The present invention provides a process for preparation of allyl alcohols.
BACKGROUND OF THE INVENTION
The allyl alcohol and its derivatives find significance in a variety of organic
10 synthesis particularly, in preparation of agrochemicals and pharmaceutical
intermediates.
Different processes are known in the art for preparation of allyl alcohols and
derivatives thereof.
CN103254036 provides a process for preparation of 3-methyl-2-buten-1-ol
15 (prenol), starting from paraformaldehyde and isobutylene in methanol. The process
requires high temperature and pressure conditions. The process involvessafety risks
and requires specialized equipment.
CN105111039A, CN105481634 and CN102924224 disclose process for
preparation of 1-chloro-3-methyl-2-butene by the reaction of isoprene (2-methyl20 1,3-butadiene) and hydrogen chloride. Isoprene, if used without dilution or with
improper dilution, tends to polymerize in the reactor before reacting with hydrogen
chloride, thereby causes choking in the reactor. Also, the use of concentrated
hydrogen chloride in the process corrodes the reactor during scale up.
CN107082740 discloses three step synthesis of 3-methyl-2-buten-1-ol from
25 isoprene. In this process, the reaction of isoprene with aqueous hydrogen chloride
in toluene gives 86% of desired 1-chloro-3-methyl-2-butene along with 10% of
undesired isomer. The esterification of 1-chloro-3-methyl-2-butene and subsequent
hydrolysis gives lower yield of 3-methyl-2-buten-1-ol.
The present invention provides a process to address all the drawbacks of reported
30 processes. The reaction of isoprene (2-methyl-1,3-butadiene) and anhydrous
hydrogen chloride is carried out by simultaneous and controlled dosing of isoprene
3
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5 and anhydrous hydrogen chloride in the reaction mixture to ensure proper dilution
of isoprene in the reaction mixture. This process is completely safe for commercial
use and prevents polymerization of isoprene in the reaction mixture, which results
in high selectivity of desired product. The present invention uses anhydrous
hydrogen chloride to prevent corrosion of the reactor.
10 Inventors have found that the undesired isomer formed in chlorination step can be
converted back into desired isomer in the esterification step by maintaining
anhydrous condition during the reaction of 1-chloro-3-methyl-2-butene (or its
mixture with undesired isomer) with metal acetate. The selectivity of esterification
and hydrolysis step is greater than 95%.
15 The present invention provides an economical and safe single step process for
preparation of prenol (3-methyl-2-buten-1-ol) from isoprene.
OBJECT OF THE INVENTION
The object of the present invention is to provide a simple, economical and safe
20 process for preparation of prenol.
The present invention uses single solvent to simplify the process and carry out the
reaction in-situ without isolation of intermediates to achieve high yield of desired
allyl alcohol.
25 SUMMARY OF THE INVENTION
The present invention provides a process for preparation of prenol, comprising the
steps of:
a) reacting isoprene with an anhydrous hydrogen chloride in presence of a
catalyst to obtain a reaction mixture 1 containing 1-chloro-3-methyl-2-
30 butene;
4
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5 b) esterifying the reaction mixture 1 using anhydrous metal acetate to obtain a
reaction mixture 2 containing 1-acetoxy-3-methyl-2-butene;
c) hydrolysing the reaction mixture 2 using an alkali metal hydroxide solution
to obtain a reaction mixture 3; and
d) recovering metal acetate and isolating prenol from reaction mixture 3;
10 wherein 1-chloro-3-methyl-2-butene and 1-acetoxy-3-methyl-2-butene are
not isolated during the process.
DETAILED DESCRIPTION OF THE INVENTION
As used herein, “undesired isomer” in chlorination step refers to 3-chloro-3-
15 methylbutene and “desired isomer” in chlorination step refers to 1-chloro-3-
methylbutene.
As used herein, “catalyst” is a quaternary alkyl ammonium chloride selected from
a group consisting of octylbenzyldimethylammonium chloride,
decylbenzyldimethylammonium chloride, tetradecylbenzyldimethyl ammonium
20 chloride, cocotrimethylammonium chloride, hexadecyltrimethylammonium
chloride, octadecyltrimethylammonium chloride and Adogen 464, a mixture of
methyltrialkyl (C8-C10) ammonium chloride.
Adogen 464 is highly active and gives good selectivity for preparation 1-chloro-3-
methyl-2-butene. In a preferred embodiment, the catalyst for chlorination is Adogen
25 464.
As used herein, “co-catalyst” is a metal chloride selected from a group consisting
of copper chloride, zinc chloride, nickel chloride, iron chloride or like.
In an embodiment, chlorination is carried out in presence of a catalyst and a cocatalyst.
30 As used herein, “parallel dosing” refers to a continuous and simultaneous addition
of two or more of reactants.
5
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5 In an embodiment of the present invention, isoprene and hydrogen chloride are
continuously and simultaneously added to the reactor.
In an embodiment, chlorination step is carried by parallel dosing of isoprene and
hydrogen chloride.
As used herein, “anhydrous” refers to moisture content of less than 0.5% and
10 preferably less than 0.3% and more preferably between 0.1-0.25%.
In an embodiment of present invention, steps of chlorination and esterification are
carried out under anhydrous condition.
In an embodiment of the present invention, the reaction of isoprene and hydrogen
chloride is carried out in presence a solvent selected from a group consisting of
15 toluene, ethylbenzene, cyclohexane, hexane, dimethyl benzene, isooctane,
petroleum ether, xylene and biphenyls or a mixture thereof.
The solvent used for present invention is preferably a single solvent.
In a preferred embodiment of the present invention, the reaction of isoprene and
hydrogen chloride is carried out in absence of a solvent.
20 In another embodiment, the step of chlorination is carried out in absence of a solvent
and a solvent is later added during the esterification step.
The molar ratio of the catalyst with respect to isoprene is in the range of 0.02-0.06:1.
The molar ratio of co-catalyst with respect to isoprene is in the range of 0.005-0.1:1
The molar ratio of hydrogen chloride with respect to isoprene is in the range of 1.0-
25 1.2:1
In an embodiment, reaction of isoprene with anhydrous hydrogen chloride is carried
out at -20°C to 10°C.
In an embodiment, reaction of isoprene with anhydrous hydrogen chloride is carried
out by parallel dosing of isoprene and anhydrous hydrogen chloride to a mixture of
30 solvent, catalyst and optionally co-catalyst in the reactor.
6
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5 In another embodiment, the reaction of isoprene with anhydrous hydrogen chloride
is carried out by parallel dosing of isoprene and anhydrous hydrogen chloride to a
mixture of isoprene, catalyst and optionally a co-catalyst in a reactor, in absence of
a solvent.
In a specific embodiment, the reaction of isoprene with anhydrous hydrogen
10 chloride is carried out by parallel dosing of isoprene and anhydrous hydrogen
chloride to a mixture of cyclohexane, cuprous chloride and Adogen 464 in reactor.
In another specific embodiment, reaction of isoprene with anhydrous hydrogen
chloride is carried out by parallel dosing of isoprene and anhydrous hydrogen
chloride to a mixture of isoprene (10% of total quantity), cuprous chloride and
15 Adogen 464 in reactor in absence of a solvent.
In a specific embodiment, chlorination of isoprene with anhydrous hydrogen
chloride is carried out by charging isoprene, cuprous chloride and Adogen 464 in a
reactor and followed normal dosing of anhydrous hydrogen chloride.
In an embodiment, reaction mixture 1 was filtered to remove mixture of catalyst
20 and recycled into chlorination step.
In another embodiment, the reaction mixture 1 containing 1-chloro-3-methyl-2-
butene is directly used in-situ for esterification.
The reaction mixture 1 containing 1-chloro-3-methyl-2-butene may further contain
3-chloro-3-methylbutene.
25 The 3-chloro-3-methylbutene is not separated from reaction mixture 1 and reaction
mixture 1 is directly used in esterification step.
In an embodiment, esterification process is carried out in presence of solvent.
In an embodiment, esterification is carried out under anhydrous conditions, keeping
the moisture level less than 0.5% and preferably, less than 0.3% and more
30 preferably between 0.1-0.25% and undesired isomer formed in chlorination step is
converted back to 1-acetoxy-3-methyl-2-butene in esterification using anhydrous
7
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5 sodium acetate, giving 95% of 1-acetoxy-3-methyl-2-butene. The use of anhydrous
condition in esterification step helps to convert undesired isomer of chlorination to
1-acetoxy-3-methyl-2-butene.
In one embodiment, esterification is carried out using a phase transfer catalyst
selected from a group consisting of tetrabutyl ammonium bromide, tetrabutyl
10 ammonium chloride, triethylmethyl ammonium chloride, triethylmethyl
ammonium bromide or like. The molar ratio of phase transfer catalyst may range
from 0.1-0.5%.
The step of esterification is carried out at a temperature of 50-150°C and preferably
at 70-130°C.
15 In an embodiment, metal acetate is added continuously or in lots to the reaction
mixture 1. The molar ratio of metal acetate is in the range from 1-2 and preferably
1-1.5.
The metal acetate is selected from a group consisting of sodium acetate, cesium
acetate, potassium acetate, lithium acetate or like.
20 The metal acetate used in the present invention is anhydrous and contains moisture
less than 0.5%, preferably less than 0.3% and more preferably between 0.1-0.25%.
In a preferred embodiment, esterification is carried out using sodium acetate or
potassium acetate.
In specific embodiment, esterification of reaction mixture 1 is carried out using
25 anhydrous sodium acetate in presence of tetrabutyl ammonium bromide at 110°C.
The esterification gives reaction mixture containing 1-acetoxy-3-methyl-2-butene
of purity greater than 94% and more preferably greater than 95%.
In an embodiment, the reaction mixture 2 containing 1-acetoxy-3-methyl-2-butene
is used in-situ for preparation of 3-methyl-2-buten-1-ol.
30 In an embodiment, hydrolysis is carried out using an aqueous solution of an alkali
hydroxide selected from a group consisting of sodium hydroxide, potassium
8
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5 hydroxide, cesium hydroxide, lithium hydroxide or an alkaline earth hydroxide
such as magnesium hydroxide or like. The preferred alkali metal hydroxide for
present invention is sodium hydroxide. The concentration of aqueous alkali metal
hydroxide solution may range from 10-45%.
In an embodiment, hydrolysis is carried out using an aqueous solution of an alkali
10 hydroxide. The molar ratio of the alkali hydroxide to crude 1-acetoxy-3-methyl-2-
butene is selected in range from 1-5:1 and preferably in range from 1-2:1.
The hydrolysis is carried out at a temperature of 50-100°C, preferably at 90°C.
In an embodiment, reaction mixture 3 is separated into aqueous and organic layer.
The aqueous layer is taken for metal acetate recovery and organic layer is distilled
15 to isolate 3-methyl-2-buten-1-ol.
In one embodiment, metal acetate used in esterification is recovered from aqueous
layer by neutralising with acetic acid to a pH of 8-9. The aqueous layer is
concentrated, dried to isolate metal acetate. The metal acetate is recycled to
esterification step-(b). The recovery % of metal acetate is greater than 99%. The
20 process eliminates generation of waste and provides economical process.
The 2-methyl-3-buten-2-ol is separated from organic and is recycled to chlorination
step.
In one embodiment, 3-methyl-2-buten-1-ol is isolated by layer separation and
distillation.
25 The present invention uses a single solvent in the process and preparing
intermediate product in-situ to achieve high yield.
In an embodiment, the present invention provides a process for preparation of
prenol, in yield of 85 to 99%.
In an embodiment, the present invention provides a process for preparation of
30 prenol of purity 99-99.9%.
9
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5 In an aspect, the present invention provides a process for preparation of prenol,
comprising the steps of:
a) chlorinating isoprene with anhydrous hydrogen chloride in presence of
Adogen 464 and cyclohexane to obtain a reaction mixture 1 containing 1-
chloro-3-methyl-2-butene;
10 b) esterification of reaction mixture 1 using anhydrous sodium acetate to
obtain a reaction mixture 2 containing 1-acetoxy-3-methyl-2-butene;
c) hydrolysing the reaction mixture 2 using a sodium hydroxide solution to
obtain a reaction mixture 3; and
d) isolating prenol from reaction mixture 3; wherein 1-chloro-3-methyl-2-
15 butene and 1-acetoxy-3-methyl-2-butene are not isolated in the process.
The reaction mixture 1 contains about 85% to about 95% of 1-chloro-3-methyl-2-
butene, about 3% to 12% of 3-chloro-3-methylbutene and greater than 0 to 2% of
isoprene.
The anhydrous sodium acetate has a moisture content of less than 5000ppm.
20 The reaction mixture 2 contains 95% to 99% of 1-acetoxy-3-methyl-2-butene and
0 to 3% of 3-acetoxy-3-methyl-3-butene;
The process of the present invention comprises the step of parallel dosing of alkene
and hydrogen chloride for the preparation of other allyl alcohols.
The compound of the present invention can be isolated using various isolation
25 techniques known in the art, for example, chemical separation, extraction, acid-base
neutralization, distillation, evaporation, column chromatography and filtration or a
mixture thereof.
In an embodiment of the present invention, the isolation is conducted by means of
filtration followed by vacuum distillation.
30 The completion of the reaction may be monitored by any one of chromatographic
techniques such as thin layer chromatography (TLC), high pressure liquid
10
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5 chromatography (HPLC), ultra-pressure liquid chromatography (UPLC), gas
chromatography (GC), liquid chromatography (LC) and alike.
Unless stated to the contrary, any of the words “comprising”, “comprises” and
includes mean “including without limitation” and shall not be construed to limit any
general statement that it follows to the specific or similar items or matters
10 immediately following it.
Embodiments of the invention are not mutually exclusive but may be implemented
in various combinations. The described embodiments of the invention and the
disclosed examples are given for the purpose of illustration rather than limitation of
the invention as set forth in the appended claims.
15 The following example is given by way of illustration and therefore should not be
construed to limit the scope of the present invention.
EXAMPLES
Example 1: Preparation of 1-chloro-3-methyl-2-butene
Cyclohexane (100 g), cuprous chloride (1.5 g) and Adogen 464 (1.5 g) were charged
20 in a reactor in one lot and reactor mixture was cooled to 0-5 °C. Isoprene (100 g)
and anhydrous hydrogen chloride gas (56 g) were simultaneously and slowly added
at 0-5°C in 1-3 hours in the reactor mixture. The reaction progress was monitored
by gas chromatography and after achieving the desired conversion, the reaction
mixture was analysed on gas chromatography.
25 Purity (GC analysis): 1-chloro-3-methyl-2-butene: 85-95%; 3-chloro-3-
methylbutene: 3-12%; Isoprene: 0-2%
Example 2: Preparation of 1-acetoxy-3-methyl-2-butene
Crude 1-chloro-3-methyl-2-butene from example 1 (250g, containing isoprene, 3-
chloro-3-methylbutene and 1-chloro-3-methyl-2-butene along with solvent) was
30 charged in a pressure reactor. Tetrabutyl ammonium bromide (1.5 g) and anhydrous
sodium acetate (120 g, moisture: 0.22%) were added in the reactor. The mixture
11
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5 was heated slowly to 110°C and stirred for 3-4 hours. Then, the reaction mass was
cooled to room temperature and filtered. The filtrate was analysed on gas
chromatography. The product was isolated in a yield of 94%.
Purity (GC analysis): 1-acetoxy-3-methyl-2-butene: 96-99%; 2-acetoxy-2-methyl3-butene: 0-3%; Isoprene: 0-2%;
10 Comparative example: Preparation of 1-acetoxy-3-methyl-2-butene
Crude 1-chloro-3-methyl-2-butene from example 1 (250g, containing isoprene, 3-
chloro-3-methylbutene and 1-chloro-3-methyl-2-butene respectively) was charged
in a pressure reactor. Tetrabutyl ammonium bromide (1.5 g) and sodium acetate
(120 g, 2.5% moisture content) were added in the reactor. The mixture was heated
15 slowly to 110°C and stirred for 3-4 hours. The reaction mass was cooled to room
temperature and filtered. The filtrate was analysed on gas chromatography.
Purity (GC analysis): Isoprene: 5%; 2-acetoxy-2-methyl-3-butene: 18%; 2-methyl3-buten-2-ol: 4%; 1-acetoxy-3-methyl-2-butene: 68%; Yield: 68%
Example 3: Preparation of prenol (parallel dosing with solvent)
20 Cyclohexane (100 g), cuprous chloride (1.5 g) and Adogen 464 (1.5 g) were charged
in a reactor in one lot and reactor mixture was cooled to 0-5°C. Isoprene (100 g)
and anhydrous hydrogen chloride gas (56 g) were simultaneously and slowly added
at 0-5°C in 1-3 hours in the reactor mixture. The reaction progress was monitored
by gas chromatography and after achieving the desired conversion. The reaction
25 mixture was filtered. The filtrate was charged into a pressure reactor and added
tetrabutyl ammonium bromide (1.5 g) and anhydrous sodium acetate (125.7 g,
moisture: 0.23%). The mixture was heated slowly to 110°C and stirred for 3-4
hours. The reaction mixture was cooled to room temperature and filtered. The
filtrate was heated to 90°C and an aqueous sodium hydroxide (136.2 g, 45%)
30 solution was added in 1-2 hours. The reaction progress was analysed on gas
chromatography. Upon reaction completion, the reaction mass was cooled, and
layers were separated. The organic layer was distilled to give prenol. The aqueous
layer was taken for sodium acetate recovery. Yield: 90%; Purity (by GC): 98%
12
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WE CLAIM:

1. A process for preparation of prenol, comprising the steps of:
a) reacting isoprene with an anhydrous hydrogen chloride in presence of a
catalyst to obtain a reaction mixture 1 containing 1-chloro-3-methyl-2-
butene;
10 b) esterifying the reaction mixture 1 using anhydrous metal acetate to obtain a
reaction mixture 2 containing 1-acetoxy-3-methyl-2-butene;
c) hydrolysing the reaction mixture 2 using an alkali metal hydroxide solution
to obtain a reaction mixture 3; and
d) recovering metal acetate and isolating prenol from reaction mixture 3;
15 wherein 1-chloro-3-methyl-2-butene and 1-acetoxy-3-methyl-2-butene are
not isolated during the process.
2. The process as claimed in claim 1, wherein the catalyst is a quaternary alkyl
ammonium chloride selected from a group consisting of
octylbenzyldimethylammonium chloride, decylbenzyldimethylammonium
20 chloride, tetradecylbenzyldimethyl ammonium chloride, cocotrimethylammonium
chloride, hexadecyltrimethylammonium chloride, octadecyltrimethylammonium
chloride and Adogen 464, a mixture of methyltrialkyl (C8-C10) ammonium
chloride.
3. The process as claimed in claim 1, wherein the chlorination step is carried out by
25 parallel dosing isoprene and hydrogen chloride.
4. The process as claimed in claim 1, wherein the molar ratio of hydrogen chloride
with respect to isoprene is selected in the range of 1.0-1.2:1
5. The process as claimed in claim 1, wherein the step of chlorination is carried out
at a temperature of -20°C to 10°C.
30 6. The process as claimed in claim 1, wherein the step of esterification is carried
out at a temperature of 50-150°C.
13
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5 7. The process as claimed in claim 1, wherein the step of chlorination is additionally
carried out using a “co-catalyst” selected from a group consisting of copper
chloride, zinc chloride, nickel chloride and iron chloride.
8. The process as claimed in claim 1, wherein the anhydrous metal acetate is
selected from a group consisting of sodium acetate, cesium acetate, potassium
10 acetate and lithium acetate.
9. The process as claimed in claim 8, wherein the anhydrous metal acetate has
moisture content less than 0.5% (w/w).
10. The process as claimed in claim 1, wherein the alkali metal hydroxide is selected
from a group consisting of sodium hydroxide, potassium hydroxide, cesium
15 hydroxide and lithium hydroxide.