http://www.chemistrymag.org/cji/2007/099043pe.htm

Sep.30, 2007  Vol.9 No.9 P.43 Copyright cij17logo.gif (917 bytes)

The reaction of aromatic aldehydes and 1,3-cyclohexanedione catalyzed by PEG-400 in water

Wang Aiqinga , Cheng Zhaolib,   Wang Jinga,  Li Jiangqiaoa, Jin Tongshoua
(aCollege of Chemistry and Environmental Science, Hebei University, Baoding 071002; b Bureau of Hydrology & Water Resources Survey，Hebei Baoding 071000，China)

Abstract Synthesis of 9-aryl-1,8-dioxooctahydroxanthene derivatives and 2,2’-arylmethylene bis(3-hydroxy- 2-cyclohexene-1-one) from aromatic aldehyde and 1,3–cyclohexadione catalyzed by polyethylene glycol 400 (PEG-400) in water was described. This method provides several advantages such as environment friendliness, high yields and simple work-up procedure. Moreover, water was chosen as a green solvent.
Keywords Aromatic aldehyde 1, 3-cyclohexadione Water PEG-400

1 INTRODUCTION   
In the past decade, there has been growing recognition that water is an attractive medium for many organic reactions not only for the advantage accorded by avoiding extensive drying reactants, catalyst and solvent, but also for the unique reactivity and selectivity that some times result.1, 2 On the other hand, organic reaction in water without using harmful organic solvents are the current great interest especially in relation to today environmental concerns. However, water as a solvent was not frequently used until recently for several reasons such as many organic materials do not dissolve in water and many reactive intermediates and catalysts are decomposed in water. So it is necessary for adding some phase-transfer catalysis (PTC) or surfactant such as hexadecyltrimethylammonium bromide (HTMAB), PEG-400, tetrabutylammonium bromide (TBAB), 4-dodecylbenesulfonic acid (DBSA), because they benefit the organic materials uniform dispersion in water in the course of synthesis. Based on our recent research, we have developed novel routes for the synthesis of some hetreocyclics compounds catalyzed by these PTC or surfactant in water.3 Our important aim of this research is to synthesize more hetreocyclics compounds in media aqueous as well.
    It has been reported that the reaction of aromatic aldehyde and 1,3-cyclohexanedione can yield 9-aryl-1,8-dioxooctahydroxanthene and their derivatives and 2,2’-arylmethylene bis(3-hydroxy-2-cyclohexene-1-one) by many methods.4-7 However, the use of PEG-400 as the catalyst in aqueous media for the synthesis of them has not been reported. In this manuscript, the authors wish to report a general and highly efficient route for the synthesis of these two produces and their derivatives using PEG-400 as catalysts. This is an efficient synthesis method, not only preserves the simplicity but also consistently gives the corresponding products in good yields (Scheme 1).

2 RESULTS AND DISCUSSION                                    
When the aromatic aldehyde 1, 1, 3-cyclohexadion 2 was performed in water in the presence of PEG-400 and NH2SO3H, high yields of products 3 and 4 were found. The results are summarized in Table 1

Scheme 1

Table 1 Synthesis of 9-aryl-1,8-dioxooctahydroxanthene derivatives and 2,2'-aryl-methylene bis(3-hydroxy-2-cyclohexene-1-one) in aqueous media by using PEG-400 or PEG-400 /NH2SO3H

Entry

Ar

Product

Yielda(%)

M. P./ oC

Found

Reported

1

C6H5 1a

3a

81

206-208

205-207
　 　

4a

84

268-270

270-271

2

4-ClC6H41b

3b

85

202-203

202-204
　 　

4b

82

285-287

289-291

3

3-ClC6H41c

3c

81

187-191

 　
　 　

4c

83

270-272

276-277

4

3,4-Cl2-C6H31d

3d

87

206-209

 　
　 　

4d

77

204-208

229

5

4-NO2C6H4 1e

3e

82

194-197

191-192
　 　

4e

86

260-261

263

6

3-NO2C6H4 1f

3f

82

196-198

 　
　 　

4f

86

282-283

286-288

7

2-NO2C6H4 1g

3g

83

194-196

 　
　 　

4g

82

239-241

245-246

8

4-HOC6H4 1h

3h

80

200-205

 　
　 　

4h

85

275-278

279-281

9

4-HO-3-CH3OC6H31i

3i

80

188-191

 　
　 　

4i

79

243

245-246

10

4-CH3C6H4 1j

3j

84

187-189

 　
　 　

4j

77

256-257

262-263

11

4-CH3OC6H4 1k

3k

83

185-188

178-180
　 　

4k

79

198-199

201-202

a Isolated yield

As shown in Table 1, the different products were obtained using different catalyst in this reaction. In a typical general experimental procedure, aromatic aldehyde 1 and 1,3-cyclohexanedione 2 were grinded in the presence of PEG-400 or PEG-400/NH2SO3H, the corresponding products 3 and 4 were obtained in good to excellent yields. The catalyst effect shows that acid is needed during the cyclization. No strongly obvious effect of electron and nature of substituents on the aromatic ring were observed. All aromatic aldehydes containing electron-withdrawing groups (such as nitro group, halide) or electron-donating groups (such as hydroxyl group, alkoxyl group) were employed and reacted well to give the corresponding products 3 and 4 in good to excellent yields under this reaction conditions.
    Taking the reaction of 3-chlorobenzaldehyde as an example, we investigate the effect of the catalyst reagents on the reaction. It was found that the catalyst plays a crucial role in the success of the reaction in terms of the rate and the yields. For example, the reaction could be carried out in the absence of PEG-400 when the mixture (1c and 2) in water, but it obtained very poor yield (46%). Increasing of the catalyst to 200mg,300mg,350mg,400mg, it results in accelerating the reaction with the yield to 80%、91%、90%、80.3% respectively. Use of just in refluxing water is sufficient to push the reaction forward. Higher amounts of the catalyst did not improve the results to a greater extent. Thus, 300mg PEG-400 was chosen as a quantitative catalyst for these reactions. At the results, the best use level of PEG-400 and NH2SO3H was 300mg/40mg.

3 CONCLUSION                                
In summary, a novel and efficient procedure for the synthesis of 9-aryl-1,8-dioxo- 1,2,3,4,6,7,8-octahydroxanthenes and 2,2’-arylmethylene bis(3-hydroxy-2-cyclohexene-1-one) through the reaction of aromatic aldehydes and 1, 3-cyclohexanedione using PEG-400 or PEG-400/ NH2SO3H as catalyst has been reported. This is a one–pot condensation in water. It is noteworthy that water solution is a clean and environmentally desirable system. No harmful organic solvents are used. This report has proposed and demonstrated a new useful and attractive process for the synthesis of these compounds.

4 EXPERIMENTAL
Liquid aldehydes were distilled before use. IR spectra were recorded on a Bio-Rad FTS-40 spectrometer (KBr). 1H NMR spectra were measured on a Bruker AVANCE 400 (400 MHz) spectrometer using TMS as internal reference and DMSO as solvent. Melting points are uncorrected.
Procedure for the synthesis of 3 and 4 using PEG-400 or PEG-400/ NH2SO3H as catalyst
A mixture of an aromatic aldehyde 1 (1.0 mmol), 1, 3-cyclohexanedione 2 (2.0 mmol) and PEG-400 (300mg) or PEG-400 / NH2SO3H (300mg/40mg) in water (20 mL) was stirred at refluxing for three hours. The progress of the reaction was monitored by thin layer chromatograph. After completion of the reactions, the mixture was cooled to room temperature and solid was filtered off and washed with H2O (40 mL) and the crude products were got. The crude products 3 and 4 were purified by recrystallization by 95% ethanol. Data of some compounds are shown below:
3a. IR (KBr):nmax 3425, 3060, 2954, 2870, 2633, 1598, 1468, 1419, 1375, 1248, 1149, 1066, 974, 870, 789 cm-1. dH 1.99 (m, 4H, 2 × CH2), 2.30-2.51 (m, 8H, 4 × CH2), 5.41 (s, 1H, CH), 7.10-7.28 (m, 5H, Ar-H), 12.15 (br, s, 1H, OH), 12.19 (br, s, 1H, OH).
3b. IR (KBr):nmax 3505, 3050, 2945, 2870, 2633, 1589, 1486, 1421, 1357, 1248, 1145, 1061, 870, 798 cm-1. dH 1.98(m, 4H, 2 × CH2), 2.30-2.48 (m, 8H, 4 × CH2), 5.39 (s, 1H, CH), 7.21-7.28 (m, 4H, Ar-H), 12.23 (br, s, 2H, OH).
3c. IR (KBr):nmax 3424, 3058, 2954, 2868, 2634, 1596, 1468, 1418, 1375, 1307, 1248, 1151, 1066, 974, 890, 870, 789 cm-1. dH 2.01 (m, 4H, 2 × CH2), 2.31-2.51 (m, 8H, 4 × CH2), 5.50 (s, 1H, CH), 6.98-7.28 (m, 4H, Ar-H), 11.57 (br, s, 1H, OH), 11.91 (br, s, 1H, OH).
3d. IR (KBr):nmax 3425, 3060, 2950, 2865, 2630, 1601, 1470, 1417, 1379, 1250, 1152, 1135, 975, 889, 790 cm-1. dH 2.03(m, 4H, 2 × CH2), 2.30-2.52 (m, 8H, 4 × CH2), 5.51 (s, 1H, CH), 6.98-7.23 (m, 3H, Ar-H), 11.57 (br, s, 1H, OH), 11.93 (br, s, 1H, OH).
3e. IR (KBr):nmax 3424, 3085, 2945, 2886, 2643, 1595, 1462, 1375, 1307, 1248, 1151, 1066, 974, 890, 870, 798 cm-1. dH 2.05 (m, 4H, 2 × CH2), 2.32-2.48 (m, 8H, 4 × CH2), 5.50 (s, 1H, CH), 6.99-7.38 (m, 4H, Ar-H), 12.07 (br, s, 1H, OH), 12.19 (br, s, 1H, OH).
3f. IR (KBr):nmax 3424, 3087, 2955, 2812, 2372, 1654, 1523, 1418, 1350, 1202,1131, 1074, 1015, 960, 860, 815, cm-1. dH 1.99 (m, 4H, 2 × CH2), 2.35-2.50 (m, 8H, 4 × CH2), 5.50 (s, 1H, CH), 6.99-7.38 (m, 4H, Ar-H), 12.01 (br, s, 1H, OH), 12.15 (br, s, 1H, OH).
3g. IR (KBr):nmax 3424, 3077, 2964, 2945, 2896, 2873, 1678, 1619, 1520, 1335, 1202, 1178, 1130, 823, 787cm-1. dH 2.02 (m, 4H, 2 × CH2), 2.36-2.52 (m, 8H, 4 × CH2), 5.42 (s, 1H, CH), 7.02-7.38 (m, 4H, Ar-H), 12.09 (br, s, 1H, OH), 12.18 (br, s, 1H, OH).
3j. IR (KBr): nmax 3434, 3057, 3031, 2953, 2892, 2820, 1658, 1616, 1510, 1360, 1201, 1175, 1126, 819, 785 cm-1; dH 1.93～2.00 (m, 4H, 2 × CH2), 2.25～2.34 (m, 8H, 4×CH2), 3.75 (s, 3H,CH3O), 5.39 (s, 1H,CH) , 6.99-7.38 (m, 4H, Ar-H), 12.07 (br, s, 1H, OH), 12.19 (br, s, 1H, OH).
3k. IR (KBr):nmax 3424, 3061, 2960, 2870, 2628, 1605, 1471, 1414, 1380, 1252, 1170, 1140, 1000, 890, 840, 790, 750, 715 cm-1. dH 1.99 (m, 4H, 2 × CH2), 2.31-2.51 (m, 8H, 4 × CH2), 5.47 (s, 1H, CH), 2.78 (s, 3H, CH3Ar), 6.92-7.21 (m, 3H, ArH), 11.57 (br, s, 1H, OH), 11.91 (br, s, 1H, OH).
4a. IR (KBr):nmax 2949, 2887, 2371, 1653, 1491, 1451, 1418, 1236, 1203, 1176, 1132, 1006, 958, 907, 830, 779, 702, 614, 538 cm-1. dH 1.81～1.90(m, 2H, CH2), 1.92～1.98 (m, 2H, CH2), 2.26～2.31 (m, 4H, 2×CH2), 2.61～2.68 (m, 4H, 2×COCH2), 4.59 (s,1H, CH), 7.12～7.22 (m, 5H, ArH);
4b. IR (KBr):nmax 3301, 3089, 3048, 2950, 2923, 2889, 2866, 2361, 1669, 1618, 1487, 1421, 1359, 201,1173, 1128, 1011, 958, 907, 836, 767, 740, 689, 608, 533 cm-1. δH 1.83～1.90 (m, 2H, CH2), 1.93～1.99 (m, 2H, CH2), 2.25～2.34 (m, 4H, 2×CH2), 2.61～2.70 (m, 4H, 2×COCH2), 4.56 (s, 1H,CH) , 7.20 (d, 2H, J＝8.4 Hz , ArH), 7.26 (d, 2H, J＝8.4 Hz, ArH).
4c: IR (KBr): nmax 2953, 2890, 1672, 1621, 1474, 1358, 1201, 1174, 1129, 847, 684 cm-1; dH 7.13 (4H, m, ArH), 4.56 (1H, s, CH), 2.64 (4H, m, 2×COCH2), 2.29 (4H, m, 2×CH2), 1.95 (2H, m, CH2), 1.88 (2H, m, CH2).
4d. IR (KBr):nmax 3087, 2955, 2887, 2812, 1654, 1621, 1523, 1418, 1350, 1202, 1173, 1131, 1074, 1015, 960, 908, 860, 815, 717, 669, 624, 535 cm-1. dH.179-1.89 (m, 2H, CH2), 1.91～1.99 (m, 2H, CH2), 2.19～2.33 (m, 4H, 2×CH2), 2.55～2.70 (m, 4H, 2×COCH2), 4.78 (s, 1H, CH), 7.19～7.22 (m, 1H, ArH), 7.25～7.31 (m, 2H, ArH).
4e. IR (KBr):nmax 295, 3113, 3081, 3043, 2948, 2895, 2870, 2818, 2446, 1665, 1607, 1521, 1422, 348,1202, 1174, 1128, 1008, 958, 906, 818, 720, 688, 604, 533 cm-1. δH 1.82～1.92 (m, 2H, CH2), 1.95～2.01 (m, 2H, CH2), 2.22～2.37 (m , 4H, 2×CH2), 2.59～2.74 (m, 4H, 2×COCH2), 4.68 (s, 1H, CH), 7.49 (d, 2H, J＝8.8 Hz, ArH), 8.09 (d, 2H, J＝8.8Hz, ArH).
4f. IR (KBr):nmax 3087, 2955, 2887, 2812, 2372, 1654, 1621, 1523, 1418, 1350, 1202, 1173,1131, 1074, 1015, 960, 908, 860, 815, 717, 669, 624, 535 cm-1. dH 1.83～1.92 (m, 2H, CH2), 1.95～2.01 (m, 2H, CH2), 2.23～2.37 (m, 4H, 2×CH2), 2.64～2.75 (m, 4H, 2×COCH2), 4.69 (s, 1H, CH), 7.52～7.56 (m, 1H, ArH), 7.65～7.67 (m, 1H, ArH), 7.99～8.03 (m, 2H, ArH).
4g. IR (KBr): nmax 3077, 2964, 2945, 2896, 2873, 1678, 1619, 1520, 1335, 1202, 1178, 1130, 823, 787 cm-1; 1dH 7.77 (1H, d, J=6.8Hz, ArH), 7.56 (1H, m, ArH), 7.35 (2H, d, J=6.8Hz, ArH), 5.40 (1H, s, CH), 2.64 (4H, m, 2×COCH2), 2.27 (4H, m, 2×CH2), 1.95 (2H, m, CH2), 1.86 (2H, m, CH2).
4h. IR (KBr): nmax 3379, 3021, 2949, 2921, 2892, 1662, 1612, 1515, 1361, 1207, 1173, 1131, 835, 762 cm-1; dH 9.19 (1H, s, OH), 6.95 (2H, d, J=8.4Hz, ArH), 6.59 (2H, d, J=8.4Hz, ArH), 4.48 (1H, s, CH), 2.63 (4H, m, 2×COCH2), 2.27 (4H, m, 2×CH2), 1.94 (2H, m, CH2), 1.86 (2H, m, CH2).
4i. IR (KBr):nmax3340, 2949, 2832, 2344, 1666, 1645, 1512, 1359, 1274, 1173, 1125, 1038, 951, 907, 852, 808, 735, 625, 538 cm-1. dH 1.80～1.91 (m, 2H, CH2), 1.92～2.10 (m, 2H, CH2), 2.28～2.31 (m, 4H, 2×CH2), 2.5～2.71 (m, 4H, 2×COCH2), 3.71 (s, 3H, OCH3), 4.51 (s, 1H, CH), 6.50～6.53 (m, 1H, ArH),6.59～6.61 (m, 1H, ArH), 6.74～6.75 (m, 1H, ArH), 8.71(s, 1H, OH).
4j. IR (KBr): nmax 3057, 3031, 2953, 2892, 2820, 1658, 1616, 1510, 1360, 1201, 1175, 1126, 819, 785 cm-1;dH 7.00 (4H, dd, J1=22Hz, J2=8Hz, ArH), 4.54 (1H, s, CH), 2.60 (4H, m, 2×COCH2), 2.25 (4H, m, 2×CH2), 1.93 (2H, m, CH2), 1.84 (2H, m, CH2).
4k. IR (KBr):nmax 3027, 2956, 2896, 2830, 2368, 1663, 1660, 1510, 1466, 1361, 1239,1176, 1131, 1033, 955, 904, 839, 758, 672, 612, 534 cm-1. dH 1.80～1.90 (m, 2H, CH2), 1.95～1.98 (m, 2H, CH2), 2.27～2.30 (m, 4H, 2×CH2), 2.61～2.65 (m, 4H, 2×COCH2), 3.68 (s, 3H, OCH3), 4.53 (s, 1H, CH), 6.77 (d, 2H, J＝8.4 Hz, ArH), 7.08 (d, 2H, J＝8.4 Hz, ArH).

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水中PEG-400催化下芳香醛和1，3-环己二酮的反应
王爱卿a，程朝立b， 王静a，李江乔a，靳通收a
（a河北大学化学与环境科学学院 保定 071002，b河北保定水文水资源勘测局 保定，071000）
摘要 以芳香醛和1，3-环己二酮为原料，以聚乙二醇-400（PEG-400）为相转移催化剂，在水中合成了一系列四酮类化合物；再以聚乙二醇-400（PEG-400）和氨基磺酸为复合催化剂，在水中合成了氧杂蒽类化合物。本实验采用的方法具有操作简单，催化剂价廉易得，对环境友好，产率较高等优点。
关键词 芳香醛 1，3-环己二酮 水相 聚乙二醇

　

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