Short Communication
CSIRO PUBLISHING
Aust. J. Chem. 2005, 58, 228–230
www.publish.csiro.au/journals/ajc
Solvent Free Rapid Synthesis of 3-Alkoxycyclohex-2-en-1-one from 1,3-Cyclohexanedione Promoted by Indium(iii) Chloride/Silica Gel R. Murugan,A R. Kamakshi,A and Boreddy S. R. ReddyA,B A
Industrial Chemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, India. author. Email:
[email protected]
B Corresponding
A convenient and environmentally friendly method for the synthesis of 3-alkoxycyclohex-2-en-1-one 1 from cyclohexane-1,3-dione on the surface of silica gel impregnated with indium(iii) chloride under microwave irradiation without any solvent has been reported. Manuscript received: 15 October 2004. Final version: 2 February 2005.
3-Alkoxycyclohex-2-en-1-ones 1 are of great synthetic interest as they provide synthons for various transformations with extensive applications. Compound 1 is derived from β-cyclohexadione, whose conversion is important for the construction of synthetic intermediates like 4alkylated cyclohex-2-enones[1,2] and 3-substituted cyclohex2-enones.[3,4] Furthermore, these synthons may act as dienophiles in Diels–Alder reactions.[5] Enone 1 has been used as a synthetic precursor for the synthesis of 2-aryland 2-alkenyl-3-alkoxy cyclohexenones as well as optically active cyclohexenones that serve as starting materials for many terpenoids.[6,7] In addition, the regiospecific syntheses of functionalized bicyclo[2.2.2.]octenones and tricycloillicinone, which is a neurotrophic substance, have also been accomplished from 1.[8,9] Acids such as HCl,[10] para-toluene sulfonic acid (PTSA),[11] and TiCl4 [12] have been found to catalyze reactions of 1,3-diketones to yield 1. These offer limited synthetic scope as a result of low yields, long reaction times, as well as catalytic and solvent excess. Reaction of 1,3diketone with trimethylorthoformate or 2,2-dimethoxy-1methylpyrrolidine as the methylating source have also been undertaken. However, the reactions take even longer and the latter procedure does not offer very good yields.[13] Attempts have also been made to synthesize 1 from acyclic compounds, but although the yields are good the procedure is tedious.[14] Therefore, the development of new convenient methods with better yields are of great interest for synthetic chemists. Surprisingly, there have been no reports on the synthesis of 3-alkoxycyclohex-2-en-1-ones using indium halides. Solid-support reagents coupled with microwave irradiation are greatly sought after by synthetic chemists because of the benefits of improved reaction rates, excellent yields, and simple work up procedures. Here, we report an efficient and rapid method for the synthesis of 3-alkoxycyclohex-2-en-1ones using indium(iii) chloride supported on silica gel under
O
O ⴙ R
InCl3/SiO2
OH
R
MWI 1– 3 min O R ⫽ alkyl, aryl
O 87 – 93%
1
Scheme 1.
microwave conditions (Scheme 1). Microwave irradiation has been explored as an alternative technique to conventional heating methods.[15–17] Indium halides have been greatly discussed as versatile catalysts for various reactions. Indium(iii) chloride in particular, as a mild Lewis acid, offers tremendous scope for catalyzing numerous reactions. It has been widely studied as a catalyst for Diels–Alder and Friedel–Crafts reactions, aldol condensations, as well as other coupling reactions.[18] Indium(iii) chloride on a solid support is also being considered as a catalyst since it offers an environmentally benign protocol with minimal catalyst loading. Herein, we report the synthesis of 3-alkoxycyclohex-2-en-1-one from 1,3-cyclohexanedione using the InCl3 /SiO2 system as a catalyst under microwave irradiation. Excellent yields (87–95%) were obtained after short reaction times (3 min). The experimental procedure is simple. 1,3-Diketone and the relevant alcohol were added to silica gel impregnated with indium(iii) chloride (20 mol%) and the resultant reaction mixture was stirred for five minutes to attain uniformity. The mixture was then exposed to microwave radiation in a domestic microwave oven for the time required to complete the reaction (1–3 min), directly charged onto a small silica gel column, and eluted with a mixture of ethyl acetate/light petroleum (2:8) to afford the desired product. The control reaction performed in the presence of silica gel alone failed to yield the desired product; this confirmed the efficiency of
© CSIRO 2005
10.1071/CH04249
0004-9425/05/030228
Solvent Free Rapid Synthesis of 3-Alkoxycyclohex-2-en-1-one
indium(iii) chloride as a catalyst for the alkylation of 1,3diketones. A screening of the efficiency of the other Lewis acids revealed that CuCl, CuI, FeCl3 , and ZnCl2 led to the formation of product, albeit in low yields in comparison to the reaction carried out in the presence of InCl3 /SiO2 under microwave irradiation. The reaction rates and yields were dramatically enhanced by microwave irradiation. The polar solid support as well as polar reactants generate the required heat energy to promote the alkylation. When the reaction (with the starting material for entry f ) was carried out in acetonitrile for six hours under conventional heating in the presence of indium(iii) chloride, only a 27% yield of the product was obtained. Similarly, when the reaction mixture was ground under dry conditions for one hour using a pestle and mortar the yield of the product was 13%. However, when the same reaction was carried out in a microwave oven for two minutes in the presence of InCl3 /SiO2 , the corresponding product was isolated in 93% yield after filtration through a small silica gel column. Invariably, the products obtained from the reaction conducted under microwave irradiation were able to be purified with greater ease. The reaction was also found to be effective for other 1,3-diketones such as dimedone, acetylacetone, and phenylacetoacetone (entries j, k, l, and m, respectively; Table 1). As shown in Table 1, the first run for f gave a conversion of 93% after two minutes reaction time. The catalyst was then washed with ethyl acetate, oven-dried, and re-used for the same conversion four times. The reactivity of the catalyst was found to decrease, the successive runs giving rise to the desired product in 89, 80, and 65% yield for the second, third, and fourth cycle, respectively. In conclusion, the present procedure catalyzed by indium(iii) chloride on a silica gel surface provides an efficient and rapid synthesis of 3-alkoxycyclohex-2-en-1-ones under solvent-free conditions. The notable advantages of this procedure are (a) fast and clean reactions; (b) operational simplicity; (c) high yield; and (d) reusability of the catalyst. We believe that this procedure will provide a better scope and more practical alternative to the existing procedures for the synthesis of 3-alkoxyhexenones.
229
Table 1. Microwave-assisted synthesis of 3-alkoxy-2-cyclohexenones All products were characterized by IR and NMR spectroscopy, and mass spectrometry. Yields refer to isolated yields after purification. Entry
Alcohol
Product
a
CH3 OH
O
b
CH3 CH2 OH
O
c
(CH3 )2 CHOH
O
d
CH3 (CH2 )3 OH
O
e
Cl(CH2 )2 OH
O
Cyclohexane-1,3-dione (1 mmol) and methoxyethanol (1 mmol) were added to silica gel impregnated with indium(iii) chloride (20 mol%), which was prepared by adding a suspension of InCl3 in a minimum amount of THF to silica gel (2 g, 100–200 mesh; activated by heating for 4 h at 150◦ C before use) followed by complete evaporation of the solvent under vacuum. The whole mass was stirred for 5 min to attain uniformity and was then transferred to a glass tube and inserted into an alumina bath inside the microwave oven. The compound was irradiated with microwaves in a domestic microwave oven (BPL, India) at 650 W for 2 min. Upon completion, the reaction mixture was directly charged onto a small column and eluted with a mixture of ethyl acetate/light petroleum (2:8) to afford the desired product. 3-(2-Methoxyethoxy)cyclohex-2-en-1-one 1f νmax /cm−1 (neat) 3071, 2944, 2889, 2821, 1651, 1604, 1359, 1220, 1032, 825. δH (CDCl3 ) 5.35 (1H, s), 3.96 (2H, t, J 4.4), 3.69 (2H, t,
Yield [%]
1
92
2
93
2
95
2
89
2
90
2
93
1
87
2
92
3
94
2
93
2
95
1
89
3
91
O
O
O
O
Cl
O
f
CH3 O(CH2 )2 OH
O O
O
g
CH2 =CHCH2 OH
O
O
h
O
OH
O O
O
i
PhCH2 OH
j
CH3 CH2 OH
k
(CH3 )2 CHOH
l
CH3 CH2 OH
m
CH3 CH2 OH
O
Experimental General Procedure
Time [min]
O O
O O
O O
O
O
O
230
R. Murugan, R. Kamakshi and B. S. R. Reddy
J 4.6), 3.42 (3H, s), 2.45 (2H, t, J 6.2), 2.35 (2H, t, J 6.4), 2.02–1.93 (2H, m). δC (CDCl3 ) 199.7, 177.7, 102.8, 70.0, 67.5, 59.0, 36.6, 30.8, 21.1. m/z 170 (12%, M+• ), 112 (19), 84 (48), 69 (39), 58 (100), 55 (21), 43 (33).
Acknowledgments R.M. thanks M. Karthikeyan and Dr P. T. Perumal, Head of Organic Chemistry Division, for their help. References [1] [2] [3] [4] [5] [6]
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