J.

Atoms and Molecules/ 3(4); 2013 / 560–563 Patel VR & Desai HT

Research Article

Journal of Atoms and Molecules

An International Online Journal
ISSN – 2277 – 1247

A DEVELOPED PROCESS FOR THE SYNTHESIS OF TRYPTOPHOL, A KEY

STARTING MATERIAL FOR INDORAMIN
Vinodkumar R. Patel1* , Hemant T. Desai2
1
Research Scholar of CMJ University, Shilong, Meghalaya, India.
2
GM (Operations), Nirma Limited (Healthcare Division), Sachana, ahmedabad-380009.
Received on: 01-08-2013 Revised on: 13-08-2013 Accepted on: 20–08–2013
ABSTRACT:
A developed process for the synthesis of tryptophol, a key starting material for Indoramin. Starting
from commercially available indole. Firstly prepared (1H-indol-3yl)-oxo-acetyl chloride from
indole by using oxalyl chloride and then prepared ethyl ester by using ethanol. Ethyl ester reduced
by sodium borohydride and getting pure tryptophol without purification within 92% yield. the
method is easy, inexpensive , without purification getting pure solid. The process is very clean, high
yielding & high quality and operationally simple.
KEY WORDS: indole, (1H-indol-3yl)-oxo-acetyl chloride,(1H-indol-3-yl)oxo-acetic acid ethyl
ester, tryptophol, oxalyl chloride, indoramin.
.

* Corresponding author
Vinodkumar R. Patel,
Email: vinod_patel88@yahoo.com
Tel : + +91 - 9428047871
INTRODUCTION:
Tryptophol is a chemical compound that
induces sleep in humans1. It is formed in the
liver after disulfiram treatment. It is also
produced by the trypanosomal parasite in
sleeping sickness. tryptophol are derivatives
of indole class which contain a C-3
hydroxyethyl chain1,2. Tryptophol and its
derivatives are communally extracted from
various natural soures3. Some of the
tryptophol derivatives exhibit biological
activity4. Here tryptophol is one of the
important chemical moiety and it has a also
pharmaceutical importance. Tryptophol was
prepared from indole . Tryptophol mainly
used for the synthesis of Indoramin.

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J. Atoms and Molecules/ 3(4); 2013 / 560–563
Indoramin hydrochloride works by blocking
alpha receptors in certain areas of the body.
Alpha receptors are found on the muscle in
the prostate gland. This gland is found only in
men and lies at the top of the tube connecting
the bladder to the outside (urethra). The
prostate gland often enlarges with advancing
age (a condition called benign prostatic
hyperplasia), pressing on the urethra and
obstructing the flow of urine from the bladder.
This can cause various urinary symptoms
such as difficulty passing urine. By blocking
the alpha receptors in the prostate gland,
indoramin causes the muscle in the prostate
gland to relax. This allows urine to flow
freely past the prostate and relieves the
urinary symptoms of this condition.
Indoramin (trade names Baratol and Doralese)
is a piperidine antiadrenergic agent. It is an
alpha-1 selective adrenoceptor antagonist5
with direct myocardial depression action;
therefore, it results in no reflex tachycardia. It
is also used in benign prostatic hyperplasia
(BPH).6 It is commonly synthesized from
tryptophol.7 Indoramin is commonly
prescribed as 20mg tablets when used in
BPH.8
Tryptophol is the key starting material for the
preparation of indoraminl. Here we are
prepare tryptophol from indole with improve
the yield and quality. So we are getting better
yield and quality in preparation of tryptophol.
The tryptophol preparation has been reported
by several methods. One of the reaction of
indole 3-acetic acid to tryptophol by reduction
with using lithium aluminum hydride. The
second method is indole to tryptophol by
using firstly prepared acid chloride and then
prepared ethyl ester and then prepared
tryptophol by using reductive catalyst sodium
borohydride with purification method
fractional distillation at high temperature.
However, upon attempting to repeat the
reported procedure. While preparing the title
All rights reserved© 2011
Patel VR & Desai HT
compound by the reported method, we
observed the inconsistency in the process, low
purity and low yield, formation of various
impurities, tedious work-up.
MATERIALS AND METHODS:
Melting points were determined on Buchi 540
melting point apparatus and are uncorrected.
FT-IR spectra were recorded as KBr pellet on
Nicolet 380 FT –IR instrument (model thermo
electron corporation spectrum one), 1H and
13C CMR (proton decoupled) spectra were
recorded on Varian 400 MHz spectrometer
using DMSO-d6, and tetramethylsilane
(TMS) as internal standard. Mass spectra
were recorded on Agilent triple quadruple
mass spectrometer equipped with turbo ion
spray interface at 375°C.
Preparation of (1H-indol-3-yl)oxo-acetic
acid ethyl ester
To A solution of lindole (25g.) in methyl
tertiary butyl ether (300 ml.) was added at
30.degree. to oxalyl chloride (20ml.) diluted
with methyl tertiary butyl ether (100 ml.).
After stirring for 1 hour the precipitate of
lindolylglyoxylyl chloride was collected by
filtration and treated with ethanol (200 ml.) to
give the ethyl ester of indol-3-ylglyoxylic acid
(37.0 g.) as a yellow powder m.p.
180.degree.-183.degree. yield : 80%. 1H
NMR (DMSO): δ 1.34(t,3H), 4.35(q,2H),
7.27 (t,1H), 7.30(t,1H), 7.55(d,1H)
,8.15(d,1H), 8.43 (d,1H), 12.40 (broad s, 1H,
NH), IR(cm-1) 3208, 3049, 2967, 2934, 2907,
1724, 1603, 1458, 1363, 1335, 1240, 1230,
1093, 1022, 941, 818, 759. Mass : 217.22.
Preparation of 3-(2-Hydroxyethyl)indole
(Tryptophol)
(1H-indol-3-yl)oxo-acetic acid ethyl ester
(37g.) was added to a stirred suspension of
sodium borohydride (18.0g.) in isopropanol
(300 ml). the exothermic reaction raising the
temperature of the mixture from 20.degree. to
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J. Atoms and Molecules/ 3(4); 2013 / 560–563 Patel VR & Desai HT

55.degree.. After heating to reflux for 5 hours
the mixture was cooled, diluted with water :
Isopropanol (20 ml : 60 ml.). Adjusted pH of
reaction mass 4.5 to 5. By using 10% HCl
solution and then extracted the product by 300
ml dichloromethane at 25-30°C. Washed the
organic layer with 1% sodium carbonate
solution (200 ml) at same temperature. The
extract was concentrated under reduced
pressure to an oil, which crystallized from
10% ethyl acetate in n-hexane solution (90
ml.)with cooling at 5-10°C. to give the title
compound as a white to pale brown crystals
(24.6 gm),Yield : 90%. m.p. 57°C – 59°C.
Purity NLT 98% by HPLC. 1H
NMR(300MHz, DMSO): 2.87 (t,2H)3.69
(q,2H), 4.68(t,1H,OH), 7.00(t,1H), 7.09(t,1H),
7.15(s,1H), 7.36(d,1H), 7.54(d,1H),
10.81(s,1H,NH) . C13 NMR: 29.31, 62.17,
111.73, 111.97, 118.56, 118.79, 121.21,
123.21, 127.86, 136.58. IR(cm-1) 3402, 3369,
3238, 3058, 2976, 2934, 2864, 2840, 1427,
1354, 1339, 1247, 1228, 1081, 1065, 930,
811, 754. Mass : 161.20.
RESULTS AND DISCUSSIONS:
As a part of our research involving synthetic
process of tyrptophol improving method for a
key intermediate of indoramin.
In our study the reaction of indole with
oxalyl chloride and then made ethyl ester of
acid chloride and then reduction of ethyl ester
was tested with different catalysts such as a
Sodium borohydride, lithium aluminum
hydride , platinum with H2 at 65-75°C for 3
hrs (table-1).

Figure 1- chemical structures of tryptophol, Indole , Indoramin

H
N
N

N
H
N
H HN
OH
Tryptophol Indole O
Indoramin

Table 1- Reduction of (1H-indol-3-yl)oxo-acetic acid ethyl ester with in the presence of various
catalyst.

Sr. no. Catalyst Conversion by TLC.

1. Sodium borohydride 90-95°%

2. Lithium aluminum hydride 75-80 %

3. platinum with H2 60-62%

It was found that NaBH4 was superior to all preparing tryptophol formation of product
the other catalysts examined and gave a good observed (60-95% by TLC) . It was found that
reaction conversion. During all reaction while the reaction proceeded smoothly and gave an

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J. Atoms and Molecules/ 3(4); 2013 / 560–563 Patel VR & Desai HT

excellent reaction conversion (90-95 % by when the solution is warmed, and very little
TLC) using NaBH4 as a reducing catalyst. tryptophol is obtained.
In the preliminary study, the reduction stage In summary, a simple and general method for
of ethyl ester , if the sodium borohydride the synthesis of tryptophol at 70°C, which
contains excess, a lot of impurities to form offers several advantages including good
yield has been developed.
Scheme-1
O O
O O

Cl OC2H5 OH
Oxalyl Chloride Ethanol
NaBH4
N N N N
H H H H
1H-Indole (1H-Indol-3-yl)-oxo-acetic acid ethyl ester
(1H-Indol-3-yl)-oxo-acetyl chloride 2-(1H-Indol-3-yl)-ethanol
(Tryptophol)

ACKNOWLEDGEMENT G, Magnus V, Jericevic B, Kunst L &

Iskric S, Plant Physiol, 76, 1984,889,(c)
The authors thank Dr. Hemant Desai for
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providing the best guidance and
Phytochemistry,36,1994,1209.
encouragement.
4) Fernando I N, Francis P L & Smith I, J
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How to cite this article:

Patel VR, Desai HT “A developed process for the synthesis of tryptophol, a key starting
material for Indoramin” J. Atoms and Molecules, 3(4), 2013: 560 – 563.

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