Journal of Labelled Compounds and Radiopharmaceuticals
J Label Compd Radiopharm 2007; 50: 440–441.
Published online in Wiley InterScience
JLCR
Short Research Article
Aryl fluoroalkanesulfonate chemistry. A new approach to
labelled arene elaborationy
JOHN M. HERBERT*, ANDREW D. KOHLER, FRANCK LE STRAT and DAVID WHITEHEAD
Isotope Chemistry and Metabolite Synthesis Department, sanofi-aventis, Willowburn Ave., Alnwick, Northumberland NE66 2JH, UK
Received 21 July 2006; Revised 7 November 2006; Accepted 21 November 2006
Keywords: aromatic substitution; halogenation; selective catalysis; aryl triflates; aryl nonaflates
Introduction
halogenation with an N-halosuccinimide in sulfuric
acid (Scheme 1; Table 1), in an adaptation of a reported
procedure3. Attempts to carry out Friedel-Crafts acyla-
tion of 1 were unsuccessful.
Labelled phenyl perfluoroalkanesulfonates are readily
available from labelled phenol1, and in this report, are
used to construct multiply substituted labelled arenes.
Further substitution of 2 or 4 gave 1,2,4-trisubsti-
tuted arenes in good yields (Scheme 2). Halophenyl
triflates 3 were further elaborated via the Grignard
reagent formed under Knochel conditions4 (Scheme 2;
Table 2) and it was possible to displace either bromide
or triflate selectively from 4a using previously reported
Results and discussion
Nitration of
1 to give 2
was reproducible2, and
4-halogenated products 3a and 4a were prepared by
methods (Scheme 2; Table 3)5–7
.
HNO3, H2SO4
OSO2R
NXS, acid
OSO2R
O2N
OSO2R
X
RT
RT
2a (R =CF3)
2b (R=C4F9)
3a (X = I, R = CF3); 3b (X = I, R = C4F9)
4a (X Br, R = CF3); 4b (X = Br, R = C4F9)
1a (R =CF3)
1b (R=C4F9)
Scheme 1
Table 1 Electrophilic substitution reactions of 1a and 1b
R
Electro-
phile
Acid
Reaction
time (h)
Yield
(%)
CF3
CF3
CF3
C4F9
C4F9
C4F9
HNO3
NIS
NBS
HNO3
NIS
H2SO4
CF3COOH or H2SO4
H2SO4
H2SO4
CF3COOH or H2SO4
H2SO4
6
4–6
6
4
4–6
20
90, 92
89–99
81, 94
90
86–93
36
*Correspondence to: John M. Herbert, Isotope Chemistry and Metabo-
lite Synthesis Department, sanofi-aventis, Willowburn Ave., Alnwick,
Northumberland NE66 2JH, UK.
E-mail: john.herbert@sanofi-aventis.com
yProceedings of the Ninth International Symposium on the Synthesis
and Applications of Isotopically Labelled Compounds, Edinburgh,
16–20 July 2006.
NBS
Copyright # 2007 John Wiley & Sons, Ltd.