Synthesis of chloro alkoxy and alkoxy derivatives of methyl oleate

Article abstract of DOI:10.1007/s11746-013-2224-1

Vegetable oil based lubricants typically have improved lubricity and biodegradability over their mineral oil based counterparts. However, vegetable oil lubricants often fail to meet the performance standards of mineral based oils with respect to cold temperature and resistance to oxidation. Olefins are an oxidatively weak point for vegetable based compounds. Removal of the olefin in a vegetable based lubricant through functionalization may increase resistance to oxidation. If the added functionality also causes branching of the alkyl chain, cold temperature properties may be improved. Any chemical modifications considered must be scalable and cost-effective to be useful in a commercial application. In this study, methyl oleate was functionalized into a chloro alkoxy derivative. Sodium hypochlorite (household bleach) and calcium hypochlorite were both used to generate hypochlorous acid in situ. Hypochlorous acid and a series of alcohols (methanol, ethanol, and butanol) were reacted with methyl oleate to make chloro alkoxy compounds in 29.8-77.9 % yields. In an effort to make a branched saturated ether we removed the chlorine moiety of the chloro alkoxy compounds. Dehalogenation was achieved under basic conditions over a Pd/C catalyst in 2-propanol. Reaction times increased substantially as the size of the adjacent alkoxy group increased. The reaction rate could be improved by heating the reactions above 100 C in a pressure reactor. Increased reaction temperature also resulted in an increase in ketone side products from the competing elimination reactions. Saturated ether yields were 4.1-43.2 %.

Full text of DOI:10.1007/s11746-013-2224-1

J Am Oil Chem Soc (2013) 90:911–917
DOI 10.1007/s11746-013-2224-1
ORIGINAL PAPER
Synthesis of Chloro Alkoxy and Alkoxy Derivatives
of Methyl Oleate
•
Benjamin A. Lowery Brad Andersh
•
Terry A. Isbell
Received: 20 September 2012 / Accepted: 25 February 2013 / Published online: 16 March 2013
Ó AOCS (outside the USA) 2013
Abstract Vegetable oil based lubricants typically have
improved lubricity and biodegradability over their mineral
oil based counterparts. However, vegetable oil lubricants
often fail to meet the performance standards of mineral
based oils with respect to cold temperature and resistance
to oxidation. Olefins are an oxidatively weak point for
vegetable based compounds. Removal of the olefin in a
vegetable based lubricant through functionalization may
increase resistance to oxidation. If the added functionality
also causes branching of the alkyl chain, cold temperature
properties may be improved. Any chemical modifications
considered must be scalable and cost-effective to be useful
in a commercial application. In this study, methyl oleate
was functionalized into a chloro alkoxy derivative. Sodium
hypochlorite (household bleach) and calcium hypochlorite
were both used to generate hypochlorous acid in situ.
Hypochlorous acid and a series of alcohols (methanol,
ethanol, and butanol) were reacted with methyl oleate to
make chloro alkoxy compounds in 29.8–77.9 % yields. In
an effort to make a branched saturated ether we removed
the chlorine moiety of the chloro alkoxy compounds.
Dehalogenation was achieved under basic conditions over
a Pd/C catalyst in 2-propanol. Reaction times increased
substantially as the size of the adjacent alkoxy group
increased. The reaction rate could be improved by heating
the reactions above 100 °C in a pressure reactor. Increased
reaction temperature also resulted in an increase in ketone
side products from the competing elimination reactions.
Saturated ether yields were 4.1–43.2 %.
Keywords Methyl oleate Á Oleic acid Á Chloro alkoxy Á
Ether Á Hypochlorous acid Á Dehalogenation
Introduction
Renewable substitutes for petroleum based products are
desirable due to economic, political, and environmental
concerns. Vegetable oils and animal fats, as well as their
derivatives, find a wide array of uses in many consumable
products. Common industrial uses include anti-slip agents
for plastic films, plasticizers, non-ionic surfactants, corro-
sion inhibitors, cosmetics and lubricants [1]. Unmodified
vegetable oils used as lubricants often fail to meet low
temperature performance standards, such as pour point and
cloud point, compared to their mineral oil counterparts [2].
However, low temperature properties can be improved by
incorporating functionality to the structure that disrupts
molecular packing, such as branching or double bonds. As
such, functionalization on the olefin of unsaturated fats can
provide chemical handles to introduce various branched
moieties. One of the many possible routes is through the
use of hypochlorous acid obtained from common house-
hold bleach. A difunctional chloro alkoxy material can be
Names are necessary to report factually on available data; however,
the USDA neither guarantees nor warrants the standard of the
product, and the use of the name by USDA implies no approval of the
product to the exclusion of others that may also be suitable.
Electronic supplementary material The online version of this
article (doi:10.1007/s11746-013-2224-1) contains supplementary
material, which is available to authorized users.
B. A. Lowery Á T. A. Isbell (&)
Bio-Oils Research Unit, National Center for Agricultural
Utilization Research, Agricultural Research Service, USDA,
1815 N University Street, Peoria, IL 61604, USA
e-mail: terry.isbell@ars.usda.gov
B. Andersh
Department of Chemistry and Biochemistry, Bradley University,
1501 W Bradley Avenue, Peoria, IL 61625, USA
123

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J Am Oil Chem Soc (2013) 90:911–917
made through the reaction of the olefin with hypochlorous
acid and alcohol (Fig. 1) [3]. The final product is a mixture
of positional isomers (9-chloro-10-alkoxy and 9-alkoxy-
10-chloro-) with the chlorine adjacent to the alkoxy sub-
stituent. In general, this is an electrophilic halogen addition
in the presence of a nucleophilic solvent. A wide variety of
halogen sources can be used including elemental halogen,
alkyl hypohalites, N-halosuccinimides, and in-situ gener-
ated hypochlorous acid [4, 5]. Hypochlorous acid generated
in situ was used in this study due to its low cost, ease of
handling, and potential to scale up. Numerous alcohol
nucleophiles will participate in the formation of the chloro
alkoxy compounds as well [3, 6].
O
Cl
OR
O
RO
Cl
+
CH3O
CH3O
7
7
7
7
chloroalkoxy isomers
[H]
O
H
7
OR
O
RO
H
+
CH3O
CH3O
7
7
7
alkoxy isomers
Fig. 2 Dechlorination of chloro alkoxy compounds to give saturated
ethers
In the present work, we propose to synthesize chloro
alkoxy derivatives of oleic acid and use these intermediate
compounds to examine their hydrodehalogenation. Spe-
cifically we are interested in replacement of the chlorine
moiety with hydrogen to give a completely saturated ether
branched structure (Fig. 2). Hydrodehalogenation can be
accomplished in several ways including sodium borohy-
dride reduction, organotin hydride reduction, and by
catalysis with a noble metal in the presence of a base
[7–11]. Hydride reductions would require stoichiometric
amounts of reducing agent and be cost prohibitive for large
scale use. Very effective systems for hydrodehalogenation
[12] have been developed even for chlorohydrins but these
mixed metal reductions using aluminum–mercury also
require stoichiometric amounts of metal. Therefore we
envisioned a catalytic system using a heterogeneous noble
metal to be attractive due to the ease of removal and the
potential recyclability of the catalyst.
1-hexanol, 1-decanol, hydrochloric acid, sulfuric acid,
hexane, ethyl acetate, potassium hydroxide, sodium
hydroxide, 10 % Pd/C, sodium phosphate monobasic, and
metallic sodium were all purchased from the Aldrich
Chemical Company (Milwaukee, WI). Bleach was manu-
factured by the Clorox Professional Products Company
(Oakland, CA). Filter paper was manufactured by Whatman
(Maidstone, England).
GC
Both chloro alkoxy synthesis and dechlorination reactions
were monitored using GC. A Supelco (Bellefonte, PA)
SPB1 30 m 9 0.25 mm 9 0.25 lm film thickness column
was used with a helium flow rate of 1.0 ml/min; a head
pressure of 142 kPa; 12:1 split ratio; and a 3.0-ml/min
septum purge. The temperature program was 225–265 °C
at 5 °C/min ramp, followed by a 2 min hold at 265 °C.
Some compounds synthesized in this study had a suffi-
ciently high molecular weight to require a hold at 265 °C
for up to 20 min. Injector and detector temperatures were
set to 250 °C.
Experimental Procedures
Materials
Oleic acid (90 %), methanol, ethanol, 1-propanol, 2-propa-
GCMS
nol, 1-butanol, tert-butanol, 2-methyl-1-propanol, 2-ethyl-
Products were identified with both electron ionization (EI)
and chemical ionization (CI) MS. The GC was equipped
with a Supelco SPB1 30 m 9 0.25 mm 9 0.25 lm film
thickness column that had a helium flow rate of
0.5 ml/min; a head pressure of 103 kPa; a 1:1 split ratio;
and a 2.9-ml/min (CI 2.2 ml/min) septum purge. The
temperature program was 150–265 °C at 5 °C/min ramp,
followed by a 10–20 min hold at 265 °C. The MS electron
multiplier voltage was 1941 V (CI, 1671 V) and the mass
range was 50–550 amu. Injector, transfer line and MS
source temperatures were set to 250, 280, and 250 °C,
respectively. CIMS was configured for positive ionization
mode using methane gas.
O
CH3O
7
7
methyl oleate
HOCl
ROH
O
Cl
OR
O
RO
Cl
+
CH3O
CH3O
7
7
7
7
chloroalkoxy isomers
Fig. 1 Synthesis of chloro alkoxy derivatives of methyl oleate
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J Am Oil Chem Soc (2013) 90:911–917
NMR Spectroscopy
913
magnetic stirrer and thermometer. The flask was cooled in
an ice bath and continuously stirred. Sulfuric acid (18 M,
6 ml) and 125 ml of alcohol were combined in a 250-ml
Erlenmeyer flask, which was then cooled in the ice bath.
The acidic alcohol was added to the round bottom flask
containing methyl oleate all at once. Solid calcium salts
remained in the bottom of the flask for the duration of the
reaction. After GC analysis indicated all starting material
had been consumed, hexane (150 ml) was added and the
reaction was then placed in a 1-l separatory funnel and
washed with pH 5 buffer solution (150 ml). The separated
bottom aqueous layer and insoluble solids were drained off.
The organic layer was dried over sodium sulfate in a
500-ml Erlenmeyer flask, gravity filtered through a fluted
#2 Whatman filter paper, and concentrated in vacuo at
55–60 °C to give the oil. Often, GC analysis showed the
presence of trans-esterified compounds that had to be
converted to methyl esters. The material was combined
with methanol (150 ml) and sulfuric acid (0.1 M) and
placed in a 250-ml round-bottom flask equipped with a
cold-water condenser and magnetic stirrer. The reaction
was constantly stirred and warmed with a heating mantle to
reflux. After 1.5–4 h the reaction was cooled to room
temperature and transferred into a 1-l separatory funnel
with hexane (150 ml). The reaction was washed twice with
pH 5 buffer (250, 100 ml) followed by a wash with a
solution of saturated sodium chloride (100 ml). The sepa-
rated bottom aqueous layer was removed after each wash.
The organic layer was dried over sodium sulfate in a
500-ml Erlenmeyer flask, gravity filtered through a fluted
#2 Whatman filter paper, and concentrated in vacuo at
55–60 °C. The reaction was heated to 80–110 °C under
vacuum (100 mT) on a Kugelrohr distillation apparatus for
1–2 h to remove residual alcohol.
NMR spectra were collected on a Bruker (Karlsruhe,
Germany) Avance 500 spectrometer using a 5-mm BBI
1
probe with an absolute frequency of 500.11 MHz for H
and 125.76 MHz for 13C. Chemical shifts are reported as
parts per million from tetramethylsilane with CDCl3 as
solvent. COSY (correlation spectroscopy), HSQC (hetero-
nuclear single quantum correlation), and HMBC (hetero-
nuclear multiple bond correlation) two-dimensional spectra
were also collected.
HPLC
Analytical purification was performed with a reversed
phase HPLC using a Dynamax Microsorb 60-8 C18
(250 mm 9 4.6 mm) column from Varian (Walnut Creek,
CA). All runs were isocratic eluting with acetonitrile and
methylene chloride at either an 80/20 or an 85/15 ratio.
General Synthesis of Chloro Alkoxy Positional Isomers
Using Bleach Extraction
Methyl oleate (50 g, 169 mmol) was combined with
150 ml of alcohol in a 500-ml round-bottom flask equipped
with a magnetic stirrer and thermometer. Dry hypochlorous
acid was prepared by adding bleach (0.826 M sodium
hypochlorite, 560 ml), ethyl acetate (105 ml), and hexane
(45 ml) to a separatory funnel followed by the addition of
hydrochloric acid (12 M, 39 ml). Initially a bright green
layer formed near the top of the aqueous layer that diffused
into the organic layer. After shaking and separation the
green color was diminished and present in both layers. The
bottom aqueous layer was drawn off and the organic layer
was dried over sodium sulfate in a 250-ml Erlenmeyer flask
and decanted into the reaction flask containing methyl
oleate all at once. After GC analysis had indicated that
all the starting material had been consumed, hexane
(100 ml) was added. The reaction was placed in a 1-l
separatory funnel and washed with saturated sodium
chloride (100 ml). The separated bottom aqueous layer was
removed and the organic layer was dried over sodium
sulfate in a 500-ml Erlenmeyer flask, gravity filtered
through a fluted #2 Whatman filter paper, and concentrated
in vacuo at 45–50 °C to give the chloro alkoxy product as
an oil.
General Dechlorination to Produce Saturated Ethers
In a 500-ml 3-neck round-bottom flask fitted with a cold
water condenser, nitrogen inlet, and temperature probe,
methyl 9-chloro-10-alkoxy-octadecanoate and methyl
10-chloro-9-alkoxy-octadecanoate (50.0 g, 143.7 mmol)
were combined with 250 ml 2-propanol, potassium
hydroxide (30.0 g, 534.7 mmol) and 10 % Pd/C (1.0 g,
2 % by weight relative to substrate). The flask was placed
under positive nitrogen pressure, magnetically stirred, and
heated to 75 °C with a heating mantle. The reaction con-
tinued for 65.5–420 h until less than 5 % of the starting
material remained as measured by GC. The reaction was
then allowed to cool to room temperature. Methanol
(300 ml) and concentrated hydrochloric acid (25 ml) were
added to the flask until a pH of 1–2 was obtained. The
solution was then vacuum filtered with #42 Whatman paper
and a layer of silica gel to remove Pd/C and insoluble salts.
General Synthesis of Chloro alkoxy Positional Isomers
Using Calcium Hypochlorite
Methyl oleate (50 g, 169 mmol) was combined with solid
calcium hypochlorite (*4 g, 110 mmol) and 125 ml of
alcohol in a 500-ml round-bottom flask equipped with a
123

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J Am Oil Chem Soc (2013) 90:911–917
Hexane (300 ml) was added and the reaction was placed in
a 2-l separatory funnel and washed with pH 5 buffer
solution (300 ml). The separated bottom aqueous layer was
removed and the organic layer was dried over sodium
sulfate in a 500-ml Erlenmeyer flask, gravity filtered
through a fluted #2 Whatman filter paper, and concentrated
in vacuo at 45–50 °C to give an oil. When GC analysis
indicated free fatty acids and soaps present in the oil, the
material was taken up in acidic methanol (200 ml, 0.1 M
H2SO4) and refluxed for 2 h to esterify soaps that had
formed during the dechlorination. Hexane (200 ml) was
added and the reaction was placed in a 1-l separatory
funnel and washed with pH 5 buffer twice. The separated
bottom aqueous layer was removed and the organic layer
was dried over sodium sulfate in a 500-ml Erlenmeyer
flask, gravity filtered through a fluted #2 Whatman filter
paper, and concentrated in vacuo at 45–50 °C to give the
final product.
hydrochloric acid (2.75 equivalents each) would be needed,
since hypochlorous acid has limited stability and the
extraction is an equilibrium process. A complete con-
sumption of the starting material was achieved when the
extraction solvent mixture was changed from 50/50 hex-
ane/ethyl acetate to 30/70 hexane/ethyl acetate, which was
due to an increased amount of hypochlorous acid being
extracted.
To further minimize side products and increase chloro
alkoxy yields, we explored using calcium hypochlorite and
sulfuric acid to generate hypochlorous acid, while
excluding water. Only a slight excess (1.3 equivalents) of
calcium hypochlorite and sulfuric acid is needed for com-
plete conversion. This synthesis of the chloro methoxy
compound resulted in similar yields as compared to the
bleach extraction methodology described above, but with
less chlorohydrin side product. Concentrated acetic acid,
hydrochloric acid, and phosphoric acid were also examined
as proton sources with inferior results compared to the
sulfuric acid.
General Flash Column Chromatography Procedure
For short chain primary alcohols, bleach extracted
hypochlorous acid worked well. Longer chain and sec-
ondary alcohols that exhibit decreased nucleophilicity
failed to produce appreciable chloro ether yields. As the
nucleophilicity of the alcohol decreased from methanol to
propanol, reaction times increased. As a result, more
chlorohydrin was generated. Bleach extracted hypochlo-
rous acid failed to completely react when 1-butanol was the
nucleophilic alcohol. For this reason 1-butyl, 2-propyl,
3-methyl-1-propyl, tert-butyl, 2-ethyl-hexyl, and decyl
chloro alkoxy derivatives were synthesized using calcium
hypochlorite and sulfuric acid. Calcium hypochlorite/sul-
furic acid reactions required longer reaction times, which
required increased amounts of reactants and allowed acid
catalyzed transesterification of the methyl ester to occur.
After workup to remove excess alcohol, the methyl ester
was regenerated by refluxing the crude products in acidic
methanol. Product distribution for all chloro alkoxy
derivatives is summarized in Table 1. Under these condi-
tions the order of reactivity observed for alcohols was
1° [ 2° ꢀ 3°. tert-Butanol required 12 days to finish even
when heated to 50 °C and produced a significantly lower
yield of chloro alkoxy products.
Flash column chromatography was used to purify the crude
reaction product eluting with hexane/diethyl ether or hex-
ane/ethyl acetate. The column 2.2 cm 9 36 cm was wet
˚
packed with silica gel (60 A) and 0.5 g of the oil was
placed onto the column with 2–3 ml of the elution solvent.
˚
Each fraction (20 ml) was spotted on a silica gel (60 A)
thin layer chromatography plate (20 cm 9 20 cm) along
with the starting material and developed using the same
solvent as the column. The plates were sprayed with 5 %
phosphomolybdic acid solution (5 g phosphomolybdic in
100 ml ethanol) and then warmed with a heat gun to
develop the stain. Fractions containing product were
combined and concentrated in vacuo at 45–50 °C to pro-
vide the purified oil.
Results and Discussion
Initial work to synthesize a chloro alkoxy compound from
methyl oleate utilized a bleach and acetic acid extraction
procedure reported by Mund and Isbell [3]. Using the
Mund and Isbell conditions, methanol and methyl oleate
produced the two desired methyl 9-chloro-10-methoxy-
octadecanoate and methyl 10-chloro-9-methoxy-octade-
canoate positional isomers (chloro methoxy), as well
as chlorohydrin, dichloro, and chloro acetate products.
Substituting hydrochloric acid for acetic acid reduced side
product formation. Hydrochloric acid has limited solubility
in the organic extraction solvents and therefore does not
participate directly or catalyze further side reactions such
as decomposition of hypochlorous acid. Preliminary
experiments showed that a large excess of bleach and
Dechlorination can be a difficult chemical transforma-
tion and chlorine is the most difficult of the halogens within
the series of Cl, Br, and I to reduce from an organic mol-
ecule. However, the formation of the chlorinated com-
pounds offers some advantages since these compounds can
be made with less expense compared to the bromo and iodo
derivatives and offer a greater degree of stability for stor-
age. However, deactivating groups adjacent to the halogen-
bearing carbon such as in the case of the alkoxy substituent
in this study increases the difficulty for removal of
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J Am Oil Chem Soc (2013) 90:911–917
915
propanol was also reacted at 70 °C due to its structural
similarity to isopropanol. Reactions (entries 2 and 3) with
ethanol and isopropanol had the highest yields with modest
amounts of ketone side product. These two reactions
required somewhat lengthy reaction times to consume the
starting material, but ultimately both solvents were suc-
cessful because their boiling points are sufficiently high
enough for the reaction to occur. Additionally, ethanol and
isopropanol are small enough so that steric interactions on
the surface of the Pd catalyst are not hindered. Table 2
entries 10 and 11 showed that potassium hydroxide and
Pt/C in ethanol were less reactive in comparison to entry 2.
Metallic sodium was reacted with ethanol and isopropanol
to form the stronger alkoxide bases for dechlorinations.
Alkoxide bases (Table 2 entries 12 and 13) reacted slightly
faster than the equivalent reactions with sodium hydroxide,
but the small increase (5.9 %) in dechlorinated product did
not merit the use of metallic sodium over the much easier
to handle sodium hydroxide. Sodium acetate, sodium
bicarbonate, and sodium carbonate were reacted to deter-
mine if a weaker base than sodium hydroxide would cat-
alyze the dechlorination, but all three failed to react.
Base optimization of the dechlorination was studied in a
series of 20 reactions as shown in Table 3. Reaction time
was limited to 24 h, which is a common requirement for
industrial scale up. Ethanol required a larger excess of base
to cause dechlorination, and at two equivalents (entries 1
and 6) neither sodium hydroxide nor potassium hydroxide
produced products. Eight equivalents of sodium hydroxide
in ethanol (entry 4) were necessary to achieve a similar
amount of products as four equivalents of potassium
hydroxide in isopropanol (entry 17). Isopropanol with four
equivalents of potassium hydroxide (entry 17) produced the
highest amount of ether (57.3 %) and the highest ratio of
product to ketone (12:1) and as such was used for all
subsequent dechlorination reactions. Additional reactions
were then completed with increasing amounts of Pd/C.
Chloro methoxy was reacted with 4, 6, 8, 10, and 20 %
Pd/C (by weight) and four equivalents of potassium
hydroxide in isopropanol. Increased Pd/C resulted in sim-
ilar yields (55.4–63 %) and product ratios (10:1–14:1) to
the reaction that contained 2 % Pd/C (by weight).
Table 1 Chloro alkoxy products from methyl oleate
Alcohol
%
Chloro
alkoxya
%
%
Reaction
Chlorohydrina Dichloroa time (h)
Methanol
Ethanol
77.9
56.3
59.3
67.4
57.8
61.4
6.0
14.1
17.7
2.6
3.9
8.4
1
2
1-Propanol
1-Butanol
2-Propanol
4.4
3
10.1
15.3
11.3
24
168
168
6.3
3-Methyl-1-
propanol
6.7
tert-Butanol
29.8
19.9
9.2
29.8
13.5
8.8
288
46
2-Ethyl-hexanol 55.7
1-Decanol
58.0
4.4
42
a
Yield from GC
chlorine. Strong hydride-type reducing agents like the
metal hydrides would be typical choices for removal of
organo chlorine compounds but would require stoichiom-
etric quantities of an expensive hydride as well as the
possibility of the unwanted reduction of the carboxyl
functionality. We envisioned a catalytic process for the
reduction of the chloro alkoxy derivates that would leave
the carboxyl functionality intact. Reduction of the chloro
methoxy was first achieved in this study using Pd/C and
sodium hydroxide in 2-propanol [9]. Base-catalyzed elim-
ination of hydrogen chloride competes with the chlorine
reduction. This elimination gives rise to a variety of side
products originating from both the chloro alkoxy com-
pound, as well as, the chlorohydrin and dichloro com-
pounds. Side products include enol ethers, enols, and vinyl
halides. Both the enol ethers and enols are susceptible to
acidic hydrolysis to give ketones as a final product.
A series of dechlorination experiments was performed to
maximize yields, minimize reaction time, and optimize
reactants. Two reactions without Pd/C or sodium hydroxide
failed to produce a chlorine reduction. As depicted in
Table 2, several alcohols were then explored to compare
product distribution and reaction times (entries 1–8).
Methanol, tert-butanol, 2-heptanol, and isobutanol all
produced low yields of the desired alkoxy compounds.
Sodium hydroxide should be more soluble in methanol in
comparison to isopropanol, but the lower reflux tempera-
ture of methanol limited the amount of products. tert-
Butanol was used to compare a tertiary alcohol to the
secondary isopropanol. 1-butanol, 2-heptanol, and glycerin
were considered to see if higher reaction temperatures
would result in shorter reaction times. Glycerin had to be
heated to 110 °C before reaction occurred and the only
product observed was ketone. Table 2 entry 9 was heated
in 10 °C increments to determine the lowest temperature at
which the reaction would proceed (70 °C). 2-methyl-1-
Chloro ethoxy, chloro 1-propoxy, and chloro 1-butoxy
were then reacted under these optimized conditions of four
equivalents of potassium hydroxide and 2 % Pd/C (by
weight). Longer chain chloro ethers required a much longer
reaction time, over 400 h for the chloro 1-butoxy com-
pound. For the dechlorination to be synthetically useful on
an industrial scale, these extended reaction times needed to
be overcome. In order to reduce the time needed to
dechlorinate longer chain chloro alkoxy compounds, initial
dechlorination was performed at 75 °C on the benchtop for
1–2 days. An observed reaction rate at 75 °C was plotted
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J Am Oil Chem Soc (2013) 90:911–917
Table 2 Dechlorination reactions of chloro methoxya
Entry
Base
Solvent
Temp (°C)
Time (h)
% Alkoxyb
% Ketoneb
% Starting Materialb,c
1
NaOH
NaOH
NaOH
NaOH
NaOHd
NaOHd
NaOHd
NaOH
NaOHd
KOH
Methanol
Ethanol
65
22
159
72
1.2
75.5
63.3
7.0
6.3
10.5
14.5
4.7
71.4
5.4
2
78
3
Isopropanol
Isobutanol
1-Butanol
tert-Butanol
2-Heptanol
Glycerin
83
0.0
4
70
119
13
58.4
10.8
74.4
32.5
67.0
8.9
5
118
82
16.5
6.2
13.8
2.0
6
23
7
100
70–110
50–70
75
24
1.4
14.6
20.5
8.1
8
95
0.0
9
Isopropanol
Ethanol
164
146
128
97
50.9
32.0
10.4
59.0
69.2
10
11e
12
13
a
8.3
20.5
44.5
7.9
KOH
Ethanol
75
20.9
17.1
6.9
Na
Ethanol
75
Na
Isopropanol
75
68
0.0
All the reactions were catalyzed with Pd/C (2 % by weight) and excess base (3–5 equivalents) except where noted
b
c
d
e
Yield from GC
Starting material chloro methoxy
12–18 equivalents of base used
Pt/C catalyst
Table 3 Effect of base concentration on dechlorinations in ethanol and isopropanola
Entry
Solvent
Base
Equivs of base
% Alkoxyb
% Ketoneb
% Starting materialb,c
Alkoxy/ketone ratio
1
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
IPA
NaOH
NaOH
NaOH
NaOH
NaOH
KOH
2.0
4.0
6.0
8.1
10.0
2.2
4.4
5.9
7.9
9.7
2.4
4.1
5.8
8.1
9.6
2.4
4.0
6.0
7.8
10.0
0.0
7.2
2.9
7.8
83.2
67.6
20.6
19.9
25.8
83.8
52.1
59.5
9.5
0.0
0.9
3.5
2.3
1.1
0.0
0.8
0.4
1.2
1.8
4.5
1.7
1.4
0.5
0.9
9.6
12.2
2.5
0.9
0.6
2
3
40.6
47.6
23.9
0.0
11.7
20.9
22.2
2.3
4
5
6
7
KOH
10.1
6.2
12.8
16.1
27.2
21.2
3.0
8
KOH
9
KOH
33.9
39.2
13.5
10.9
6.3
10
11
12
13
14
15
16
17
18
19
20
a
KOH
7.4
NaOH
NaOH
NaOH
NaOH
NaOH
KOH
72.2
62.7
70.4
77.6
75.2
30.2
1.0
IPA
6.4
IPA
4.5
IPA
3.1
6.5
IPA
5.1
5.6
IPA
36.6
57.3
30
3.8
IPA
KOH
4.7
IPA
KOH
12.1
20.9
31.9
29.5
32.1
21.1
IPA
KOH
18.4
19.1
IPA
KOH
24 h at 75 °C, Pd/C (2 % by weight), 1 g of chloro methoxy and 10 ml alcohol
GC Yields
b
c
Methyl oleate
on a 1st order rate plot and then extrapolated to estimate a
temperature would double the reaction rate, a higher
reaction temperature was chosen that would complete the
reaction in approximately 24 h. The reactions were then
time for the reaction to consume the starting material.
Using the approximation that a 10 °C increase in reaction
123

J Am Oil Chem Soc (2013) 90:911–917
917
Table 4 Dechlorination of chloro alkoxy compoundsa
ID
Temp (°C)
Time (h)
% Alkoxyb
% Ketoneb
% Starting materialb
Methoxy
Ethoxy
75
65
43.2
37.0
42.3
25.7
38.7
19.3
19.3
4.1
9.9
7.4
2.6
7.8
2.2
0.8
4.3
6.9
5.9
27.6
7.3
75
160
328
24
Propoxy
Propoxy
Butoxy
Isopropoxyc
Isobutoxyd
2-EH ethere
Decoxyf
a
75
9.3
105
75
17.3
8.8
424
24, 24
24
115, 125
125
125
125
13.4
19.3
16.3
18.2
24
24
21.7
*50 g of chloro alkoxy in 250 ml IPA with Pd/C (2 % by weight) and KOH (4 equivalents)
Yield from GC
b
c
d
e
f
No reaction at 75 °C, 18 % starting material unreacted at 115 °C
8.8 % product after 24 h at 75 °C
2-ethyl-hexyl, no reaction at 75 °C
2.9 % product after 24 h at 75 °C
4. Larock RC (1999) Comprehensive organic transformations
(A guide to functional group preparation), 2nd edn. John Wiley,
New York, pp 641–643
5. Boguslavskaya LS (1972) Preparation of vicinal difunctional
compounds by the converted electrophilic halogenations of
multiple bonds. Russ Chem Rev 41:740
transferred to a pressurized bomb and carried out at this
elevated temperature. This strategy produced modest yields
of ethers while simultaneously increasing ketone prod-
ucts as shown in Table 4 for most of the chloro alkoxy
compounds.
6. Rodriguez J, Dulcere JP (1993) Cohalogenation in organic syn-
thesis. Synthesis 1177
7. Bell HM, Vasderslice CW, Spehar A (1969) Reduction of organic
halogen compounds by sodium borohydride. J Org Chem 34(12):
3923–3926
Acknowledgments We wish to thank Dr. Karl Vermillion for NMR
analysis and Dr. Steven Cermak for insightful conversations. Assis-
tance in the laboratory by Jonathan L A Phillips was very much
appreciated.
8. Kuivila HG, Menapace LW (1963) Reduction of alkyl halides by
organotin hydrides. J Org Chem 28(9):2165–2167
9. Imai H, Nishiguchi T, Tanaka M, Fukuzumi K (1977) Transfer
hydrogenation and transfer hydrogenolysis. 14. Cleavage of carbon–
halogen bond by the hydrogen transfer from organic compounds
catalyzed by noble metal salts. J Org Chem 42(13):2309–2313
10. Wiener H, Blum J, Sasson Y (1991) Transfer hydrogenolysis of
aryl halides and other hydrogen acceptors by formate salts in the
presence of Pd/C catalyst. J Org Chem 56(21):6145–6148
11. Alonso F, Beletskaya IP, Yus M (2002) Metal mediated reductive
dehalogenation of organic halides. Chem Rev 102:4009–4091
12. Wang Y-C, Yan T-H (2000) Al–Hg promoted chemoselective
dehalogenation of halohydrin aldol adducts. Chemm Commun
7:545–546
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