Novel and efficient access to theieno[3,4-c]cinnolines

Article abstract of DOI:10.3987/COM-08-11472

New substituted methyl thieno[3,4-c]cinnoline-3-carboxylate compounds were synthesized from the corresponding methyl 3-aminothiophene-2-carboxylate precursors by a new route using a modified Sandmeyer reaction. Under proper conditions, Sandmeyer reaction

Full text of DOI:10.3987/COM-08-11472

HETEROCYCLES, Vol. 75, No. 12, 2008
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HETEROCYCLES, Vol. 75, No. 12, 2008, pp. 3015 - 3024. © The Japan Institute of Heterocyclic Chemistry
Received, 24th June, 2008, Accepted, 25th July, 2008, Published online, 28th July, 2008. COM-08-11472
NOVEL AND EFFICIENT ACCESS TO THIENO[3,4-c]CINNOLINES
Karine Gehanne, Jean-Charles Lancelot, Stéphane Lemaître, Hussein El-
Kashef, and Sylvain Rault*
Centre d’Etudes et de Recherche sur le Médicament de Normandie
UPRES EA 4258 PR CNRS INC3M - Université de Caen Basse-Normandie,
U.F.R. des Sciences Pharmaceutiques, 5, rue Vaubénard - 14032 Caen, France
*Corresponding author:
tel. +33 2 31 93 4169; fax +33 2 31 93 1188; e-mail sylvain.rault@unicaen.fr
Abstract – New substituted methyl thieno[3,4-c]cinnoline-3-carboxylate
compounds were synthesized from the corresponding methyl 3-aminothiophene-
2-carboxylate precursors by a new route using a modified Sandmeyer reaction.
Under proper conditions, Sandmeyer reaction led to the formation of thieno[3,4-c]
cinnoline compounds by a regioselective intramolecular cyclization, instead of the
expected substitution of the amino group by a bromine atom.
INTRODUCTION
The thienocinnoline system is scarcely described in literature, likewise furocinnoline1 and other similar
cinnoline systems.2 Thomas et al.3 reported that the cinnoline derivatives of formula I posses
antiangiogenic properties and they exhibit effects on VEGF, a property which could be useful in the
treatment of a number of diseases including cancer and rheumatoid arthritis. Nakao et al.4 have
synthesized the thienocinnolines II which showed anxiolytic, hypnotic, antiepileptic and nootropic
activities, they are potent agonists, partially agonists or inverse agonists of the benzodiazepine receptors
(Chart 1).
Chart 1
S
(R)n
R
R1
W
N
R2
R3
N
N
N
O
I
II
Ar
W = O, NH, S, CH2
n = 1 to 5
R = H, hal, alkyl

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HETEROCYCLES, Vol. 75, No. 12, 2008
Barton5 described the synthesis of thieno[2,3-c]-, thieno[3,2-c]- and especially thieno[3,4-c]cinnolines
from the corresponding 2-aminophenylthiophenes. As depicted in scheme 1, the thieno[2,3-c]cinnoline
Vb was obtained in 69% yield via intramolecular electrophilic attack of the diazonium cation at the free
α-position of 3-(2-aminophenyl)thiophene IIIb. Thieno[3,4-c]cinnoline ring system was constructed by
the same direct diazotisation procedure through an intramolecular electrophilic attack of the diazonium
cation at the less reactive β-position of the thiophene ring. For example, 1,3-dimethylthieno[3,4-
c]cinnoline Va was obtained from 3-(2-aminophenyl)-2,5-dimethylthiophene IIIa, in 54% yield.
Scheme 1
S
Va
N
S
S
R
R
R
R
N
i
NH2
ii
N+
S
N
N
N
X
Vb
IIIa R = Me
IIIb R = H
IVa-b
NaNO2, H2O, 3N HCl, 1N EtCO2H, 0.15N H2SO4, 0-3 °C, 1 h; (ii) NaOAc, H2O, 0-3 °C, 1 h, then rt, 24 h.
Va (54%), Vb (69%).
The synthesis of thieno[3,2-c]cinnoline Vc was also described, using 2-aminophenylthiophene IIIc as a
starting material, via an azaborine VI5 in analogy with the synthesis of benzo[c]cinnoline described by
Dewar and Poesche6 (Scheme 2).
Scheme 2
S
S
S
i, ii
iii, iv
N+
N
NH2
B
N
H
OH
IIIc
VI
Vc
(i) BCl3, xylene, reflux ; (ii) H2O; (iii) NaNO2, HCl ; (iv) NaOAc (29-36%).
In this paper, we wish to describe a new efficient methodology for the synthesis of thieno[3,4-c]
cinnolines, using an alternative approach based on the reactivity of aminothiophenes.7

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RESULTS AND DISCUSSION
During the synthesis of new methyl-4-aryl-3-bromothiophene-2-carboxylates 4 from the corresponding
aminothiophene esters 1 under the classical Sandmeyer reaction conditions, using the procedure described
by Corral et al.,8 we have observed that in some cases the yields were rather low and the formed
bromothiophenes 4 were accompanied by a non-halogenated by-product. It is worthy to mention that
when the aryl group was a simple phenyl or a phenyl group bearing an electron-withdrawing substitutent,
the reaction was univocal and led to the expected bromo derivatives in good yields (Scheme 3).
Scheme 3
S
S
CO2Me
CO2Me
i
NH2
Br
R
R
R
R
60-90%
R = H, EWG
(i) NaNO2, Cu2Br2, HBr 48%, H2O, 0 °C to 60 °C, 1.5 h.
However, when the phenyl group of the aminoesters 1a-c bears one or two electron-donating groups, the
results obtained were quite different where several by-products including deaminated products, thiophene
dimers and poly-halogenated products were formed.
Thus, upon optimizing Sandmeyer reaction conditions by heating the aminoesters 1a-c in hydrobromic
acid with sodium nitrite in the presence of copper(I) bromide (protocol A), a mixture of two products, the
bromo derivatives 4a-c and the thieno[3,4-c]cinnolines 3a-c were obtained. These two products were
easily separated by column chromatography, and their structures were confirmed by elemental and
spectral analyses. (Scheme 4)
Nevertheless, under the classical Sandmeyer reaction conditions, the above reaction led to the formation
of numerous by-products including deaminated products, thiophene dimers and poly-halogenated
products.
Unfortunately, this protocol A did not lead to a selective synthesis of either compound 3 or 4. So,
consequently, we tried an other protocol (B) previously described by Doyle who recommended to use
tert-butyl nitrite and copper(II)bromide to prepare bromo derivatives from the corresponding amino

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HETEROCYCLES, Vol. 75, No. 12, 2008
compounds.9,10 Following this new protocol, treatment of 1a and 1b gave only the thieno[3,4-c]cinnolines
3a and 3b respectively with very high yield (≥ 90%) without any trace of a bromo derivatives.
Surprisingly, treatment of 1c gave exclusively the bromo derivative 4c in high yield (95%) (Scheme 5).
Scheme 4. Sandmeyer reaction with optimised conditions – Protocol A
S
S
S
S
CO2Me
CO2Me
CO2Me
R'
CO2Me
i
+
R'
N+
N
NH2
Br
N
R'
R'
R
N
Br
R
1a-c
4a-c
3a-c
2a-c
R
R
a : R = R' = OMe
b : R = OMe and R' = OCH2C6H5
c : R = OMe and R' = H
NaNO2 (1.0 eq.), HBr 48% / H2O (2:1), 0 °C, 30 min., then Cu2Br2 (1.0 eq.), HBr 48%, 50°C, 1h.
3a/4a (40/60), 3a (30%); 3b/4b (40/60), 3b (30%); 3c/4c (20/80), 3c (15%).
Scheme 5. Sandmeyer reaction with modified conditions – Protocol B
S
3a,b
R'
CO2Me
N
R
N
a : R = R' = OMe
b : R = OMe and R' = OCH2C6H5
S
S
CO2Me
CO2Me
i
N+
N
NH2
R'
R'
Br
S
CO2Me
R
1a-c
R
2a-c
4c
Br
R'
R
c : R = OMe and R' = H
(i) t-BuONO (1.5 eq.), CuBr2 (1.2 eq.), MeCN, 60-70 °C, 4 h, then H2O/HCl 20%, 0 °C-rt.
3a 97%; 3b 90%; 4c 95%.
In order to verify that the cupric salt had no influence on the intramolecular cyclization, we repeated this
protocol B in the absence of cupric bromide. For 1a and 1b, the results were the same as those obtained in
the presence of copper bromide and the thieno[3,4-c]cinnolines 3a-b were isolated in a similar yield.
However in the case of compound 1c the diazonium salt did not cyclize and the sole reaction product was
found to be the deaminothiophene 5c7 (Scheme 6).

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3019
Scheme 6. Modified Sandmeyer reaction
S
3a,b
R'
CO2Me
a : R = R' = OMe
b : R = OMe and R' = OCH2C6H5
N
R
N
S
CO2Me
i
S
CO2Me
NH2
R'
5c
R
1a-c
R'
c : R = OMe and R' = H
R
(i) t-BuONO (1.5 eq.), MeCN, 60-70 °C, 4 h, then H2O/HCl 20%, 0 °C-rt.
3a 92%; 3b 90%; 5c 95%.
Finally in order to isolate the intermediate diazonium salts we tried another route using tetrafluoroboric
acid and sodium nitrite following the procedure described in the literature.10a,11,12 This protocol allowed
us to isolate the two tetrafluoroborate diazonium salts 6a and 6c as very stable solids. However, the
diazonium salt 6b could not be isolated even at very low temperature and also we could not check its
stability since the thieno[3,4-c]cinnoline 3b was directly formed. When the tetrafluoroborate 6a was
dissolved in MeCN at rt, it led to the formation of the thieno[3,4-c]cinnoline 3a, while 6c did not cyclize
even upon heating at reflux temperature of MeCN, and it gave only the deamino thiophene 5c7 (Scheme
7).
In conclusion we have described an efficient method for the synthesis of new thieno[3,4-c]cinnolines
bearing an ester functionality which could be used to design new compounds of therapeutic importance.
Scheme 7. Synthesis of diazonium tetrafluoroborate salts
S
R'
CO2Me
CO2Me
3a R = R' = OMe
N
R
N
S
S
CO2Me
CO2Me
i
ii
S
N+
NH2
F
B
R'
R'
N
F
F
5c R = OMe and R' = H
F
R'
R
R
6a,c
1a,c
R
(i) HBF4.H2O (50%), H2O, 50 °C, 1 h, then NaNO2 (1.1 eq.), H2O, –15 °C, 1.5 h, (90%) ; (ii) MeCN, rt to
reflux, 1 h. 6a 93%; 6c 98%; 3a 80%; 5c 85%.

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EXPERIMENTAL
Melting points were determined on a Köfler melting point apparatus and are uncorrected. IR spectra were
taken with a Perkin Elmer BX FT-IR. HRMS (EI) determinations were made using a spectrometer JEOL
1
JMS GCMate. ESI-MS was performed using a spectrometer LC-MS Waters alliance 2695 (ESI+). H-
NMR (400 MHz) and 13C-NMR (100 MHz) were recorded on a JEOL Lambda 400 Spectrometer.
Chemical shifts are expressed in parts per million downfield from tetramethylsilane as an internal
standard. Thin layer chromatography (TLC) was performed on silica gel 60F-264 (Merck). Elemental
analyses were performed at the ‘Institut de Recherche en Chimie Organique Fine’ (Rouen).
Classical procedure of the Sandmeyer reaction (Protocol A)
Methyl 7-methoxythieno[3,4-c]cinnoline-3-carboxylate (3c)
To a stirred solution, cooled to 0 ˚C, of sodium nitrite (0.20 g, 2.99 mmol) in H2O (4 mL), a solution of
methyl 3-amino-4-(4-methoxyphenyl)thiophene-2-carboxylate 1c (0.80 g, 2.99 mmol) in HBr (48%, 8
mL) was dropwise added. Stirring was continued for 30 min at the same temperature then a solution of
Cu2Br2 (0.50 g, 2.99 mmol) in HBr was added, followed by heating the reaction mixture at 70 ˚C till the
evolution of nitrogen gas ceased, and the completion of the reaction was checked by TLC. After cooling,
the reaction mixture was poured onto cold water and the solid precipitate was filtered, washed with water
and air dried. Compounds 3c and 4c were separated by silica gel column chromatography using AcOEt as
an eluent (Rf 3c = 0.5, Rf 4c = 0.9). Compound 3c was crystallized from EtOH to give an orange powder
1
(0.12 g, 15% yield), mp 228 °C. IR (KBr): 3426, 2925, 2248, 1704, 1607-1415, 1274, 1118 cm-1. H
NMR (DMSO-d6) δ 8.04 (s, 1H, H1); 7.64 (s, 1H, H6); 7.44 (d, 3JH8H9 = 8.2 Hz, 1H, H8);7.20 (d, 3JH9H8
=
8.2 Hz, 1H, H9); 3.88 (s, 3H, OMe); 3.84 (s, 3H, CO2OMe). 13C NMR (DMSO-d6) δ 163.1 (s, 1C, CO);
159.1 (s, 1C, C7); 155.6 (s, 1C, CIV); 153.2 (s, 1C, CIV); 147.5 (s, 1C, C3); 145.6 (s, 1C, C6H); 142.9 (s,
1C, C8H); 140.6 (s, 1C, C9H); 130.1 (s, 1C, C1H); 117.3 (s, 1C, CIV); 115.7 (s, 1C, CIV); 55.1 (s, 1C,
Meester); 54.0 (s, 1C, OMe). MS m/z (%): 275 (21) [M+.]; 244 (100) [M+-(OMe)]; 216 (42) [M+-(CO2Me)];
157 (16). Anal. Calcd for C13H10N2O3S: C, 56.92; H, 3.67; N, 10.21. Found: C, 56.85; H, 3.48; N, 10.25.
Compound 4c is identical to that obtained following the modified procedure described below.
Methyl 3-bromo-4-(3,4-dimethoxyphenyl)thiophene-2-carboxylate (4a)
This compound was obtained following the same procedure described above for 3c, using methyl 3-
amino-4-(3,4-dimethoxyphenyl)thiophene-2-carboxylate 1a. Compounds 3a and 4a were separated by
silica gel column chromatography using AcOEt as eluent (Rf 3a = 0.5, Rf 4a = 0.9). Compound 4a was

HETEROCYCLES, Vol. 75, No. 12, 2008
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crystallized from EtOH as colorless crystals (2.30 g, 38% yield), mp 138 °C. IR (KBr): 2958, 1726, 1610-
1
1421, 1251, 1231, 1074, 785 cm-1. H NMR (DMSO-d6) δ 8.45 (s, 1H, H5); 7.97 (s, 1H, HAr); 7.78 (d,
3JHH = 8.0 Hz, 1H, HAr); 6.96 (d, 3JHH = 8.0 Hz, 1H, HAr); 3.85 (s, 3H, OMe); 3.83 (s, 3H, OMe); 3.76 (s,
3H, CO2Me). 13C NMR (DMSO-d6) δ 163.8 (s, 1C, CO); 159.9 (s, 1C, CAr); 159.7 (s, 1C, CIV); 149.8 (s,
1C, C3); 147.7 (s, 1C, C2); 126.9 (s, 1C, CHAr); 126.6 (s, 1C, CHAr); 125.4 (s, 1C, C4); 114.9 (s, 1C, C5H);
114.5 (s, 1C, CHAr); 95.8(s, 1C, CHAr); 55.2 (s, 1C, OMe); 55.1 (s, 1C, OMe); 50.7 (s, 1C, Me). MS m/z
(%): 356-358 (29) [M+.]; 325-327 (100) [M+-(OMe)]; 297-299 (35) [M+-(CO2Me)]; 218 (30) [M+-(Br,
CO2Me)]; 204 (17). Anal. Calcd for C14H13BrO4S: C, 47.07; H, 3.67. Found: C, 46.85; H, 3.48.
Compound 3a is idenitical to that obtained following the modified procedure described below.
Methyl 4-[3-(benzyloxy)-4-methoxyphenyl]-3-bromothiophene-2-carboxylate (4b)
This compound was obtained following the same procedure described above for 3c, using methyl 3-
amino-4-(3-benzyloxy-4-methoxyphenyl)thiophene-2-carboxylate 1b. Compounds 3b and 4b were
separated by silica gel column chromatography using AcOEt as eluent (Rf 3b = 0.5, Rf 4b = 0.9).
Compound 4b was crystallized from EtOH as beige crystals (0.72 g, 36% yield), mp 148 °C. IR (KBr):
3014, 1731, 1603-1420, 1246, 1229, 1074, 765 cm-1. 1H NMR (DMSO-d6) δ 8.25 (s, 1H, H5); 8.04 (s, 1H,
HAr); 7.78 (d, 3JHH = 8.0 Hz, 1H, HAr); 7.55 (d, 3JHoHm = 7.0 Hz, 2H, Ho); 7.50 (d, 3JHH = 8.0 Hz, 1H, HAr);
3
3
3
7.41 (dd, JHmHo = 7.0 Hz, JHmHp = 7.6 Hz, 2H, Hm); 7.37 (t, JHpHm = 7.6 Hz, 1H, Hp); 5.39 (s, 2H,
OCH2); 4.01 (s, 3H, OMe); 3.89 (s, 3H, CO2Me). 13C NMR (DMSO-d6) δ 162.8 (s, 1C, CO); 159.9 (s, 1C,
CAr); 159.7 (s, 1C, CAr); 149.8 (s, 1C, C3); 147.7 (s, 1C, C2); 126.9 (s, 1C, CHAr); 126.6 (s, 1C, CHAr);
125.4 (s, 1C, C4); 114.9 (s, 1C, C5H); 114.5 (s, 1C, CHAr); 110.3 (s, 2C, CHo); 110.2 (s, 2C, CHm); 108.8
(s, 1C, CHp); 95.8 (s, 1C, CHAr); 55.9 (s, 1C, CH2); 55.1 (s, 1C, OMe); 50.7 (s, 1C, Me). MS m/z (%):
432-434 (10) [M+.]; 401-403 (100) [M+-(OMe)]; 373-375 (47) [M+-(CO2Me)]; 294 (23) [M+-(Br,
CO2Me)]; 266 (9). Anal. Calcd for C20H17BrO4S: C, 55.44; H, 3.95. Found: C, 55.75; H, 3.68.
Compound 3b is identical to that obtained following the modified procedure described below.
Modified procedure of the Sandmeyer reaction (Protocol B)
Methyl 7,8-dimethoxythieno[3,4-c]cinnoline-3-carboxylate (3a)
To a hot (70°C) stirred solution of anhydrous CuBr2 (0.9 g, 4.09 mmol) and tert-butylnitrite (0.7 mL, 5.11
mmol, 90%) in MeCN (20 mL) was added slowly methyl 3-amino-4-(3,4-dimethoxyphenyl) thiophene-2-
carboxylate 1a (1.0 g, 3.41 mmol). The reaction was stirred at this temperature till completion of the
reaction (TLC). After cooling to rt the reaction mixture was poured into an aqueous solution of HCl. The

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residue obtained after the usual work-up was purified by silica gel column chromatography using AcOEt
/MeOH (9:1) as an eluent to give compound 3a as a bright yellow crystals (1.16 g, 97% yield), mp 236 °C.
IR (KBr): 3438, 3180, 1717, 1636-1424, 1315, 1268, 1246, 1072, 1069 cm-1. 1H NMR (DMSO-d6) δ 9.16
(s, 1H, H1); 8.06 (s, 1H, H6); 8.04 (s, 1H, H9); 4.06 (s, 3H, OMe); 4.02 (s, 3H, OMe); 3.99 (s, 3H,
CO2Me). 13C NMR (DMSO-d6) δ 163.5; 159.9; 159.2; 155.4; 155.3; 147.5; 145.7; 143.5; 130.0; 126.8;
117.3; 55.2; 54.1; 53.5. LC-MS: tr = 2.88 min. 305 [M+]. Anal. Calcd for C14H12N2O3S: C, 55.26; H,
3.97; N, 9.21. Found: C, 54.99; H, 3.72; N, 9.44.
Methyl 8-benzyloxy-7-methoxythieno[3,4-c]cinnoline-3-carboxylate (3b)
This compound was obtained following the same procedure described for 3a using methyl 3-amino-4-(3-
benzyloxy-4-methoxyphenyl)thiophene-2-carboxylate 1b. Bright orange powder (0.93 g, 90% yield), mp
1
236 °C. IR (KBr): 3090, 2925, 2237, 1704, 1607-1415, 1274, 1259, 1247, 1199, 1190, 1118 cm-1. H
NMR (DMSO-d6) δ 9.11 (s, 1H, H1); 8.20 (s, 1H, H6); 8.05 (s, 1H, H9); 7.57 (d, 3JHoHm = 5.9 Hz, 2H, Ho);
7.44 (dd, 3JHmHo = 3JHmHp = 5.9 Hz, 2H, Hm); 7.37 (t, 3JHpHm = 5.9 Hz, 1H, Hp); 5.37 (s, 2H, OCH2); 4.02 (s,
3H, OMe); 3.99 (s, 3H, CO2Me). 13C NMR (DMSO-d6) δ 160.8 (s, 1C, CO); 159.7 (s, 1C, CIV); 158.7 (s,
1C, CIV); 155.4 (s, 1C, CIV); 154.3 (s, 1C, CIV); 147.4 (s, 1C, CIV); 145.7 (s, 1C, CH); 144.9 (s, 1C, CH);
129.9 (s, 1C, C1H); 116.6 (s, 1C, CIV); 114.6 (s, 1C, CIV); 110.3 (s, 2C, CHo); 110.1 (s, 2C, CHm); 109.7
(s, 1C, CHp); 55.6 (s, 1C, CH2); 55.1 (s, 1C, Meester); 54.4 (s, 1C, OMe). LC-MS: tr = 10.02 min.; 381
[M+]. Anal. Calcd for C20H16N2O4S: C, 63.15; H, 4.24; N, 7.36. Found: C, 62.85; H, 4.48; N, 7.25.
Methyl 3-bromo-4-(4-methoxyphenyl)thiophene-2-carboxylate (4c)
This compound was obtained following the same procedure described for 3a using methyl 3-amino-4-(4-
methoxyphenyl)thiophene-2-carboxylate 1c
Crystallization from EtOH gave colorless crystals (8.14 g, 95% yield), mp 124 °C. IR (KBr): 3054, 1720,
1
3
1602-1418, 1275, 1117 cm-1. H NMR (DMSO-d6) δ 8.06 (s, 1H, H5); 7.37 (d, JHH = 7.8 Hz, 2H, HAr);
7.01 (d, 3JHH = 7.8 Hz, 2H, HAr); 3.84 (s, 3H, OMe); 3.79 (s, 3H, CO2Me). 13C NMR (DMSO-d6) δ 160.6
(s, 1C, CO); 159.2 (s, 1C, C2); 143.5 (s, 1C, CAr); 130.5 (s, 2C, CHAr); 130.0 (s, 1C, C5H); 127.3 (s, 1C,
C4); 126.7 (s, 1C, C3); 117.3 (s, 1C, CAr); 113.8 (s, 2C, CHAr); 55.2 (s, 1C, Meester); 52.5 (s, 1C, OMe).
MS m/z (%): 327-329 (19) [M+.]; 296-298 (100) [M+-(OMe)]; 268-270 (29) [M+-(CO2Me)]; 188 (35)
[M+-(Br, CO2Me)]; 173 (10). Anal. Calcd for C13H11BrO3S: C, 47.72; H, 3.39. Found: C, 47.89; H, 3.51.
Synthesis of diazonium tetrafluoroborate salts

HETEROCYCLES, Vol. 75, No. 12, 2008
3023
4-(3,4-Dimethoxyphenyl)-2-(methoxycarbonyl)thiophene-3-diazonium tetrafluoroborate (6a)
A solution of methyl 3-amino-4-(3,4-dimethoxyphenyl)thiophene-2-carboxylate 1a (1.0 g, 3.41 mmol) in
an aqueous solution of tetrafluoroboric acid (5 mL, 50%) was stirred at 50 °C during 30 min. Then, the
solution was cooled to –15 °C and a solution of sodium nitrite (0.3 g, 3.75 mmol) in H2O (3 mL) was
slowly added during 20 min and the resulting solution was kept at this temperature for 1 h. The reaction
mixture was then treated with ether and the diazonium salt precipitate was filtered, washed with ether and
air dried to give red powder. (1.25 g, 93% yield), mp 216 °C. IR (KBr): 3093, 2958, 2269, 1702, 1603-
1438, 1300, 1249, 1202, 1065, 727 cm-1. 1H NMR (DMSO-d6) δ 8.45 (s, 1H, H5); 7.97 (s, 1H, HAr); 7.78
(d, 3JHH = 7.8 Hz, 1H, HAr); 7.20 (d, 3JHH = 7.8 Hz, 1H, HAr); 4.01 (s, 3H, OMe); 3.98 (s, 3H, OMe); 3.85
(s, 3H, CO2Me).
13C NMR (DMSO-d6) δ 160.8 (s, 1C, CO); 158.9 (s, 1C, C2); 145.7 (s, 1C, CAr); 142.6 (s, 1C, CAr); 130.7
(s, 1C, CHAr); 130.2 (s, 1C, C5H); 129.5 (s, 1C, C3); 127.2 (s, 1C, C4); 117.1 (s, 1C, CAr); 113.9 (s, 2C,
CHAr); 55.3 (s, 1C, Meester); 52.3 (s, 1C, OMe); 52.1 (s, 1C, OMe). LC-MS: tr = 7.78 min.; 306 [M+].
2-(Methoxycarbonyl)-4-(4-methoxyphenyl)thiophene-3-diazonium tetrafluoroborate (6c)
This compound was obtained following the same procedure described for 6a using methyl 3-amino-4-(4-
methoxyphenyl)thiophene-2-carboxylate 1c. Red powder (1.3 g, 98% yield), mp 162 °C. IR (KBr): 3412,
1
3112, 2966, 2248, 1714, 1609-1470, 1438, 1413, 1271, 1256, 1062, 1023 cm-1. H NMR (DMSO-d6)
3
3
δ 8.45 (s, 1H, H5); 7.78 (d, JHmHo = 7.8 Hz, 2H, HAr); 7.19 (d, JHoHm = 7.8 Hz, 2H, HAr); 4.06 (s, 3H,
13
OMe); 3.85 (s, 3H, CO2Me). C NMR (DMSO-d6) δ 160.8 (s, 1C, CO); 158.9 (s, 1C, C2); 143.5 (s, 1C,
CAr); 130.7 (s, 2C, CHAr); 130.2 (s, 1C, C5H); 129.4 (s, 1C, C3); 127.3 (s, 1C, C4); 117.1 (s, 1C, CAr);
114.0 (s, 2C, CHAr); 55.3 (s, 1C, Meester); 52.1 (s, 1C, OMe). LC-MS: tr = 7.73 min.; 276 [M+].
ACKNOWLEDGMENTS
The authors thank «Les laboratoires Servier» and the « Conseil Régional de Basse-Normandie- France »
for their financial support.
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