An improved procedure for the preparation of radiochemically pure (carbonyl-14C)diuron

Full text of DOI:10.1002/jlcr.1252

Journal of Labelled Compounds and Radiopharmaceuticals
J Label Compd Radiopharm 2007; 50: 541–542.
Published online in Wiley InterScience
JLCR
(www.interscience.wiley.com). DOI: 10.1002/jlcr.1252
Short Research Article
An improved procedure for the preparation of
radiochemically pure [carbonyl-14C]diurony
DEEPAK B. KALGUTKAR, SANJAY P. PATIL, NARATH JAYACHANDRAN* and V. K. P. UNNV
Labelled Compounds Laboratory, Board of Radiation & Isotope Technology, BARC Vashi Complex, Navi Mumbai 400 705, India
Received 30 June 2006; Revised 30 December 2006; Accepted 2 January 2007
Keywords: [carbonyl– 14C]diuron; Curtius reaction; [7-14C]-dichlorobenzoic acid
Introduction
efficacy of diuron in paints and effect on aquatic
environment.
Urea herbicides are widely used in modern agricultural
practice. Diuron is a herbicide that inhibits photosynth-
esis and is used for the general weed control on non-
crop areas. Till the year 2003, tributyltin (TBT) was
used as a booster biocide in hull paints on ships but
now it has been banned due to adverse effects on the
aquatic environment.1,2 Hence, alternative booster bio-
cides are studied and diuron is one of them. [14C]-
Diuron, the radiolabelled analogue, is therefore required
for carrying out studies on monitoring performance
An improved procedure for the preparation of radio-
chemically pure diuron labelled with carbon-14 in its
urea carbon position is described.3–5 [7-14C]-Dichlor-
obenzoic acid 1 was transformed to its isocyanate via
Curtius reaction which was finally reacted with
dimethylamine to give [carbonyl-14C] diuron 5 having
specific activity of 1.09 mCi/mmol (40.33 MBq/mmol).
The radiochemical yield was 77.3% based on [7-14C]-
dichlorobenzoic acid and the product had a radio-
chemical purity greater than 99% (Scheme 1).
Cl
Cl
Cl
O
Cl
HO
NaN3 / acetone
∗
SOCl2
∗
Cl
∗
Cl
Cl
-N
N+
N
reflux
O
O
1
2
3
80 - 1000C
toluene
CH3
N
Cl
Cl
H
N
dimethylamine
∗
O
CH3
∗
C
dichloromethane
N
O
Cl
Cl
5
4
Scheme 1
*Correspondence to: Narath Jayachandran, Labelled Compounds
Laboratory, Board of Radiation & Isotope Technology, BARC Vashi
Complex, Navi Mumbai 400 705, India.
E-mail: jayan 16@rediffmail.com
yProceedings of the Ninth International Symposium on the Synthesis
and Applications of Isotopically Labelled Compounds, Edinburgh,
16–20 July 2006.
Copyright # 2007 John Wiley & Sons, Ltd.

542 D. B. KALGUTKAR ET AL.
UV_VIS_1
WVL:250 nm
UV_VIS_1
WVL:250 nm
DIURON #80
5,000
sample
DIURON #81
mAU
sample
5,000
4,500
4,000
3,500
3,000
2,500
2,000
1,500
1,000
500
mAU
2 - 47.226
4,500
1 - 47.600
1 - 37.705
4,000
3,500
3,000
2,500
2,000
1,500
1,000
500
0
0
min
min
-500
-500
0.0
10.0
20.0
30.0
40.0
50.0
64.8
0.0
10.0
20.0
30.0
40.0
50.0 56.1
Figure 1 RP-HPLC of diuron obtained on carrying out the
final reaction at room temperature. Figure available in colour
online at www.interscience.wiley.com
Figure 2 RP-HPLC of diuron obtained on carrying out the
final reaction at ice-cold temperature. Figure available in
colour online at www.interscience.wiley.com
Results and discussion
trile:water (40:60) at a flow rate of 6 ml/min. Retention
time for the impurity was 37.7 min and retention time
for diuron was 47.2 min (Figure 1).
In all the previously reported methods for the prepara-
tion of 14C-diuron labelled in its urea carbon position,
[7-14C]-dichlorobenzoic acid was transformed to its
isocyanate via Curtius reaction and finally reacted with
dimethylamine to give [carbonyl-14C] diuron. Dimethy-
lamine was used either as a chloroform solution or 33%
ethanolic solution or it was generated in situ from
dimethylamine hydrochloride. In our procedure, we
used dimethylamine as a 33% absolute ethanolic
solution and we were able to prepare the labelled
analogue having radiochemical purity greater than
99% in a radiochemical yield of 77.3%, based on
[7-14C]-dichlorobenzoic acid.
When reaction of phenyl isocyanate with dimethyl
amine (33% in absolute ethanol) was carried out at ice-
cold temperature for 2 h, the product obtained on HPLC
analysis showed a single peak of diuron at the retention
time of 47.6 min (Figure 2). The above noted modified
conditions were used during the preparation of carbon-
14-labelled diuron. The crude pale brownish coloured
final product was purified by preparative RP-HPLC to
get chromatographically (HPLC and radio-TLC) pure
[
14C]diuron as a white solid.
The phenyl isocyanate reaction with dimethyl amine
(33% in absolute ethanol) was carried out at room
temperature for 2 h. Analytical RP-HPLC3–5 was per-
formed using methanol:water (80:20) and acetonitrile:-
water (65:35) as the mobile phases at a flow rate of
1 ml/min and the UV-detector was set at 250 nm. The
chromatogram showed one single peak of diuron in this
solvent system in contrast to the two peaks shown
during RP-HPLC analysis when performed using acet-
onitrile:water (40:60). Preparative RP-HPLC was car-
ried out to separate the impurity from diuron and it was
successfully achieved in the solvent system acetoni-
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Copyright # 2007 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2007; 50: 541–542
DOI: 10.1002.jlcr