From glycerol to chlorohydrin esters using a solvent-free system. Microwave irradiation versus conventional heating

Article abstract of DOI:10.1016/j.tet.2009.10.048

Esterification-chlorination of glycerol provides chlorohydrin esters in high yields. A ratio of reagents close to equivalence can be used, so that atom economy of the reaction is optimized. The reaction can be carried out using either classical or microwa

Full text of DOI:10.1016/j.tet.2009.10.048

Tetrahedron 65 (2009) 10370–10376
Contents lists available at ScienceDirect
Tetrahedron
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From glycerol to chlorohydrin esters using a solvent-free system. Microwave
irradiation versus conventional heating
a
a
,
b
b
b
a
*
`
´
Marc Escriba , Jordi Eras , Miquel Duran , Sılvia Simon , Cristina Butchosa , Gemma Villorbina ,
a
a,
*
`
Merce Balcells , Ramon Canela
a Department of Chemistry, Lleida University, 25198-Lleida, Spain
b Institute of Computational Chemistry and Department of Chemistry, Girona University, Campus de Montilivi 17071-Girona, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 June 2009
Received in revised form 9 October 2009
Accepted 14 October 2009
Available online 31 October 2009
Esterification–chlorination of glycerol provides chlorohydrin esters in highyields. A ratio of reagents close to
equivalence can be used, so that atom economy of the reaction is optimized. The reaction can be carried out
using either classical or microwave heating, and no solvent is required. 2-Chloro-1-(chloromethyl)ethyl
esters can be obtained in high regioisomeric relationship when either low or moderate temperature is used.
In contrast, microwave irradiation allows the use of higher reaction temperatures that render mixtures of
both regioisomers in variable relationships. Kinetic control of the process is proposed for classical heating,
and experimental results are analyzed with the aid of ab initio calculated values. Non-thermal phenomena
can be used to explain the high efficiency of microwave irradiation at low temperature.
On the occasion of Professr Pelayo Camps’
retirement
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Chlorohydrin esters
CTMS
Glycerol
MW
Nucleophilic substitution
Rearrangement
1. Introduction
esterification is widely described, and its ability to produce chlo-
rohydrin esters has been demonstrated using different diols4a and
The interest in new industrial applications of glycerol is in-
creasing parallel to the growth of biodiesel production. Recently,
new procedures have been patented to convert this compound to
a mixture of chlorohydrin esters and then to epichlorohydrin.1 One
of the main goals of these methods is to use a low-cost renewable
feedstock such as glycerol.2 The transformation of glycerol to
dichloropropyl derivatives allows the preparation of several com-
pounds with wide applications.3
We have already described how dichloropropyl esters can be
obtained by an esterification–substitution reaction from both
glycerol and 4-hydroxymethyl-2,2-dimethyl-1,3-dioxolane (sol-
ketal), a monoketal from glycerol, using diverse reagents. Among
them chlorotrimethylsilane (CTMS) has shown to be the more re-
liable one.4 These results have prompted us to study deeply the use
of CTMS for a direct esterification–substitution of glycerol to pre-
pare dichloropropyl esters. The use of CTMS as an acidic catalyst in
carboxylic acids.5 Herein, we report the direct transformation of
glycerol (1) into dichloropropyl esters (Scheme 1). No solvent is
required for the reaction and the energy needed for the reaction
can be provided using either classical heating or microwave sys-
tems. The mechanism proposed for this transformation is sup-
ported by the experimental results and a computational analysis
approach. Moreover, the effect of microwave irradiation at low
temperature could be explained by considering non-thermal mi-
crowave effects.6
R
O
R
OH
O
80 oC
48 h
O
O
O
+ R
+
CTMS
+
OH
OH OH
Cl
3a-n
Cl
Cl
Cl
4a-n
1
2a-n
R
a
n
Table 1
: entries to according to
* Corresponding authors. Tel.: þ34 973 702840; fax: þ34 973 238264 (J.E.);
tel.: þ34 973 702589; fax: þ34 973 238264 (R.C.).
Scheme 1. Simultaneous esterification and chlorination of glycerol using carboxylic
acids, chlorotrimethylsilane (CTMS) and classical heating.
E-mail addresses: eras@quimica.udl.cat (J. Eras), canela@quimica.udl.cat
(R. Canela).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.048

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M. Escriba et al. / Tetrahedron 65 (2009) 10370–10376
10371
2. Results and discussion
Trying to determine the reason for the different results observed
among both energy providing systems, a set of experiments were
planned using a microwave reactor and palmitic acid as a model
system (Table 2). First, the reaction was carried out at the same
temperature as classical heating. After 16 h, the reaction was almost
completed, and the 2-chloro-1-(chloromethyl)ethyl regioisomer
was the main isomer synthesized. Classical heating provided 64%
yield for the same temperature and reaction period. Once we had
determined that classical and microwave heating gave similar
regioisomeric ratios at 80 ꢀC, experiments at higher temperatures
were carried out using microwave irradiation. The reaction period
was progressively diminished to avoid product decomposition.
Nevertheless, changes introduced in the reaction time were always
tested, at the corresponding temperature, to determine that the
regioisomeric ratio was not strongly affected by the reaction time.
Table 2 shows that 2,3-dichloropropyl ester 4a increased parallel to
temperature increase. Finally, the reaction was carried out at 115 ꢀC
for 48 h using classical heating. Crude yield was similar to those
obtained at 80 ꢀC. However, the regioisomeric 3a:4a ratio was
88:12 in this case.
Consequently, regioisomeric ratio seems to be dependent of the
temperature and independent of the heating system used. Never-
theless, considering that irradiation power in the experiments de-
scribed above changed automatically to achieve the desired
temperature and that non-thermal effects7 have been adduced to
explain some results in microwave irradiation studies, we decided to
carryoutanewsetofexperimentsusingthehighestirradiationpower
yielded by the reactor (300 W) but maintaining the temperature at
30–35 ꢀC. These reactionswere carried out in anopenvessel provided
with a low temperature accessory. Using this approach, we tried to
determineifnon-thermalmicrowaveeffectswereabletopromotethe
formation of the 2,3-dichloropropyl esters 4. Caprylic acid (2b) was
used in this experiment to assure a liquid homogeneous system.
First, a mixture of glycerol (1) with the corresponding carboxylic
acid (2a–n) in a fivefold molar excess of CTMS was heated for 48 h at
80 ꢀC. All of the tested acids led to the formation of the corre-
sponding 2-chloro-1-(chloromethyl)ethyl carboxylates (3a–o) as
the main regioisomer (Table 1). To improve the atom economy of the
process, experiments were carried out using a mole ratio of 1.2:1:2.2
glycerol:carboxylic acid:CTMS. Crude yields and regioisomeric ra-
tios were in most cases similar tothose obtained with the 2:1:5 mole
ratio (Table 1). Only dinitrobenzoic acids exhibited lower yields. In
these cases, the corresponding intermediate 9 (Scheme 2) was
present in yields of around 30% (determined by 1H NMR). To shorten
the reaction time, the same reactions were carried out using a mole
ratio of 2:1:5 glycerol:carboxylic acid:CTMS and a pressurized
monomode microwave oven at 2.45 GHz. The reaction for most of
the compounds synthesized was carried out by programming the
microwave oven temperature at 250 ꢀC for 20 min. The microwave
reactor automatically controls the reaction pressure, the power ir-
radiation, and the cooling time. Using these conditions, the reaction
temperature was 243–247 ꢀC. Reactions using dinitrobenzoic acids
(2i and 2j) were carried out at 170–175 ꢀC (microwave oven tem-
perature 175 ꢀC) for 20 min to avoid product decomposition. Al-
though the yields after 20 min of reaction were similar to those
obtained by conventional heating, the ratio of regioisomers (3:4)
changed significantly (Table 1). Finally, equivalentexperimentswere
carried out using a mole ratio of 1.2:1:2.2 glycerol:carboxylic
acid:CTMS. Crude yields were in most cases lower to those obtained
with the 2:1:5 mole ratio (Table 1). Nevertheless, regioisomeric ra-
tios were similar (Table 1). The formation of insoluble materials was
observed in these experiments. These materials could be produced
from some of the intermediate compounds when temperature is
high and CTMS is not present in enough molar excess.
Table 1
Percentage yields and regioisomeric ratio of chlorohydrin esters 3:4 obtained using different reaction conditions and heating systems
Entry
R
Classicala
Classicalb
Microwavec
Microwaved
e
Isolated yield% Molar 3:4 ratio Crude yield%e Molar 3:4 ratio Isolated yield% Molar 3:4 ratio Crude yield%
Molar 3:4 ratio
a
b
c
d
e
f
g
h
i
j
k
l
m
n
CH3(CH2)14
CH3(CH2)6
(CH3)3C
91
88
95
88
80
85
92
90
77
81
89
82
84
98:2
85:15
99:1
99:1
100:0
98:2
100
92
94
96
83
100
89
91
52
30
97:3
81:19
100:0
100:0
99:1
99:1
100:0
98:2
99:1
100:0
99:1
100:0
98:2
100:0
86
81
90
80
73
78
73
78
77f
75f
82
76
78
72
37:63
39:61
41:59
35:65
41:59
35:65
41:59
30:70
54:46
59:41
36:64
37:63
35:65
36:64
70
73
62
64
64
61
52
60
57g
65g
55
60
55
63
38:62
35:65
33:67
39:61
44:56
41:59
43:57
36:64
55:45
58:42
37:63
41:59
33:67
39:61
C6H5
C6H5–CH]CH
o–Cl–C6H4
o–HO–C6H4
m-NO2–C6H4
3,5-(NO2)2–C6H4
2,4-(NO2)2–C6H4
1-Naphthyl
2-Naphthyl
2-Furyl
97:3
100:0
100:0
99:1
100:0
100:0
96:4
93
100
94
2-Thiophencarboxyl 88
99:1
90
a
Mole ratio 1:2:CTMS, 2:1:5, reaction temperature 80 ꢀC, reaction time 48 h.
Mole ratio 1:2:CTMS, 1.2:1:2.2, reaction temperature 80 ꢀC, reaction time 48 h.
b
c
d
e
f
Mole ratio 1:2:CTMS, 2:1:5, reaction temperature 243–247 ꢀC, reaction time 20 min.
Mole ratio 1:2:CTMS, 1.2:1:2.2, reaction temperature 243–247 ꢀC, reaction time 20 min.
Determined by GC using an internal standard.
Mole ratio 1:2:CTMS, 2:1:5, reaction temperature 170–175 ꢀC, reaction time 20 min.
Mole ratio 1:2:CTMS, 1.2:1:2.2, reaction temperature 170–175 ꢀC, reaction time 20 min.
g
The different regioisomeric ratios obtained for the various acids
When the reaction was carried out at 30–35 ꢀC and 300 W for
2 h, dichloropropyl caprylates (3b and 4b) were obtained with 95%
yield. Similar yields were obtained carrying out the reaction for
48 h at 30–31 ꢀC without microwave irradiation. The 3b:4b
regioisomeric ratios, 85:15, were similar in both cases. In conclu-
sion, high microwave irradiation power at low temperature did not
produce the increase of 2,3-regioisomeric ester but significantly
decreased the reaction time needed to obtain high conversion
could be explained according to the charge density at the carboxylic
carbon of the various acids.5 Moreover, microwave irradiation usually
tends to promote thermodynamically stable products.6 This effect is
enhanced whenpolar intermediates occurduring the reactionprocess.7
Nevertheless, some experiments show that microwave can also modify
activation parameters.14 Consequently, different compounds can be
obtained.

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M. Escriba et al. / Tetrahedron 65 (2009) 10370–10376
10372
OH
OH
O
HO
R
+
+
(CH3)3SiCl
OH
1
2a-n
R
O
R
O
O
O
5a-n
+
6a-n
Cl-
Cl-
OH
HO
Cl-
O
O Cl
O
Cl-
Cl
R
Cl
O
O
R
8a-n
9a-n
7a-n
OH
HO
O
R
OH
O
O
R
OH
R
OH
Cl
10a-n
11a-n
Cl
O
O
Path I
Path II
O
O
Cl
13a-n
Cl
12a-n
R
R
O
O
Cl-
Cl-
Cl-
3a-n
4a-n
R entry a to n according to Table 1
:
Scheme 2. Putative mechanistic pathways to explain the formation of chlorohydrin esters using CTMS as reagent and catalyst.
Table 2
Percentage yields and regioisomeric ratio of chlorohydrin palmitates 3a:4a (in parentheses) obtained at different temperatures and reaction times
Temp ꢀC (SD)a
Reaction timeb (h)
1/12
1/3
2
5
8
16
80.0 (0.5)c
99.9 (0.7)c
149.8 (0.6)c
199.4 (0.8)c
234.1 (8.3)c
80.0 (1.0)d
52% (96:4)
54% (92:8)
95% (84:16)
72% (95:5)
85% (95:5)
96% (90:10)
96% (85:15)
98% (40:60)
93% (32:68)
95% (62:38)
96% (57:43)
9% (94:6)
35% (97:3)
64% (98:2)
a
Standard deviation.
b
Yields determined by GC using an internal standard.
Mole ratio 1:2:CTMS, 2:1:5, microwave irradiation.
Mole ratio 1:2:CTMS, 2:1:5, classical heating.
c
d

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M. Escriba et al. / Tetrahedron 65 (2009) 10370–10376
10373
yields. This effect has been extensively described in the literature
and is best observed when polar products such as glycerol are
present in the reaction medium. Non-thermal processes have been
proposed to explain such results.6b Glycerol, a highly polar mole-
cule, will instantaneously absorb a high amount of microwave en-
ergy.7 The rotational motion of such molecules is then increased.
This causes a kinetic energy increase in the molecules that could
drive the reaction to completion faster than using conventional
heating.
These results could be explained assuming the kinetic control of
the reaction at low temperature. Reaction will be thermodynamic
controlled as the temperature increases. Nevertheless, diverse
pathways could be proposed to obtain these two regioisomers
(Scheme 2). Pathway II will allow a kinetic versus thermodynamic
control of the reaction, whereas pathway I will allow a different
way to obtain the 2,3-regiosomer. This pathway could be favored by
using the microwave reactor.
to confirm that the corresponding 2-chloro-1-(chloromethyl)ethyl
esters (3) are less thermodynamically stable than the 2,3-dichloro
propyl esters (4) (13.16 kJ molꢁ1 for R]C(CH3)3 and 8.58 kJ molꢁ1
for C6H5). Therefore, classical heating at low temperature will drive
the process to the kinetically controlled products, whereas high
temperatures, easy reached with microwave heating, favor ther-
modynamic control of the reaction. Pews and Davis9 have shown
that the 2-chloro-1-(chloromethyl)ethyl acetate can be partially
isomerized to 2,3-dichloro-1-propyl acetate at 180 ꢀC, which con-
firms our hypothesis. However, intermediate 7 is more stable than 8
(59.49 kJ molꢁ1 for R]C(CH3)3 and 46.52 kJ molꢁ1 for C6H5) and 9
(6.99 kJ molꢁ1 and 7.04 kJ molꢁ1, respectively), both containing the
carboxylic group in the
a position. Moreover, 1,3-dioxolanic com-
pounds 11 are is more stable than the corresponding 1,3-dioxanic
isomers 10 (4.83 kJ molꢁ1 and 4.54 kJ molꢁ1). Protonation of 10 and
11 proceeds spontaneous to the loose of H2O, giving 12 and 13,
being 13 the most stable compound for both substituents
(3.03 kJ molꢁ1 and 5.83 kJ molꢁ1 for R]C(CH3)3 and C6H5),
respectively.
To propose a feasible mechanism for this one-pot esterification–
chlorination reaction, an isomerization set of experiments and
a computational analysis were carried out.
2-Chloro-1-(chloromethyl)ethyl palmitate 3a was heated either
in a solvent-free system or in the presence of several solvents to
evaluate the putative isomerization of 3a to 4a (Scheme 2, Pathway
II) in diverse conditions. Table 3 shows that conventional heating at
80 ꢀC for 7 d or no-heating for one year produce no or little isom-
erization of 3a–4a. However, 3a can be partially isomerized to 4a by
conventional heating at 150 ꢀC for 48 h or microwave irradiation
whatever the reaction medium used. Similar results were described
by Derbesy and Naudet8 studying the isomerization of 1-chloro-2-
propyl and 4-chloro-2-butyl esters and for the isomerization of
dihalopropyl acetates.9 In contrast, Nayler10 described the isomeri-
zation of 2,3-dibromopropyl aryl esters to the corresponding 2-
bromo-1-(bromomethyl)ethyl esters by classical heating. In this
case, none of the 2,3-regioisomers remained at the end of the re-
action. Nevertheless, the authors reported that 2,3-dibromopropyl
alkyl esters did not isomerize to the 2-bromo-1-(bromomethyl)ethyl
esters under the same reaction conditions.
Table 4
DFT B3LYP/6-311þþG(d,p) electronic energies for the formation of dichloropropyl
pivaloates (c) and dichloropropyl benzoates (d) (a.u.)
Entry
c
d
3
4
5
6
7
8
9
10
11
12
13
ꢁ1384.317846
ꢁ1384.322864
ꢁ539.454866
ꢁ539.454574
ꢁ999.939768
ꢁ999.962433
ꢁ999.959785
ꢁ999.940996
ꢁ999.942836
ꢁ923.831767
ꢁ923.832924
ꢁ1458.135040
ꢁ1458.138310
ꢁ613.274373
ꢁ613.271013
ꢁ1073.756168
ꢁ1073.773905
ꢁ1073.771218
ꢁ1073.746778
ꢁ1073.748508
ꢁ997.64845
ꢁ997.650673
These results prompted us to propose that glycerol is trans-
formed to the 2,3-dichlorohydrin regioisomer by the 4-chloro
methyldioxolanic (pathway II) rather than the 5-chlorodioxanic
(pathway I) whatever the heating system used. Kinetic control will
determine the final regioisomeric ratio of the reaction when low
temperature is used. The rearrangement process from 1,3- to 2,3-
regioisomers will involve a nucleophilic attack of the sp2 oxygen
present in the carboxylic group to form the 1,3-dioxolane cations
(13a–n). A similar rearrangement process was proposed by Nay-
ler10 and Pews and Davis9 during the studies described above, and
Steblyanko et al.14 in the polymerization of acyloxymethyl five-
member cyclic dithiocarbonates. Non-purely thermal specific MW
effects will be consistent with the solvent-free conditions and the
polar mechanisms proposed (more polar transition states when
compared to their ground states).7
Table 3
Final regioisomeric ratio obtained after 2-chloro-1-(chloromethyl)ethyl palmitate
3a was subjected to diverse isomerization conditions
Solvent
Reaction time
1 ha
2 ha
ꢂ48 ha
95:5
98:2
60:40
Noneb
Nonec
Noned
Nonee
30:70
60:40
40:60
30:70
40:60
70:30
30:70
30:70
d
Isooctanee
Xylenee
30:70
d
Chloroforme
Chlorotrimethylsilanee
Hexamethyldisiloxanee
Butanonee
tert-Butanole
d
40:60
50:50
d
d
a
Molar 3a:4a ratio determined by GC using an internal standard.
One year at 25 ꢀC.
b
c
Classical heating at 80 ꢀC for 7 days.
d
e
Classical heating at 150 ꢀC for 48 h.
Microwave irradiation (300 w max, 17 atm max, 243–247 ꢀC).
3. Summary
Glycerol can be transformed into 2-chloro-1-(chloromethyl)ethyl
alkyl and aryl esters through a kinetically controlled process. These
esters could be partially transformed to the corresponding 2,3-
dichloropropyl regioisomer using a monomode microwave oven and
sufficiently high temperature. Microwave irradiation maintaining
low temperature dramatically increases the reaction rate, main-
taining kinetic control of the reaction. This effect can be explained by
assuming non-thermal microwave effects. A plausible mechanism is
proposed on the basis of computational and experimental studies.
Once the isomerization process was studied, a B3LYP11 calcula-
tions at the 6–311þþG(d,p)12 level were carried out for the differ-
ent species using the Gaussian0313 package.
The calculation of harmonic frequencies was performed to
confirm that they were minima. Table 4 shows electronic energies
for each different intermediate and the final products for pivalic
(2c) and benzoic (2d) acids as model compounds. These data seem

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M. Escriba et al. / Tetrahedron 65 (2009) 10370–10376
10374
4. Experimental section
4.4. General procedure for 2-chloro-1-(chloromethyl)ethyl
palmitate (3a) isomerization studies
4.1. Material and methods
Pure ester 3a (366 mg, 1 mmol) and the corresponding solvent
(5 mmol), when required (see Table 4), were added to a reaction
vial fitted with a PTFE-lined cap. The mixture was subjected to
diverse reaction conditions (see Table 4). After cooling, when re-
quired, t-butyl methyl ether was added, and the mixture was
washed three times with water. The organic layer was dried over
anhydrous MgSO4, and the solvent was evaporated under vacuum.
The crude product was analyzed by GC/FID to determine the final
regioisomeric ratio.
1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were
recorded on a VARIAN 400 spectrometer. All Chemical shifts are
reported in delta units (d), parts per million (ppm) relative to the
singlet at 7.26 ppm of CDCl3 for 1H and center line of a triplet at
77.00 ppm for 13C NMR. The following abbreviations are used; s:
singlet, d: doublet, t: triplet, q: quartet, quin: quintet, m: multiplet.
GC-FID analyses were performed in an Agilent Technologies 6890 N
equipped with a DB5-MS column (J&W) (30 mꢃ0.25 mꢃ0.25 mm)
m
and He as carrier gas. The following chromatographic conditions were
used: constant flow 2 mL/min, split injection ratio 20:1 at 300 ꢀC. Oven
started at 50 ꢀC for 5 min, temperature was increased at 5 ꢀC/min to
110 ꢀC, then increased at 10 ꢀC/min until final temperature of 260 ꢀCfor
15 min. Tridecane from Aldrich was used as internal standard to carry
out GC quantification.
4.5. General procedure for dichloropropyl caprylates (3b and
4b) synthesis at low temperature
Caprylic acid (144 mg, 1 mmol, 2b), glycerol (184 mg, 2 mmol, 1)
and CTMS (540 mg, 5 mmol) were added to a reaction vial. The mix-
ture was either classically heated at 30 ꢀC for 48 h or irradiated using
the power-time mode of the Discover LabMate microwave reactor
(CEM, Matthews, USA). Irradiation power was fixed at 300 W, and the
temperature was maintained at 30–35 ꢀC for 2 h using the Cool Mate
low temperature accessory (CEM, Matthews, USA). t-Butyl methyl
etherwas added,andthemixturewaswashedthreetimeswithwater.
The organic layer was dried over anhydrous MgSO4, and the solvent
was evaporated under vacuum. The crude product was analyzed by
GC/FID using tridecane as the internal standard.
GC–MS analyses were performed in an Agilent Technologies 6890 N
equipped with a DB5-MS column (J&W) (30 mꢃ0.25 mꢃ0.25 mm)
m
coupled to an Agilent Technologies 5973 Network detector and He as
carrier gas. The following chromatographic conditions were used:
constant flow 2 mL/min, split injection ratio 20:1 at 280 ꢀC. Oven started
at 50 ꢀC for 5 min, temperature was increased at 5 ꢀC/min to 110 ꢀC,
then increased at 10 ꢀC/min until final temperature of 260 ꢀCfor15 min.
IR spectra were recorded on a Magna IR 560 NicoleT FTIR
spectrophotometer in the range 4000–600 cmꢁ1 with KBr pellets
or with diamond HATR from SpectraTech as specified. Spectra are
reported in reciprocal centimeters (cmꢁ1).
4.6. Analytical data
High-resolution mass spectral (HRMS) data were obtained by
direct infusion on LC-TOF-MS Waters LCT Premier XE using ESI or
APCI or on Waters GCT Premier using EI as specified.
Melting points are uncorrected and were determined on a Gal-
lenkamp capillary melting point apparatus.
4.6.1. 1,3-Dichloro-2-propyl palmitate (3a). [CAS: 72165-62-9]: The
analytical and spectroscopic data are in accordance with the
literature.4a
Elemental analysis of was performed in a Carlo Erba Instruments
EA 1108.
4.6.2. 1,3-Dichloro-2-propyl caprylate (3b). 1H NMR (CDCl3),
d: 5.12
(quin, J¼5.2 Hz, 1H, O–CH), 3.68 (dd, J1¼5.7 Hz, J2¼2.2 Hz, 4H,
2CH2–Cl), 2.31 (t, J¼7.6 Hz, 2H, CH2 ( ) (C]O)), 1.58 (quin, J¼7.4 Hz,
a
4.2. General procedure for dichloropropyl ester synthesis.
(3a–n, 4a–n)
2H, CH2 ( ) (C]O)), 1.24 (m, 8H, CH2), 0.82 (t, J¼7.2 Hz, 3H, CH3). 13
C
b
RMN (CDCl3), d: 173 (C]O), 72 (O–CH), 42 (CH2–Cl), 34.4 (CH2 (
a)
(C]O)), 32.1 (CH2–CH2–CH3), 29.5 (CH2), 25 (CH2 ( (C]O)), 22.5
b)
The corresponding acid, glycerol, and CTMS (see Table 1) were
added in a reaction vial fitted with a PTFE-lined cap. The mixture was
either heated at 80 ꢀCfor48 horirradiated toheatthereaction mixture
at 250 ꢀC or 175 ꢀC (maximum power irradiation 300 W, maximum
reaction pressure 17 atm, see Table 1) for 20 min using a Discover
LabMate microwave reactor (CEM, Matthews, USA) equipped with
magnetic stirring and an air cooling system. After cooling, an organic
solvent was added, and the mixture was washed three times with
water. The organic layer was dried over anhydrous MgSO4, and the
solvent was evaporated under vacuum. The crude product was purified
by crystallization, distillation, or SiO2 column chromatography.
(CH2–CH3), 14.5 (CH3). GC–MS, m/z: 254.1 [M]þ, 183 [M-2Cl]þ, 143
[M-C3H5Cl2]þ, 127 [M-OC3H5Cl2]þ, 111 [C3H5Cl2]þ. IR (ATR), nmax
:
2957, 2927, 2856, 1742, 1154, 1102, 1050, 846, 769 cmꢁ1. HRMS (EIþ)
calculated for C11H20O2Cl2: 254.0840, found: 254.0836.
4.6.3. 1,3-Dichloro-2-propyl pivaloate (3c). [CAS: 220499-01-4]:
The analytical and spectroscopic data are in accordance with the
literature.15
4.6.4. 1,3-Dichloro-2-propyl benzoate (3d). [CAS: 36847-76-4]: 1H
NMR (CDCl3),
(m, 2H, CHar), 5.36 (quin, J¼5.3 Hz, 1H, O–CH), 3.82 (m, 4H, 2CH2–
Cl). 13C RMN (CDCl3),
: 163.4 (C]O), 131.7, 127.9, 127.2, 126.6 (Car),
70.1 (O–CH), 40.5 (CH2–Cl). GC–MS, m/z: 232 [M]þ, 122 [M-
d: 8.00 (m, 1H, CHar ( ) (C]O)), 7.53 (m, 1H, CHar), 7.39
a
4.3. General procedure for 2-chloro-1-(chloromethyl)ethyl
palmitate (3a) synthesis studies
d
C3H5Cl2]þ; 105 [M-OC3H5Cl2]þ; 77 [M-CO2C3H5Cl2]þ. IR (KBr), nmax
:
Palmitic acid (256 mg,1 mmol, 2a), glycerol (184 mg, 2 mmol,1),
and CTMS (540 mg, 5 mmol) were added to a reaction vial fitted
with a PTFE-lined cap. The mixture was heated or irradiated using
a Discover LabMate microwave reactor (CEM, Matthews, USA)
equipped with magnetic stirring and an air cooling system to reach
the corresponding temperature for 1/12, 1/3, 2, 5, 8, or 16 h (see
Table 3). After cooling, t-butyl methyl ether was added, and the
mixture was washed three times with water. The organic layer was
dried over anhydrous MgSO4, and the solvent was evaporated un-
der vacuum. The crude product was analyzed by GC/FID using tri-
decane as the internal standard.
3078, 2966, 1720, 1249, 1095, 705, 685 cmꢁ1. bp: 100 ꢀC/130 Torr
(glass oven B-585 Kugelrohr) (271.7ꢄ20.0 ꢀC/760 Torr).15b HRMS
(EIþ) calculated for C10H10Cl2O2: 232.0058, found: 232.0058.
4.6.5. 1,3-Dichloro-2-propyl cinnamate (3e). [CAS: 157140-94-8]:
The analytical and spectroscopic data are in accordance with the
literature.16
4.6.6. 1,3-Dichloro-2-propyl 2-chlorobenzoate (3f). 1H NMR (CDCl3),
d
: 7.83 (m, 1H, CHar–C]O), 7.40 (m, 2H, CHar), 7.28 (m, 1H, CHar–Cl),
5.38 (quin, J¼5.3 Hz, 1H, O–CH), 3.83 (d, J¼5.0 Hz, 4H, 2CH2–Cl). 13
C

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M. Escriba et al. / Tetrahedron 65 (2009) 10370–10376
10375
RMN (CDCl3),
d
: 164.5 (C]O), 134.4 (Car–Cl), 133.4, 131.9, 131.5,
J¼8.4 Hz, 1H, CHar), 7.84 (d, J¼8.8 Hz, 1H, CHar), 7.83 (d, J¼8 Hz, 1H,
CHar), 7.53 (m, 2H, 2CHar), 5.44 (quin, J¼4.8 Hz, 1H, O–CH), 3.88 (d,
129.1, 126.9 (Car), 72.9 (O–CH), 42.5 (CH2–Cl). GC–MS, m/z: 266
[M]þ, 156 [M-C3H5Cl2]þ; 139 [M-OC3H5Cl2]þ; 111 [M-CO2C3H5Cl2]þ.
IR (KBr), nmax: 3072, 3030, 2968, 1736, 1591, 1436, 1287, 1246, 1115,
1051, 747, 689 cmꢁ1. Elem. Anal. calcd for C10H9Cl3O2: C, 44.89; H,
3.39; Cl, 39.75; O, 11.96. Found: C, 45.04; H 3.40; Cl, 40.86; O, 10.70.
J¼4.8 Hz, 4H, 2CH2–Cl). 13C RMN (CDCl3),
d: 165.8 (C]O), 136.0,
132.7, 131.9, 129.7, 128.9, 128.6, 128.0, 127.1, 126.6, 125.4 (CHar), 72.4
(O–CH), 42.7 (CH2–Cl). GC–MS, m/z: 282 [M]þ, 212 [M-Cl2]þ; 172
[M-C3H5Cl2]þ; 155 [M-OC3H5Cl2]þ; 127 [M-CO2C3H5Cl2]þ. IR (ATR),
nmax: 3061, 2968, 1717, 1630, 1276, 1192, 1088, 775, 760, 703 cmꢁ1
.
4.6.7. 1,3-Dichloro-2-propyl salicylate (3g). [CAS: 64496-72-6]: 1H
mp: 62.5–65.9 ꢀC. Elem. Anal. calcd for C14H12Cl2O2: C, 59.39; H,
4.27; Cl, 25.04; O, 11.30. Found: C, 59.38; H, 4.29; Cl, 24.83; O, 11.50.
NMR (CDCl3),
d
: 7.89 (dd, J1¼8.2 Hz, J2¼1.6 Hz,1H, CHar), 7.49 (m,1H,
CHar), 7.01 (dd, J1¼8.6 Hz, J2¼0.8 Hz, 1H, CHar), 6.92 (m, 1H, CHar),
4.6.13. 1,3-Dichloro-2-propyl 2-furoate (3m). 1H NMR (CDCl3),
d:
5.46 (quin, J¼5.1 Hz, 1H, O–CH), 3.89 (d, J¼5.1 Hz, 4H, 2CH2–Cl). 13
C
7.57 (m, CHar), 7.21 (dt, J1¼3.5 Hz, J2¼0.8 Hz, 1H, CHar), 6.48 (m, 1H,
RMN (CDCl3), d: 169.1 (C]O),162.1 (Car-OH),136.7,130.3,119.7,117.9,
111.8 (Car), 72.7 (O–CH), 42.5 (CH2–Cl). GC–MS, m/z: 248 [M]þ, 137
[M-C3H5Cl2]þ; 120 [M-HOC3H5Cl2]þ; 93 [M-HCO2C3H5Cl2]þ. IR
(ATR), nmax: 3248, 3079, 2962, 1677, 1613, 1677, 1613, 1484, 1289,
1156, 1085, 755, 698 cmꢁ1. mp: 44.3–44.7 ꢀC. (49–50 ꢀC).17
CHar), 5.33 (quin, J¼5.1 Hz, 1H, O–CH), 3.80 (d, J¼5.1 Hz, 4H, CH2–
Cl). 13C RMN (CDCl3),
d: 156.9 (C]O), 146.5 (CHar), 143.7 (Car–C]O),
119.8, 112.1 (CHar), 72.3 (O–CH), 43.1 (CH2–Cl). GC–MS, m/z: 222
[M]þ, 187 [M-Cl]þ; 112 [M-C3H5Cl2]þ; 95 [M-OC3H5Cl2]þ. IR (ATR),
nmax: 3180, 3175, 2960, 1705, 1410, 1261, 1122, 1045, 750, 660 cmꢁ1
.
4.6.8. 1,3-Dichloro-2-propyl m-nitrobenzoate (3h). 1H NMR (CDCl3),
HRMS (EIþ) calcd for C8H8Cl2O3: 221.9850, found: 221.9840.
d
: 8.81 (t, J¼2.0 Hz, 1H, CHar), 8.37 (m, 2H, CHar), 7.64 (t, J¼8.2 Hz,
1H, CHar), 5.43 (quin, J¼5.1 Hz, 1H, O–CH), 3.85 (d, J¼5.1 Hz, 4H,
2CH2–Cl). 13C RMN (CDCl3),
: 163.8 (C]O), 151.1 (Car-NO2), 134.7
4.6.14. 1,3-Dichloro-2-propyl 2-thiophencarboxylate (3n). 1H NMR
(CDCl3),
d
: 7.79 (dd, J1¼3.9 Hz, J2¼1.2 Hz, 1H, CHar), 7.61 (dd,
d
J1¼5.1 Hz, J2¼1.2 Hz, 1H, CHar), 7.05 (dd, J1¼5.1 Hz, J2¼3.9 Hz, 1H,
(Car–C]O), 130, 129.8, 122.7 (CHar), 73.3 (O–CH), 42.5 (CH2–Cl). GC–
MS, m/z: 278 [M]þ, 231 [M-NO2]þ; 150 [M-OC3H5Cl2]þ; 122 [M-
CO2C3H5Cl2]þ; 104 [M-NO2OC3H5Cl2]þ; 76 [M-NO2CO2C3H5Cl2]þ. IR
(ATR), nmax: 3111, 2966, 1726, 1525, 1343, 1262, 1100, 1014, 872, 716,
670 cmꢁ1. Elem. Anal. calcd for C10H9Cl2NO4: C, 43.19; H, 3.26; Cl,
25.50; N, 5.04; O, 23.01. Found: C, 43.48; H, 3.28; Cl, 24.50; N, 5.08;
O, 23.66. mp: 56.5–56.7 ꢀC.
CHar), 5.31 (quin, J¼5.1 Hz, 1H, O–CH), 3.79 (d, J¼5.1 Hz, 4H, CH2–
Cl). 13C RMN (CDCl3),
d: 161.1 (C]O), 144.8 (CHar), 143.8 (Car–C]O),
122.5, 118.1 (CHar), 72.2 (O–CH), 42.8 (CH2–Cl). GC–MS, m/z: 238
[M]þ, 202 [M-Cl]þ; 128 [M-C3H5Cl2]þ; 111 [M-OC3H5Cl2]þ. IR (ATR),
nmax: 3170, 2988, 1710, 1430, 1251, 1152, 1145, 760, 640 cmꢁ1. HRMS
(EIþ) calcd for C8H8Cl2O2S: 237.9622, found: 237.9611.
4.6.9. 1,3-Dichloro-2-propyl 3,5-dinitrobenzoate (3i). 1H NMR
4.6.15. 1,3-Dichloro-2-propyl palmitate (3a) and 2,3-dichloro-1-
propyl palmitate (4a). 3a Regioisomer: GC tr: 32,5 min. 1H NMR
(COCD6),
d
: 9.21 (t, J¼2.3 Hz 1H, CHar), 9.13 (d, J¼2.4 Hz, 2H, CHar),
5.67 (quin, J¼5.1 Hz, 1H, O–CH), 4.12 (d, J¼4.9 Hz, 4H, CH2–Cl). 13
C
(CDCl3),
hidden by the signals of the 4 regioisomer. 4a Regioisomer: GC tr:
32,8 min. 1H NMR (CDCl3),
: 4.45 (m, 2H, O–CH2), 4.18(m. 1H, CH–
d
: 5.18 (quin, J¼5.2 Hz,1H, O–CH). All other NMR signals are
RMN (COCD6), d: 164.4 (C]O), 149.1 (Car-NO2), 134.3 (Car–C]O),
d
128, 122.8 (CHar), 76.3 (O–CH), 43.5 (CH2–Cl). GC–MS, m/z: 323
[M]þ, 275 [M-NO2]þ; 229 [M-2NO2]þ; 252 [M-2Cl]þ; 195 [M-
OC3H5Cl2]þ. IR (KBr), nmax: 3099, 2963, 2884,1735,1544, 1346, 1275,
1165, 720 cmꢁ1. Elem. Anal. calcd for C10H8Cl2N2O6: C, 37.17; H,
2.50; Cl, 21.95; N, 8.67; O, 29.71. Found: C, 37.23; H, 2.51; Cl, 21.82;
N, 8.61; O, 29.83. mp: 131.6–131.8 ꢀC.
Cl), 3.75 (m, 2H, CH2–Cl), 2.37 (t, J¼7 Hz, 2H, CH2 ( ) (C]O)),1.65 (m,
a
2H, CH2 ( (C]O)), 1.26 (m, 24H, CH2), 0.88 (t, J¼7 Hz, 3H, CH3).
b
)
4.6.16. 1,3-Dichloro-2-propyl caprylate (3b) and 2,3-dichloro-1-pro-
pyl caprylate (4b). 3b Regioisomer: GC tr: 24,0 min. 1H NMR (CDCl3),
d
: 5.12 (quin, J¼5.2 Hz, 1H, O–CH), 3.80 (dd, J1¼5.7 Hz, J2¼2.2 Hz,
4H, 2CH2–Cl). All other NMR signals are hidden by the signals of the
4 regioisomer. 4a Regioisomer: GC tr: 24,5 min. 1H NMR (CDCl3),
4.6.10. 1,3-Dichloro-2-propyl 2,4-dinitrobenzoate (3j). 1H NMR
d
:
(CDCl3),
d
: 8.87 (d, J¼2.0 Hz, 1H, CHar), 8.58 (dd, J¼8.2, J¼2.0 Hz, 1H,
4.40 (m, 2H, O–CH2), 4,25 (m, 1H, CH–Cl), 3.75 (m, 2H, CH2–Cl), 2.37
(t, J¼7 Hz, 2H, CH2 ( ) (C]O)), 1.65 (m, 2H, CH2 ( ) (C]O)), 1.26 (m,
CHar), 7.96 (d, J¼8.2 Hz, 1H, CHar), 5.50 (quin, J¼5.1 Hz, 1H, O–CH),
a
b
3.88 (d, J¼4.7 Hz, 4H, CH2–Cl). 13C RMN (CDCl3),
d: 163.2 (C]O),
24H, CH2), 0.88 (t, J¼7 Hz, 3H, CH3).
149.8, 147.9 (Car-NO2), 132.7 (Car–C]O), 131.6, 129.1, 120.2 (CHar),
74.3 (O–CH), 42.1 (CH2–Cl). GC–MS, m/z: 323 [M]þ, 275 [M-NO2]þ;
4.6.17. 1,3-Dichloro-2-propyl pivaloate (3c) and 2,3-dichloro-1-pro-
pyl pivaloate (3c). 3c Regioisomer: GC tr: 17,0 min. 1H NMR (CDCl3),
230 [M-2NO2]þ; 252 [M-2Cl]þ; 195 [M-OC3H5Cl2]þ. IR (KBr), nmax
:
.
3107, 3058, 2960, 2885, 1743, 1541, 1349, 1283, 1110, 834 cmꢁ1
d
: 5.14 (quin, J¼5.2 Hz, 1H, O–CH), 3.76 (m, 4H, 2CH2–Cl). All other
NMR signals are hidden by the signals of the 4 regioisomer. 4a
Regioisomer: GC tr: 17,9 min. 1H NMR (CDCl3),
: 4.38 (m, 2H, O–
Elem. Anal. calcd for C10H8Cl2N2O6: C, 37.17; H, 2.50; Cl, 21.95; N,
8.67; O, 29.71. Found: C, 37.67; H, 2.50; Cl, 21.90; N, 8.57; O, 29.36.
d
CH2), 4.230 (m, 1H, CH–Cl), 3.66 (m, 2H, CH2–Cl), 2.37 (t, J¼7 Hz, 2H,
4.6.11. 1,3-Dichloro-2-propyl 1-naphthoate (3k). 1H NMR (CDCl3),
d:
CH2 ( ) (C]O)), 1.65 (m, 2H, CH2 ( ) (C]O)), 1.26 (m, 24H, CH2), 0.88
a
b
8.93 (dd, J1¼8.8 Hz, J2¼0.8 Hz, 1H, CHar), 8.28 (dd, J1¼7.6 Hz,
J2¼1.6 Hz, 1H, CHar), 8.07 (d, J¼8.4 Hz, 1H, CHar), 7.91 (d, J¼7.6 Hz,
1H, CHar), 7.65 (m, 1H, CHar), 7.54 (m, 2H, 2CHar), 5.54 (quin,
J¼4.8 Hz, 1H, O–CH), 3.96 (d, J¼4.8 Hz, 4H, 2CH2–Cl). 13C RMN
(t, J¼7 Hz, 3H, CH3).
4.6.18. 1,3-Dichloro-2-propyl benzoate (3d) and 2,3-dichloro-1-pro-
pyl benzoate (4d). 3d Regioisomer: GC tr: 24,3 min. 1H NMR (CDCl3),
(CDCl3),
d
: 166.3 (C]O), 134.4, 134.1, 131.6, 131.2, 128.9, 128.4, 126.6,
d
: 5.36 (quin, J¼5.3 Hz, 1H, O–CH). All other NMR signals are hidden
by the signals of the 4 regioisomer. 4d Regioisomer: GC tr: 24,8 min.
1H NMR (CDCl3),
: 8.00 (m, 1H, CHar ( ) (C]O)), 7.53 (m, 1H, CHar),
125.9, 125.8, 124.8 (CHar), 72.4 (O–CH), 42.8 (CH2–Cl). GC–MS, m/z:
282 [M]þ, 212 [M-Cl2]þ; 172 [M-C3H5Cl2]þ; 155 [M-OC3H5Cl2]þ; 127
[M-CO2C3H5Cl2]þ. IR (ATR), nmax: 3051, 2964, 1716, 1509, 1236, 1191,
1126, 1036, 776, 752, 655 cmꢁ1. mp: 65.4–65.8 ꢀC. Elem. Anal. calcd
for C14H12Cl2O2: C, 59.39; H, 4.27; Cl, 25.04; O, 11.30. Found: C,
59.41; H, 4.28; Cl, 24.93; O, 11.38.
d
a
7.39 (m, 2H, CHar), 4.58 (m, 2H, O–CH2), 4.35 (m, 1H, CH–Cl), 3.82
(m, 2H, CH2–Cl).
4.6.19. 1,3-Dichloro-2-propyl cinnamate (3e) and 2,3-dichloro-1-
propyl cinnamate (4e). 3e Regioisomer: GC tr: 27,9 min. 1H NMR
4.6.12. 1,3-Dichloro-2-propyl 2-naphthoate (3l). 1H NMR (CDCl3),
8.58 (s, 1H, CHar), 8.01 (dd, J1¼8.8 Hz, J2¼1.6 Hz, 1H, CHar), 7.92 (d,
d:
(CDCl3),
d
: 5.26 (quin, J¼5.2 Hz, 1H, O–CH), 3.81 (dd, J1¼5.2 Hz,
J2¼0.8 Hz, 4H, 2CH2–Cl). All other NMR signals are hidden by the

`
M. Escriba et al. / Tetrahedron 65 (2009) 10370–10376
10376
signals of the 4 regioisomer. 4e Regioisomer: GC tr: 28,3 min. 1H NMR
(CDCl3), 7.71 (d, J¼16 Hz, 1H, CHar), 7.48 (t, J¼3.5 Hz, 2H, 2CHar), 7.34
(m, 3H, 2CHar), 6.45 (dd, J1¼15.8 Hz, J2¼0.9 Hz, 2H, Ph–CH]CH), 4.47
(m, 2H, O–CH2), 4.31(m, 1H, CH–Cl), 3.65 (d, J1¼5.1 Hz, 2H, CH2–Cl).
(CDCl3),
CH2–Cl). All other NMR signals are hidden by the signals of the 4
regioisomer. 4m Regioisomer: GC tr: 22,7 min. 1H NMR (CDCl3),
7.57 (m, CHar), 7.21 (dt, J1¼3.5 Hz, J2¼0.8 Hz, 1H, CHar), 6.48 (m, 1H,
CHar), 4.62 (m, 2H, O–CH2) 4.38 (m, 1H, CH–Cl), 3.80 (d, J¼5.3 Hz,
2H, CH2–Cl).
d
: 5.41 (quin, J¼5.1 Hz, 1H, O–CH), 3.90 (d, J¼5.1 Hz, 4H,
d
:
4.6.20. 1,3-Dichloro-2-propyl 2-chlorobenzoate (3f) and 2,3-di-
chloro-1-propyl 2-chlorobenzoate (4f). 3f Regioisomer: GC tr:
26,3 min. 1H NMR (CDCl3),
d
: 5.38 (quin, J¼5.3 Hz, 1H, O–CH). All
other NMR signals are hidden by the signals of the 4 regioisomer. 4f
Regioisomer: GC tr: 26,8 min. 1H NMR (CDCl3),
: 7.83 (m, 1H, CHar–
4.6.28. 1,3-Dichloro-2-propyl 2-thiophencarboxylate (3n) and 2,3-
dichloro-1-propyl 2-thiophencarboxylate (4n). 3n Regioisomer: GC
d
tr: 24,3 min. 1H NMR (CDCl3),
d
: 5.31 (quin, J¼5.1 Hz, 1H, O–CH). All
other NMR signals are hidden by the signals of the 4 regioisomer.
4n Regioisomer: GC tr: 24,7 min. 1H NMR (CDCl3),
: 7.79 (dd,
C]O), 7.40 (m, 2H, CHar), 7.28 (m, 1H, CHar–Cl), 4.60 (m, 2H, O–CH2,
4.35 (m, 1H, CH–Cl), 3.81 (m, 2H, CH2–Cl).
d
J1¼3.9 Hz, J2¼1.2 Hz, 1H, CHar), 7.61 (dd, J1¼5.1 Hz, J2¼1.2 Hz, 1H,
CHar), 7.05 (dd, J1¼5.1 Hz, J2¼3.9 Hz, 1H, CHar), 4.62 (m, 2H, O–CH2)
4.38 (m, 1H, CH–Cl), 3.79 (m, 2H, CH2–Cl).
4.6.21. 1,3-Dichloro-2-propyl salicylate (3g) and 2,3-dichloro-1-pro-
pyl salicylate (4g). 3g Regioisomer: GC tr: 25,1 min. 1H NMR (CDCl3),
d
: 5.46 (quin, J¼5.1 Hz, 1H, O–CH). All other NMR signals are hidden
by the signals of the 4 regioisomer. 4g Regioisomer: GC tr: 25,5 min.
1H NMR (CDCl3),
Acknowledgements
d
: 7.89 (dd, J1¼8.2 Hz, J2¼1.6 Hz, 1H, CHar), 7.49 (m,
1H, CHar), 7.01 (dd, J1¼8.6 Hz, J2¼0.8 Hz, 1H, CHar), 6.92 (m, 1H,
CHar), 4.55 (m, 2H, O–CH2, 1H, CH–Cl), 3.91 (m, 2H, CH2–Cl).
This work was supported in part by a Grant-in-Aid for the Sec-
´
´
´
´
retarıa de Estado de Polıtica Cientıfica y Tecnologica of the Spanish
Ministry of Education and Culture (Contract grant number:
CTQ2006-07451/PPQ). The authors are grateful to the Comissionat
4.6.22. 1,3-Dichloro-2-propyl m-nitrobenzoate (3h) and 2,3-di-
chloro-1-propyl m-nitrobenzoate (4h). 3h Regioisomer: GC tr:
28,5 min. 1H NMR (CDCl3),
d
: 5.48 (quin, J¼5.1 Hz, 1H, O–CH). All
other NMR signals are hidden by the signals of the 4 regioisomer.
4h Regioisomer: GC tr: 28,9 min. 1H NMR (CDCl3),
: 8.81 (t,
´
per a Universitats i Recerca del Departament d’Innovacio, Uni-
versitats i Empresa de la Generalitat de Catalunya and to the the
`
European Social Fund (ESF) for the FI grant of Marc Escriba
d
´
Gelonch.. The assistance of Joan Salles. Dpt. of Mass Spectrometry,
J¼2.0 Hz, 1H, CHar), 8.37 (m, 2H, CHar), 7.64 (t, J¼8.2 Hz, 1H, CHar),
and Miquel Perica`s. Director of the Institut Catala` d’Investigacio´
4.71 (m, 2H, O–CH2), 4.39 (m, 1H, CH–Cl), 3.95 (m, 2H, CH2–Cl).
´
Quımica (Tarragona, Spain), for obtaining HRMS spectra is grate-
fully acknowledged. The contribution of Albert Toma`s for his
technical assistance is greatly appreciated.
4.6.23. 1,3-Dichloro-2-propyl 3,5-dinitrobenzoate (3i) and 2,3-di-
chloro-1-propyl 3,5-dinitrobenzoate (4i). 3i Regioisomer: GC tr:
31,9 min. 1H NMR (COCD6),
d
: 9.21 (t, J¼2.3 Hz 1H, CHar), 9.13 (d,
J¼2.4 Hz, 2H, CHar), 5.67 (quin, J¼5.1 Hz, 1H, O–CH), 4.12 (d,
References and notes
J¼4.9 Hz, 4H, CH2–Cl). 4i Regioisomer: GC tr: 32,3 min. 1H NMR
(CDCl3), d: 4.65 (m, 2H, O–CH2) 4,43 (m, 1H, CH–Cl). All other NMR
1. (a) Schreck, D.J.; Kruper, W.J. Jr.; Varjian, R.D.; Jones, M.E.; Campbell, R.M.;
Kearns, K.; Hook, B.D.; Briggs, J.R.; Hippler, J.G. W.O. Patent 2006020234, 2006.
(Dow Global Technologies Inc., USA); (b) Kruper, W.J.; Arrowood, T.; Bell, B.M.;
Briggs, J.; Campbell, R.M.; Hook, B.D.; Nguyen, A.; Theriault, C.; Fitschen, R. U.S.
Patent 20080015369, 2008; (c) Hook, B.D.; Briggs, J.; Campbell, R.M.; Kruper, W.
J.; Schreck, D.J.; Varjian, R.D.; Hippler, J.G. U.S. Patent 20080015370, 2008.
signals are hidden by the signals of the 3 regioisomer.
4.6.24. 1,3-Dichloro-2-propyl 2,4-dinitrobenzoate (3j) and 2,3-di-
chloro-1-propyl 2,4-dinitrobenzoate (4j). 3j Regioisomer: GC tr:
31,5 min. 1H NMR(CDCl3),
d
: 8.87 (d, J¼2.0 Hz,1H, CHar), 8.58 (dd, J¼8.2,
´
ˆ
2. Jerome, F.; Pouilloux, Y.; Barrault, J. ChemSusChem 2008, 1, 586–615.
3. (a) Krysiak, M.; Myszkowski, J.; Zielinski, A. Z. Przem. Chem. 1968, 47, 622–625;
(b) Kasai, N.; Suzuki, T.; Furukawa, Y. J. Mol. Catal. B: Enzymatic 1998, 4, 237–
252; (c) Pagliaro, M.; Ciriminna, R.; Kimura, H.; Rossi, M.; Della Pina, C. Angew.
Chem. Int. Ed. 2007, 46, 4434–4440; (d) Zheng, Y.; Chen, X.; Shen, Y. Chem. Rev.
2008, 108, 5253–5277; (e) Zhou, C.-H. C.; Beltramini, J. N.; Fana, Y.-X.; Lu, G. Q.
M. Chem. Soc. Rev. 2008, 37, 527–549; (f) Eras, J.; Escriba, M.; Villorbina, G.;
J¼2.0 Hz,1H, CHar), 7.96 (d, J¼8.2 Hz,1H, CHar), 5.50 (quin, J¼5.1 Hz,1H,
O–CH), 3.88 (d, J¼4.7 Hz, 4H, CH2–Cl). 4j Regioisomer:GC tr:31,9 min.1H
NMR (CDCl3), d:4.67(m, 2H, O–CH2), 4.45 (m1H, CH–Cl). All other NMR
signals are hidden by the signals of the 3 regioisomer.
`
Balcells, M.; Canela, R. Tetrahedron 2009, 65, 4866–4870; (g) Escriba, M.; Bar-
4.6.25. 1,3-Dichloro-2-propyl 1-naphthoate (3k) and 2,3-dichloro-1-
propyl 1-naphthoate (4k). 3k Regioisomer: GC tr: 30,0 min. 1H NMR
but, M.; Eras, J.; Canela, R.; Avilla, J.; Balcells, M. J. Agric. Food Chem. 2009, 57,
4849–4853.
´
4. (a) Eras, J.; Mendez, J. J.; Balcells, M.; Canela, R. J. Org. Chem. 2002, 67, 8631–
9634; (b) Eras, J.; Balcells, M.; Canela, R. Afinidad. 2007, 64, 203–206; (c) Vil-
lorbina, G.; Tomas, A.; Escriba, M.; Oromı-Farrus, M.; Eras, J.; Balcells, M.;
Canela, R. Tetrahedron Lett. 2009, 50, 2828–2830.
5. Me´ndez, J. J.; Eras, J.; Balcells, M.; Canela, R. Synth. Commun. 2006, 36, 1167–
1175.
(CDCl3),
Cl). All other NMR signals are hidden by the signals of the 4 regioisomer.
4k Regioisomer: GC tr: 30,5 min.1H NMR (CDCl3),
d: 5.54 (quin, J¼4.8 Hz,1H, O–CH), 3.96 (d, J¼4.8 Hz, 4H, 2CH2–
`
`
´
´
d: 8.93 (dd, J1¼8.8 Hz,
J2¼0.8 Hz, 1H, CHar), 8.28 (dd, J1¼7.6 Hz, J2¼1.6 Hz, 1H, CHar), 8.07 (d,
J¼8.4 Hz, 1H, CHar), 7.91 (d, J¼7.6 Hz, 1H, CHar), 7.65 (m, 1H, CHar), 7.54
(m, 2H, 2CHar), 4.62 (m, 2H, O–CH2), 4.40 (m, 1H, CH–Cl), 3.81 (d,
J¼4.9 Hz, 2H, CH2–Cl).
6. (a) Kuhnert, N.; Danks, T. N. Green Chem. 2001, 3, 68–70; (b) de la Hoz, A.; Dı´az-
´
Ortiz, A.; Moreno, A. Chem. Rev. 2005, 34, 164–178.
7. Loupy, A. C.R. Chimie 2004, 7, 103–112.
8. Derbesy, M.; Naudet, M. Bull. Soc. Chim. Fr. 1968, 4531–4539.
9. Pews, R. G.; Davis, R. A. J. Chem. Soc., Chem. Commun. 1973, 269.
10. Nayler, J. H. C. J. Chem. Soc. 1959, 189–195.
4.6.26. 1,3-Dichloro-2-propyl 2-naphthoate (3l) and 2,3-dichloro-1-
propyl 2-naphthoate (4l). 3l Regioisomer: GC tr: 30,4 min. 1H NMR
11. (a) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785–789; (b) Miehlich, B.;
Savin, A.; Stoll, H.; Preuss, H. Chem. Phys. Lett. 1989, 157, 200–206; (c) Becke, A.
D. J. Chem. Phys. 1993, 98, 5648–5652; (d) Stephens, P. J.; Devlin, F. J.; Chaba-
lowski, C. F.; Frisch, M. J. J. Phys. Chem. 1994, 98, 11623–11627.
12. (a) Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys. 1980, 72, 650–
654; (b) McLean, A. D.; Chandler, G. S. J. Chem. Phys. 1980, 72, 5639–5648.
13. Gaussian 03, Version Revision C.02; Gaussian: Wallingford, CT, 2004.
14. Steblyanko, A.; Choi, W.; Sanda, F.; Endo, T. J. Polym. Sci., Part A: Polym. Chem.
2001, 39, 3967–3980.
(CDCl3),
2CH2–Cl). All other NMR signals are hidden by the signals of the 4
regioisomer. 4l Regioisomer: GC tr: 30,8 min. 1H NMR (CDCl3),
d
: 5.44 (quin, J¼4.8 Hz, 1H, O–CH), 3.88 (d, J¼4.8 Hz, 4H,
d:
8.58 (s, 1H, CHar), 8.01 (dd, J1¼8.8 Hz, J2¼1.6 Hz, 1H, CHar), 7.92 (d,
J¼8.4 Hz, 1H, CHar), 7.84 (d, J¼8.8 Hz, 1H, CHar), 7.83 (d, J¼8 Hz, 1H,
CHar), 7.53 (m, 2H, 2CHar), 4.65 (m, 2H, O–CH2), 4.38 (m, 1H, CH–Cl),
3.76 (d, J¼4.9 Hz, 2H, CH2–Cl).
15. (a) Mormann, W.; Demeter, J.; Wagner, T. Acta Polym. 1999, 50, 20–27; (b) ZIC/
VINITI data file. InfoChem Gesellschaft fu¨r chemische Information mbH.
Landsberger Straße 408/V D-81241. Mu¨nchen, Germany.
4.6.27. 1,3-Dichloro-2-propyl 2-furoate (3m) and 2,3-dichloro-1-
propyl 2-furoate (4m). 3m Regioisomer: GC tr: 22,3 min. 1H NMR
16. Qian, C.; Zhu, D. Synth. Commun. 1994, 24, 2203–2214.
17. Laboratoires OM S. A., Switz FR. Patent 2337552 19770805, 1977.