Ind. Eng. Chem. Res.

2009, 48, 6287–6290 6287

Synthesis of Dimethyl Pimelate from Cyclohexanone and Dimethyl Carbonate

over Solid Base Catalysts
Dudu Wu* and Zhi Chen
School of Pharmacy, Guangdong Medical College, Dongguan 523808, China

The synthesis of dimethyl pimelate (DMP) was carried out from cyclohexanone and dimethyl carbonate in
the presence of solid base catalysts. The results showed that the intermediate carbomethoxycyclohexanone
(CMCH) was produced from cyclohexanone with DMC in the first step, and then CMCH further converted
to DMP by reacting with methoxide group. The function of basic catalysts was mainly attributed to the activation
of cyclohexanone via the abstraction of proton in the R position by base sites, and solid base with moderate
strength, such as MgO, facilitated the formation of DMP.

1. Introduction
Dimethyl pimelate (DMP) is valued as an important inter-
mediate in pharmaceuticals, perfumes, lubricants, and other
organic compounds.1 It was usually obtained by esterification
from pimelic acid with alcohols. However, the process of
pimelic acid production often entailed concerns relative to high
toxicity, corrosion, and separation problems. And the esterifi-
cation, with alcohols also involved in two or more stages, led
to highly complex products.1,2 In particular, a stoichiometric
amount of water was produced in this process, which required
tedious procedures for disposal.1,2
Dimethyl carbonate (DMC), as an effective additive to
gasoline, has been attracting much attention in recent years
because of its high oxygen content and high octane value in
the energy field.3 It could also be an environmentally benign
building block in fine chemistry due to its versatile chemical
property and low toxicity.4 DMC is a safe substitute for methyl
halides or dimethyl sulfate as methylating and carboxylating
agents.5,6 In the presence of a base, it can also react with a
number of nucleophilic anions generated from different sub-
strates such as ketones, amines, oximes, indoles, and phenols
to give the methoxycarbonylation products.7-12
The synthetic route for DMP from cyclohexanone with DMC
was an ecofriendly alternative due to the gentle reaction
condition and environmentally benign reactant sources. In the
1970s, Ruset first reported such a route for the synthesis of
carbomethoxycyclohexanone (CMCH), which might be the
intermediate to DMP, from the reaction of cyclohexanone with
organic carbonates over NaH.13 Later, others reported that DMC
reacted with cyclohexanone to produce DMP in the presence
of homogeneous catalysts such as Cs2CO3-crown ether,
CH3ONa, and organic amine.14-17 However, homogeneous
reactions gave rise to the problems of products separation and
the catalyst reuse.
Recently, due to its economic and ecological significance,
the study of solid base catalysts has become an important
research topic. The replacement of homogeneous bases by solid
base catalysts would have the advantages of decreasing corrosion
and environmental problems, while allowing easier separation
and recovery of the catalysts.18,19 Thus, solid bases were used
as catalysts for the production of DMP from DMC with
* To whom correspondence should be addressed. Tel.: +86 769
22896376. Fax: +86 769 22896560. E-mail: wududu@china.com.cn.
10.1021/ie801852e CCC: $40.75  2009 American Chemical Society
Published on Web 05/22/2009
cyclohexanone, and the function of the solid base catalysts has
been discussed in the present work.
2. Experimental Section
2.1. Preparation of Catalysts. CaO, MgO, and ZrO2 were
prepared by thermal decomposition of calcium carbonate
(CaCO3, Tianjin Kermel Chemical Reagent Co. Ltd., A.R.
grade) at 800 °C for 2 h, magnesium hydroxide (Mg(OH)2,
Tianjin Kermel Chemical Reagent Co. Ltd., A.R. grade) at 500
°C for 5 h, and zirconium hydroxide (Zr(OH)4, Tianjin Kermel,
A.R. grade) at 500 °C for 5 h under nitrogen atmosphere,
respectively. Lanthana (La2O3, Tianjin Kermel, A.R. grade) and
alumina (Al2O3, Tianjin Kermel, A.R. grade) were purchased
and then calcined at 700 and 500 °C, respectively, for 5 h in
N2 before use. A series of Al/MgO catalysts with molar ratios
of 0.01-0.3 were also prepared using the impregnation method.
The desired amount of aluminum isopropoxide was dissolved
in benzene solution before being added into Mg(OH)2 to form
the impregnated samples. The samples were dried at 100 °C
overnight and then thermally decomposed to Al/MgO catalysts
at 500 °C for 5 h.
BET surface areas of the samples were determined with the
BET method using a Micromeritics ASAP-2000 apparatus. Basic
properties of the catalysts were measured by temperature
programmed desorption of CO2 (CO2-TPD). The measurement
was performed with 0.10 g of sample at a rate of 10 °C/min
under N2 flow (50 mL/min), and the CO2 desorbed was detected
by a Balzers Omnistar mass spectrometer after the catalysts were
pretreated under the preparation conditions.
2.2. Experimental Setup and Procedure. The catalytic
performance was carried out in a 150 mL batch reactor with
assigned mole ratios of DMC and cyclohexanone, catalysts
amounts, reaction temperature, and reaction time. After the
reaction, the reactor was cooled to room temperature, and the
products were analyzed by a gas chromatograph with a flame
ionization detector and a HP-5 column after filtration from
the catalyst. The main reaction products were DMP and CMCH.
The methlylated product (2-methylcyclohexanone and 2-methyl
dimethyl pimelate) and the self-condensation products of
cyclohexanone such as 2-(1-cyclohexenyl)cyclohexanone were
also detected. The selectivity was defined as mA/∑mA × 100%,
where mA was the weight of product A, and ∑mA was the total
weight of the products.
6288 Ind. Eng. Chem. Res., Vol. 48, No. 13, 2009

Figure 1. CO2-TPD profiles of solid bases (where, for example, 4.00E-013 Figure 2. CO2-TPD profiles of MgO with different Al contents (where, for
represents 4.00 × 10-13). example, 4.00E-013 represents 2.50 × 10-13).
Table 1. CO2 Uptake of Solid Bases Table 2. Synthesis of DMP from DMC and Cyclohexanone over
CO2 uptake Solid Bases

catalyst BET surface area (m2/g) mmol/g mmol/m2 selectivity (%)

-3 -5 cyclohexanone other
ZrO2 152 3.22 × 10 2.12 × 10
entry catalyst temp (°C) conversion (%) DMP CMCH productsc
La2O3 7.4 1.69 × 10-3 2.28 × 10-4
CaO 12.3 6.37 × 10-2 5.18 × 10-3 1a - 260 - - - -
MgO 122.5 1.78 × 10-2 1.45 × 10-4 2b K2CO3 200 31.6 40.2 8.91 50.9
Al/MgO(0.01) 100.1 6.49 × 10-3 6.48 × 10-5 3a K2CO3 260 66.5 24.2 0.93 74.9d
Al/MgO(0.05) 75.3 3.61 × 10-3 4.79 × 10-5 4a Al2O3 260 57.0 traces traces 100
Al/MgO(0.1) 75.8 3.56 × 10-3 4.70 × 10-5 5a ZrO2 260 41.2 12.0 7.80 80.2
Al/MgO(0.2) 69.6 1.57 × 10-3 2.26 × 10-5 6b MgO 200 11.0 5.61 34.6 59.8
Al/MgO(0.3) 58.7 8.78 × 10-4 1.50 × 10-5 7a MgO 260 83.6 51.8 6.33 41.9
8a La2O3 260 19.2 38.2 15.8 46.0
3. Results and Discussion 9a CaO 260 65.0 51.5 2.24 46.3
3.1. Catalyst Characterization. Figure 1 depicts the CO2 a
Reaction conditions: cyclohexanone:DMC ) 1:4; time ) 5 h:
desorption profiles on ZrO2, MgO, La2O3, and CaO. CaO catalyst wt % ) 1.5%. b Reaction conditions: cyclohexanone:DMC:
catalyst (molar ratio) ) 1:20:2; time ) 11.4 h. c Other products )
exhibited the strong basic sites with a sharp desorption peak at 2-methylcyclohexanone + 2-methyl dimethyl pimelate + 2-(1-cyclo-
550 °C. La2O3 showed relatively strong basic strength with CO2 hexenyl)cyclohexanone. d Selectivity of 2-methyl dimethyl pimelate was
desorption peak at 450 °C. As for MgO, there were three 40.8%.
desorption peaks at 150, 210, and 310 °C, respectively,
suggesting that MgO had weak and moderate strength basic obtained over MgO (entry 7), which was even higher than that
sites, but, for ZrO2, only weak basic sites with CO2 desorption of K2CO3 (the major product was 2-methyl dimethyl pimelate
peak at 170 °C were observed. Their basic strength followed at 260 °C; entries 3 and 7). This suggested that solid bases with
the order CaO > La2O3 > MgO > ZrO2, but the basic numbers moderate strength (MgO) could show excellent catalytic per-
of catalysts ranked in this order: CaO > MgO > La2O3 > ZrO2 formances, better than the best known basic systems such as
(see Table 1). The addition of alumina did not change the basic K2CO3. As for other solid base, ZrO2 and La2O3 showed lower
character of MgO (see Figure 2), but the basicity decreased with DMP yields, which might be due to the relatively lower basic
the increase of the Al contents (see Table 1). numbers than those of MgO. As far as CaO was concerned, it
3.2. Catalytic Performance. Table 2 gives the catalytic also showed lower cyclohxanone conversion and DMP selectiv-
performance of solid catalysts in synthesis DMP from cyclo- ity despite its high basic numbers. This could be attributed to
hexanone with DMC. In the absence of catalyst, no products the acid strength of Ca cation being too weak to stabilize the
were detected. Over solid acids such as Al2O3, only the aldol carbanion species.20 As a result, both basic numbers and basic
condensation products of cyclohexanone and a trace amount of strength played an important role in the reaction, and the basic
DMP and CMCH were detected (entry 4). This suggested that sites with moderate strength were effective for the synthesis of
solid acids were inactive toward the methoxycarbonylation DMP from cyclohexanone with DMC.
reactions. With solid bases as the catalysts, the methoxycarbo- To further understand the effect of moderate basic strength
nylation products were obtained, which were consistent with on catalytic performance, a series of MgO with different Al
the literature,13-17 and the catalytic performance was strongly contents were prepared to supply the different amount of
dependent on both total basicity and basic strength (entries 5-9). moderate basic sites (see Figure 2). It was found that the DMP
Selva had reported this route by using K2CO3 as the catalysts, yield could be linearly correlated with the amount of moderate
and the yield of DMP reached 11%;14 likewise, a similar result basic sites (see Figure 3). Thus, this confirmed again the
was observed when we repeated this experiment (entry 2). While synthesis of DMP should be closely related to the moderate
MgO, which possessed the moderate basic strength, was basic sites.
employed as the catalyst, the major methoxycarbonylation The recycling of MgO in the reaction of DMC with
product was CMCH at lower temperature (entry 6). However, cyclohexanone is given in Table 3. It was found that cyclohexa-
with the rise of reaction temperature, higher DMP yield was none conversion decreased by 24.9% and DMP selectivity
 Ind. Eng. Chem. Res., Vol. 48, No. 13, 2009 6289

Figure 4. Effect of reaction time on the conversion of cyclohexanone and

selectivity of products over MgO.
Figure 3. Relationship between DMP yield and moderate basicity.

Table 3. Recycling of MgO in the Reaction of DMC and

Cyclohexanone
selectivity (%)
2-methyl
cyclohexanone dimethyl other
a
catalyst conversion (%) DMP CMCH pimelate productsd
MgO 83.6 51.8 6.33 8.09 33.8
MgO (r1)b 71.3 41.7 3.38 20.2 34.7
MgO (r2)b 68.7 40.8 3.05 25.3 30.8
MgO (r3)b 62.9 32.6 2.87 33.4 31.1
MgO (r5)b 58.7 30.3 1.57 39.5 28.6
MgO (r1)*c 82.1 50.9 7.38 8.83 32.9
MgO (r2)*c 83.8 52.3 5.87 8.15 33.7
MgO (r3)*c 83.5 50.4 7.77 8.46 33.4
MgO (r5)*c 81.4 51.5 5.24 9.05 34.2
a
Reaction conditions: cyclohexanone:DMC ) 1:4; T ) 260 °C; time
) 5 h; catalyst wt % ) 1.5%. b The used catalysts obtained from the
filtration of the reaction mixture. c The used catalysts obtained by Figure 5. Effect of reaction temperature on the conversion of cyclohexanone
calcination at 500 °C for 5 h under nitrogen atmosphere after filtration and selectivity of products over MgO.
from the reaction mixture. d Other products ) 2-methylcyclohexanone +
2-(1-cyclohexenyl)cyclohexanone.
Scheme 1. Plausible Mechanism of the Reaction of DMC with
Cyclohexanone
decreased by 21.5% after the catalysts were used five times.
Meanwhile, the selectivity of 2-methyl dimethyl pimelate
reached 39.5%, which was comparable with that of K2CO3 (see
Table 2). These may illustrate that Mg salts of carbonates were
generated, which was due to the formation of carbon diox-
ide in the methylation reaction. Fortunately, the activity of used
catalysts could be recovered through calcination; under the
preparation conditions even the catalysts were used several times
(see Table 3).
3.3. Plausible Reaction Mechanism. Figure 4 shows the
effect of reaction time on the reaction of DMC with cyclohex-
anone over MgO. The conversion of cyclohexanone gradually
increased and then became stable after 5 h. The selectivity of
CMCH decreased, while the selectivity of DMP increased, and
the selectivity of other products almost remained unchanged.
A similar tendency was also observed for the influence of the
reaction temperature (see Figure 5). These suggested that the
reaction proceeded via CMCH as the intermediate. On the basis
of the above facts, the plausible reaction mechanism for the
synthesis of DMP was proposed as follows (see Scheme 1a):
initially, a carbanion of cyclohexanone (1-) was generated due
to the abstracting of the proton in R position (HR) by the solid led to CMCH as the primary product. Afterward, the resulting
base, and 1- and proton were absorbed on acidic sites (Mn+) intermediate reacted with methoxide anion to yield the corre-
and basic sites (O2-) of the solid base surface, respectively. sponding carbanion (2-), which was subjected to opening the
Then, 1- attacked the carbonyl group of DMC molecule, which ring to give DMP as the final product.
6290 Ind. Eng. Chem. Res., Vol. 48, No. 13, 2009
Similarly, the aldol condensation products (2-(1-cyclohex-
enyl)cyclohexanone) and the methylation products (2-methyl-
cyclohexanone, 2-methyl dimethyl pimelate) were also produced
as the byproduct. As shown in Scheme 1b, 1- could attack a
second cyclohexanone molecule to produce 2-(1-cyclohexenyl)-
cyclohexanone and water. Likewise, 1- reacted with the methyl
group of DMC to produce the methylation products of 2-me-
thylcyclohexanone, which was accompanied by the formation
of methanol and carbon dioxide (see Scheme 1c). Then,
2-methylcyclohexanone could react with DMC to give 2-methyl
dimethyl pimelate as a further product (see Scheme 1c).
4. Conclusions
The synthesis of DMP from cyclohexanone with DMC was
investigated over solid base catalysts. The results revealed that
MgO showed the best performance among the solid base
investigated. The reaction was found to be closely related to
the moderate basic sites, and the function of basic catalysts was
mainly to activate the ketone via abstraction of proton in R
position by base sites. The possible reaction pathway, which
included CMCH as intermediate, was thus proposed.
Acknowledgment
We acknowledge the financial support from State Key Pro-
gram for Development and Research of Guangdong province.
(Grant No. 2006B14701008).
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ReceiVed for reView December 3, 2008
ReVised manuscript receiVed February 19, 2009
Accepted May 2, 2009
IE801852E