. T o this solution was added a solution of 4.50 g (30.0 mmol) of tert-butylchlorodimethylsilanein 10 mL of CH2C12. After the reaction mixture was stirred for 10 min, a solution of 4.08 g (20.0 mmol) of diethyl 3-hydroxypentanedioate (11) in 10 mL of CHzClzwas added dropwise. The mixture was stirred for 18 h at room temperature and partitioned between 250 mL of ether and 50 mL of water. The layers were separated, the organic phase was washed with 50 mL of brine, and the combined aqueous washings were extracted with 100 mL of ether. After drying the combined organic fractions over MgS04, the solvent was removed with a rotary evaporator to afford 6.13 g of yellow liquid. The crude material was purified by silica gel column chromatography with 1:8 ether/hexanes as the eluant to obtain 6.07 g (95% yield) of 12 as a colorless liquid: IR (film) 2940, 2865, 1745 cm-'; 'H NMR 6 0.07 (s, 6), 0.84 (e, 9), 1.26 (t, 6, J = 7.1), 2.54 (d, 4, J = 6.2), 4.12 (4, 2, J = 7.1), 4.13 (q, 2, J = 7.2), 4.55 (quintet, 1, J = 6.2). Anal. Calcd for C1SH3006Si:C, 56.56; H, 9.50. Found: C, 56.71; H, 9.35. Diethyl 3 4 (trimethylsilyl)oxy]pentanedioate (14): IR (film) 2975, 1730, 1370, 1250 cm-'; 'H NMR 6 0.01 (s, 9), 1.16 (t, 6, J = 7.2), 2.42 (d, 4, J = 6.3), 4.02 (dd, 2, J = 5.4, 7.2), 4.08 (dd, 2, J = 5.4,7.2), 4.46 (m, 1). Anal. Calcd for Cl2HUO5Si:C, 52.14; H, 8.75. Found: C, 51.92; H, 8.56. 3 4 (tert-Butyldimethylsily1)oxy Ipentanedioic Anhydride (13). Under a nitrogen atmosphere, into a 100-mL round-bottomed flask equipped with a rubber septum and a magnetic stirring bar was placed 4.40 g (13.8 mmol) of diester 12 and 1.10 g (27.6 mmol) of NaOH. T o the system was added 15 mL of methanol, and the mixture was stirred overnight at room temperature. The solvent was removed with a rotary evaporator, and residual methanol was removed under high vacuum (5 h, 0.9 torr) to obtain a tan solid. The system was equipped with a reflux condenser, charged with 30 mL of benzene and 20 mL of acetic anhydride, and heated at reflux for a period of 1.5 h. After being cooled to room temperature, the reaction mixture was partitioned between 300 mL of CHCl, and 100 mL of brine, the layers were separated, and the organic phase was washed with three 100-mL portions of aqueous NaHCO,. The CHC1, solution was dried over MgS04 and the solvent was removed with a rotary evaporator. The resulting pale brown oil crystallized under high vacuum (4 h, 50 "C, 0.7 torr). The crude material was washed with hexanes and recrystallized from hexanes to obtain 2.36 g (70% yie1d)'O of 13 as white plates: mp 80-81 "C; IR (CHClJ 2925,2860,1820, 1765, 1255 cm-'; 'H NMR 6 0.10 (s, 6),0.86 ( 8 , 9), 2.72 (dd, 2, J = 2.7, 16), 2.92 (dd, 2, J = 3.8, 16), 4.38 (m, 1). Anal. Calcd for CllH2004Si: C, 54.08; H, 8.25. Found: C, 53.93; H, 8.27. Racemic Methyl tert -Butyldimethylsilyl 3-[ (tert-Butyldimethylsilyl)oxy]pentanedioate (7 and 8). Under a nitrogen atmosphere, into a 50-mL round-bottomed flask equipped with a rubber septum and a magnetic stirring bar was placed 6 mL of methanol. T o the system was added 176 mg (7.66 mmol) of sodium, and the mixture was stirred at room temperature until all the sodium had reacted (20 min). T o the system, a t 0 "C, was added a solution of 1.50 g (6.15 mmol) of anhydride 13 in 6 mL of methanol, and the mixture was stirred for 1 h a t 0 "C. The solvent was removed with a rotary evaporator, and residual methanol was removed under high vacuum (1 h, 0.4 torr). The resulting oil was partitioned between 30 mL of CHzClzand 7 mL of 5% aqueous hydrochloric acid, the layers were separated, and the organic phase was washed with two 10-mL portions of brine. The CHC13 solution was dried over MgSO,, and the solvent was removed with a rotary evaporator to obtain 1.68 g of crude methyl 3-[ (tert-butyldimethylsilyl)oxy]pentanedioate,which was silylated without further purification. Under a nitrogen atmosphere, into a 50-mL round-bottomed flask equipped with a rubber septum and a magnetic stirring bar was placed 868 mg (12.7 mmol) of imidazole in 6 mL of CH2C12. T o the resulting solution was added 960 mg (6.38 mmol) of tert-butylchlorodimethylsilanein 1.5 mL of CH2Cl2 After 10 min a solution of the foregoing crude silyloxy acid (1.68 g, 6.09 mmol)
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in 4.5 mL of CH2Clzwas added, and the mixture was stirred for 1h at room temperature. The reaction mixture was diluted with 40 mL of ether and washed with two 5-mL portions of water, 5 mL of saturated aqueous NaHC03, and 5 mL of brine. The organic phase was dried over MgS04, and the bulk of the solvent was removed with a rotary evaporator. The residue was subjected to high vacuum (1h, 0.4 torr) to obtain 2.13 g (89% yield from 13) of racemic silyl ester; mp 40-41 "C. The 'H NMR spectrum of the product thus obtained was identical with that of the optically active material (7). The racemic compound was converted to a 1:l mixture of diastereomeric amides 9 and 10 by the procedure outlined above. Analysis of the crude product mixture by HPLC indicated a 9:lO ratio of 49.850.2. Registry NO. 5, 87118-53-4; 6, mii&64-7; 7,91424-35-0;(h1-7, 91465-61-1; 8, 91424-36-1; 9, 91424-37-2; 10, 91424-38-3; 11, 32328-03-3; 12,91424-39-4; 13, 91424-40-7; 14,91424-41-8; tertbutylchlorodimethylsilane, 18162-48-6.
Convenient Preparation of N,N-Dimethylacetamide Dimethyl Acetal Robert G. Salomon* and Swadesh R. Raychaudhuri
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106 Received March 6, 1984
N,N-Dimethylacetamide acetals are valuable reagents for C-C connective syntheses of y96-unsaturatedamides' from allylic alcohols (eq 1) and (o-methylaryl)acetamidesl8 from arene methanols (eq 2) via amide-Claisen rearrangements. These syntheses exploit a facile reversible in situ generation of 1-(dimethylamino)-1-alkoxyethylenes2 from N,N-dimethylacetamide acetals (eq 3). A
3
(0
(2)
Previously, N,N-dimethylacetamide acetals were prepared from dimethylacetamide by reaction with trialkyloxonium fluoborates followed by sodium al~oholate.~ We now report experimental details for a different synthesis of N,N-dimethylacetamide dimethyl acetal4 which is patterned after a synthesis of dimethylformamide dimethyl acetal5 from dimethylformamide-dimethyl sulfate complex.ld The present methods is more convenient because (1) (a) Wick, A. E.; Felix, D.; Steen, K.; Eschenmoser, A. Helu. Chim. Acta 1964,47,2425. (b) Hill, R. K.; Soman, R.; Sawada, S. J.Org. Chem. 1972,37,3737. (c) Ziegler, F. E.; Bennett, G. B. J.Am. Chem. SOC.1973, 95, 7458. (d) Bredereck, H.; Effenberger, F.; Simchen, G.Chem. Ber. 1963, 96, 1350. (e) Meerwein, H.; Florian, W.; Schon, N.; Stopp, G. Liebigs. Ann. Chem. 1961, 641, 1. (2) Felix, D.; Gschwend-Steen, K.; Wick, A. E.; Eschenmoser, A. Helu. Chim. Acta 1969,52, 1030. (3) Meerwein, H.; Florian, W.; Schon, N.; Stopp, G. Liebigs Ann. Chem. 1961,641, 1. (4) 1,l-Dimethoxy-1-(dimethy1amino)ethane. (5) Bredereck, H.; Simchen, G.; Rebstdat, S.; Kantlehner, W.; Horn, P.; Wahl, R.; Hoffmann, H.; Grieshaber, P. Chem. Ber. 1968, 101,41.
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dialkyl sulfates are more readily available (less expensive) and easier to handle than the oxonium salts. 0-Methylation of N,N-dimethylacetamidewith dimethyl sulfate proceeds readily at 70-80 "C in a few hours to afford an oily salt in excellent yield. Reaction of the latter with sodium methoxide provides the target acetal in 58% overall yield from N,N-dimethylacetamide. n
N (CH3)2
I
H3CC(OCH3 12
Experimental Section Eastman dimethyl sulfate was used as received. Eastman NJV-dimethylacetamidewas purified by stirring with barium oxide for 3 days followed by distillation of the supernatant under water aspirator vacuum and was stored over 4-A molecular sieves. Fisher ACS Certified benzene was freshly distilled from potassium benzophenone ketyl. Ether was freshly distilled from LiA1H4. Methanol was freshly distilled from sodium methoxide prepared by addition of metallic sodium to Fisher ACS Certified anhydrous methanol. NJV-DimethylacetamideDimethylSulfate Complex. In a 2-L three-necked, round-bottom flask with a magnetic stirrer, thermometer, and dry nitrogen inlet were placed 630 g (473 mL, 5 mol) of dimethyl sulfate and 435 g (464 mL, 5 mol) of N,Ndimethylacetamide. The mixture was heated a t 70-80 "C with a heating mantle for 3 h with magnetic stirring. After cooling with an ice-water bath, the reaction mixture was then washed successively with 350 mL of dry benzene and twice with 250 mL of dry ether. The washings were conveniently removed from the reaction vessel with a large hypodermic syringe. The last traces of wash solvents were removed from the product by evaporation under reduced pressure, first with a water aspirator vacuum and then with a mechanical pump. The complex was obtained as a colorless viscous oil: 1042 g (98% yield); n20D1.4700; 'H NMR (CDC13) 8 2.68 (3 H, s), 3.35 (3 H, s), 3.52 (3 H, s), 3.67 (3 H, s), 4.33 (3 H, 8). N,N-Dimethylacetamide Dimethyl Acetal: In a 5-L three-necked, round-bottom flask with a mechanical stirrer, 1-L pressure-equalizing addition funnel, and condenser topped with
1984,49, 3660-3662 a gas inlet for maintaining an atmosphere of dry nitrogen were placed 1585 mL of anhydrous methanol. Then 112.5 g (4.9 mol) of sodium was added in small pieces (3-5 g each) gradually. After all of the sodium had reacted, the resulting sodium methoxide solution was cooled to 1-4 "C with an ice-salt-water bath, and 1042 g of NJV-dimethylacetamide-dimethylsulfate complex was added dropwise with vigorous stirring over 3 h. The reaction mixture was stirred at room temperature for 20 h and then allowed to stand for an additional 20 h.I The addition funnel was then replaced with a stopper and the reflux condenser was set for distillation. The reaction mixture was heated with a mantle and methanol was distilled from the reaction mixture at atmospheric pressure. Methanol containing some NJV-dimethylacetamide dimethyl acetal was collected with a boiling range of 60" to 78 "C. After most of the methanol had been distilled, the receiver was changed. A second fraction was collected into a receiver which was cooled in an ice-salt-water bath, and the pressure was gradually reduced with a water aspirator while the temperature of the mantles was gradually increased to 160-170 "C. The first fraction was then carefully fractionated by distillation through a 17 mm X 40 cm column packed with glass helices and surrounded by a 5 cm X 40 cm glass insulating jacket which can be heated by a nichrome wire helix with approximately 1 turn per cm. The product boiling in the range 100-118 "C was collected as N,Ndimethylacetamide dimethyl acetal. During the redistillation of the first fraction, methanol distilled first. Then the fractionating column was gradually and gently heated as needed to allow distillation of the desired NJV-dimethylacetamide dimethyl acetal. This product, 162 g, shows nmD 1.4158. The 'H NMR spectrum of this product in CDC1, shows resonances associated with the desired N,N-dimethylacetamide dimethyl acetal at S 1.2 (3 H, s), 2.27 (6 H, s), 3.2 (6 H, s). In addition, a few very small resonances appear a t 6 1.43, 2.57, 3.27, and 3.6 owing to minor impurities. The second fraction, collected under aspirator vacuum, was also carefully fractionated by distillation a t atmospheric pressure through the glass helices-packed column. The product boiling in the range 110-118 "C was collected as N,N-dimethylacetamide dimethyl acetal: 221 g; n20D1.4118. This light yellow oil shows 'H NMR resonances in CDC1, at 6 1.2,2.27,3.2 only (vide supra). The total yield, 383 g, is 59%.
Acknowledgment. We thank the National Science Foundation for generous financial support. Registry No. Me2S04, 77-78-1; CH3C(0)NMe2, 127-19-5; CH3C(0)NMe2-Me2S0,, 920-98-9; MeONa, 124-41-4; CH3C(OMe),NMe2, 18871-66-4. (7) The precipitate of Na03SOCH3became too heavy to stir. (8) Measured with an iron-constantan thermocouple.
(6) A similar synthesis is suggested in footnote 3 of ref la.
Communications Structure of Aphanamol I and I1
grandifolia is a timber tree of Meliaceous family occuring
Summary: Unique sesquiterpenoids, named aphanamol I and 11, have been obtained from a Meliaceous plant A p h a n a m i x i s grandifolia as minor toxic principles. Structures 1 and 2 were established by spectral study, in which the two-dimensional NMR pulse sequence COSY/COSY-45 takes an essential role.
in Java, Indonesia, and produces poisonous fruits. Extraction of this fruit peel afforded three kinds of active constituents. The major toxic component was a known triterpenoid, aphanamixin, which was already reported as a constituent of a related species, A. p o l y ~ t a c h y a . The ~ minor toxic compounds were found to be new hydroazulene-type sesquiterpenoids with a unique carbon
Sir: In a series of investigation of Indonesian tropical plant constituents showing interesting biological properties, much interest has been focused on toxic principles of various Meliaceous plants which have traditionally been employed as fish or dart arrow poisons.lp2 A p h a n a m i x i s
(1)Nishizawa, M.; Nishide, H.; Hayashi, Y.; Kosela, S. Tetrahedron Lett. 1982,23, 1349 J. Org. Chem. 1983,48, 4462. (2) Nishizawa, M.; Inoue, A.; Sastrapradja, S.; Hayashi, Y. Phytochemistry 1983, 22, 2083. (3) Chatterjee, A.; Kundu, A. B. Tetrahedron Lett. 1967, 1471.
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