Solid-state condensation reactions between aldehydes and 5,5-dimethyl-1,3-cyclohexanedione by grinding at room temperature

Article abstract of DOI:10.1080/00397910500187282

An efficient and convenient approach to the synthesis of the two different products from aldehydes and 5,5-dimethyl-1,3-cyclohexanedione in the solid state by grinding is described. This method provides several advantages such as environmental friendlines

Full text of DOI:10.1080/00397910500187282

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Solid‐State Condensation
Reactions Between
Aldehydes and
5,5‐Dimethyl‐1,3‐cyclohexanedione
by Grinding at Room
Temperature
Tong‐Shou Jin a , Jian‐She Zhang a , Ai‐Qing Wang a &
Tong‐Shuang Li a
a Department of Chemistry, College of Chemistry
and Environmental Science, Hebei University,
Baoding, Hebei Province, China
Available online: 18 Aug 2006
To cite this article: Tong‐Shou Jin, Jian‐She Zhang, Ai‐Qing Wang & Tong‐Shuang
Li (2005): Solid‐State Condensation Reactions Between Aldehydes and
5,5‐Dimethyl‐1,3‐cyclohexanedione by Grinding at Room Temperature, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 35:17, 2339-2345
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Synthetic Communicationsw, 35: 2339–2345, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500187282
Solid-State Condensation Reactions
Between Aldehydes and 5,5-Dimethyl-
1,3-cyclohexanedione by Grinding
at Room Temperature
Tong-Shou Jin, Jian-She Zhang, Ai-Qing Wang,
and Tong-Shuang Li
Department of Chemistry, College of Chemistry and Environmental
Science, Hebei University, Baoding, Hebei Province, China
Abstract: An efficient and convenient approach to the synthesis of the two different
products from aldehydes and 5,5-dimethyl-1,3-cyclohexanedione in the solid state
by grinding is described. This method provides several advantages such as environ-
mental friendliness, high yields, and simple workup procedure.
Keywords: Aldehydes, cyclohexanedione, grinding, solid state, synthesis
INTRODUCTION
The grinding method has increasingly been used in organic synthesis in recent
years. Compared with traditional methods, many organic reactions occur more
efficiently in the solid state than in solution and in many cases even more
selectively, because molecules in the crystals are arranged tightly and
regularly.[1] Furthermore, the solid-state reaction has many advantages:
little pollution, low cost, and simplicity in progress and handling. A large
Received in Japan February 28, 2005
Address correspondence to Tong-Shou Jin, Department of Chemistry, College of
Chemistry and Environmental Science, Hebei University, No. 88 Hezuo Road,
Baoding 071002, Hebei Province, China. E-mail: orgsyn@mail.hbu.edu.cn
2339

2340
T.-S. Jin et al.
number of organic reactions can be carried out simply and in high yield under
mild conditions by this method.[2]
It has been reported that the reaction of aromatic aldehyde and 5,5-di-
methyl-1,3-cyclo-hexanedione can obtain 2,20-arylmethylene bis(3-hydroxy-
5,5-dimethyl-2-cyclohexene-1-one) and 1, 8-dioxo-octahydroxanthene and
their derivatives in many methods.[3] However, no catalyst or the use of
TiO2/SO242 solid superacid as the catalysts in the solid state for the
synthesis of the 2,20-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohex-
ene-1-one) or 1,8-dioxooctahydroxanthene and their derivatives have not
been reported. In this article, we report a general and highly efficient route
for the synthesis of these two products and their derivatives with no catalyst
or using an inexpensive and commercially available TiO2/SO242 solid
superacid as the catalyst. This is an efficient synthesis in solid state, which
not only preserves the simplicity but also consistently gives the corresponding
products in good to excellent yields (Scheme 1).
A series of examples illustrating this method for the synthesis 3 and 4
were studied. The reaction proceeded smoothly by grinding to give the corre-
sponding products in good to excellent yields. The results are summarized in
Table 1 and Table 2.
It was found that different products were obtained using no catalyst or
TiO2/SO242 in the reaction (Scheme 1). The reaction in absence of catalyst
afforded the product 3 in good yield, but addition of a catalytic amount of
TiO2/SO242 resulted in the product 4. The result showed that the TiO2/
SO242 solid superacid had catalytic effect on the synthesis of 4. From this
fact, we suggest that the acid is essential for producing 4.
The reaction of aromatic aldehyde or aliphatic aldehyde and 5,5-
dimethyl-1,3-cyclohexanedione gave different experimental results.
Table 1 shows that aromatic aldehyde gives better results than aliphatic
aldehyde. For instance, 4-chlorobenzaldehyde and 4-nitrobenzaldehyde
reacted with 5,5-dimethyl-1,3-cyclohexanedione in grinding and gave
Scheme 1.

Solid-State Condensation Reactions
2341
Table 1. Synthesis of 3 with no catalyst in solid state by grinding
Mp (8C)
Reported[3a]
Yielda
(%)
Entry
R
Product
Found
1
2
C6H5 1a
3a
3b
3c
3d
3e
3f
86
90
89
90
85
89
88
89
87
89
90
86
89
87
86
89
65
86
39
38
46
56
193–194
143–145
188–190
203–204
203–204
190–191
198–199
141–142
144–145
195–196
187–189
205–206
176–177
215–216
196–197
203–204
165–166
192–193
182–184
241–242
153–154
232–234
194–195
141–143[3c]
4-ClC6H4 1b
3-ClC6H4 1c
2-ClC6H4 1d
2,4-Cl2C6H3 1e
4-O2NC6H4 1f
3-O2NC6H4 1g
4-CH3C6H4 1h
4-CH3OC6H4 1i
4-(CH3)2NC6H4 1j
4-HOC6H4 1k
2-HOC6H4 1l
3,4-(OCH2O)C6H3 1m
C6H5CH55CH 1n
4-HO-3-CH3OC6H3 1o
3-BrC6H4 1p
C6H5CH2 1q
H 1r
3
4
205
5
6
188–190
197–198
7
3g
3h
3i
8
9
142–143
10
11
12
13
14
15
16
17
18
19
20
21
22
3j
194.5–195.5
188–190
205–206
3k
3l
3m
3n
3o
3p
3q
3r
3s
175.5–177
215–217
195.5–196.5
164–165
191–191.5
CH3 1s
COOH 1t
3t
239
153–154.5
228
i-C3H7 1u
CHO 1v
3u
3v
aIsolated yield.
yields of 3b (90%) and 3f (89%) respectively. When acetaldehyde and
i-butylraldehyde were treated with 5,5-dimethyl-1,3-cyclohexanedione
under the same conditions, they gave isolated yields of 3s (39%) and 3u
(46%) respectively. But, aliphatic aldehyde cannot give the corresponding
compounds for the synthesis of 4. The reason is that instability of
aliphatic aldehyde makes the reaction difficult.
The catalyst TiO2/SO242 solid superacid was easily regenerated by
filtering the reaction mixture, washing it with hot ethanol, and drying it at
1208C for 2 h. The catalyst could be reused six times for the synthesis of 4b
without significant loss of activity. The results are summarized in Table 3.
In addition, it must be pointed out that all of the products were characterized
1
by Mp, IR, H NMR, and elemental analyses.
In conclusion, we have described a general and highly efficient procedure
for the preparation of 2,20-alkylmethylene bis(3-hydroxy-5,5-dimethyl-2-
cyclohexene-1-one) or 1,8-dioxo-octahydroxanthene and their derivatives in

2342
T.-S. Jin et al.
Table 2. Synthesis of 4 catalyzed by TiO2/SO242 in solid state by grinding
Mp (8C)
Yielda
(%)
Entry
Ar
Product
Found
Reported[3a]
1
2
C6H5 1a
4-ClC6H4 1b
4a
4b
4c
4d
4e
4f
88
92
91
92
89
90
89
90
91
87
88
89
90
89
89
204–205
229–231
184–186
225–226
250–252
222–223
170–172
246–248
246–247
242–243
221–222
218–219
227–228
217–218
176–178
204–205
230–231[3d]
3
3-ClC6H4 1c
2-ClC6H4 1d
4
224–226
253–254[3e]
222
5
2,4-Cl2C6H3 1e
4-NO2C6H4 1f
3-NO2C6H4 1g
2-NO2C6H4 1h
4-HOC6H4 1i
6
7
4g
4h
4i
171.5–172.5
246–248[3d]
246
241–243[3d]
220–222
217–218[3e]
226–228
8
9
10
11
12
13
14
15
4-CH3OC6H4 1j
4-Me2NC6H4 1k
4-CH3C6H4 1l
4j
4k
4l
4-HO-3-CH3OC6H3 1m
3,4-(OCH2O)C6H3 1n
C6H5CH55CH 1o
4m
4n
4o
218.5–220
175–177[3e]
aIsolated yields.
the solid state by grinding. In addition, the reaction in the solid state by
grinding methods is less expensive and less toxic than reactions using
organic solvents. Moreover, the procedure offers several advantages
including high yields, operational simplicity, cleaner reactions, and minimal
environmental impact, which make it a useful and attractive process for the
synthesis of these compounds.
EXPERIMENTAL
Liquid aldehydes were purified by distillation before use. IR spectra were
1
recorded on a Bio-rad FIS-40 spectrometer (KBr). H NMR spectra were
Table 3. Reuse of the catalyst for synth-
eses of 4b in solid state by grinding
Entry
Yield (%)
1
2
3
4
5
6
92
91
90
88
89
88

Solid-State Condensation Reactions
2343
measured on an AVAVCE-400 spectrometer using TMS as internal standard
and CDCl3 as solvent. Elemental analysis was measured on a HERAEUS
(CHN, Rapid) analyzer.
Preparation of the Catalyst TiO2/SO242 Solid Superacid
The catalyst TiO2/SO242 solid superacid was prepared as follows. Ti(OH)4
was obtained by hydrolyzing TiCl4 with aqueous ammonium hydroxide,
washing the precipitates, drying them at 1208C for 4 h, and powdering the pre-
cipitates below a 100 mesh. The hydroxide was treated with 2 N H2SO4 for 4 h,
filtrated, dried, and calcined in furnace at 4758C for 4 h, and finally stored in a
desiccator until use.
General Procedure for the Preparation of 3
Aldehyde 1 (2 mmol) and 5,5-dimethyl-1,3-cyclohexanedione 2 (4 mmol)
were added to a mortar. The mixture was ground by mortar and pestle at
room temperature for 40 min and was kept at room temperature for 48 h.
The product was extracted with dichloromethane; the solvent was evaporated
under reduced pressure and the crude products were obtained. The crude
products 3 were purified by recrystallization from ethanol (95%).
General Procedure for the Preparation of 4
Aromatic aldehyde
1 (2 mmol), 5,5-dimethyl-1,3-cyclohexanedione 2
(4 mmol), and TiO2/SO242 solid superacid (100 mg) were added to a mortar.
The mixture was ground by mortar and pestle at room temperature for
30 min and kept at room temperature for 24 h. It was monitored by TLC.
After completion of the reaction, the product was extracted with dichloro-
methane and the catalyst TiO2/SO242 was filtered off and recycled, the
solvent was evaporated under reduced pressure, and the crude products 4
were obtained. The crude products were purified by recrystallization from
ethanol (95%).
Data of some compounds are shown here:
3c. IR (KBr): nmax ¼ 3424, 3058, 2954, 2868, 2634, 1596, 1468, 1418,
1
1375, 1248, 1151, 974, 890, 870, 789 cm21. H NMR (CDCl3, 400 MHz):
d ¼ 1.12 (s, 6H, 2 ꢀ CH3), 1.25 (s, 6H, 2 ꢀ CH3), 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). Anal. calcd. for C23H27ClO4: C, 68.56; H, 6.25.
Found: C, 68.76; H, 6.14.
3e. IR (KBr): nmax ¼ 3425, 3060, 2950, 2865, 2630, 1601, 1470, 1417,
1379, 1250, 1152, 1135, 889, 790 cm21 1H NMR (CDCl3, 400 MHz):
.

2344
T.-S. Jin et al.
d ¼ 1.13 (s, 6H, 2 ꢀ CH3), 1.25 (s, 6H, 2 ꢀ CH3), 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). Anal. calcd. for C23H26Cl2O4: C, 63.16; H,
5.99. Found: C, 63.02; H, 5.84.
3h. IR (KBr): nmax ¼ 3424, 3061, 2960, 2870, 2628, 1605, 1471, 1380,
1
1170, 1000, 890, 715 cm21. H NMR (CDCl3, 400 MHz): d ¼ 1.12 (s, 6H,
2 ꢀ CH3), 1.24 (s, 6H, 2 ꢀ CH3), 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). Anal. calcd. for C24H30O4: C, 73.36; H,
7.91. Found: C, 73.58; H, 7.68.
3n. IR (KBr): nmax ¼ 3443, 3073, 2960, 2870, 1610, 1500, 1494, 1425,
1365, 1298, 1215, 875, 743 cm21.1H NMR (CDCl3, 400 MHz): d ¼ 1.12
(s, 6H, 2 ꢀ CH3), 1.25 (s, 6H, 2 ꢀ CH3), 2.31–2.51 (m, 8H, 4 ꢀ CH2),
2.48 (s, 1H, CH), 6.25–6.33 (m, 2H, 22CH55CH22), 6.85–7.01 (m, 5H,
ArH), 11.58 (br, s, 1H, OH), 11.92 (br, s, 1H, OH). Anal. calcd. for
C25H30O4: C, 76.89; H, 7.74, Found: C, 76.78; H, 7.93.
3o. IR (KBr): nmax ¼ 3425, 3065, 2955, 2870, 1605, 1466, 1418, 1374,
1
1270, 1195, 995, 870, 710 cm21. H NMR (CDCl3, 400 MHz): d ¼ 1.16
(s, 6H, 2 ꢀ CH3), 1.25 (s, 6H, 2 ꢀ CH3), 6.95–7.24 (m, 8H, 4 ꢀ CH2),
3.75 (s, 3H, OCH3), 5.45 (s, 1H, CH), 6.89–7.16 (m, 3H, ArH), 11.55
(s, 1H, OH), 11.93 (s, 1H, OH). Anal. calcd. for C24H30O6: C, 69.54; H,
7.29. Found: C, 69.75; H, 7.03.
3p. IR (KBr): nmax ¼ 3422, 3060, 2955, 2868, 1594, 1466, 1414, 1374,
1248, 1151, 974, 866, 749 cm21
.
1H NMR (CDCl3, 400 MHz): d ¼ 1.12
(s, 6H, 2 ꢀ CH3), 1.25 (s, 6H, 2 ꢀ CH3), 2.31–2.51 (m, 8H, 4 ꢀ CH2), 5.51
(s, 1H, CH), 7.03–7.33 (m, 4H, ArH), 11.67 (br, s, 1H, OH), 11.92 (br, s, 1H,
OH). Anal. calcd. for C23H27BrO4: C, 61.75; H, 6.08. Found: C, 61.98; H, 5.92.
3s. IR (KBr): nmax ¼ 3365, 3025, 2980, 2850, 1665, 1587, 1548, 1505,
1375, 1240, 1196, 850, 756 cm21. H NMR (CDCl3, 400 MHz): d ¼ 1.12
1
(s, 12H, 4 ꢀ CH3), 1.14 (d, 3H, J ¼ 6.4 Hz, CH3), 2.29–2.37 (m, 8H,
4 ꢀ CH2), 3.67 (q, 1H, J ¼ 6.4 Hz, CH), 11.65 (br, s, 1H, OH), 11.95 (br, s,
1H, OH). Anal. calcd. for C18H26O4: C, 70.56; H, 8.55; Found: C, 70.78; H, 8.32.
3v. IR (KBr): nmax ¼ 3425, 3080, 2970, 2930, 2840, 1640, 1560, 1495,
1440, 1385, 1275, 1045, 935, 790 cm21 1H NMR (CDCl3, 400 MHz):
.
d ¼ 1.14 (s, 6H, 2 ꢀ CH3), 1.18 (s, 6H, 2 ꢀ CH3), 2.28 (s, 2H, CH2), 2.42
(s, 2H, CH2), 2.55 (s, 2H, CH2), 2.81 (s, 2H, CH2), 7.28 (d, 1H, J ¼ 5.3 Hz,
CH), 8.74 (d, 1H, J ¼ 5.3 Hz, CHO), 11.64 (br, s, 1H, OH), 11.98 (br, s, 1H,
OH). Anal. calcd. for C18H24O5: C, 67.48; H, 7.55. Found: C, 67.69; H, 7.36.
4c. IR (KBr): nmax ¼ 3030, 2980, 1685, 1660, 1620, 1490, 1365, 1200,
1
1135, 1000, 850, 840 cm21. H NMR (CDCl3): d ¼ 1.00 (s, 6H, 2 ꢀ CH3),
1.13 (s, 6H, 2 ꢀ CH3), 2.31 (dd, 4H, J ¼ 1.6 Hz, J ¼ 3.2 Hz, 2 ꢀ CH2, H-4,
5), 2.47 (s, 4H, 4 ꢀ CH2, H-2, 7), 4.78 (s, 1H, H-9), 7.13–7.25 (m, 4H, ArH).
Anal. calcd. for C23H25ClO3: C, 71.77; H, 6.54. Found: C, 71.89; H, 6.45.
4n. IR (KBr): nmax ¼ 3030, 2980, 1725, 1680, 1560, 1510, 1495, 1383,
1
1275, 1045, 945, 790 cm21. H NMR (CDCl3): d ¼ 0.98 (s, 6H, 2 ꢀ CH3),

Solid-State Condensation Reactions
2345
1.11 (s, 6H, 2 ꢀ CH3), 2.18 (dd, 4H, J ¼ 1.6, J ¼ 2.4, 2 ꢀ CH2, H-4, 5), 2.45
(s, 4H, 2 ꢀ CH2, H-2, 7), 4.56 (s, 1H, H-9), 5.86 (s, 2H, OCH2O), 6.77–6.86
(m, 3H, ArH). Anal. calcd. for C24H26O5: C, 73.07; H, 6.64. Found: C, 73.13;
H, 6.71.
ACKNOWLEDGMENTS
This project was supported by the National Natural Science Foundation of
China (Nos. 29872011 and 29572039); Educational Ministry of China,
Educational Department of Hebei Province (990104); and Science and
Technology Commission of Hebei Province.
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