Selective pyrolysis of bifunctional compounds: gas-phase elimination of carbonate-ester functionalities

Article abstract of DOI:10.1016/j.tet.2008.01.002

Compounds containing both carbonate and ester functionalities were synthesized and then subjected to online-GC gas-phase pyrolysis. The carbonate groups were cleaved selectively in all elimination reactions. The end products of the reaction were found to be affected by the nature of the substrate. The presence of hydrogen and carbonyl substituents on the carbon β to the carbonate group resulted in further product decomposition through a concerted six-membered transition state. Results from flash vacuum pyrolysis (FVP) and analysis of the GC data indicate that the cleavage of the carbonate group is fast, and that the slower secondary decomposition reactions are independent of the presence of the carbonate group. Spectroscopic analyses of the products are reported.

Full text of DOI:10.1016/j.tet.2008.01.002

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 4126e4134
www.elsevier.com/locate/tet
Selective pyrolysis of bifunctional compounds: gas-phase elimination
of carbonateeester functionalities
*
Talal F. Al-Azemi , Hicham H. Dib, Nouria A. Al-Awadi, Osman M.E. El-Dusouqui
Chemistry Department, Kuwait University, PO Box 5969, Safat 13060, Kuwait
Received 15 July 2007; received in revised form 10 December 2007; accepted 3 January 2008
Available online 5 January 2008
Abstract
Compounds containing both carbonate and ester functionalities were synthesized and then subjected to online-GC gas-phase pyrolysis. The
carbonate groups were cleaved selectively in all elimination reactions. The end products of the reaction were found to be affected by the nature
of the substrate. The presence of hydrogen and carbonyl substituents on the carbon b to the carbonate group resulted in further product decom-
position through a concerted six-membered transition state. Results from flash vacuum pyrolysis (FVP) and analysis of the GC data indicate that
the cleavage of the carbonate group is fast, and that the slower secondary decomposition reactions are independent of the presence of the
carbonate group. Spectroscopic analyses of the products are reported.
Ó 2008 Published by Elsevier Ltd.
Keywords: Online-GC gas-phase pyrolysis; Selectivity; Carbonateeester bifunction
1. Introduction
and thioesters has been reported.9e11 The studies show that
the carbonate and ester groups have different thermal stability,
that the pyrolytic reactions of the carbonate group are about
10-fold faster than ester pyrolysis, and that these reactions pro-
ceed by a concerted cis-elimination pathway. Exploiting the
difference in the thermal stability of the ester and carbonate
groups, we report in this work the utility of gas-phase pyroly-
sis as an alternative route in the selective deprotection of com-
pounds containing both carbonate and ester functionalities.
The pyrolytic reactions were preformed using an online-GC
pyrolyzer. Where appropriate, FVP was used to separate the
constituents of the pyrolyzates.
Gas-phase pyrolyses have been utilized as economic and ef-
ficient methodologies in alternative and selective syntheses.1e7
These reactions were used successfully in the preparation of
2-glucosyl-1,2,4-triazole-3(2H)-thione, which is a biologically
important compound.1 A novel heterocyclic ring system,
benzo[1,2-b]cinnoline has also been synthesized by the gas-
phase pyrolysis of benzotriazole derivatives.2 Besides, flash
vacuum pyrolysis (FVP) technique was used effectively to
functionalize alkynes and various related systems, and to con-
vert substituted phosphorus ylides into 1,3-diene derivatives;
all these compounds being useful precursors for organic
synthesis.6,7
2. Results and discussion
Ester and carbonate moieties are used extensively in the
protection of hydroxyl groups.8 The selective removal of ei-
ther the ester or carbonate group when both are present in
the same molecule could be problematic because of their sim-
ilar reactivity. Pyrolysis of carbonates, thiocarbonates, esters,
The hydroxycarbonate and the carbonateeester compounds
under study were synthesized starting with substituted 1,3-diol
precursors (1e7)a. The diols were cyclized into the carbonate
derivatives (1e7)b using ethyl chloroformate in tetrahydro-
furan (THF) in the presence of Et3N. The cyclic carbonate
compounds were opened by an acid catalyst in ethanol to
obtain acyclic hydroxycarbonate compounds (1e7)c. The
* Corresponding author. Tel.: þ965 4985540; fax: þ965 4816482.
E-mail address: t.alazemi@kuniv.edu (T.F. Al-Azemi).
0040-4020/$ - see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.01.002

T.F. Al-Azemi et al. / Tetrahedron 64 (2008) 4126e4134
4127
O
O
O
O
HO
R
OH
R'
O
O
O
R
O
R
O
HO
R
O
O
(iii)
(i)
(ii)
R'
R'
R'
(1-7)c
(1-7)d
67-90%
(1-7)a
(1-7)b
47-87%
68-93%
1: R = R' = H
5: R = R' = CH2CH2CH2CH3 (Bun)
6: R = CH3; R' = CO2C2H5
7: R = CH3; R' = CO2CH2Ph (Bn)
2: R = H; R' = CH3
3: R = R' = CH3
4: R = R' = CH2CH3
Scheme 1. Synthesis of carbonateeester bifunctional compounds: (i) ethyl chloroformate, Et3N/THF; (ii) ethanol/TFA, (iii) propanoic anhydride/DMAP.
hydroxyl group subsequently was acylated with propanoic
anhydride in presence of DMAP as catalyst to produce the
target carbonateeester compounds (1e7)d as shown in
Scheme 1.
On the other hand, the hydroxymonoesters were prepared
by reacting the diols (1e7)a with propanoic anhydride in
a 1:1 ratio using THF as solvent and DMAP as catalyst. The
hydroxyalkyl ester product was isolated by column chroma-
tography with 20% ethyl acetate in petroleum ether as eluent
(Scheme 2).
pyrolyzer raised incrementally, and pyrolysis was monitored
by GC. In all cases, thermal decomposition started at
>500 ꢀC. Peak heights of the ester compounds gradually in-
creased with temperature (Fig. 1). The pyrolytic reactions
were deemed complete when the peaks for the starting carbo-
nateeester compounds disappeared at ca. 700 ꢀC. No hy-
droxycarbonate peaks were detected in the GC for any
substrate, which indicated that the pyrolytic reactions are
highly selective.
The rate coefficients (k, sꢁ1) and Arrhenius parameters of
compounds (1e7)d are shown in Table 1. Kinetic analysis
was conducted at the temperature range 840e953 K. Rate con-
stants were calculated and plotted against 1/T. The Arrhenius
plots were strictly linear; an example is shown in Figure 2 for
substrate 3d. The activation energy (Ea, kJ molꢁ1) calculated
from the slope of the plot, the Arrhenius log A (sꢁ1), and the
first-order-rate constant (k, sꢁ1) at 900 K are given in Table
1. The kinetic data show little difference in rate coefficients.
The products of pyrolysis, however, were clearly affected by
the nature of the substrates. When the R and R0 substituents
are methyl, ethyl, or butyl groups only ester compounds are
formed. Initial pyrolysis proceeds through a cyclic six-mem-
bered transition state, which is the preferred pyrolytic reaction
pathway (Scheme 3),10,12 and subsequent secondary decompo-
sition leads to loss of a stable CO2 fragment and formation of
the hydroxyester product.
O
HO
R
OH
R'
HO
R
O
(iv)
R'
(1-7)a
(1-7)e
29-36%
Scheme 2. Synthesis of hydroxyesters: (iv) propanoic anhydride, DMAP/THF.
Carbonate, carbonateeester, and ester compounds (c, d, e)
were first injected in the gas chromatograph and the retention
times were recorded for each set of compounds. The online-GC
pyrolyzer was then used to perform the gas-phase pyrolysis
reactions. An internal standard (chlorobenzene, 1,3-dichloro-
benzene, or 1,2,4-trichlorobenzene) was added to the carbo-
nateeester compounds (1e7)d, the temperature of the
100
75
O
Internal
Standard
O
O
HO
O
O
O
O
T7 = 670 °C
T
6 = 650 °C
5 = 630 °C
T
50
T4 = 610 °C
3 = 580 °C
T
25
T2 = 570 °C
T1 = 560 °C
0
-9
5.0
7.5
10.0
12.5
15.0
17.5
Minutes
Figure 1. GC gas-phase pyrolysis chromatograms of 3d as function of reaction temperature.

4128
T.F. Al-Azemi et al. / Tetrahedron 64 (2008) 4126e4134
Table 1
Rate coefficients (k, sꢁ1) and Arrhenius parameters of reactions of compounds
(1e7)d
1.19
0.99
0.79
0.59
0.39
0.19
Compound
T/K
k/sꢁ1
log A/sꢁ1
Ea/kJ molꢁ1
k
900 K/sꢁ1
1d
843.15
853.15
873.15
883.15
893.15
923.15
833.15
853.25
883.15
893.15
903.15
913.15
933.15
953.15
833.15
848.15
863.15
878.15
893.15
908.15
923.15
843.15
858.15
888.15
918.15
933.15
948.15
848.15
878.15
893.15
908.15
923.15
848.15
863.15
938.15
953.15
878.15
893.15
908.15
953.15
1.5
2.0
3.5
4.9
7.5
16.1
1.5
2.4
4.3
5.3
6.8
8.0
11.0
17.3
1.1
1.9
2.5
3.9
5.1
7.0
9.8
0.3
0.5
1.9
5.3
7.0
13.6
1.5
3.6
5.9
8.8
13.3
0.5
0.8
1.1
1.5
1.5
2.4
4.3
17.0
12.3ꢂ0.3
196.4ꢂ5.6
8.4
2d
8.4ꢂ0.3
131.5ꢂ2.2
6.2
1.05
1.07
H
1.09
1.11
1.13
1000/T
1.15
1.17
1.19
Figure 2. Arrhenius plot for 3d.
3d
9.4ꢂ0.2
149.4ꢂ4.3
6.0
H
O
O
O
O
O
O
OH
R'
O
R
O
O
R
O
O
O
Δ
Δ
-CO2
-H2C=CH2
R
R'
R'
Scheme 3. Pyrolysis of compounds (1e5)d.
4d
5d
14.3ꢂ0.5
11.7ꢂ0.2
238.9ꢂ8.3
187.8ꢂ3.5
2.6
7.0
OH
O
O
O
β
Δ
OH
+
OH
Slow
R'
H
R'
Scheme 4. Ester pyrolysis by elimination of b-hydrogen.
680 ꢀC, respectively. The products from FVP were isolated
and analyzed by NMR and MS. Further pyrolysis of the hyd-
roxyesters gave the alkene and carboxylic acid observed for
the (slower) secondary pyrolytic reaction. Since both carbo-
nateeester compounds and hydroxyester compounds gave
the same reaction products, the proposed mechanism of ester
pyrolysis does not require the presence of the carbonate group.
For compounds 1d and 1e the alkene fragment is allyl alcohol
and the acid is propanoic acid. Compounds 2d and 2e formed
2-methylprop-2-en-1-ol and propanoic acid. Authentic sam-
ples and the pyrolyzate fragments gave the same GC retention
times.
In the case of compounds 6d and 7d, the presence of a
carbonyl group at the b-carbon affects the pyrolysis pathway.
Initially (lower temperature), the reactions proceed by the
selective elimination of the carbonate group. With the increase
of temperature, new peaks indicative of secondary decomposi-
tion begin to appear. At 665 ꢀC, compound 6d shows starting
material, ester compound, and product peaks; at 695 ꢀC, only
the starting material and the product peaks are present; at
710 ꢀC, the starting material and the hydroxyester compound
peaks disappear. Pyrolysis of compound 7d follows the same
pattern (Figs. 3 and 4). Analyzing the GC chromatograms of
the products of reaction of compounds 6d and 7d, we conclude
that the reactions commence by the elimination of the carbon-
ate group, followed by secondary pyrolytic reaction involving
a cyclic six-membered transition state, in which the hydroxyl
and the carbonyl groups play noticeable roles. The proposed
6d
7d
13.5ꢂ0.5
224.6ꢂ8.3
227.4ꢂ5.3
2.9
3.2
13.7ꢂ0.31
For compounds 1d and 2d, even when the reaction shows
selectivity in cleavage of the carbonate group, the GC chro-
matograms still show minor peaks at relatively high reaction
temperature. The common feature of these two sets of com-
pounds is that they have H at the b-carbon to an ester group,
which is reported in the literature to facilitate further slow
pyrolysis through a concerted six-membered transition state
as the preferred reaction pathway (Scheme 4, R¼H).12 Kinet-
ically, for compounds 1d and 2d the fast pyrolytic reaction
step is the cleavage of the carbonate group and the slower
step is the elimination of the b-hydrogen. This seemed obvious
to us because at the initial stages of the pyrolysis we detect
only the peaks corresponding to the hydroxyester compounds
resulting from the elimination of the carbonate groups.
To confirm the proposed b-hydrogen elimination pathway,
flash vacuum pyrolysis (FVP) was carried out on the carbo-
nateeester compounds 1d and 2d, from which the hydroxy-
ester compounds 1e and 2e were obtained at 650 and

T.F. Al-Azemi et al. / Tetrahedron 64 (2008) 4126e4134
4129
Internal
O
Standard
15
10
5
T = 665 °C
OH
O
OH
6d
6e
(i
0
T = 695 °C
15
10
5
(ii
0
15
10
5
T = 710 °C
(iii
0
5.0
7.5
10.0
12.5
Minutes
15.0
17.5
20.0
Figure 3. Gas-phase pyrolysis chromatograms of reaction of 6d as function of reaction temperature.
7d
5
Internal
Standard
4
3
2
1
0
7e
(i
T = 635 °C
O
100
75
OH
50
25
(ii
0
150
125
100
75
O
O
50
25
(iii
0
5
10
15
Minutes
20
25
30
Figure 4. (i) Gas-phase pyrolysis chromatograms of compound 7d at 635 ꢀC; (ii) chromatogram of propanoic acid; (iii) chromatogram of benzyl methacrylate.
reaction mechanism is shown in Scheme 5. The pyrolytic re-
action of compound 6d gave methacrylic acid and propanoic
acid, the ethyl ester group being unstable under the conditions
of reaction, whereas compound 7d resulted in the formation of
benzyl methacrylate and propanoic acid, because the benzyl
ester is much more stable than the ethyl ester.
The same procedure of authentication used for compounds
1d and 2d was employed for compounds 6d and 7d and 6e
and 7e: validation by GC retention times of benzyl meth-
acrylate, methacrylic acid, and propanoic acid (Figs. 3 and 4).
3. Conclusion
Flash vacuum pyrolysis has been carried out for compounds
6d and 7d and 6e and 7e at 750 ꢀC to ensure complete
pyrolysis of the compounds. The products of pyrolysis were
separated by column chromatography and full spectral data
were recorded. The data confirmed the suggested products.
Carbonateeester bifunctional compounds were synthesized
and then pyrolyzed in order to investigate the selective re-
moval of one group or the other as a strategy toward selective
deprotection. The results indicate that gas-phase pyrolysis
H
O
H
O
O
O
O
-CO2
O
O
O
-H2CO
+
R2
R1
OCOC2H5
-H2C=CH2
HO
R1
OCOC2H5
R1 = OC2H5 or OBn
R2 = OH or OBn
Scheme 5. FVP of compounds (6e7)d at 750 ꢀC.

4130
T.F. Al-Azemi et al. / Tetrahedron 64 (2008) 4126e4134
favors removal of the carbonate groups; the reactions being
monitored using GC retention times of synthetic authentic
samples of substrates and products. The kinetic data in Table
1 reveal small differences in rate coefficients. The most reac-
tive substrates were the unsubstituted compound (1d) and that
with the longest alkyl chain (5d). The shorter alkyl chains and
the alkyl and benzyl carboxylate groups of compounds (4d,
6d, 7d) reduced reactivities threefold compared to 1d; the ef-
fect of the alkyl groups in 2d and 3d was smaller. However,
the nature of the products of pyrolysis was affected by the na-
ture of the substrate. Hydrogen and carbonyl substituents on
the b-carbon resulted in secondary decomposition of the reac-
tion products. FVP was employed to separate and isolate the
constituents of the pyrolyzates. Authentic samples were used
to confirm and establish the retention times of the products
of the gas-phase pyrolysis reactions. The accepted reaction
mechanism involves a cyclic six-membered transition state,
which is the dominant reaction pathway in this type of gas-
phase pyrolytic reactions.9 Work is in progress on the alterna-
tive biocatalytic selective deprotection of carbonateeester
bifunctional compounds.
the substrate with respect to the internal standard was calcu-
lated from the ratio of the substrate peak area to the peak
area of the internal standard. The kinetic rate was obtained
by tracing the rate of disappearance of the substrate with re-
spect to the internal standard as follows: 1 mL of the solution
is injected in the pyrolyzer, which is set at non-pyrolysis con-
ditions to get the initial ratio of the sample to the internal
standard A0 (standardization value). The sample was then
passed through GC (oven temperature: 140e200 ꢀC, flow
rate: 1e1.5 mL/min, injection port temperature: 250 ꢀC, and
FID detector temperature: 300 ꢀC). The GC column used
was SUPELCO SPB-20 fused silica capillary column (30 m
length, 0.32ꢃ0.25 mm film thickness). This procedure is
repeated after each 10e15 ꢀC rise in the temperature of the py-
rolyzer until ꢄ90% pyrolysis takes place. The relative ratios of
the integration values of the sample and the internal standard
(A) at the pyrolysis temperature are then determined. The rate
coefficients were calculated using the expression for a first-
order reaction: kt¼ln(A0/A). The Arrhenius parameters were
obtained from a plot of log k against 1/T (K). The residence
time (t) was calculated from the relation t¼PVTm/PmTG, where
P is the atmospheric pressure, V is the volume of the reactor, Tm
is room temperature (K), T is the reactor temperature (K) and G
is the carrier gas flow rate (mL/s).16,17
4. Experimental section
4.1. General
4.3. Flash vacuum pyrolysis (FVP)
All chemicals including compounds (1e5)a were purchased
from Aldrich and used as-received unless otherwise indicated.
1H NMR spectra were recorded on a BRUKER DPX 400 MHz
Superconducting NMR spectrometer. Mass spectra were mea-
sured on Vg Auto-Spes-Q (high resolution, high performance,
tri-sector GC/MS/MS) and with LCeMS using Agilent 1100
series LC/MSD with an API-ES/APCI Ionization Mode, Posi-
tive/Negative Polarity, Autosampler, Quaternary Pump and
Agilent Chemstation Software. Microanalyses were performed
on LECO CHNS-932 Elemental Analyser. GC analyses were
performed on Varian GC CP-3800 with FID Detector,
Capillary Injector Port, and Varian Star 5.51 Chromatography
Workstation Software. Pyrolysis was carried out using SGE
Pyrojector II on-line pyrolyzer (continuous mode) with tem-
perature range 0e900 ꢀC under non-oxidizing conditions.
The hot zone is a quartz glass liner with 60 mm length and
2 mm internal diameter.
The apparatus used has been described in recent publica-
tions.4 The sample was volatilized from a tube in a Buchi
¨
Kugelrohr oven through a 30ꢃ2.5 cm horizontal fused quartz
tube. This was heated externally by a Carbolite Eurotherm
tube furnace MTF-12/38A to a temperature of 750 ꢀC, the
temperature being monitored by a Pt/Pte13%Rh thermocou-
ple situated at the center of the furnace. The products were
collected in a U-shaped trap cooled in liquid nitrogen. The
whole system was maintained at a pressure of 10ꢁ2 Torr by
an Edwards Model E2M5 high capacity rotary oil pump, the
pressure being measured by a Pirani gauge situated between
the cold trap and the pump. Under these conditions the contact
time in the hot zone was estimated to be w10 ms. The differ-
ent zone samples of the products collected in the U-shaped
1
trap were analyzed by H NMR, LCeMS, and GCeMS. Rel-
ative and percent yields were determined from GC and com-
pared with authentic samples.
4.2. Kinetic measurements
4.4. Synthesis
A stock solution (4 mL) was prepared by dissolving 6e
10 mg of the substrate in acetonitrile as solvent to give a con-
centration of 1000e2000 ppm. An internal standard was then
added, the amount being adjusted to give the desired peak area
ratio of substrate to standard (2.5:1). The solvent and the inter-
nal standard are selected such that both are stable under the
conditions of pyrolysis, and because they would not react
with either substrate or product. The internal standards used
in this study are chlorobenzene, 1,3-dichlorobenzene or
1,2,4-trichlorobenzene. Each solution was filtered to ensure
that a homogeneous solution is obtained. The weight ratio of
4.4.1. Ethyl 2,2-bis(hydroxymethyl)propanoate (6a)
Bis(hydroxymethyl)propanoic acid (10 g, 74.6 mmol) was
dissolved in (50 mL) ethanol and a few drops of H2SO4
were added. The reaction mixture was refluxed. After 3 h,
the reaction mixture was cooled and ethanol was evaporated.
The residue was dissolved in ethyl acetate and washed with so-
dium bicarbonate solution followed by water. Following the
extraction, the organic layer was dried over anhydrous sodium
sulfate, filtered, and then evaporated to obtain 6a as a colorless
ꢅ
1
oil (9.3 g, 77% yield); MS: m/z 162 (Mþ ); H NMR (CDCl3)

T.F. Al-Azemi et al. / Tetrahedron 64 (2008) 4126e4134
4131
ppm: 1.07 (s, 3H, CH3), 1.31 (t, J¼7.2 Hz, 3H, CH3), 3.04 (br
s, 1H, OH), 3.72 (d, J¼10.8 Hz, 2H, CH2), 3.91 (d,
J¼10.8 Hz, 2H, CH2), 4.23 (q, J¼7.2 Hz, 2H, CH2). 13C
NMR (CDCl3) ppm: 14.7 (CH3), 17.7 (CH3), 49.6 (CH),
69.7 (OCH2), 68.9 (2OCH2), 176.6 (OC]O). Anal. Calcd
for C7H14O4: C, 51.84; H, 8.70. Found: C, 51.51; H, 8.79.
(CDCl3) ppm: 0.94 (t, J¼7.1 Hz, 6H, 2CH3), 1.24e1.63 (m,
12H, 6CH2), 4.14 (s, 4H, OCH2). 13C NMR (CDCl3) ppm:
14.5 (2CH3), 23.7 (2CH2), 25.5 (2CH2), 30.9 (2CH2), 33.9
(C), 76.0 (2OCH2), 159.0 (OC]OO). Anal. Calcd for
C12H22O3: C, 67.26; H, 10.35. Found: C, 66.46; H, 10.36.
4.4.3.6. Ethyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate (6b).
White crystals (78% yield); mp: 51 ꢀC; MS: m/z 189
(Mþþ1, 54%), 157 (27%), 143 (40%), 127 (10%), 115
4.4.2. Benzyl 2,2-bis(hydroxymethyl)propanoate (7a)
Compound 7a was synthesized according to the literature
procedure,13 and was obtained as white crystals (13.4 g, 80%
1
(95%), 99 (75%), 86 (60%), 72 (92%), 57 (100%); H NMR
ꢅ
yield); mp: 75 ꢀC; MS: m/z 224 (Mþ ); 1H NMR (CDCl3) ppm:
(CDCl3) ppm: 1.33 (t, J¼7.1 Hz, 3H, CH3), 1.36 (s, 3H,
CH3), 4.22 (d, J¼10.6 Hz, 2H, CH2), 4.28 (q, J¼7.1 Hz, 2H,
CH2), 4.72 (d, J¼10.6 Hz, 2H, CH2). 13C NMR (CDCl3)
ppm: 14.4 (CH3), 18.0 (CH3), 40.5 (C), 62.7 (OCH2), 73.4
(2OCH2), 147.9 (OC]OO), 171.5 (OC]O). Anal. Calcd
for C8H12O5: C, 51.06; H, 6.43. Found: C, 50.65; H, 6.34.
1.11 (s, 3H, CH3), 2.95 (s, 2H, 2OH), 3.76 (d, J¼11.3 Hz, 2H,
OCH2), 3.97 (d, J¼11.2 Hz, 2H, OCH2), 5.24 (s, 2H, OCH2),
7.34e7.43 (m, 5H, ArH). 13C NMR (CDCl3) ppm: 17.7
(CH3), 49.8 (CH), 67.3 (OCH2), 68.9 (2OCH2), 128.5 (ArC),
128.9 (ArC), 129.2 (ArC), 136.2 (ArC), 176.3 (OC]O).
Anal. Calcd for C7H14O4: C, 64.27; H, 7.19. Found: C, 63.70;
H, 7.00.
4.4.3.7. Benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate (7b).þ13
White crystals (85% yield); mp: 75 ꢀC; MS: m/z 250 (M ,
2%), 144 (5%), 107 (18%), 100 (30%), 91 (100%), 85
4.4.3. General procedure for synthesis of cyclic carbonates
(1e7)b
1
(11%), 77 (8%), 65 (11%); H NMR (CDCl3) ppm: 1.35 (s,
The cyclic carbonate compounds were prepared according
to the literature procedures.13,14
3H, CH3), 4.23 (d, J¼10.8 Hz, 2H, CH2), 4.73 (d,
J¼10.8 Hz, 2H, CH2), 5.24 (s, 2H, CH2), 7.35e7.43 (m, 5H,
ArH). 13C NMR (CDCl3) ppm: 18.0 (CH3), 40.6 (C), 68.3
(OCH2), 73.3 (2OCH2), 128.6 (ArC), 129.1 (ArC), 129.2
(ArC), 135.1 (ArC), 147.8 (OC]OO), 171.3 (OC]O).
4.4.3.1. 1,3-Dioxan-2-one (1b).14 White crþystals (9.3 g, 70%
yield); mp: 47e48 ꢀC; MS: m/z 102 (M , 100%) and 57
1
(87%); H NMR (CDCl3) ppm: 2.17 (quin, J¼5.7 Hz, 2H,
CH2), 4.48 (t, J¼5.7 Hz, 4H, 2CH2). Anal. Calcd for
4.4.4. General procedure for the synthesis of open-ring
carbonates (1e7)c
C4H6O3: C, 47.06; H, 5.92. Found: C, 46.81; H, 6.34.
Compounds (1e7)b (2 g) were dissolved in ethanol
(30 mL) and few drops of trifluoroacetic acid (TFA) were
added, while the mixture is being stirred at room temperature.
After addition was completed, ethanol was evaporated and the
residue was dissolved in ethyl acetate. The organic layer was
extracted with sodium bicarbonate solution and water, then
dried with anhydrous sodium sulfate and ethyl acetate was
finally evaporated to recover the pure compound.15
4.4.3.2. 5-Methyl-1,3-dioxan-2-one (2b). Colorless oil (59%
1
yield); MS: m/z 116 (Mþ, 34%), 75 (47%), 57 (100%); H
NMR (CDCl3) ppm: 1.02 (d, J¼6.8 Hz, 3H, CH3), 2.34e
2.38 (m, 1H, CH), 4.05 (t, J¼10.1 Hz, 2H, OCH2), 4.38 (d,
J¼10.6, 4.3 Hz, 2H, OCH2). 13C NMR (CDCl3) ppm: 12.4
(CH3), 26.8 (CH), 73.7 (2OCH2), 149.1 (OC]OO).
4.4.3.3. 5,5-Dimethyl-1,3-dioxan-2-one (3b). White crystals
(66% yield); mp: 96e97 ꢀC; MS m/z 130 (Mþ, 10%), 101
(14%), 86 (76%), 71 (20%), 56 (100%); H NMR (CDCl3)
ppm: 1.15 (s, 6H, 2CH3), 4.10 (s, 4H, 2CH2). 13C NMR
(CDCl3) ppm: 21.6 (2CH3), 28.9 (C), 78.1 (2OCH2), 148.7
(OC]OO). Anal. Calcd for C6H10O3: C, 55.37; H, 7.74.
Found: C, 55.36; H, 7.63.
4.4.4.1. Ethyl (3-hydroxypropyl) carbonate (1c). Colorless oil
(72% yield); MS: m/z 131 (50%), 103 (100%), 59 (50%);
1H NMR (CDCl3) ppm: 1.32 (t, J¼7.2 Hz, 3H, CH3), 1.69
(br s, 1H, OH), 1.94 (quin, J¼6.0 Hz, 2H, CH2), 3.77 (t,
J¼6.0 Hz, 2H, OCH2), 4.23 (q, J¼7.2 Hz, 2H, OCH2), 4.29
(t, J¼6.0 Hz, 2H, OCH2). 13C NMR (CDCl3) ppm: 14.8
(CH3), 32.2 (CH2), 59.6 (OCH2), 64.7 (OCH2), 65.3
(OCH2), 156.1 (OC]OO).
1
4.4.3.4. 5,5-Diethyl-1,3-dioxan-2-one (4b). White crystals
(70% yield); mp: 49e50 ꢀC; MS: m/z 159 (Mþþ1, 5%), 84
1
(60%), 69 (100%), 55 (68%); H NMR (CDCl3) ppm: 0.92
4.4.4.2. Ethyl (3-hydroxy-2-methylpropyl) carbonate (2c).
Colorless oil (68% yield); MS: m/z 162 (Mþ, 1%), 135
(t, J¼7.6 Hz, 6H, 2CH3), 1.50 (q, J¼7.6 Hz, 4H, 2CH2),
4.15 (s, 4H, 2OCH2). 13C NMR (CDCl3) ppm: 7.7 (2CH3),
23.2 (2CH2), 34.1 (C), 75.5 (2OCH2), 149.2 (OC]OO).
Anal. Calcd for C8H14O3: C, 60.74; H, 8.92. Found: C,
60.42; H, 8.85.
1
(10%), 117 (100%), 73 (44%), 57 (72%); H NMR (CDCl3)
ppm: 0.96 (d, J¼7.0 Hz, 3H, CH3), 1.30 (t, J¼7.1 Hz, 3H,
CH3), 1.99e2.04 (m, 1H, CH), 2.33 (br s, 1H, OH), 3.50e
3.59 (m, 2H, OCH2), 4.12 (d, J¼5.9 Hz, 2H, OCH2), 4.19
(q, J¼7.1 Hz, 2H, OCH2). 13C NMR (CDCl3) ppm: 14.0
(CH3), 14.8 (CH3), 35.9 (CH), 64.7 (OCH2), 70.0 (2OCH2),
156.2 (OC]OO). Anal. Calcd for C7H14O4: C, 51.84; H,
8.70. Found: C, 50.93; H, 8.70.
4.4.3.5. 5,5-Dibutyl-1,3-dioxan-2-one (5b). Colorless oil (62%
yield); MS: m/z 213 (Mþꢁ1, 5%), 157 (7%), 140 (18%), 110
1
(7%), 97 (30%), 83 (64%), 70 (47%), 56 (100%); H NMR

4132
T.F. Al-Azemi et al. / Tetrahedron 64 (2008) 4126e4134
4.4.4.3. Ethyl (3-hydroxy-2,2-dimethylpropyl) carbonate (3c).
Colorless oil (82% yield); MS: m/z 152 (20%), 91 (100%),
73 (60%), 69 (58%), 56 (95%); 1H NMR (CDCl3) ppm:
0.96 (s, 6H, 2CH3), 1.34 (t, J¼7.1 Hz, 3H, CH3), 2.16 (br s,
1H, OH), 3.38 (s, 2H, OCH2), 4.01 (s, 2H, OCH2), 4.23 (q,
J¼7.1 Hz, 2H, CH2). 13C NMR (CDCl3) ppm: 14.8 (CH3),
21.9 (2CH3), 37.1 (C), 64.8 (OCH2), 68.6 (OCH2), 73.6
(OCH2), 156.5 (OC]OO). Anal. Calcd for C8H16O4: C,
54.53; H, 9.15. Found: C, 53.53; H, 9.28.
(OC]OO), 174.6 (OC]O). Anal. Calcd for C15H20O6: C,
60.80; H, 6.80. Found: C, 60.53; H, 6.99.
4.4.5. General procedure for the synthesis of carbonatee
ester compounds (1e7)d
Compounds (1e7)c (1 g) were dissolved in dry THF
(10 mL) with 5% by weight of DMAP. Propanoic anhydride
[1.5 equiv] was added, while the reaction mixture was stirred
at room temperature. After the reaction was completed, the
THF was evaporated and the residue dissolved in ethyl acetate
and extracted with sodium bicarbonate solution and water.
The organic layer was dried with anhydrous sodium sulfate,
and ethyl acetate was then evaporated to obtain the pure
product.
4.4.4.4. Ethyl [2-ethyl-2-(hydroxymethyl)butyl] carbonate (4c).
Colorless oil (89% yield); MS: m/z 187 (20%), 173 (10%), 159
1
(25%), 97 (100%), 83 (75%), 69 (25%), 55 (65%); H NMR
(CDCl3) ppm: 0.86 (t, J¼7.5 Hz, 6H, 2CH3), 1.24e1.39 (m,
7H, CH3, 2CH2), 2.14 (br s, 1H, OH), 3.39 (s, 2H, OCH2),
4.05 (s, 2H, OCH2), 4.23 (q, J¼7.1 Hz, 2H, OCH2). 13C
NMR (CDCl3) ppm: 7.5 (2CH3), 14.8 (CH3), 22.3 (2CH2),
41.9 (C), 64.7 (OCH2), 64.9 (OCH2), 69.9 (OCH2), 156.6
(OC]OO). Anal. Calcd for C10H20O4: C, 58.80; H, 9.87.
Found: C, 58.95; H, 10.08.
4.4.5.1. 3-(Ethoxycarbonyloxy)propyl propanoate (1d). Color-
less oil (90% yield); MS: m/z 131 (25%), 115 (80%), 97
1
(25%), 83 (30%), 69 (62%), 57 (100%); H NMR (CDCl3)
ppm: 1.16 (t, J¼7.6 Hz, 3H, CH3), 1.33 (t, J¼7.1 Hz, 3H,
CH3), 2.03 (quin, J¼6.2 Hz, 2H, CH2), 2.35 (q, J¼7.6 Hz,
2H, CH2), 4.20e4.25 (m, 6H, 3OCH2). 13C NMR (CDCl3)
ppm: 9.7 (CH3), 14.8 (CH3), 28.1 (CH2), 28.6 (CH2), 61.1
(OCH2), 64.6 (OCH2), 64.9 (OCH2), 155.7 (OC]OO),
175.0 (OC]O). Anal. Calcd for C9H16O5: C, 52.93; H,
7.90. Found: C, 52.60; H, 7.92.
4.4.4.5. 2-Butyl-2-(hydroxymethyl)hexyl ethyl carbonate (5c).
Colorless oil (69% yield); MS: m/z 243 (34%), 229 (32%),
215 (60%), 201 (20%), 171 (30%), 153 (92%), 140 (100%),
1
111 (40%), 97 (95%), 83 (100%), 69 (70%), 55 (70%); H
NMR (CDCl3) ppm: 0.93 (t, J¼7.2 Hz, 6H, 2CH3), 1.18e
1.35 (m, 15H, CH3, 6CH2), 2.02 (1H, OH), 3.39 (s, 2H,
OCH2), 4.04 (s, 2H, OCH2), 4.23 (q, J¼7.2 Hz, 2H, OCH2).
13C NMR (CDCl3) ppm: 14.4 (2CH3), 14.7 (CH3), 23.9
(2CH2), 25.1 (2CH2), 30.9 (2CH2), 41.6 (C), 64.5 (OCH2),
65.1 (OCH2), 70.5 (OCH2), 156.4 (OC]OO). Anal. Calcd
for C14H28O4: C, 64.58; H, 10.84. Found: C, 64.51; H, 11.11.
4.4.5.2. 3-[(Ethoxycarbonyl)oxy]-2-methylpropyl propanoate
(2d). Colorless oil (67% yield); MS: m/z 145 (12%), 129
1
(95%), 117 (25%), 72 (9%), 57 (100%); H NMR (CDCl3)
ppm: 1.03 (d, J¼6.9 Hz, 3H, CH3), 1.16 (t, J¼7.6 Hz, 3H,
CH3), 1.33 (t, J¼7.1 Hz, 3H, CH3), 2.20e2.25 (m, 1H, CH),
2.36 (q, J¼7.6 Hz, 2H, CH2), 4.02e4.15 (m, 4H, 2OCH2),
4.22 (q, J¼7.1 Hz, 2H, OCH2). 13C NMR (CDCl3) ppm: 9.7
(CH3), 14.3 (CH3), 14.8 (CH3), 28.1 (CH), 33.1 (CH2), 64.6
(OCH2), 66.0 (OCH2), 69.7 (OCH2), 155.8 (OC]OO),
175.0 (OC]O). Anal. Calcd for C10H18O5: C, 55.03; H,
8.31. Found: C, 55.23; H, 8.54.
4.4.4.6. Ethyl 3-[(ethoxycarbonyl)oxy]-2-(hydroxymethyl)-2-
methylpropanoate (6c). Colorless oil (88% yield); MS: m/z
234 (Mþ, 7%), 189 (60%), 115 (40%), 99 (50%), 69
(100%), 57 (80%); 1H NMR (CDCl3) ppm: 1.24 (s, 3H,
CH3), 1.28e1.35 (m, 6H, 2CH3), 2.52 (t, J¼6.9 Hz, 1H,
OH), 3.73 (d, J¼6.6 Hz, 2H, OCH2), 4.20e4.24 (m, 4H,
2OCH2), 4.27 (d, J¼11.2 Hz, 1H, OCH), 4.45 (d,
J¼10.9 Hz, 1H, OCH). 13C NMR (CDCl3) ppm: 14.6 (CH3),
14.8 (CH3), 18.1 (CH3), 48.7 (C), 61.8 (OCH2), 64.9
(OCH2), 65.4 (OCH2), 69.4 (OCH2), 155.9 (OC]OO),
174.8 (OC]O). Anal. Calcd for C10H18O6: C, 51.27; H,
7.75. Found: C, 51.14; H, 7.77.
4.4.5.3. 3-[(Ethoxycarbonyl)oxy]-2,2-dimethylpropyl propanoate
(3d). Colorless oil (87% yield); MS: m/z 232 (Mþ, 8%), 208
(50%), 143 (48%), 105 (54%), 91 (80%), 77 (52%), 69
(70%), 57 (100%); 1H NMR (CDCl3) ppm: 0.98 (s, 6H,
2CH3), 1.15 (t, J¼7.6 Hz, 3H, CH3), 1.33 (t, J¼7.1 Hz, 3H,
CH3), 2.37 (q, J¼7.6 Hz, 2H, CH2), 3.92 (s, 2H, OCH2),
3.98 (s, 2H, OCH2), 4.21 (q, J¼7.1 Hz, 2H, OCH2). 13C
NMR (CDCl3) ppm: 9.7 (CH3), 14.8 (CH3), 22.2 (2CH3),
28.1 (CH2), 35.2 (C), 64.6 (OCH2), 69.4 (OCH2), 73.1
(OCH2), 155.8 (OC]OO), 174.9 (OC]O). Anal. Calcd for
C11H20O5: C, 56.88; H, 8.68. Found: C, 56.90; H, 8.92.
4.4.4.7. Benzyl 3-[(ethoxycarbonyl)oxy]-2-(hydroxymethyl)-2-
methylpropanoate (7c). Colorless oil (93% yield); MS: m/z
296 (Mþ, 27%), 279 (30%), 189 (40%), 131 (40%), 91
(100%), 72 (40%); 1H NMR (CDCl3) ppm: 1.26 (s, 3H,
CH3), 1.32 (t, J¼7.1 Hz, 3H, CH3), 2.47 (br s, 1H, OH),
3.76 (d, J¼5.7 Hz, 2H, OCH2), 4.20 (q, J¼7.1 Hz, 2H,
CH2), 4.30 (d, J¼10.9 Hz, 1H, CH), 4.46 (d, J¼11.1 Hz,
1H, CH), 5.21 (s, 2H, CH2), 7.35e7.39 (m, 5H, ArH). 13C
NMR (CDCl3) ppm: 14.8 (CH3), 18.0 (CH3), 48.9 (C), 65.0
(OCH2), 65.4 (OCH2), 67.3 (OCH2), 69.4 (OCH2), 128.5
(ArCH), 128.9 (ArCH), 128.2 (ArCH), 136.1 (ArC), 155.9
4.4.5.4. 2-[(Ethoxycarbonyl)oxy]methyl-2-ethylbutyl propanoate
ꢅ
(4d). Colorless oil (83% yield); MS: m/z 260 (Mþ ); 1H NMR
(CDCl3) ppm: 0.85 (t, J¼7.5 Hz, 6H, 2CH3), 1.16 (t,
J¼7.6 Hz, 3H, CH3), 1.31e1.40 (m, 7H, CH3, 2CH2), 2.36
(q, J¼7.6 Hz, 2H, CH2), 3.96 (s, 2H, OCH2), 4.02 (s, 2H,
OCH2), 4.20 (q, J¼7.2 Hz, 2H, OCH2). 13C NMR (CDCl3)
ppm: 7.6 (2CH3), 9.7 (CH3), 14.8 (CH3), 23.4 (2CH2), 28.2

T.F. Al-Azemi et al. / Tetrahedron 64 (2008) 4126e4134
4133
(CH2), 40.2 (C), 64.6 (OCH2), 65.8 (OCH2), 69.8 (OCH2),
155.8 (OC]OO), 174.9 (OC]O). Anal. Calcd for
C13H24O5: C, 59.98; H, 9.29. Found: C, 60.38; H, 9.37.
4.4.6.1. 3-Hydroxypropyl propanoate (1e). Colorless oil (29%
yield); MS: m/z 111 (10%), 97 (20%), 81 (42%), 69 (90%), 57
(100%); 1H NMR (CDCl3) ppm: 1.13 (t, J¼7.6 Hz, 3H, CH3),
1.86 (quin, J¼6.2 Hz, 2H, CH2), 2.33 (q, J¼7.6 Hz, 2H, CH2),
4.4.5.5. 2-Butyl-2-[(2-ethoxy-2-oxoethoxy)methyl]hexyl propa-
noate (5d). Colorless oil (82% yield); MS: m/z 243 (24%),
227 (60%), 213 (35%), 139 (40), 97 (70%), 83 (77%), 69
(54%), 57 (100%); 1H NMR (CDCl3) ppm: 0.92 (t,
J¼7.2 Hz, 6H, 2CH3), 1.16 (t, J¼7.6 Hz, 3H, CH3), 1.20e
1.35 (m, 15H, CH3, 6CH2), 2.36 (q, J¼7.6 Hz, 2H, CH2),
3.94 (s, 2H, OCH2), 3.95 (s, 2H, OCH2), 4.21 (q, J¼7.2 Hz,
2H, OCH2). 13C NMR (CDCl3) ppm: 9.7 (CH3), 14.4
(2CH3), 14.8 (CH3), 23.9 (2CH2), 25.3 (2CH2), 28.2 (CH2),
31.3 (2CH2), 40.1 (C), 64.5 (OCH2), 66.5 (OCH2), 70.3
(OCH2), 155.8 (OC]OO), 174.8 (OC]O). Anal. Calcd for
C17H32O5: C, 64.53; H, 10.19. Found: C, 64.97; H, 10.50.
3.68 (t, J¼6.0 Hz, 2H, CH2), 4.22 (t, J¼6.2 Hz, 2H, CH2). 13
C
NMR (CDCl3) ppm: 9.7 (CH3), 28.1 (CH2), 32.3 (CH2), 59.7
(OCH2), 61.8 (OCH2), 175.6 (OC]O).
4.4.6.2. 3-Hydroxy-2-methylpropyl propanoate (2e). Colorless
oil (32% yield); MS: m/z 146 (Mþ, 4%), 97 (25%), 74 (30%),
69 (44%), 57 (100%); 1H NMR (CDCl3) ppm: 0.94 (d,
J¼7.0 Hz, 3H, CH3), 1.14 (t, J¼7.6 Hz, 3H, CH3), 1.96e
2.00 (m, H, CH), 2.22 (br s, 1H, OH), 2.34 (q, J¼7.6 Hz,
2H, CH2), 3.48e3.54 (m, 2H, OCH2), 4.03e4.12 (m, 2H,
OCH2). 13C NMR (CDCl3) ppm: 9.7 (CH3), 14.0 (CH3),
28.1 (CH2), 36.0 (CH2), 64.9 (OCH2), 66.6 (OCH2), 175.7
(OC]O). Anal. Calcd for C7H14O3: C, 57.51; H, 9.65. Found:
C, 56.35; H, 9.78.
4.4.5.6. Ethyl 3-[(ethoxycarbonyl)oxy]-2-methyl-2-[(propionyl-
oxy)methyl]propanoate (6d). Colorless oil (88% yield); MS:
m/z 291 (Mþþ1, 35%), 245 (40%), 217 (68%), 201 (47%),
144 (40%), 114 (64%), 99 (64%), 99 (52%), 69 (43%), 57
(100%); 1H NMR (CDCl3) ppm: 1.15 (t, J¼7.6 Hz, 3H,
CH3), 1.26e1.34 (m, 9H, 3CH3), 2.35 (t, J¼7.6 Hz, 3H,
CH3), 4.18e4.37 (m, 8H, 4OCH2). 13C NMR (CDCl3) ppm:
9.6 (CH3), 14.6 (CH3), 14.8 (CH3), 27.9 (CH2), 46.8 (C),
61.8 (OCH2), 64.8 (OCH2), 65.7 (OCH2), 68.9 (OCH2),
155.4 (OC]OO), 173.1 (OC]O), 174.4 (OC]O). Anal.
Calcd for C13H22O7: C, 53.78; H, 7.64. Found: C, 54.20; H,
7.77.
4.4.6.3. 3-Hydroxy-2,2-dimethylpropyl propanoate (3e). Col-
orless oil (30% yield); MS: m/z 143 (10%), 129 (10%), 97
1
(40%), 81 (50%), 69 (100%), 57 (95%); H NMR (CDCl3)
ppm: 0.94 (s, 6H, 2CH3), 1.18 (t, J¼7.6 Hz, 3H, CH3), 2.23
(br s, 1H, OH), 2.39 (q, J¼7.6 Hz, 2H, CH2), 3.31 (s, 2H,
OCH2), 3.96 (s, 2H, OCH2). 13C NMR (CDCl3) ppm: 9.8
(CH3), 22.1 (2CH3), 28.2 (CH2), 37.0 (C), 68.8 (OCH2),
69.8 (OCH2), 175.8 (OC]O).
4.4.6.4. 2-Ethyl-2-(hydroxymethyl)butyl propanoate (4e). Col-
orless oil (34% yield); MS: m/z 84 (100%), 69 (40%), 57
(90%); 1H NMR (CDCl3) ppm: 0.84 (t, J¼7.6 Hz, 6H,
2CH3), 1.16 (t, J¼7.6 Hz, 3H, CH3), 1.21e1.33 (m, 4H,
2CH2), 2.31 (br s, 1H, OH), 2.38 (q, J¼7.6 Hz, 2H, CH2),
3.32 (s, 2H, OCH2), 3.99 (s, 2H, OCH2). 13C NMR (CDCl3)
ppm: 7.5 (2CH3), 9.8 (CH3), 22.6 (2CH2), 28.2 (CH2), 41.8
(C), 64.8 (OCH2), 66.5 (OCH2), 175.9 (OC]O). Anal. Calcd
for C10H20O3: C, 63.80; H, 10.71. Found: C, 62.90; H, 10.93.
4.4.5.7. Benzyl 3-[(ethoxycarbonyl)oxy]-2-methyl-2-[(propio-
nyloxy)methyl]propanoate (7d). Colorless oil (80% yield);
MS: m/z 352 (Mþ, 15%), 279 (28%), 263 (55%), 245 (72%),
205 (44%), 189 (80%), 173 (83%), 128 (67%), 107 (56%),
92 (100%), 65 (84%), 57 (76%); 1H NMR (CDCl3) ppm:
1.10 (t, J¼7.6 Hz, 3H, CH3), 1.30 (s, 3H, CH3), 1.32 (t,
J¼7.1 Hz, 3H, CH3), 2.24e2.30 (m, 2H, CH2), 4.16e4.38
(m, 6H, 3OCH2), 5.19 (s, 2H, OCH2), 7.33e7.40 (m, 5H,
ArH). 13C NMR (CDCl3) ppm: 9.6 (CH3), 14.8 (CH3), 18.3
(CH3), 27.9 (CH2), 47.0 (C), 64.9 (OCH2), 65.8 (OCH2),
67.4 (OCH2), 68.9 (OCH2), 128.6 (ArCH), 128.9 (ArCH),
129.2 (ArCH), 136.1 (ArC), 155.4 (OC]OO), 173.0
(OC]O), 174.4 (OC]O). Anal. Calcd for C18H24O7: C,
61.35; H, 6.86. Found: C, 61.44; H, 7.14.
4.4.6.5. 2-Butyl-2-(hydroxymethyl)hexyl propanoate (5e). Col-
orless oil (31% yield); MS: m/z 244 (Mþ, 20%), 140 (100%);
1H NMR (CDCl3) ppm: 0.93 (t, J¼7.2 Hz, 6H, 2CH3), 1.18 (t,
J¼7.6 Hz, 3H, CH3), 1.20e1.33 (m, 12H, 6CH2), 2.25 (t, J¼
6.8 Hz, 1H, OH), 2.39 (q, J¼7.6 Hz, 2H, CH2), 3.33 (d,
J¼6.8 Hz, 2H, OCH2), 4.00 (s, 2H, OCH2). 13C NMR
(CDCl3) ppm: 9.8 (CH3), 14.6 (2CH3), 24.1 (2CH2), 25.3
(2CH2), 28.2 (CH2), 30.6 (2CH2), 41.7 (C), 65.6 (OCH2),
67.2 (OCH2), 175.9 (OC]O). Anal. Calcd for C14H28O3: C,
68.81; H, 11.55. Found: C, 68.56; H, 11.79.
4.4.6. General procedure for the synthesis of ester
compounds (1e7)e
Compounds (1e7)a (1 g) were dissolved in dry THF
(10 mL) with 5% by weight of DMAP. Propanoic anhydride
[1:1 mole ratio] was added and the reaction was let to stir at
room temperature. After the reaction was completed, the
THF was evaporated and the residue dissolved in ethyl acetate
and extracted with sodium bicarbonate solution and water. The
organic layer dried with anhydrous sodium sulfate, and ethyl
acetate was then evaporated. The mono-acetate product was
separated using silica gel flash column chromatography, elut-
ing with 20% ethyl acetate/petroleum ether.
4.4.6.6. Ethyl 3-hydroxy-2-methyl-2-[(propionyloxy)methyl]-
propanoate (6e). Colorless oil (36% yield); MS: m/z 218
(Mþ, 40%), 201 (65%), 173 (64%), 145 (65%), 114 (84%),
99 (56%), 86 (45%), 69 (100%), 57 (87%); 1H NMR
(CDCl3) ppm: 1.12 (t, J¼7.5 Hz, 3H, CH3), 1.18 (s, 3H,
CH3), 1.25 (t, J¼7.1 Hz, 3H, CH3), 2.33 (q, J¼7.6 Hz, 2H,
CH2), 2.84 (br s, 1H, OH), 3.65 (dd, J¼11.5, J¼6.3 Hz,
2H, OCH2), 4.14e4.21 (m, 3H, OCH, OCH2), 4.30 (d,

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T.F. Al-Azemi et al. / Tetrahedron 64 (2008) 4126e4134
J¼11.1 Hz, 1H, OCH). 13C NMR (CDCl3) ppm: 9.7 (CH3),
14.7 (CH3), 18.1 (CH3), 28.1 (CH2), 48.6 (C), 61.6 (OCH2),
65.5 (OCH2), 66.3 (OCH2), 175.1 (OC]O), 175.2
(OC]O). Anal. Calcd for C10H18O5: C, 55.03; H, 8.31.
Found: C, 54.50; H, 8.48.
the authors (H.H.D.) wishes to thank the College of Graduate
Studies, Kuwait University for a Ph.D. candidacy.
References and notes
1. Ibrahim, Y. A.; Abbas, A. A.; Elwahy, H. M. Carbohydr. Lett. 1999, 3, 331.
2. Dib, H. H.; Al-Awadi, N. A.; Ibrahim, Y. A.; El-Dusouqui, O. M. E.
Tetrahedron 2003, 59, 9455.
4.4.6.7. Benzyl 3-hydroxy-2-methyl-2-[(propionyloxy)methyl]-
propanoate (7e). Colorless oil (32% yield); MS: m/z 280
(Mþ, 62%), 262 (65%), 180 (45%), 172 (100%), 130 (15%),
3. Dib, H. H.; Al-Awadi, N. A.; Ibrahim, Y. A.; El-Dusouqui, O. M. E.
J. Phys. Org. Chem. 2004, 17, 267.
1
4. Al-Awadi, N. A.; Ibrahim, Y. A.; Kaul, K.; Dib, H. H. Heteroat. Chem.
2003, 14, 50.
106 (45%), 91 (100%), 57 (70%); H NMR (CDCl3) ppm:
1.11 (t, J¼7.6 Hz, 3H, CH3), 1.25 (s, 3H, CH3), 2.30 (q,
J¼7.6 Hz, 2H, CH2), 2.54 (t, J¼6.9 Hz, 1H, OH), 3.66e3.76
(m, 2H, OCH2), 4.25 (d, J¼11.2 Hz, 1H, OCH), 4.37 (d,
J¼11.2 Hz, 1H, OCH), 5.22 (d, J¼12.4 Hz, 1H, OCH), 5.18
(d, J¼12.4 Hz, 1H, OCH), 7.35e7.40 (m, 5H, ArH). 13C
NMR (CDCl3) ppm: 9.6 (CH3), 18.1 (CH3), 27.9 (CH2),
48.8 (C), 65.5 (OCH2), 66.3 (OCH2), 67.3 (OCH2), 128.6
(ArCH), 128.9 (ArCH), 129.2 (ArCH), 136.2 (ArC), 174.9
(OC]O), 175.2 (OC]O). Anal. Calcd for C15H20O5: C,
64.27; H, 7.19. Found: C, 63.92; H, 7.48.
5. Al-Awadi, N. A.; Ibrahim, Y. A.; Kaul, K.; Dib, H. H.; Ibrahim, M. R.;
George, B. J.; Abdallah, M. R. Tetrahedron 2006, 62, 6214.
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O.; Gibson, S.; Grob, A.; Kumar, A.; Roder, T. Eur. J. Org. Chem. 2003, 840.
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Acknowledgements
The support of the University of Kuwait received through
research grant (SC01/06) and the facilities of ANALAB/SAF
(GS02/01, GS03/01) are gratefully acknowledged. One of
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2000, 13, 499.
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