Sequential construction of complex pyrrole-pyrrole or pyrrole-pyrazole systems from 1,2-diaza-1,3-butadienes

Article abstract of DOI:10.1055/s-1999-2848

The treatment of cyanoacetic acid hydrazide or ethyl 3-hydrazino-3- oxopropionate with methyl 2-chloroacetoacetate leads to the corresponding hydrazone derivatives. In the presence of sodium carbonate, these compounds react at room temperature with acetoacetanilide or 2,4-pentanedione to give the relevant 1-aminopyrrole rings. In the presence of sodium methoxide, the activated methylene group present on the 1-amino side chain of these heterocycles attacks at room temperature 1,2-diaza-1,3-butadienes affording the respective hydrazonic 1,4-adducts. Under basic conditions, these adducts surprisingly cyclise at room temperature in different way providing pyrrole- pyrrole or pyrrole-pyrazole systems depending on the starting cyano or ethylcarboxylate group, respectively.

Full text of DOI:10.1055/s-1999-2848

LETTER
1367
Sequential Construction of Complex Pyrrole-Pyrrole or Pyrrole-Pyrazole
Systems from 1,2-Diaza-1,3-butadienes
Orazio A. Attanasi, Lucia De Crescentini, Paolino Filippone,* Barbara Guidi, Francesca R. Perrulli, Stefania
Santeusanio
Istituto di Chimica Organica della Facoltà di Scienze, Università di Urbino, Piazza della Repubblica 13, 61029 Urbino, Italy
Fax +39.0722.2907; E-mail: attanasi@fis.uniurb.it
Received 16 June 1999
ene group present on the 1-amino side chain of 1-ami-
nopyrrole rings (6a–d) attacks in THF at room
temperature 1,2-diaza-1,3-butadienes (7a–c)13 affording
the respective hydrazonic 1,4-adducts (8a–f).11 In the
Abstract: The treatment of cyanoacetic acid hydrazide or ethyl 3-
hydrazino-3-oxopropionate with methyl 2-chloroacetoacetate leads
to the corresponding hydrazone derivatives. In the presence of sodi-
um carbonate, these compounds react at room temperature with ac-
etoacetanilide or 2,4-pentanedione to give the relevant 1- presence of freshly generated sodium methoxide, these
aminopyrrole rings. In the presence of sodium methoxide, the acti-
adducts surprisingly cyclise in THF/MeOH mixture at
vated methylene group present on the 1-amino side chain of these
room temperature with different fate providing pyrrole-
heterocycles attacks at room temperature 1,2-diaza-1,3-butadienes
pyrrole (9a–c) or pyrrole-pyrazole (9d–f) systems de-
affording the respective hydrazonic 1,4-adducts. Under basic condi-
pending on the starting cyano or ethylcarboxylate group,
tions, these adducts surprisingly cyclise at room temperature in dif-
respectively. In the intramolecular pyrrole closure of 1,4-
adducts 8a–c to produce 9a–c,11 the hydrazonic nitrogen
atom (>C=N-NH-) and the cyano group of the former cy-
anoacetic acid hydrazide cooperate while in pyrazole clo-
sure affording 9d–f,11 the amino nitrogen atom (>C=N-
NH-) of the 1,4-adducts 8d–f and the carboxylate group of
the 1,2-diaza-1,3-butadiene molecule 7 are involved with
loss of an alcohol molecule. Since the second pyrrole clo-
sure was expected being in agreement with our previous
results,3a,b,d,12 it is noteworthy that the pyrazole closure was
quite surprising keeping in mind the formation of 1H-pyr-
rol-2(3H)-ones observed in previous similar circumstanc-
es,14 although the pyrazole annulation otherwise has also
been detected (see Scheme and Table).3c,d
ferent way providing pyrrole-pyrrole or pyrrole-pyrazole systems
depending on the starting cyano or ethylcarboxylate group, respec-
tively.
Key words: hydrazones, 1,2-diazal, 3-butadienes, cyclization, pyr-
roles, pyrazoles
The reactive heterodiene moiety of 1,2-diaza-1,3-buta-
dienes allows valuable organic functionalizations and
preparation of various heterocyclic derivatives, especially
pyrroles and pyrazoles.1-4 These rings represent the core
of a number of interesting organic, polymeric, natural,
biological, medicinal, analytical and agricultural
products.3a-c,4d,5-10
In continuation of our ongoing activity aimed to investi-
gate closely the synthetic usefulness of this class of build-
ing blocks, we now report the convenient construction of
complex pyrrole-pyrrole or pyrrole-pyrazole systems in-
volving the sequential utilization of different conjugated
azo-alkene species followed by heteroring closures.
Table Yield, melting point, and reaction time of a-chlorohydrazones
(3a-b), 1-aminopyrroles (6a-d), 1,4-adducts (8a-f), pyrrolo-pyrroles
(9a-c), and pyrrolo-pyrazoles (9d-f).
The treatment of cyanoacetic acid hydrazide (1a) or ethyl
3-hydrazino-3-oxopropionate (1b) with methyl 2-chloro-
acetoacetate (2) in THF at room temperature leads to the
corresponding a-chlorohydrazone derivatives (3a–b).11 In
the presence of sodium carbonate, these last compounds
react in THF at room temperature with acetoacetanilide or
2,4-pentanedione to give the relevant 1-aminopyrrole
rings (6a–d).11 Presumably, this latter reaction occurs via
the formation in situ of the conjugated azoalkene interme-
diate 5, as shown by the appearance of the typical red co-
lour of such a compound due to the base-promoted
dehydrohalogenation of the corresponding a-chlorohy-
drazone derivative. The subsequent fading of the red co-
lour occurs when the compound 5 loses the conjugated
double bonds by addition of the b-dicarbonyl derivative.
This hypothesis is also supported by previous analogous
findings.12 Under basic conditions, the activated methyl-
aYield of pure isolated products. bMelting points are uncorrected.
cMelting point occurs with decomposition.
Synlett 1999, No. 9, 1367–1370 ISSN 0936-5214 © Thieme Stuttgart · New York

1368
O. A. Attanasi et al.
LETTER
O
O
O
O
Cl
Na2CO3, THF/rt
R1
N
R1
NH2
COOCH3
R1
N
+
R2
CH3
N
COOCH3
N
H
H3C
N
H
COOCH3
CH3
Cl
CH3
3a-b
O
O
5
2
4a-b
1a-b
CH3OOC
CH3
CH3OOC
CH3
O
O
COOR3
R2
N
R1
MeONa, THF/rt
N
R2
N
N
COOR4
N
H
COOR4
N
H
N
R3OOC
N
O
CH3
O
R1
8a-f
NaH, THF+MeOH/rt
CH3
H
CH3
CH3
7a-c
6a-d
R1 = CN
R1 = COOEt
COOR4
CH3OOC
CH3
COOR3
CH3
O
CH3OOC
R2
CH3
N
O
H
O
R2
N
N
N
H
N
N
H
N
COOR4
CH3
O
CH3
H2N
NH
O
R1
CH3
9a-c
9d-f
Scheme
(M.U.R.S.T.-Roma), the Consiglio Nazionale delle Ricerche
(C.N.R.-Roma) and the Università degli Studi di Urbino.
It is worth emphasising that pyrrole and/or pyrazole rings
linked by -CO-NH- bridge are known to possess antitu-
mor activity.15
References and Notes
In conclusion, this method offers a new, mild, simple, and
convenient entry to 1-aminopyrrole, pyrrole-pyrrole, and
pyrrole-pyrazole derivatives.
(1) Schantl, J. G. in Houben-Weyl, 4th ed., Vol. E15; Kropf, H.;
Schaumann, E., Eds.; Thieme: Stuttgart, 1990, p. 909. Schantl,
J. G. Il Farmaco 1995, 50, 379; and the references cited
therein.
(2) Attanasi, O. A.; Caglioti, L. Org. Prep. Proced. Int. 1986, 18,
299; and the references cited therein.
Acknowledgement
This work was supported by financial assistance from the Ministero
dell'Università
e della Ricerca Scientifica e Tecnologica
Synlett 1999, No. 9, 1367–1370 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Sequential Construction of Complex Pyrrole-Pyrrole
1369
(3) a) Attanasi, O. A.; Filippone, P.; Serra-Zanetti, F. in Trends in
Heterocyclic Chemistry; Menon, J., Ed.; 1993, Vol. 3, p. 461.
b) Attanasi, O. A.; Filippone, P.; Serra-Zanetti, F. in Progress
in Heterocyclic Chemistry; Suschitzky, H.; Scriven, E. F. V.,
Eds.; Pergamon: Oxford, 1995; Vol. 7, p. 1. c) Attanasi, O. A.;
Filippone, P. in Topics in Heterocyclic Systems - Synthesis,
Reactions and Properties; Attanasi, O. A.; Spinelli, D., Eds.;
1996, Vol. 1, p. 157. d) Attanasi, O. A.; Filippone, P. Synlett
1997, 1128; and the references cited therein.
(4) a) Ferguson, G.; Lough, A. J.; Mackay, D.; Weeratunga, G. J.
Chem. Soc. Perkin Trans. 1 1991, 3361. b) Avalos, M;
Babiano, R.; Cintas P.; Jiménez, J. L.; Molina, M. M.;
Palacios, J. C.; Sánchez, J. B. Tetrahedron Lett. 1991, 32,
2513. c) Gilchrist, T. L.; Lemos, A. J. Chem. Soc. Perkin
Trans. 1 1993, 1391. d) South, M. S.; Jakuboski, T. L.;
Westmeyer, M. D.; Dukesherer, D. R. J. Org. Chem. 1996, 61,
8921.
(5) Gribble, G. W. Pyrroles and Benzo Derivatives: Applications,
Vol. 2, Chapt. 4, Katritzky, A. R.; Rees, C. W.; Scriven E. F.
V., Eds.; In Comprehensive Heterocyclic Chemistry II,
Pergamon-Elsevier Science: Amsterdam, 1996. Cirrincione,
G.; Almerico, A. M.; Aiello, E.; Dattolo, G. Pyrroles Part
Two: The Synthesis, Reactivity, and Physical Properties of
Substituted Pyrroles, Chapt. 3, Aminopyrroles; p. 299, Jones,
R. A., Ed.; In The Chemistry of Heterocyclic Compounds;
John Wiley & Sons: New York, 1992.
(6) Katritzky, A. R.; Rees, C. W.; Scriven E. F. V., Eds.;
Comprehensive Heterocyclic Chemistry II, Pergamon-
Elsevier Science: Amsterdam, 1996. Suschitzky, H.; Gribble,
G. W., Eds.; Progress in Heterocyclic Chemistry; Pergamon
Press: Oxford, 1996; Vol. 8. Gribble, G. W.; Gilchrist, T. L.,
Eds.; Progress in Heterocyclic Chemistry; Pergamon Press:
Oxford, 1997; Vol. 9. Gribble, G. W.; Gilchrist, T. L., Eds.;
Progress in Heterocyclic Chemistry; Pergamon Press: Oxford,
1998; Vol. 10.
Na2SO4 and evaporated in vacuo. The residue afforded pure 1-
aminopyrrole 6a or 6b by crystallization from MeOH-Et2O or
by chromatographic purification on silica gel column, eluting
with cyclohexane-ethyl acetate mixtures, respectively.
6a: white powder, mp 238-242 °C (dec.); IR (nujol) 3356,
3168, 2262, 1728, 1688, 1636, 1603 cm-1; 1H-NMR (DMSO-
d6) d 2.12 (s, 3 H, CH3), 2.29 (s, 3 H, CH3), 3.65 (s, 3 H,
OCH3), 4.10 (s, 2 H, CH2, D2O exch.), 7.03 (t, 1 H, J = 7.5 Hz,
Ar), 7.30 (t, 2 H, J = 7.5 Hz, Ar), 7.68 (d, 2 H, J = 7.5 Hz, Ar),
10.17 (s, 1 H, NH, D2O exch.), 11.57 (s, 1 H, NH, D2O exch.);
13C-NMR (DMSO-d6) d 9.52 (q), 10.34 (q), 24.07 (t), 51.05
(q), 107.53 (s), 115.28 (s), 116.05 (s), 119.31 (d), 122.90 (d),
126.53 (d), 130.32 (s), 134.60 (s), 139.66 (s), 162.58 (s),
163.32 (s), 164.52 (s); MS m/z (relative intensity) 354 (M+,
16), 262 (100). Anal. calcd. for C18H18N4O4: C, 61.01; H,
5.12; N, 15.81. Found: C, 61.11; H, 5.08; N, 15.89.
6b: colorless crystals, mp 175-177 °C; IR (nujol) 3297, 3169,
1751, 1724, 1683, 1635, 1596 cm-1; 1H-NMR (DMSO-d6) d
1.22 (t, 3 H, J = 7.2 Hz, OCH2CH3), 2.13 (s, 3 H, CH3), 2.30
(s, 3 H, CH3), 3.54 (s, 2 H, CH2, D2O exch.), 3.65 (s, 3 H,
OCH3), 4.16 (q, 2H, J = 7.2 Hz, OCH2CH3), 7.03 (t, 1 H, J =
7.5 Hz, Ar), 7.29 (t, 2 H, J = 7.5 Hz, Ar), 7.66 (d, 2 H, J = 7.5
Hz, Ar), 10.18 (s, 1 H, NH, D2O exch.), 11.42 (s, 1 H, NH,
D2O exch.); 13C-NMR (DMSO-d6) d 9.50 (q), 10.31 (q),
13.93 (q), 40.60 (t), 51.02 (q), 61.03 (t), 107.35 (s), 115.88 (s),
119.28 (d), 122.85 (d), 128.50 (d), 130.50 (s), 134.94 (s),
139.68 (s), 163.35 (s), 164.62 (s), 164.77 (s), 166.97 (s); MS
m/e (relative intensity) 401 (M+, 10), 309 (100). Anal. calcd.
for C20H23N3O6: C, 59.84; H, 5.78; N, 10.47. Found: C, 59.66;
H, 5.94; N, 10.57.
Preparation of 1,4-adducts 8a and 8d. 1,2-Diaza-1,3-
butadiene 7a (1.0 mmol) prepared according to Ref.13,
dissolved in THF (5 ml), was slowly added to a magnetically
stirred solution of the pyrrole 6a or 6b (1.0 mmol) in THF (5
ml) containing a catalytic amount of sodium methoxide. The
reaction mixture was allowed to stand at r.t. until the complete
disappearance of the reagents (monitored by TLC). The
solvent was removed under reduced pressure and the residue,
dissolved in EtOAc, was washed with H2O in a separatory
funnel. The organic layer, dried over anhydrous Na2SO4, was
evaporated in vacuo. Pure derivative 8a was obtained after a
chromatographic purification on silica gel column, eluting
with cyclohexane-ethyl acetate mixtures, while 8d was
obtained after crystallization from EtOAc-Et2O.
(7) Elguero, J. in Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Ed.; Pergamon Press: Oxford, 1984; Vol. 5,
p. 167.
(8) Lednicer, D. The Organic Chemistry of Drug Synthesis, John
Wiley & Sons: New York, 1995. Blaney, J. M.; Hansch, C.
Comprehensive Medicinal Chemistry; Hansch, C.; Sammes,
P. G.; Taylor, J. B.; Ramsden, C. A., Eds.; Pergamon Press:
Oxford, 1990. Goodman Gilman, A.; Rall, T. W.; Nies, A. S.;
Taylor, P., Eds.; Goodman and Gilman’s The
Pharmacological Basis of Therapeutics; 8th ed.; Pergamn
Press: Oxford, 1990.
(9) Gasparic, J.; Svobodová, D.; Matysová, A. J. Chromatogr.
1974, 88, 364.
(10) Copping, L.; Kidd, H.; Tomilin, C., Eds.; The Pesticide Index,
British Crop Protection Council and The Royal Society of
Chemistry, Cambridge: 1995. Kidd, H.; James, D. R., Eds.;
The Agrochemicals Handbook, The Royal Society of
Chemistry, Cambridge: 1991.
8a: white powder, mp 148-153 °C (dec.); IR (nujol) 3294,
3275, 2266, 1756, 1720, 1709, 1687, 1640 cm-1; 1H-NMR
(DMSO-d6) d 1.14-1.26 (m, 3 H, OCH2CH3), 1.43-1.46 (m, 9
H, OC(CH3)3), 1.95-2.29 (m, 9 H, 3 CH3), 3.64 (s, 3 H,
OCH3), 4.08-4.22 (m, 3 H, OCH2CH3 and CH), 4.66-4.70 (m,
1 H, CH, D2O exch.), 7.03 (t, 1 H, J = 7.3 Hz, Ar), 7.29 (t, 2
H, J = 7.3 Hz, Ar), 7.67 (d, 2 H, J = 7.3 Hz, Ar), 9.97 (bs, 1 H,
NH, D2O exch.), 10.14 (bs, 1 H, NH, D2O exch.), 12.07 (bs, 1
H, NH, D2O exch.). Anal. calcd. for C29H36N6O8: C, 58.38; H,
6.08; N, 14.09. Found: C, 58.22; H, 6.23; N, 14.17.
8d: white powder, mp 176-178 °C (dec.); IR (nujol) 3289,
3194, 3133, 1747, 1707, 1658, 1640, 1599 cm-1; 1H-NMR
(DMSO-d6) d 1.15-1.26 (m, 6 H, 2 OCH2CH3), 1.43-1.47 (m,
9 H, OC(CH3)3), 1.94-2.27 (m, 9 H, 3 CH3), 3.64 (s, 3 H,
OCH3), 3.89-4.01 (m, 1 H, CH), 4.08-4.19 (m, 4 H, 2
OCH2CH3), 4.21-4.37 (m, 1 H, CH, D2O exch.), 7.03 (t, 1 H,
J = 7.3 Hz, Ar), 7.30 (t, 2 H, J = 7.3 Hz, Ar), 7.68 (d, 2 H, J =
7.3 Hz, Ar), 9.79 (bs, 1 H, NH, D2O exch.), 10.16 (bs, 1 H,
NH, D2O exch.), 11.88 (bs, 1 H, NH, D2O exch.). Anal. calcd.
for C31H41N5O10: C, 57.84; H, 6.42; N, 10.88. Found: C,
57.70; H, 6.50; N, 10.72.
(11) A representative procedure for the preparation of 3a, 3b,
6a, 6b, 8a, 8d, 9a, and 9d is as follows:
Preparation of a-chlorohydrazones 3a and 3b. These
compounds were prepared according to the previous paper.12a
Preparation of 1-aminopyrroles 6a and 6b. a-
Chlorohydrazone derivative 3a or 3b (1.0 mmol) was added
portionwise to a stirred suspension of acetoacetanilide 4a (2.0
mmol) and anhydrous sodium carbonate (1.5 mmol) in THF
(10 ml). The reaction mixture was allowed to stand at r.t. until
the complete disappearance of a-chloro-hydrazone 3a or 3b
(monitored by TLC). The reaction solvent was evaporated
under reduced pressure, the residue suspended in ethyl acetate
and washed in a separatory funnel with HCl 2N (until pH 2)
and with H2O. The organic layer was dried over anhydrous
Preparation of pyrrolo-pyrrole 9a or pyrrolo-pyrazole 9d. To
a magnetically stirred solution of 1,4-adduct 8a or 8b (1.0
Synlett 1999, No. 9, 1367–1370 ISSN 0936-5214 © Thieme Stuttgart · New York

1370
O. A. Attanasi et al.
LETTER
mmol) in a mixture 1:1 of THF-MeOH (10 ml) was added
sodium hydride 60% pure in mineral oil (1.1 mmol).The
reaction mixture was allowed to stand at r.t. until the complete
disappearance of compound 8a or 8b (monitored by TLC).
THF was removed under reduced pressure and the residue was
suspended in ethyl acetate, treated in a separatory funnel with
HCl 2N until pH 5.5 (for derivative 9a) or pH 1 (for derivative
9d) and then washed with H2O. The organic layer, dried over
anhydrous Na2SO4, was evaporated in vacuo. The crude was
crystallized from Et2O or EtOAc-Et2O to afford pure 9a or 9d
derivative, respectively.
9a: white powder, mp 160-162 °C (dec.); IR (nujol) 3442,
3332, 3194, 1726, 1667, 1654, 1621, 1615, 1597, 1566 cm-1;
1H- NMR (DMSO-d6) d 1.32 (t, 3 H, J = 7.2 Hz, OCH2CH3),
1.47 (s, 9 H, OC(CH3)3), 2.14 (s, 3 H, CH3), 2.27 (s, 3 H,
CH3), 2.31 (s, 3 H, CH3), 3.67 (s, 3 H, OCH3), 4.30 (q, 2 H, J
= 7.2 Hz, OCH2CH3), 6.65 (bs, 2 H, NH2, D2O exch.), 7.03 (t,
1 H, J = 7.5 Hz, Ar), 7.30 (t, 2 H, J = 7.5 Hz, Ar), 7.69 (d, 2
H, J = 7.5 Hz, Ar), 10.24 (s, 2 H, 2 NH, D2O exch.), 11.79 (s,
1 H, NH, D2O exch.); 13C-NMR (DMSO-d6) d 9.84 (q), 10.65
(q), 11.10 (q), 14.00 (q), 27.79 (q), 50.99 (q), 60.87 (t), 81.32
(s), 85.75 (s), 103.81 (s), 106.90 (s), 115.53 (s), 119.25 (d),
122.78 (d), 128.48 (d), 131.30 (s), 134.13 (s), 135.70 (s),
139.74 (s), 148.82 (s), 153.85 (s), 163.42 (s), 164.39 (s),
164.90 (s), 167.26 (s). Anal. calcd. for C29H36N6O8: C, 58.38;
H, 6.08; N, 14.09. Found: C, 58.26; H, 6.17; N, 14.16.
9d: white powder, mp 173-175 °C (dec.) IR (nujol) 3170,
3120, 1755, 1730, 1695, 1665, 1635, 1610, 1590 cm-1; 1H-
NMR (DMSO-d6) d 1.21 (t, 3 H, J = 7.2 Hz, OCH2CH3), 1.53
(s, 9 H, OC(CH3)3), 2.02 (s, 3 H, CH3), 2.14 (s, 3 H, CH3),
2.33 (s, 3 H, CH3), 3.65 (s, 3 H, OCH3), 4.19 (q, 2 H, J = 7.2
Hz, OCH2CH3), 4.64 (s, 1 H, CH, D2O exch.), 7.02 (t, 1 H, J
= 7.7 Hz, Ar), 7.29 (t, 2 H, J = 7.7 Hz, Ar), 7.67 (d, 2 H, J =
7.7 Hz, Ar), 10.16 (s, 1 H, NH, D2O exch.), 11.58 (s, 1 H, NH,
D2O exch.), 11.72 (bs, 1 H, NH, D2O exch.); 13C-NMR
(DMSO-d6) d 9.46 (q), 10.26 (q), 11.90 (q), 13.92 (q), 27.64
(q), 45.08 (d), 51.05 (q), 61.65 (t), 84.03 (s), 96.53 (s), 107.39
(s), 115.82 (s), 119.27 (d), 119.37 (s), 122.93 (d), 128.53 (d),
130.72 (s), 135.14 (s), 139.59 (s) 146.42 (s), 151.89 (s),
163.25 (s), 164.63 (s), 166.54 (s), 167.87 (s). Anal. calcd. for
C29H35N5O9: C, 58.28; H, 5.90; N, 11.72. Found: C, 58.36; H,
5.78; N, 11.64.
(12) a) Attanasi, O. A.; De Crescentini, L.; Giorgi, R.; Perrone, A.;
Santeusanio, S. Heterocycles 1996, 43, 1447. b) Attanasi, O.
A.; De Crescentini, L.; Filippone, P.; Perrulli, F. R.;
Santeusanio, S. Synlett 1999, 339. c) Attanasi, O. A.;
Colombani, S. M.; De Crescentini, L.; Giorgi, R.; Monti, S.;
Perrone, A.; Perrulli, F. R.; Renzetti, A. R.; Santeusanio, S. Il
Farmaco 1999, 54, 64.
(13) Attanasi, O. A.; Filippone, P.; Mei, A.; Santeusanio, S.
Synthesis 1984, 873. Sommer, S. Tetrahedron Lett. 1977, 117.
(14) Attanasi, O. A.; Filippone, P.; Mei, A.; Bongini, A.; Foresti,
E. Tetrahedron 1990, 46, 5685. Attanasi, O. A.; Filippone, P.;
Giovagnoli, D.; Mei, A. Synth. Commun. 1994, 24, 453.
Attanasi, O. A.; De Crescentini, L.; Foresti, E.; Serra-Zanetti,
F. Can. J. Chem. 1994, 72, 2305. Arcadi, A.; Attanasi, O. A.;
De Crescentini, L.; Rossi, E.; Serra-Zanetti, F. Tetrahedron
1996, 52, 3997.
(15) Arcamone, F. Il Farmaco 1993, 48, 143. Baraldi, P. G.;
Cacciari, B.; Guiotto, A.; Romagnoli, R.; Zaid, A. N.;
Spalluto, G. Il Farmaco 1999, 54 , 15; and the references cited
therein.
Article Identifier:
1437-2096,E;1999,0,09,1367,1370,ftx,en;L08199ST.pdf
Synlett 1999, No. 9, 1367–1370 ISSN 0936-5214 © Thieme Stuttgart · New York