Synthesis of homo- and heterobiarylmethylamines

Article abstract of DOI:10.1055/s-2006-942353

A variety of homo- and heterobiarylmethylamines were prepared in modest to high yields via a convenient one-pot process. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-942353

1858
PAPER
Synthesis of Homo- and Heterobiarylmethylamines
B
iarylmethylamine
i
s
ncent Terrasson, Sylvain Marque, Annabelle Scarpacci, Damien Prim*
Université de Versailles, Insitut Lavoisier, UMR CNRS 8180, 45, avenue des Etats-Unis, 78035 Versailles Cedex, France
Fax +33(1)39254452; E-mail: prim@chimie.uvsq.fr
Received 20 January 2006; revised 16 February 2006
Me
Abstract: A variety of homo- and heterobiarylmethylamines were
prepared in modest to high yields via a convenient one-pot process.
N
N
N
R2
Key words: biarylmethylamines, imines, nitriles, nucleophilic ad-
dition
R1
NH2
2
NH2
3
N
N
NH2
Diarylmethylamines represent an important subclass of
benzylic amines that can be divided into homobiarylmeth-
ylamines and heterobiarylmethylamines. The former are
found in biologically active compounds such as the hista-
mine H1-receptor antagonist cetirizine dihydrochloride1
or the selective opioid receptor agonist SNC80.2 The
1
N
N
N
R1 = R2 = H
NH2
5
4
NH2
Figure 1 Biarylmethylamines 1–5
structures of heterobiarylmethylamines are characterized zonitrile and phenylmagnesium chloride followed by the
by the presence of one or two heterocycles. The propensi- reduction of the intermediate imine8 or through catalytic
ty of homobiarylmethylamine subunits based on hetero- addition of boronic acids to sulfinimes.1 In the azine se-
cycles to form transition metal complexes attracted much ries, two- or three-step strategies, involving the isolation
interest in recent years. For instance, palladium complex- of ketone intermediates, the formation of the correspond-
es efficiently catalyze the formation of C–C and C–N ing oximes followed by reduction, were mostly devel-
bonds.3 Copper,4 zinc4 and ruthenium5 complexes have oped.9
been prepared and characterized. Moreover, vanadium6
We wish to report a general one-pot procedure providing
and iron7 complexes of polydendate heterocyclic ligands
homo- and heterobiarylmethylamines including mixed
based on homobiarylmethylamine moieties have been
combinations of various heterocycles. The strategy is
found to act as catalysts in oxidation reactions of various
based on the direct addition of metalated (hetero)aromat-
substrates, to mimic natural peroxidases and to cleave
ics to aryl nitriles and the subsequent reduction of in situ
DNA. While variously substituted diphenylmethylamines
generated imines by sodium borohydride (Scheme 1).
1 have been prepared, the heterobiarylmethylamine fami-
We first investigated the preparation of symmetric targets
lies are to date restricted to four azine-based skeletons
(Scheme 1: Ar1 = Ar2, Table 1). In the case of diphenyl-
methylamine 1, several nucleophiles (Li, Mg, Cu) have
2–5 as shown below (Figure 1).
Surprisingly, homo- or heterodiarylmethylamines based
been tested.10 The best combination, involving phenyl-
on N, S, O five-membered heterocycles and polyhetero-
magnesium chloride and benzonitrile in THF, afforded the
atomic heterocycles combinations remain unreported.
expected compound in 64 to 73% yields. The amines were
Conceptually, approaches of their synthesis are based on
easily purified by careful acidic-basic treatment of the
nucleophilic additions to imine derivatives. Indeed,
crude material. Arylmagnesium chlorides have been pre-
diphenylmethylamines were prepared by reacting ben-
pared using the aryl halide and either magnesium turnings
Ar1, Ar2
N
Ar2 CN , THF
Ar1
Ar2
NH2
1.
Ar1 [M]
N
N
N
2. NaBH4, MeOH
S
N
O
S
[M] = Li, Mg, Cu
Me
Scheme 1 General one-pot synthesis of biarylmethylamines
SYNTHESIS 2006, No. 11, pp 1858–1862
x
x.
x
x
.
2
0
0
6
Advanced online publication: 05.05.2006
DOI: 10.1055/s-2006-942353; Art ID: Z02006SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Biarylmethylamines
1859
cleanly afforded the expected product 15 as the major
component of the crude material. Unfortunately, all at-
tempts to purify the crude product only led to degrada-
tions. However, characteristic signals in 1H and 13C NMR
spectra at 5.3 and 54.7 ppm, respectively, account for the
benzylic CH moiety and evidenced the formation of the
expected product.
Table 1 Homobiarylmethylamines 1, 3, and 7 Prepared
Entry Ar1 = Ar2
Homobiarylmethylamines
Yield (%)
64–73
1
2
Ph
1
3
NH2
2-pyridyl
53
The results gathered in Table 2 seem to indicate that CA
is the preferred process in most cases, regardless of the
p-acceptor or the p-donor character of the aromatic ring.
If a marked effect is observed when p-acceptor heterocy-
cles, such as pyridine or pyrimidine, are involved
(Table 2, entries 1 and 2), the overall influence of elec-
tronic effects over the one-pot two-step process remains
unclear. Indeed, in mixed p-acceptor and p-donor combi-
nations (entries 6–9), electronic effects probably neutral-
ize each other partially.
N
N
NH2
(6)
(28)11
N
N
+
NH
N
All new compounds were fully characterized. Both 1H and
13C NMR spectra show characteristic chemical shifts for
diarylmethylamines 1, 3 and 7–16 (Table 3). Benzylic H
and C atoms resonate from 5.08 to 5.75 and from 52.0 to
61.9 ppm respectively. Interestingly the shielding of the
benzylic carbon DdC is in good agreement with the p-ac-
ceptor and p-donor character of the aromatic substituents
(Table 3). Indeed, a clear difference appeared between
p-acceptor and p-donor aromatics, the former being char-
acterized by a positive shielding, while the later typically
show a large negative shielding. If one compares the
shielding values for compounds 13, 14 and 16, where both
electronic effects are mixed, to 10, 11 and 12, respective-
ly, an increase is observed reflecting an averaged influ-
ence of both heterocyclic partners.
3
2-thienyl
7
30
S
S
NH2
or isopropylmagnesium chloride. Activation of the nitrile
moiety by addition of Lewis acids (BF3·OEt2) did not im-
prove yields.
Among the heterocyclic substrates studied, both pyridyl-
and thienyllithium derivatives gave unsatisfactory results.
Their addition to 2-cyanopyridine or 2-cyanothiophene,
respectively, afforded low yields of the expected substi-
tuted methylamine and required tedious purification due
to the presence of numerous side products such as 6 which
was isolated in 28% yield.11 Although the use of organo-
magnesium derivatives was preferred it did not complete-
ly avoid the formation of by-products such as 2,2¢-
bipyridine or 2,2¢-bithiophene. Pyridyl- and thienylmag-
nesium chlorides were reacted with 2-cyanopyridine and
2-cyanothiophene, respectively, to afford the symmetric
dipyridyl- and dithienylmethylamines 3 and 7 in 53 and
30% yield, respectively. The use of two or three fold ex-
cesses of the nucleophile with respect to the nitrile deriv-
atives shows only moderate influence on the isolated yield
of the corresponding methylamine. Moreover, increase of
reaction times as well as inversion of mode of addition of
both reactants did not improve the yield of compounds 3
and 7.
In a similar way, the shielding of the benzylic proton DdH,
except for the N-methylpyrrolyl substituent, seems also to
be in agreement with the p-acceptor and p-donor character
of the aromatic groups. For instance, in the presence of a
pyridine or pyrimidine moiety a small difference of 0.02
and 0.09 ppm is noted. In comparison, p-donor substitu-
ents values of 0.24 and 0.27 were obtained for 11 and 12.
By replacing both phenyl groups in 1 for two thienyl
groups affording 7, the shielding observed increased to
0.52 ppm.
In conclusion, new homo-and heterobiarylmethylamines
bearing combinations of p-acceptor/p-acceptor, p-donor/
p-donor as well as mixed p-donor/p-acceptor aromatics
have been successfully prepared. Targets could be ob-
tained via the one pot nucleophilic addition-reduction se-
quence starting from aromatic and heterocyclic nitriles.
We next turned our attention to unsymmetrical structures.
In this series, targets have been envisioned through either
cross (CA) and reverse cross-additions (RCA). New
mixed diarylmethylamines have been obtained; their
structures and yields of CA and RCA are gathered in
Table 2. All diarylmethylamines could be obtained from
NMR spectra were recorded on a Bruker AC spectrometer at 200
MHz or 300 MHz (1H) and 75 MHz (13C). Mass spectra were re-
corded on a HP MS Eingin 5989B using a Brandford Analytica
source. Solvents were freshly distilled prior to use. THF was dis-
both pathways. Yields ranged from 24 to 96% in case of tilled from sodium/benzophenone ketyl and MeOH was distilled
from MgI2. All other reagents were commercially available and
were used as received. All reactions were carried out under argon,
unless otherwise stated.
cross addition and from 32 to 80% in case of reverse
cross-additions. Only methylamine 15 could not be isolat-
ed (entry 8). Both cross addition and the reverse process
Synthesis 2006, No. 11, 1858–1862 © Thieme Stuttgart · New York

1860
V. Terrasson et al.
PAPER
Table 2 Synthesis of Heterobiarylmethylamines Through Cross- and Reverse Cross-Additions
Entry
1
Ar1
Ar2
Ph
Diarylmethylamine
Yield (%)
CA
RCA
45
2-pyridyl
8
9
90
55
24
94
91
56
96
N
NH2
a
2
3
4
5
6
7
8
9
2-pyrimidyl
2-pyrrolyl
2-thienyl
2-thiazolyl
2-pyrrolyl
2-thienyl
2-furyl
Ph
–
N
N
NH2
Ph
10
11
12
13
14
15
16
32
52
80
N
Me
NH2
Ph
S
NH2
Ph
N
S
NH2
b
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
–
N
N
Me
NH2
56
S
N
NH2
c
c
–
–
O
N
NH2
N
b
2-thiazolyl
–
64
S
N
NH2
a Product decomposed.
b Not determined.
c Not isolated.
Table 3 Benzylic Chemical Shifts for Products 1–16
Entry
Nuclear Chemical Shifts (CDCl3, d)
1
3
7
8
9
10
11
12
13
14
16
1
2
3
4
1H
5.23
59.9
–
5.36
65.7
+5.8
+0.13
5.75
52.0
–7.9
+0.52
5.25
61.1
+1.2
+0.02
5.32
61.9
+2.0
+0.09
5.08
53.4
–6.5
–0.15
5.47
56.2
–3.7
+0.24
5.50
55.7
–4.2
+0.27
5.32
54.3
–5.6
+0.11
5.47
57.2
–2.7
+0.24
5.50
58.9
–1.0
+0.27
13C
DdC
DdH
–
Synthesis 2006, No. 11, 1858–1862 © Thieme Stuttgart · New York

PAPER
Biarylmethylamines
1861
One-Pot Synthesis of Biarylmethylamines 1, 3, 7–14, 16; Gener-
al Procedure
MS (EI, 70 eV): m/z (%) = 185 (M+, 30), 169 (M+ – NH2, 10), 108
(M+ – Ph, 30), 106 (M+ – Pyr, 100), 85 (40), 83 (50), 79 (Pyr+, 50),
77 (Ph+, 40), 51 (10).
To a stirred solution of the aryl halide (5 mmol, 1 equiv) in anhyd
THF (10 mL) was added isopropylmagnesium chloride (2 M in
THF, 2.5 mL, 1 equiv). The mixture was stirred at r.t. for 2 h under
argon. The aromatic nitrile (5 mmol, 1 equiv) was then added and
the mixture stirred for 3 h. The solvent was removed by evapora-
tion, and the residue dissolved in anhyd MeOH (20 mL). NaBH4 (5
mmol, 1 equiv) was added and the mixture was stirred at r.t. for 16
h. After concentration under vacuum, 1 M HCl (20 mL) was added
and the aqueous layer was washed with EtOAc (3 × 20 mL). The
aqueous phase was basified with aq 3 M NaOH up to pH 9–10, and
extracted with EtOAc (3 × 20 mL). The combined organic layers
were dried (MgSO4), filtered and concentrated under vacuum. The
crude product was purified by flash chromatography (Tables 1
and 2).
MS (CI, NH3): m/z (%) = 186 (M + H+, 100), 185 (70), 184 (30), 169
(M+ – NH2, 50), 106 (M+ – Pyr, 60).
MS (TOF, ES+): m/z (%) = 407 (10), 352 (10), 186 (M + H+, 10),
169 (M+ – NH2, 100).
2-(N-Methylpyrrolyl)phenylmethylamine (10)
Yield: 32%.
1H NMR (300 MHz, CDCl3): d = 1.79 (br, 2 H, NH2), 3.35 (s, 3 H,
CH3), 5.08 (s, 1 H, HCNH2), 5.96–6.02 (m, 2 H, HCHCN and HCH-
CHCN), 6.48 (t, 3J = 2.2 Hz, 1 H, HCN), 7.16–7.22 (m, 5 H, C6H5).
13C{1H} NMR (CDCl3): d = 34.1 (NCH3), 53.4 (CNH2), 106.5
(HCHCHCN), 106.6 (HCHCN), 122.6 (HCN), 127.1 (2 CHarom-m),
127.2 (CHarom-p), 128.6 (2 CHarom-o), 136.0 (NCCH), 144.3 (Carom-ipso).
Diphenylmethylamine (1)
Yield: 73%.
1H NMR (300 MHz, CDCl3): d = 3.17 (br, 2 H, NH2), 5.23 (s, 1 H,
HCNH2), 7.29–7.41 (m, 10 Harom). Data are in accordance with pre-
viously reported results.8b
MS (EI, 70 eV): m/z (%) = 186 (M+, 50), 170 (M+ – NH2, 50), 156
(40), 109 (M+ – Ph, 100), 82 (60).
2-Thienylphenylmethylamine (11)
Yield: 94%.
1H NMR (300 MHz, CDCl3): d = 2.08 (br, 2 H, NH2), 5.44 (s, 1 H,
Di(2-pyridyl)methylamine (3)
Yield: 53%.
3
3
HCNH2), 6.88 (d, J = 3.2 Hz, 1 H, HCHCHCS), 6.97 (t, J = 3.5
Hz, 1 H, HCHCS), 7.24 (d, 3J = 3.8 Hz, 1 H, HCS), 7.33 (d, 3J = 6.8
Hz, 1 Harom-p), 7.40 (t, J = 7.4 Hz, 2 Harom-m), 7.47 (d, J = 7.5 Hz, 2
Harom-o).
1H NMR (300 MHz, CDCl3): d = 2.45 (br, 2 H, NH2), 5.36 (s, 1 H,
HCNH2), 7.17 (dd, 3J = 4.9, 7.6 Hz, 2 H, HCHCN), 7.43 (d, 3J = 7.2
Hz, 2 H, HCHCHCHCN), 7.64 (t, 3J = 7.4 Hz, 2 H, HCCHCHN),
8.55 (d, 3J = 5.1 Hz, 2 H, HCN). Data are in accordance with previ-
ously reported results.9b
13C{1H} NMR (CDCl3): d = 56.2 (CNH2), 123.9 (HCHCHCS),
124.4 (HCS), 126.6 (HCHCS), 126.7 (2 CHarom-o), 127.5 (CHarom-p),
128.6 (2 CHarom-m), 145.3 (Carom-ipso), 150.1 (SCCH).
Di(2-thienyl)methylamine (7)
Yield: 30%.
MS (EI, 70 eV): m/z (%) = 189 (M+, 100), 173 (M+ – NH2, 20), 112
(M+ – Ph, 60), 104 (50), 85 (30), 77 (Ph+, 30), 51 (20).
1H NMR (300 MHz, CDCl3): d = 2.84 (br, 2 H, NH2), 5.72 (s, 1 H,
MS (TOF, ES+): m/z (%) = 299 (20), 173 (M+ – NH2, 100).
3
HCNH2), 6.95 (dd, J = 3.6, 5.0 Hz, 2 H, HCHCS), 7.00 (m, 2 H,
HCHCHCS), 7.24 (dd, 3J = 1.3, 5.1 Hz, 2 H, HCS).
2,2¢-Thiazolylbenzylamine (12)
Yield: 80%.
13C{1H} NMR (CDCl3): d = 52.0 (CNH2), 124.1 (HCHCHCS),
124.6 (HCS), 126.7 (HCHCS), 149.9 (SCCH).
MS (EI, 70 eV): m/z (%) = 195 (M+, 80), 194 (40), 179 (M+ – NH2,
80), 112 (M+ – Thio, 70), 111 (100), 110 (90), 85 (90), 83 (Thio+,
60).
1H NMR (300 MHz, CDCl3): d = 2.23 (br, 2 H, NH2) 5.50 (s, 1 H,
HCNH2), 7.24 (d, 3J = 3.1 Hz, 1 H, HCS), 7.29–7.39 (m, 3 H, C6H5),
7.46–7.49 (m, 2 H, C6H5), 7.72 (d, 3J = 3.1 Hz, 1 H, HCN).
13C{1H} NMR (CDCl3): d = 55.7 (CNH2), 116.5 (CHS), 124.4 (2
CHarom-o), 125.4 (CHarom-p), 126.3 (2 CHarom-m), 140.2 (HCN), 140.6
(Carom-ipso), 173.8 (SCN).
MS (CI, NH3): m/z (%) = 372 (20), 287 (20), 195 (30), 194 (30), 179
(M+ – NH2, 100), 111 (10).
MS (EI, 70 eV): m/z (%) = 361 (2 M+ – NH3 – H, 25), 276 (100), 190
MS (TOF, ES+): m/z (%) = 179 (M+ – NH2, 100).
(M+, 10), 174 (M+ – NH2, 95), 77 (Ph+, 20).
2-Pyridylphenylmethylamine (8)
Yield: 90%.
MS (CI, NH3): m/z (%) = 362 (100), 361 (60), 277 (30), 276 (60),
174 (M – NH2, 40).
1H NMR (300 MHz, CDCl3): d = 2.33 (br, 2 H, NH2), 5.28 (s, 1 H,
HCNH2), 7.16 (t, 3J = 6.1 Hz, 1 H, HCHCN), 7.28 (m, 2 H, Harom-p
and HCHCHCHCN), 7.35 (t, 3J = 7.6 Hz, 2 Harom-m), 7.45 (d,
3J = 7.7 Hz, 2 Harom-o), 7.62 (t, 3J = 7.7 Hz, 1 H, HCHCHCN), 8.60
(d, 3J = 3.8 Hz, 1 H, HCN). Data are in accordance with previously
reported results.9c
MS (TOF, ES+): m/z (%) = 362.1 (100) 174.0 (95).
2-(N-Methylpyrrolyl)-2¢-pyridylmethylamine (13)
Yield: 56%.
1H NMR (300 MHz, CDCl3): d= 2.94 (br, 2 H, NH2), 3.54 (s, 3 H,
CH3), 5.32 (s, 1 H, HCNH2), 5.98 (dd, 3J = 2.0, 3.5 Hz, 1 H, HCH-
CNMe), 6.07 (t, 3J = 3.2 Hz, 1 H, HCHCHCNMe), 6.58 (t, 3J = 2.2
Hz, 1 H, HCNMe), 7.14–7.21 (m, 2 H, HCHCHCHCN and HCH-
CN), 7.63 (t, 3J = 7.5 Hz, 1 H, HCHCHCN), 8.58 (d, 3J = 4.6 Hz, 1
H, HCN).
13C{1H} NMR (CDCl3): d = 34.3 (NCH3), 54.3 (CNH2), 106.8
(HCHCHCNMe), 107.1 (HCHCNMe), 121.7 (HCHCN), 122.2
(HCHCHCHCN), 122.9 (HCNMe), 134.5 (MeNCCH), 136.8
(HCHCHCN), 148.9 (HCN), 162.3 (NCCH).
2-Pyrimidylphenylmethylamine (9)
Yield: 55%.
1H NMR (300 MHz, CDCl3): d = 3.16 (br, 2 H, NH2), 5.32 (s, 1 H,
HCNH2), 7.06 (t, 3J = 4.9 Hz, 1 H, HCHCN), 7.22 (d, 3J = 7.1 Hz,
3
3
1 Harom-p), 7.30 (t, J = 7.3 Hz, 2 Harom-m), 7.43 (d, J = 6.9 Hz, 2
Harom-o), 8.64 (d, J = 5.0 Hz, 2 H, HCN).
13C{1H} NMR (CDCl3): d = 61.5 (CNH2), 119.2 (HCHCN), 126.9
(2 CHarom-o), 127.4 (C-8), 128.6 (CHarom-p), 144.1 (Carom-ipso), 157.2
(HCN), 171.7 (NCN).
MS (EI, 70 eV): m/z (%) = 187 (M+, 30), 170 (20), 109 (M+ – Pyr,
100), 108 (40), 82 (50).
Synthesis 2006, No. 11, 1858–1862 © Thieme Stuttgart · New York

1862
V. Terrasson et al.
PAPER
2-Thienyl-2¢-pyridylmethylamine (14)
References
Yield: 69%.
(1) Bolshan, Y.; Batey, R. A. Org. Lett. 2005, 7, 1481.
1H NMR (300 MHz, CDCl3): d = 2.28 (br, 2 H, NH2), 5.47 (s, 1 H,
HCNH2), 6.89–6.95 (m, 2 H, HCHCHCS and HCHCS), 7.14–7.22
(m, 2 H, HCS and HCHCN), 7.32 (d, 3J = 7.9 Hz, 1 H, HCHCHCH-
CN), 7.64 (t, 3J = 7.7 Hz, 1 H, HCHCHCN), 8.57 (d, 3J = 4.8 Hz, 1
H, HCN).
13C{1H} NMR (CDCl3): d = 57.2 (CNH2), 121.4 (HCHCHCHCN),
122.4 (HCHCN), 124.2 (HCHCHCS), 124.8 (HCS), 126.7
(HCHCS), 136.8 (HCHCHCN), 149.2 (SCCH), 149.3 (HCN),
162.8 (NCCH).
(2) Calderon, S. N.; Rothman, R. B.; Porreca, F.; Flippen-
Anderson, J. L.; McNutt, R. W.; Xu, H.; Smith, L. E.; Bilsky,
E. J.; Davis, P.; Rice, K. C. J. Med. Chem. 1994, 37, 2125.
(3) (a) Gil-Molto, J.; Karlström, S.; Najera, C. Tetrahedron
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S.; Falvello, L. R. Org. Lett. 2003, 5, 1451. (c) Silberg, J.;
Schareina, T.; Kempe, R.; Wurst, K.; Buchmeiser, M. R. J.
Organomet. Chem. 2001, 622, 6.
(4) Arnold, P. J.; Davies, S. C.; Dilworth, J. R.; Durrant, M. C.;
Griffiths, D. V.; Hughes, D. L.; Richards, R. L.; Sharpe, P.
C. J. Chem. Soc., Dalton Trans. 2001, 736.
(5) Chang, J.; Plummer, S.; Berman, E. S. F.; Striplin, D.;
Blauch, D. Inorg. Chem. 2004, 43, 1735.
MS (EI, 70 eV): m/z (%) = 190 (M+, 40), 174 (M+ – NH2, 20), 112
(M+ – Pyr, 100), 105 (20), 85 (60), 79 (30), 78 (Pyr+, 40), 51 (20).
MS (TOF, ES+): m/z (%) = 174 (M+ – NH2, 100).
(6) Ligtenbarg, A. G. J.; Spek, A. L.; Hage, R.; Feringa, B. L. J.
Chem. Soc., Dalton Trans. 1999, 659.
2-Thiazolyl-2¢-pyridylmethylamine (16)
Yield: 56%.
(7) See, for example: (a) van den Heuvel, M.; van den Berg, T.
A.; Kellog, R. M.; Choma, C. T.; Feringa, B. L. J. Org.
Chem. 2004, 69, 250. (b) Choma, C. T.; Schudde, E. P.;
Kellog, R. M.; Robillard, G. T.; Feringa, B. L. J. Chem. Soc.,
Perkin Trans. 1 1998, 769; and references cited therein.
(8) See, for example: (a) Dejaegher, Y.; Mangelinckx, S.; De
Kimpe, N. Synlett 2001, 113. (b) Weiberth, F. J.; Hall, S. S.
J. Org. Chem. 1986, 51, 5338.
(9) (a) Bluhm, M. E.; Ciesielski, M.; Gorls, H.; Doring, M.
Angew. Chem. Int. Ed. 2002, 41, 2962. (b) Renz, M.;
Hemmert, C.; Meunier, B. Eur. J. Org. Chem. 1998, 1271.
(c) Niemers, E.; Hiltmann, R. Synthesis 1976, 593.
(10) (a) In some cases, the use of additives such as CuBr has been
described. See ref. 8b. (b) See also: Weiberth, F. J.; Hall, S.
S. J. Org. Chem. 1987, 52, 3901.
1H NMR (300 MHz, CDCl3): d = 2.70 (br, 2 H, NH2), 5.49 (s, 1 H,
HCNH2), 7.20 (dd, 3J = 4.8, 7.5 Hz, 1 H, HCHCN), 7.26 (d, 3J = 3.3
Hz, 1 H, HCS), 7.42 (d, 3J = 7.9 Hz, 1 H, HCHCHCHCN), 7.65 (t,
3J = 7.7 Hz, 1 H, HCHCHCN), 7.71 (d, 3J = 3.5 Hz, 1 H, HCHCS),
8.58 (d, 3J = 4.8 Hz, 1 H, HCN).
13C{1H} NMR (CDCl3): d = 58.9 (CNH2), 119.3 (HCS), 122.0
(HCHCN), 122.7 (HCHCHCHCN), 136.8 (HCHCHCN), 142.6
(HCHCS), 149.4 (HCN), 160.5 (NCCH), 175.5 (NCS).
MS (EI, 70 eV): m/z (%) = 191 (M+, 10), 190 (30), 175 (M+ – NH2,
10), 162 (40), 161 (20), 112 (20), 105 (20), 79 (30), 78 (Pyr+, 100),
58 (30), 51 (30).
(11) (a) Compound 6 has already been observed under similar
conditions: Grosjean, B.; Compagnon, P.-L. Bull. Soc.
Chim. Fr. 1975, 775. (b) In case of pyridine substrates, ring
opening by-products have also been observed: Strekowski,
L.; Watson, R. A.; Faunce, M. A. Synthesis 1987, 579.
Synthesis 2006, No. 11, 1858–1862 © Thieme Stuttgart · New York