Syntheses in the nitrogen π-deficient heterocycles series using a barbier type reaction under sonication. Diazines. Part 29

Article abstract of DOI:10.1016/S0040-4020(00)00291-X

Barbier type reaction with lithium metal has been tested under sonication on pyridines, a cinnoline and on various diazines. This very convenient method allows a very fast and smooth functionalization of these heterocycles. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00291-X

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 3709±3715
Syntheses in the Nitrogen p-De®cient Heterocycles Series Using a
Barbier Type Reaction Under Sonication. Diazines. Part 29
*
à  Â
Anne Lepretre, Alain Turck, Nelly Ple and Guy Queguiner
 Â
IRCOF, Laboratoire de Chimie Organique Fine et Heterocyclique, UPRES-A 6014, B.P. 08, 76131 Mont St Aignan Cedex, France
Received 7 January 2000; accepted 17 April 2000
AbstractÐBarbier type reaction with lithium metal has been tested under sonication on pyridines, a cinnoline and on various diazines. This
very convenient method allows a very fast and smooth functionalization of these heterocycles. q 2000 Elsevier Science Ltd. All rights
reserved.
Introduction
p-de®cient heterocyclic series. So we decided to study
this method in these series using a simple ultrasonic
cleaning device.
The lithiation reaction is a well-known and powerful tool
to functionalize the nitrogen p-de®cient heterocyclic
compounds. The metalation reaction1 has been extensively
studied in the pyridine series and more recently in the
diazine series. Lithiated derivatives can also be prepared
by the halogen±metal exchange reaction on pyridines1a,2
and on diazines.3 This less developed way can be performed
with lithium alkyls or exceptionally with lithium alkyl-
amides.4 A problem often encountered with these reactions
is that they must be performed at very low temperature
(2758C) because these organolithium compounds are
excessively reactive. However, this problem can be solved
by the use of the Barbier reaction5 which allows the lithio
derivatives formed in situ to react immediately with the
electrophile. The slow attack of the metal by the halogen
derivatives can be a problem, but this can be solved by the
use of sonication. Indeed, sonication is known to afford an
enhancement in the preparation of lithium or magnesium
derivatives from metal powder. Luche6 has described easy
syntheses using this technique and has obtained very good
yields under mild conditions. However, to our knowledge,
this very useful method has not been described in the
In a ®rst step, we have tested different experimental con-
ditions with 5-bromopyrimidine 1, then we have extended
this reaction to the three diazines, two pyridines and a
benzodiazine.
Results and Discussion
Experimental conditions were determined with the commer-
cially available 5-bromopyrimidine 1, using benzaldehyde
as the electrophile (Scheme 1).
The reaction was tested with various solvents: THF, ether,
cyclohexane, toluene and gave only results with THF. The
relative proportion of the reactants and the reaction time
were tested and the best result (55%) was obtained with
2.2 equiv. of lithium powder for 1 equiv. of 5-bromo-
pyrimidine, a larger excess of lithium powder decreased
the yield. The reaction time was 0.5 h, increasing this time
did not enhance the yield.
Scheme 1. Tests on 5-bromopyrimidine.
Keywords: Barbier reaction; lithium; diazines; sonochemistry.
* Corresponding author. Tel.: 133-2-3552-29-00; fax: 133-2-3552-29-62; e-mail: guy.queguiner@insa-rouen.fr
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00291-X

Ã
A. Lepretre et al. / Tetrahedron 56 (2000) 3709±3715
3710
Table 1. Variation of the yield as a function of the temperature
Entry
T (8C)
Yield (%)
1
2
3
4
5
10
20
30
40
60
21
55a
43
40
38
Scheme 2. Tests on pyrazines.
Table 2. Yields with pyrazines
a Without sonication: 27%.
Entry
Compound
Electrophile
Product
Yield (%)
1
2
3
4
5
6
3
3
3
7
7
7
PhCHO
4
5
6
8
9
10
70
64
44
70
60
33
C5H11CHO
PhSSPh
PhCHO
C5H11CHO
PhSSPh
Figure 1. In¯uence of the temperature on the yield.
noticed that the presence of a methoxy or a methyl-
sulfanyl group does not interfere with the reaction;
although, it has been demonstrated that these groups
could be cleaved in the presence of lithium powder.8
The temperature was varied using the experimental condi-
tions determined above (2.2 equiv. Li, 0.5 h). The results are
listed in the following table and a curve has been pictured
(Table 1, Fig. 1).
In the pyridazine series and with a cinnoline (Scheme 4,
Table 4):
It can be noticed that the best yield occurred at room
temperature. Lowering or increasing the reaction tempera-
ture decreased the yield. This is a well-known result for the
reactions under sonication for which an optimum range of
temperature exists.6c At low temperature, the ultrasonic
irradiation is not totally ef®cient, whereas at higher tempera-
ture, the cavitation is less ef®cient. Indeed, in this case, the
presence of relatively large amounts of vaporized liquid in
the bubbles of cavitation makes the collapse less energetic.
The cinnoline 28 gave no reaction when hexanal was used
as the electrophile and the starting material was
recovered.
In the pyridine series:
Thanks to the easy availability of bromo and iodo
derivatives of pyridine, we could test the in¯uence of
the nature of the halogen, thus we used 2-bromopyridine
31, 2-iodopyridine 32 and the benzaldehyde as an elec-
trophile. The yields of alcohol 33 were 58 and 60%,
respectively. As the reactivity of these two compounds
was similar, we decided to use the commercially avail-
able 2-bromopyridine 31 and 3-bromopyridine 36
(Scheme 5, Table 5).
In order to check the usefulness of the sonication, a silent
reaction was performed: the reaction rate was reduced and
the yield was only 27% instead of 55%. When a very long
time (one night) was used, the yield of the silent reaction
was limited to 43%. These results proved the ef®ciency of
sonication for this reaction.
A comparison of all these results (Tables 1±5) indicates that
the yields often followed the sequence: benzaldehyde.
hexanal.diphenyl disul®de. These results could be
explained by the fact that benzaldehyde is not enolizable
contrary to hexanal and that diphenyl disul®de is a weaker
electrophile than the aldehydes.
Once suitable experimental conditions have been deter-
mined, we have extended this reaction to other nitrogen
p-de®cient heterocycles. Three electrophiles have been
used: benzaldehyde, hexanal and diphenyl disul®de.
In the pyrazine series (Scheme 2, Table 2):
It must also be emphasized that the purity and the particle
size of the lithium powder play a great role. The best results
were obtained with a 0.5% amount of sodium in the lithium
powder and a 50±200 m particle size. In some cases, Luche6
found that a small amount of water in THF did not hinder
the Barbier reaction under sonication but our tests with wet
THF gave no reaction products, so it was necessary to avoid
cautiously the presence of water with azines.
The good results observed with the chloro substituted
derivative 7 reveals a good compatibility of this method
with halogen substituents.
In the pyrimidine series:
The 5-bromopyrimidine and two iodopyrimidines were
tested too, as shown in the following scheme (Scheme
3, Table 3).
Conclusion
Benzaldehyde was not used as an electrophile with the
2-iodo-4-methoxypyrimidine 13 because the alcohol so
obtained was previously found to be unstable.7 It can be
To our knowledge, it is the ®rst time that the Barbier
reaction has been studied in these heterocyclic series. This

Ã
A. Lepretre et al. / Tetrahedron 56 (2000) 3709±3715
3711
Scheme 3. Tests on pyrimidines.
Table 3. Yields with pyrimidines
Entry
Compound
Electrophile
Product
Yield (%)
1
2
3
4
5
6
7
8
1
1
1
13
13
16
16
16
PhCHO
C5H11CHO
PhSSPh
C5H11CHO
PhSSPh
PhCHO
2
55
22
25
48
30
52
48
39
11
12
14
15
17
18
19
C5H11CHO
PhSSPh
Scheme 4. Tests on pyridazines and a cinnoline.
Table 4. Yields with pyridazines and a cinnoline
Entry
Compound
Electrophile
Product
Yield (%)
1
2
3
4
5
6
7
8
9
20
20
20
24
24
24
28
28
28
PhCHO
21
22
23
25
26
27
29
±
72
58
49
65
50
38
64
±
C5H11CHO
PhSSPh
PhCHO
C5H11CHO
PhSSPh
PhCHO
C5H11CHO
PhSSPh
30
35

Ã
A. Lepretre et al. / Tetrahedron 56 (2000) 3709±3715
3712
Tetrahydrofuran was distilled from benzophenone/sodium
solution and used immediately. Water content of the solvent
was estimated by the modi®ed Karl Fischer method (THF
less than 50 ppm water). Reactions were performed under
an argon atmosphere. Reagents were handled with syringes
through septa.
Lithium powder was purchased from Fluka Chemika:
lithium powder containing 0.5% of sodium (50±200 m).
The reactions were performed in an ultrasound cleaning
device (Transsonic 950/H, Prolabo).
Scheme 5. Tests on pyridines.
Table 5. Yields with bromopyridines
Some compounds are commercially available: 5-bromo-
pyrimidine 1, 2-bromopyridine 31 and 3-bromopyridine 36.
Entry
Compound
Electrophile
Product
Yield %
The following compounds were synthesized according to
the literature: 2-iodopyrazine9 3, 2-chloro-3-iodopyrazine10
7, 4-iodo-2-methylsulfanylpyrimidine11 16, 4-iodo-3,6-
dimethoxypyridazine12 20, 3-iodo-6-methoxypyridazine13
24, 2-iodo-4-methoxypyrimidine7 13, 4-iodo-2-methoxy-
cinnoline14 28, 2-iodopyridine15 32.
1
2
3
4
5
6
31
31
31
36
36
36
PhCHO
33
34
35
37
±
58
51
21
54
±
C5H11CHO
PhSSPh
PhCHO
C5H11CHO
PhSSPh
38
24
General procedure for Barbier reaction
allowed a convenient functionalization of these rings at
room temperature with a short reaction time. Furthermore,
it has been demonstrated that the use of sonication is an
essential factor.
The diazine derivative (1.0 mmol), the lithium powder
(2.2 mmol, 16 mg) and the electrophile (1.1 mmol), were
introduced in 3 mL of THF under an atmosphere of dry
argon. The reaction medium was placed in the ultrasound
cleaning bath during 30 min. Elimination of the remaining
lithium powder was then carried out using 3 mL of ethanol.
The reaction medium was then diluted with 3 mL of water
and evaporated. The aqueous layer was extracted with ethyl
acetate (4£10 mL). The organic layer was dried over
magnesium sulphate and evaporated. The crude product
was puri®ed by column chromatography on silica gel.
These results may be compared with the ones obtained by
the halogen lithium exchange reaction. In the diazine series,
very few exchange reactions have been performed3 because
the use of lithium alkyls can lead to addition reactions. The
main results in these series dealt with 5-bromopyrimidine or
its derivatives. The best yield obtained by Van Der Plas3g
was 80% at 21008C. In the pyridazine series, the sole paper
by Rosseels3a described an exchange reaction with 3,6-
dichloropyridazine affording a 23% yield at 2158C. In the
pyrazine series, the best yield (57%) was obtained by
Spoerri3l with 2-iodo-3,6-dimethylpyrazine at 2508C.
(Pyrimidin-5-yl)phenylmethanol (2). Barbier reaction
with 1 (1.0 mmol, 159 mg) according to the general pro-
cedure with benzaldehyde (1.1 mmol, 0.11 mL), gave after
puri®cation by column chromatography (eluent: dichloro-
methane) 102 mg (55%) of 2 as a yellow oil. Product
previously described in reference.3g
In the pyridine series, the halogen lithium exchange reaction
has been largely developed1a,2 and the yields are often very
good but as for diazines, these reactions must ever be carried
out at low temperature.
(Pyrazin-2-yl)phenylmethanol (4). Barbier reaction with 3
(1.0 mmol, 206 mg) according to the general procedure with
benzaldehyde (1.1 mmol, 0.11 mL), gave after puri®cation
by column chromatography (eluent: dichloromethane)
129 mg (70%) of 4 as a white solid. Product previously
described in reference.7
In conclusion, we have highlighted that the Barbier reaction
known for many decades could be ef®cient in present day
organometallic diazine and pyridine syntheses when allied
with an ultrasonic irradiation. We have also shown that this
reaction could afford good results even in the presence of
substituents on the ring such as methylsulfanyl, methoxy or
chloro group.
1-(Pyrazin-2-yl)hexan-1-ol (5). Barbier reaction with 3
(1.0 mmol, 206 mg) according to the general procedure
with hexanal (1.1 mmol, 0.13 mL), gave after puri®cation
by column chromatography (eluent: dichloromethane)
116 mg (64%) of 5 as colorless oil. Product previously
described in reference.7
Experimental
Melting points were determined on a Ko¯er hot stage. The
1H- and 13C NMR spectra were recorded in deuteriochloro-
form on a Bruker AC 200 instrument. Microanalyses were
performed on a Carlo Erba CHNOS 1160 apparatus. The IR
spectra were obtained as a potassium bromide pellets with a
Perkin Elmer FTIR 1650 spectrophotometer. Mass spectra
were recorded at 70 eV (EI) on a JEOL JMS-AX 500
spectrometer.
2-(Phenylsulfanyl)pyrazine (6). Barbier reaction with 3
(1.0 mmol, 206 mg) according to the general procedure
with diphenyl disul®de (1.1 mmol, 242 mg), gave after
puri®cation by column chromatography (eluent: dichloro-
methane) 83 mg (44%) of 6 as a colorless oil. Product
previously described in reference.16

Ã
A. Lepretre et al. / Tetrahedron 56 (2000) 3709±3715
3713
(3-Chloropyrazin-2-yl)phenylmethanol (8). Barbier reac-
tion with 7 (1.0 mmol, 240.5 mg) according to the general
procedure with benzaldehyde (1.1 mmol, 0.11 mL), gave
after puri®cation by column chromatography (eluent:
dichloromethane) 154 mg (70%) of 8 as a white solid.
Product previously described in reference.7
1322, 1237, 1178, 1022, 903, 822, 748, 690 cm21. Anal.
Calcd for C11H10N2OS (218.28): C, 60.53; H, 4.62; N,
12.83. Found: C, 60.40; H, 4.48; N, 12.79.
[2-(Methylsulfanylpyrimidin-4-yl)]phenylmethanol (17).
Barbier reaction with 16 (1.0 mmol, 252 mg) according to
the general procedure with benzaldehyde (1.1 mmol,
0.11 mL), gave after puri®cation by column chromato-
graphy (eluent: dichloromethane) 121 mg (52%) of 17 as
a yellow solid. Product previously described in reference.7
1-(3-Chloropyrazin-2-yl)hexan-1-ol (9). Barbier reaction
with 7 (1.0 mmol, 240.5 mg) according to the general pro-
cedure with hexanal (1.1 mmol, 0.13 mL), gave after
puri®cation by column chromatography (eluent: dichloro-
methane) 126 mg (60%) of 9 as a colorless oil. Product
previously described in reference.7
1-[2-(Methylsulfanyl)pyrimidin-4-yl)]hexan-1-ol (18).
Barbier reaction with 16 (1.0 mmol, 252 mg) according to
the general procedure with hexanal (1.1 mmol, 0.13 mL),
gave after puri®cation by column chromatography (eluent:
dichloromethane) 108 mg (48%) of 18 as colorless oil.
Product previously described in reference.7
2-(Phenylsulfanyl)-3-chloropyrazine (10). Barbier reac-
tion with 7 (1.0 mmol, 240.5 mg) according to the general
procedure with diphenyl disul®de (1.1 mmol, 242 mg), gave
after puri®cation by column chromatography (eluent:
dichloromethane) 74 mg (33%) of 10 as a beige solid.
Product previously described in reference17 (patent); mp
2-(Methylsulfanyl)-4-(phenylsulfanyl)pyrimidine (19).
Barbier reaction with 16 (1.0 mmol, 252 mg) according to
the general procedure with diphenyl disul®de (1.1 mmol,
242 mg), gave after puri®cation by column chromatography
(eluent: dichloromethane) 79 mg (39%) of 19 as a yellow
1
1028C; H NMR (CDCl3): d 8.08 (d, Jˆ2.6 Hz, 1H), 7.95
(d, Jˆ2.6 Hz, 1H), 7.49 (m, 2H, HPh), 7.40 (m, 3H, HPh); ir:
n 3470, 3060, 2928, 1477, 1440, 1337, 1322, 1136, 1123,
.
1050, 1023, 860, 747, 689 cm21
Anal. Calcd for
oil; H NMR (CDCl3): d 8.01 (d, Jˆ4.8 Hz, 1H, H6), 7.49
1
C10H7ClN2S (222.70): C, 53.93; H, 3.17; N, 12.58. Found:
C, 54.08; H, 3.12; N, 12.69.
(m, 2H, HPh), 7.38 (m, 3H, HPh), 6.36 (d, Jˆ4.8 Hz, 1H, H5),
2.30 (s, 3H, SCH3); 13C NMR (CDCl3): d 171.6; 171.0;
154.5; 134.9; 129.0; 128.7; 127.8; 111.1; 12.9; ir: n 3057,
3020, 2962, 2925, 1539, 1521, 1476, 1440, 1402, 1337,
1213, 1166, 1023, 812, 749, 691 cm21. Anal. Calcd for
C11H10N2S (202.28): C, 65.32; H, 4.98; N, 13.85. Found:
C, 65.69; H, 5.29; N, 14.17.
1-(Pyrimidin-5-yl)hexan-1-ol (11). Barbier reaction with 1
(1.0 mmol, 159 mg) according to the general procedure with
hexanal (1.1 mmol, 0.13 mL), gave after puri®cation by
column chromatography (eluent: dichloromethane) 40 mg
1
(22%) of 11 as a yellow oil; H NMR (CDCl3): d 9.00 (s,
1H, H2); 8.46 (s, 2H, H4, H6); 3.95 (m, 1H, CH); 3.00 (s, 1H,
OH); 1.25 (m, 6H, 4£CH2); 0.90 (m, 3H, CH3); ir: n 3058,
2925, 2855, 1727, 1582, 1540, 1476, 1440, 1399, 1025,
744, 720, 691 cm21. Anal. Calcd for C10H16N2O (180.25):
C, 66.64; H, 8.95; N, 15.54. Found: C, 66.67; H, 8.81; N,
15.63.
(3,6-Dimethoxypyridazin-4-yl)phenylmethanol
(21).
Barbier reaction with 20 (1.0 mmol, 266 mg) according to
the general procedure with benzaldehyde (1.1 mmol,
0.11 mL), gave after puri®cation by column chromato-
graphy (eluent: dichloromethane) 178 mg (72%) of 21 as
a white solid. Product previously described in reference.7
5-(Phenylsulfanyl)pyrimidine (12). Barbier reaction with
1 (1.0 mmol, 159 mg) according to the general procedure
with diphenyl disul®de (1.1 mmol, 242 mg), gave after
puri®cation by column chromatography (eluent: dichloro-
methane) 47 mg (25%) of 12 as a yellow oil. Product
previously described in reference.18
1-(3,6-Dimethoxypyridazin-4-yl)hexan-1-ol (22). Barbier
reaction with 20 (1.0 mmol, 266 mg) according to the
general procedure with hexanal (1.1 mmol, 0.13 mL),
gave after puri®cation by column chromatography (eluent:
dichloromethane) 139 mg (58%) of 22 as a yellow oil.
Product previously described in reference.7
1-(4-Methoxypyrimidin-2-yl)hexan-1-ol (14). Barbier
reaction with 13 (1.0 mmol, 236 mg) according to the
general procedure with hexanal (1.1 mmol, 0.13 mL),
gave after puri®cation by column chromatography (eluent:
dichloromethane) 100 mg (48%) of 14 as a white oil.
Product previously described in reference.7
3,6-Dimethoxy-4-(phenylsulfanyl)pyridazine (23). Barbier
reaction with 20 (1.0 mmol, 266 mg) according to the
general procedure with diphenyl disul®de (1.1 mmol,
242 mg), gave after puri®cation by column chromatography
(eluent: dichloromethane) 121 mg (49%) of 23 as an orange
oil. Product previously described in reference.7
4-Methoxy-2-(phenylsulfanyl)pyrimidine (15). Barbier
reaction with 13 (1.0 mmol, 236 mg) according to the
general procedure with diphenyl disul®de (1.1 mmol,
242 mg), gave after puri®cation by column chromatography
(eluent: dichloromethane) 65 mg (30%) of 15 as a yellow
(6-Methoxypyridazin-3-yl)phenylmethanol (25). Barbier
reaction with 24 (1.0 mmol, 236 mg) according to the
general procedure with benzaldehyde (1.1 mmol,
0.11 mL), gave after puri®cation by column chromato-
graphy (eluent: dichloromethane) 140 mg (65%) of 25 as
a white solid. Product previously described in reference.19
1
oil; H NMR (CDCl3): d 8.10 (d, Jˆ5.5 Hz, 1H, H6), 7.54
(m, 2H, HPh), 7.32 (m, 3H, HPh), 6.30 (d, Jˆ5.5 Hz, 1H, H5),
3.66 (s, 3H, OCH3); 13C NMR (CDCl3): d 172.2; 169.4;
157.8; 135.5; 130.1; 129.5; 129.3; 108.3; 54.0; ir: n 3440,
3060, 2994, 2927, 2854, 1726, 1555, 1470, 1441, 1407,
1-(6-Methoxypyridazin-3-yl)hexan-1-ol (26). Barbier
reaction with 24 (1.0 mmol, 236 mg) according to the
general procedure with hexanal (1.1 mmol, 0.13 mL),

Ã
A. Lepretre et al. / Tetrahedron 56 (2000) 3709±3715
3714
gave after puri®cation by column chromatography (eluent:
dichloromethane) 105 mg (50%) of 26 as a yellow oil; H
3-(Phenylsulfanyl)pyridine (38). Barbier reaction with 36
(1.0 mmol, 158 mg) according to the general procedure with
diphenyl disul®de (1.1 mmol, 242 mg), gave after puri®ca-
tion by column chromatography (eluent: dichloromethane)
45 mg (24%) of 38 as a yellow oil. Product previously
described in reference.15
1
NMR (CDCl3): d 7.59 (d, Jˆ9.1 Hz, 1H, H6), 6.63 (d,
Jˆ9.1 Hz, 1H, H5); 5.05 (m, 1H, CH); 4.01 (s, 3H,
OCH3); 3.55 (br, 1H, OH); 2.24 (m, 2H, CH2); 1.30 (m,
6H, 3£CH2); 0.80 (m, 3H, CH3); ir: n 3418, 2931, 2860,
1732, 1463, 1394, 1316, 1249, 1176, 1116, 1006 cm-1. Anal.
Calcd for C11H18N2O2 (210.28): C, 62.83; H, 8.63; N, 13.32.
Found: C, 62.97; H, 8.55; N, 13.40.
All mentioned products had satisfactory analyses.
6-Methoxy-3-(phenylsulfanyl)pyridazine (27). Barbier
reaction with 24 (1.0 mmol, 236 mg) according to the
general procedure with diphenyl disul®de (1.1 mmol,
242 mg), gave after puri®cation by column chromatography
(eluent: dichloromethane) 83 mg (38%) of 27 as a yellow
solid. Product previously described in reference.20
Acknowledgements
We thank M. Paillot, an undergraduate student, for technical
support.
(3-Methoxycinnolin-4-yl)phenylmethanol (29). Barbier
reaction with 28 (1.0 mmol, 286 mg) according to the
general procedure with benzaldehyde (1.1 mmol,
0.11 mL), gave after puri®cation by column chromato-
graphy (eluent: dichloromethane) 170 mg (64%) of 29 as
a beige solid. Product previously described in reference.14
References
Â
1. (a) Queguiner, G.; Marsais, F.; Snieckus, V.; Epsztajn, J. Adv.
Â
Heterocycl. Chem. 1992, 52, 187. (b) Turck, A.; Ple, N.;
Â
Queguiner, G. Heterocycles 1994, 37, 2149. (c) Godard, A.;
 Â
Marsais, F.; Ple, N.; Trecourt, F.; Turck, A.; Queguiner, G. Hetero-
Â
Â
cycles 1995, 40, 1055. (d) Queguiner, G. Bull. Soc. Chim. Belg.
1996 105, 701.
3-Methoxy-4-(phenylsulfanyl)cinnoline (30). Barbier
reaction with 28 (1.0 mmol, 286 mg) according to the
general procedure with diphenyl disul®de (1.1 mmol,
242 mg), gave after puri®cation by column chromatography
(eluent: dichloromethane) 68 mg (24%) of 30 as a red solid,
mp 988C; 1H NMR (CDCl3): d 8.29 (m, 1H); 8.14 (m, 1H);
7.52 (m, 2H); 7.09 (s, 5H, HPh); 4.15 (s, 3H, OCH3); ir: n
3054, 2991, 2952, 2895, 1580, 1550, 1524, 1460, 1324,
1239, 1110, 751, 691 cm21. Anal. Calcd for C16H16N2OS
(284.38): C, 67.58; H, 5.67; N, 9.85. Found: C, 67.79; H,
5.81; N, 9.89.
2. (a) Gilman, H.; Melstrom, D. S. J. Am. Chem. Soc. 1946, 68,
103. (b) Gilman, H.; Spatz, S. M. J. Org. Chem. 1951, 16, 1485.
(c) Gilman, H.; Gregory, W. A.; Spatz, S. M. J. Org. Chem. 1951,
16, 1788. (d) Wibaut, J. P.; Heeringa, L. G. Recl. Trav. Chim.
Pays-Bas 1955, 74, 1003. (e) Parham, W. E.; Piccirilli, R. M.;
J. Org. Chem. 1977, 42, 257. (f) Newcome, G. R.; Roper, J. M.
Â
J. Organomet. Chem. 1980, 186, 147. (g) Mallet, M.; Queguiner,
G. Tetrahedron 1986, 42, 2253. (h) Mallet, M.; Branger, G.;
Â
Marsais, F.; Queguiner, G. J. Organomet. Chem. 1990, 382, 319.
(i) Cai, D.; Hughes, D. L.; Verhoeven, T. R. Tetrahedron Lett.
1996, 35, 2537. (j) Gu, Y. G.; Bayburt, E. K. Tetrahedron Lett.
1996, 37, 2565. (k) Furneaux, R. H.; Limberg, G.; Tyler, P. C.;
Schramm, V. L. Tetrahedron 1997, 53, 2915. (l) Peterson, M. A.;
Mitchell, J. R. J. Org. Chem. 1997, 62, 8237.
(Pyridin-2-yl)phenylmethanol (33). Barbier reaction with
31 (1.0 mmol, 158 mg) according to the general procedure
with benzaldehyde (1.1 mmol, 0.11 mL), gave after puri®-
cation by column chromatography (eluent: dichloro-
methane) 107 mg (58%) of 33 as a yellow solid. Product
previously described in reference.21
3. (a) Rosseels, G. Bull. Soc. Chim. Belges 1966, 75, 5.
(b) Gronowitz, S.; Roe, J. Acta Chem. Scand. 1965, 19, 1741.
(c) Sandosham, J.; Bennecke, T.; Moller, B. S.; Undheim, K.
Acta Chem. Scand., Ser. B 1988, 455. (d) Arukwe, J.; Benneche,
T.; Undheim, K. J. Chem. Soc., Perkin Trans 1 1989, 255.
(e) Parkanyi, C.; Cho, N. S.; Yoo, G. S. J. Organomet. Chem.
1988, 1, 342. (f) Taylor, H. M.; Jones, C. D.; Davenport, J. D.;
Hirsch, K. S.; Kress, T. J.; Weaver, D. J. Med. Chem. 1987, 30,
1359. (g) Frissen, A. E.; Marcelis, A. T. M.; Buurman, D. G.;
Pollmann, C. A. M.; Van Der Plas, H. C. Tetrahedron 1989, 45,
5611. (h) Rho, T.; Abuh, Y. F. Synthetic Commun. 1994, 24, 253.
(i) Heinisch, G.; Holzer, W.; Langer, T.; Lukavsky, P. Hetero-
cycles 1996, 43, 151. (j) Shimura, A.; Momotake, A.; Togo, H.;
Yokoyama, M. Synthesis 1999, 3, 495. (k) Hetrz, H. S.;
Kabacinski, F. F.; Spoerri, P. E. J. Heterocyclic Chem. 1969, 6,
239. (l) Hirschberg, A.; Peterkoski, A.; Spoerri, P. E. J. Hetero-
cyclic Chem. 1965, 2, 209.
1-(Pyridin-2-yl)hexan-1-ol (34). Barbier reaction with 31
(1.0 mmol, 158 mg) according to the general procedure with
hexanal (1.1 mmol, 0.13 mL), gave after puri®cation by
column chromatography (eluent: dichloromethane) 92 mg
(51%) of 34 as a yellow oil. Product previously described
in reference.21
2-(Phenylsulfanyl)pyridine (35). Barbier reaction with 31
(1.0 mmol, 158 mg) according to the general procedure with
diphenyl disul®de (1.1 mmol, 242 mg), gave after puri®ca-
tion by column chromatography (eluent: dichloromethane)
39 mg (21%) of 35 as a yellow oil. Product previously
described in reference.18
 Â
4. Ple, N.; Turck, A.; Couture, K.; Queguiner, G. J. Org. Chem.
(Pyridin-3-yl)phenylmethanol (37). Barbier reaction with
36 (1.0 mmol, 158 mg) according to the general procedure
with benzaldehyde (1.1 mmol, 0.11 mL), gave after puri®-
cation by column chromatography (eluent: dichloro-
methane) 100 mg (54%) of 37 as a yellow solid. Product
previously described in reference.15
1995, 60, 3781.
5. Barbier, P. C. R. Acad. Sci. Paris 1899, 128, 100.
6. (a) Luche, J. L.; Damiano, J. C. J. Am. Chem. Soc. 1980, 102,
Â
7926. (b) De Souza-Barboza, J. C.; Petrier, C.; Luche, J. L. J. Org.
Chem. 1988, 53, 1212. (c) Luche, J. L. In Grenoble Sciences,
Synthetic Organic Sonochemistry. Plenum: New York, 1998.

Ã
A. Lepretre et al. / Tetrahedron 56 (2000) 3709±3715
3715
à  Â
7. Lepretre, A.; Ple, N.; Turck, A.; Knochel, P.; Queguiner, G.
Â
15. Trecourt, F.; Breton, G.; Bonnet, V.; Mongin, F.; Marsais, F.;
Â
Queguiner, G. Tetrahedron 2000, 56, 1349.
Tetrahedron 2000, 56, 265.
8. Maercker, A. Angew. Chem., Int. Ed. Engl. 1987, 26, 972.
 Â
9. Ple, N.; Turck, A.; Heynderickx, A.; Queguiner, G. Tetrahedron
16. Shimazaki, M.; Hikita, M.; Hosoda, T.; Ohta, A. Heterocycles
1991, 32, 937.
1998, 54, 9701.
10. Turck, A.; Mojovic, L.; Queguiner, G. Synthesis 1988, 881.
17. Patent, Ciba-Geigy, AG. FR2218101 1974, DE2406930 1976,
Chem. Abstr. EN, 86, 121372.
Â
11. Majeed, A. J.; Antonsen, O.; Benneche, T.; Undheim, K.
Tetrahedron 1989, 45, 993.
18. Jixiang, C.; Crisp, G. Synthetic Commun. 1992, 22, 683.
19. Heinisch, G.; Langer, T. J. Heterocyclic Chem. 1993, 30,
1685.
Â
20. Turck, A.; Ple, N.; Pollet, P.; Mojovic, L.; Du¯os, J.;
Â
Queguiner, G. J. Heterocyclic Chem. 1997, 34, 621.
12. Ndzi, B. Ph.D. Thesis, University of Rouen, France, 1990.
13. Coad, P.; Coad, R. A.; Clough, S.; Hyepock, J.; Salisbury, J.;
Wilkin, C. J. Org. Chem. 1963, 28, 218.
 Â
14. Turck, A.; Ple, N.; Tallon, V.; Queguiner, G. Tetrahedron
1995, 51, 13045.
Á
21. Gros, P.; Fort, Y.; Caubere, P. J. Chem. Soc., Perkin Trans. 1
1997, 3071.