A facile synthesis of high specific activity sodium [1-14C] lauryl sulphate under microwave irradiation

Article abstract of DOI:10.1002/jlcr.966

A highly efficient and optimized synthesis of sodium[1-¹⁴C] lauryl sulphate having high specific activity (50 mCi/mmol) is described. Lauric acid was converted to undecyl bromide using a modified Hunsdiecker reaction. This was treated with potassium ¹⁴C cyanide (specific activity 50 mCi/mmol) using phase transfer catalysis to yield [1-¹⁴C] lauronitrile, which was subsequently hydrolysed with a mixture of concentrated hydrochloric acid:propionic acid (1:2 v/v) under microwave irradiation for 2 min to obtain [1-¹⁴C] lauric acid in quantitative yield. The latter on reaction with chlorosulphonic acid and subsequent neutralization with sodium bicarbonate yielded the title compound. Copyright

Full text of DOI:10.1002/jlcr.966

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS
J Label Compd Radiopharm 2005; 48: 1055–1058.
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jlcr.966
A facile synthesis of high specific activity sodium
[1-14C] lauryl sulphate under microwave irradiation
S. Ravi*, K. M. Mathew, V. K. P. Unny and N. Sivaprasad
Labelled Compounds, Radiopharmaceuticals, Immunoassay, Labelled Compounds and
Jonaki Board of Radiation and Isotope Technology, Navi Mumbai 400705, India
Summary
A highly efficient and optimized synthesis of sodium[1-14C] lauryl sulphate having
high specific activity (50 mCi/mmol) is described. Lauric acid was converted to
undecyl bromide using a modified Hunsdiecker reaction. This was treated with
potassium 14C cyanide (specific activity 50 mCi/mmol) using phase transfer catalysis
to yield [1-14C]lauronitrile, which was subsequently hydrolysed with a mixture of
concentrated hydrochloric acid:propionic acid (1:2 v/v) under microwave irradiation
for 2 min to obtain [1-14C] lauric acid in quantitative yield. The latter on reaction with
chlorosulphonic acid and subsequent neutralization with sodium bicarbonate yielded
the title compound. Copyright # 2005 John Wiley & Sons, Ltd.
Key Words: [1-14C]lauronitrile; hydrolysis; microwave; [1-14C]lauric acid; sodium
[1-14C]lauryl sulphate
Introduction
Sodium [1-14C] lauryl sulphate having high specific activity (50 mCi/mmol) is
required for use as a radiotracer in studies related to: (a) the correlation of the
inflammatory response associated with skin barrier function damage induced
by sodium lauryl sulphate; (b) its skin permeability; and (c) evaluation of the
kinetics of its skin reaction. Preparation of higher fatty acids using Grignard
carbonation, a synthetic route often employed, requires scrupulously dry
conditions and relatively large amounts of substrate for the preparation of the
Grignard reagent. Moreover, it can be time consuming. Due to the ease with
which a cyano group can be introduced to different moieties by methods such
as nucleophilic displacement, addition to carbonyl groups of aldehydes and
ketones, hydrocyanation of a, b unsaturated compounds and aromatic
substitution into various molecules, the nitrile function is an extremely useful
*Correspondence to: S. Ravi, Labelled Compounds, Radiopharmaceuticals, Immunoassay, Labelled
Compounds and Jonaki Board of Radiation and Isotope Technology, Navi Mumbai 400705, India. E-mail:
ravisesh@rediffmail.com
Copyright # 2005 John Wiley & Sons, Ltd.
Received 9 March 2005
Revised 12 May 2005
Accepted 17 May 2005

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S. RAVI ET AL.
precursor for carboxylic acids. Hence, a preferred route for the preparation of
long chain fatty acids is by the hydrolysis of the corresponding nitriles.
Various methods are reported in the literature for the hydrolysis of nitriles.1–10
These methods are generally carried out at high temperatures (100–1908C) and
can be time consuming. Hence, these methods, although applicable, are not
quite suitable for the preparation of radioisotopically labelled carboxylic
acids, as prolonged heating at high temperature can often lead to poor yields
due to the radiolytic decomposition. In recent times, microwave technology
has taken an undeniable place in chemical laboratory practice as a very
effective and non-polluting method of activating reactions.4 Examples of the
use of this technology in organic synthesis are numerous.11 The use of
microwaves provides fast heating of the chemicals above their boiling points
thus enhancing the reaction rates and dramatically reducing the reaction times
in comparison with conventional heating. Generally degradation reactions do
not occur using microwave heating thereby enhancing yields.12 Chemat has
reported the preparation of carboxylic acids from their corresponding nitriles
in 30 min by a dry hydrolysis reaction using microwave technology with
phthalic acid or anhydride in the absence of water and solvent.13
We report here a facile and convenient preparation of sodium [1-14C] lauryl
sulphate by hydrolysis of [1-14C] lauronitrile using a hydrochloric acid/
propionic acid system under microwave irradiation followed by reaction with
chlorosulphonic acid and neutralization with alkali, see Scheme 1.
Lauric acid on decarboxylative bromination with red mercuric oxide and
bromine gave undecyl bromide (confirmed by PMR showing a triplet at
d ¼ 3:38, ðJ ¼ 5 HzÞ due to the proton of the methylene group next to the
bromine). This was also further confirmed by the absence of bands at 3500–
3000 and 1710 cmꢀ1 corresponding to acid hydroxyl group and acid carbonyl
group in the IR spectrum. This was treated with potassium 14C cyanide
(specific activity 50 mCi/mmol) using phase transfer catalysis to yield
[1-14C]lauronitrile, which was hydrolysed using the hydrochloric acid/
*
ii
i
CH3(CH2)10COOH
iii
CH3(CH2)10Br
iv
CH3(CH2)10CN
*
*
CH3(CH2)10COOH
CH3(CH2)10CH2OH
*
v
vi
CH3(CH2)10CH2OSO3H
CH3(CH2)10CH2OSO3Na
(
* denotes C-14 label)
i) HgO/Br ii)K*CN iii) Hydrolysis iv) Reduction, LAH
2
v) ClOSO H vi) NaHCO
3
3
Scheme 1.
Copyright # 2005 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2005; 48: 1055–1058

SYNTHESIS OF SODIUM [1ꢀ14C] LAURYL SULPHATE
1057
propionic acid system under microwave irradiation for 2 min. The formation
of the [1-14C] lauric acid was confirmed by TLC followed by autoradiography
and IR spectroscopy, by comparison with the data reported in the literature
and with an authentic sample. The absence of a band at 2250–2200 cmꢀ1 and
presence of bands at 3500–3000 cmꢀ1 corresponding to the carboxylic acid and
1710 cmꢀ1 due to the acid carbonyl group confirmed the formation of the acid.
The product was subsequently reacted with chlorosulphonic acid at room
temperature followed by neutralization to furnish sodium [1-14C] lauryl
sulphate.
Experimental
Undecyl bromide: Bromine (4 g, 1.3 ml, 25 mmol) was added dropwise to a
stirred mixture of lauric acid (5 g, 25 mmol) and red mercuric oxide (3.44 g,
5.8 mmol) in carbon tetrachloride (150 ml) over a period of 30 min at room
temperature. Thereafter the reaction mixture was slowly heated to reflux and
heating is continued for a further period of 2 h. It was cooled to room
temperature, filtered and the filter cake washed with carbon tetrachloride. The
combined organic layer was washed with water, brine and dried. Removal of
solvent and subsequent distillation at 1388C and 18 mm of Hg afforded
undecyl bromide (4.7 g, 80%). IR 2960, 1470, 1260 PMR d 0.9 (br, 3H), 1.2(m,
18H), 3.38(t, 24, J ¼ 5 Hz).
[1-14C] lauronitrile: Toluene (2.5 ml) was added to undecyl bromide (0.1 ml,
0.44 mmol), potassium 14C-cyanide (6.0 mCi, specific activity 50 mCi/mmol,
0.12 mmol), tetrabutylammonium bromide (70 mg) and water (0.13 ml). The
reaction mixture was heated at reflux for 6 h and extracted with ether
(3 ꢁ 15 ml). After removal of the solvent, the residue was purified by column
chromatography (silica, 0–15% ethyl acetate in hexane) to yield pure
[1-14C]lauronitrile (5.8 mCi, 96%). TLC (silica, 15% ethyl acetate in hexane
v/v). Rf for undecylbromide 0.9 and Rf for [1-14C] lauronitrile 0.5.
[1-14C]lauric acid: [1-14C]lauronitrile (0.114 mmol, 5.7 mCi) and a mixture
of concentrated hydrochloric acid:propionic acid (1:2 v/v, 300 ml) in a sealed
glass ampoule, was heated using a domestic microwave oven, for 2 min. The
ampoule was cut open and the reaction mixture was extracted with ether. The
product obtained was purified by column chromatography (silica, 15% ethyl
acetate in hexane) giving [1-14C] lauric acid in quantitative yield. The
formation of [1-14C] lauric acid was confirmed by TLC (silica gel, 15% ethyl
acetate in hexane v/v) followed by autoradiography and IR spectroscopy. Rf
for [1-14C] lauric acid was 0.2 and Rf for [1-14C]lauronitrile was 0.5. IR 3500–
3000, 1710 cmꢀ1
.
[1-14C] lauryl alcohol: [1-14C] lauric acid (0.11 mmol, 5.5 mCi, 50 mCi/
mmol) in dry ether (10 ml) was added to a solution of LiAlH4 (36 mg) in 25 ml
dry ether and heated at reflux for 1 h. The reaction mixture was quenched with
Copyright # 2005 John Wiley & Sons, Ltd.
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S. RAVI ET AL.
ethyl acetate. The solution was filtered and the organic layer was washed with
water, brine, and dried. Removal of the solvent and subsequent purification of
the residue by column chromatography (silica, 0–25% ethyl acetate in hexane)
gave pure [1-14C] lauryl alcohol (5.3 mCi, 96%). TLC (silica, hexane:ethyl
acetate 10:2 (v/v) Rf 0.9).
Sodium [1-14C] lauryl sulphate: [1-14C] Lauryl alcohol (0.1 mmol, 5.1 mCi)
in chloroform (10 ml) was treated with chlorosulphonic acid (8 ml, 0.11 mmol)
and the mixture was stirred at room temperature for 30 min. The reaction
mixture was neutralized with sodium bicarbonate and dried under reduced
pressure. The residue was taken up in ethyl acetate and was loaded on to a
silica column. The column was washed with ethyl acetate and with methanol
to elute pure sodium [1-14C] lauryl sulphate (5 mCi, 98%). The purity was
checked by TLC (silica, hexane:ethyl acetate 10:2 (v/v), Rf 0.05).
Acknowledgements
The authors wish to express their thanks to Mr J.K. Ghosh, Chief Executive,
BRIT and Dr D. Padmanabhan, Manager LC/ILCJ, BRIT for their support
and encouragement. Thanks are also due to Mrs Neelambari M. Parkar for
the in house preparation and supply of potassium 14C cyanide.
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