Nitrilimine cycloadditions onto partially saturated furo[3,4- c]thieno[2,3-d]pyrazoles. A problem in site selectivity

Article abstract of DOI:10.3987/com-99-8811

Partially saturated furo[3,4-c]thieno[2,3-d]pyrazoles (7-10) have been submitted to 1,3-dipolar cycloaddition with a variety of nitrilimines. The competitive formation of products due to the dipolar attack at different dipolarophilic sites has been observed. The experimental evidence is discussed by taking into account electronic features of the reactive species as well as their steric encumbrance.

Full text of DOI:10.3987/com-99-8811

HETEROCYCLES, Vol. 53, No. 4, 2000, pp. 917 - 927, Received, 19th November, 1999
NITRILIMINE CYCLOADDITIONS ONTO PARTIALLY SATURATED
FURO[3,4-c]THIENO[2,3-d]PYRAZOLES.
A
PROBLEM IN SITE
SELECTIVITY
Gianluigi Broggini,b Luisa Garanti,a* Giorgio Moltenia, and Gaetano Zecchib
aDipartimento di Chimica Organica e Industriale dell’Università and Centro CNR,
Via Golgi 19, 20133, Milano, Italy
bDipartimento di Scienze Chimiche, Fisiche e Matematiche, Università
dell'Insubria, via Lucini 3, 22100 Como, Italy
Abstract - Partially saturated furo[3,4-c]thieno[2,3-d]pyrazoles (7-10) have been
submitted to 1,3-dipolar cycloaddition with a variety of nitrilimines. The
competitive formation of products due to the dipolar attack at different
dipolarophilic sites has been observed. The experimental evidence is discussed by
taking into account electronic features of the reactive species as well as their steric
encumbrance.
In the course of our research programme on intramolecular nitrilimine cycloadditions onto heteroaromatic
rings,1,2 we synthesised a number of strained tricyclic pyrazolines, including furo[3,4-c]thieno[2,3-d]-
pyrazoles (FTP). The latter were capable of further intermolecular cycloaddition due to the presence of
the dipolarophilic C=C and C=N bonds. Double cycloaddition products were actually obtained, but the
observed site-preference revealed somewhat puzzling. Aimed at a better understanding of the factors
governing the discrimination between the two dipolarophilic functionalities, we undertook a systematic
investigation on the behavior of nitrilimines (4-6) towards FTP (7-10) as a function of the electron-
withdrawing or -donating character of substituents R and R1.
RESULTS AND DISCUSSION
As suitable precursors of the desired nitrilimines (4-6), we synthesised the hydrazonoyl chlorides (1-3) by
coupling of the appropriate diazonium salts on benzyl 2-chloro-3-oxobutanoate (Scheme 1). In order to
promote the in situ generation of the above-mentioned nitrilimines, base treatment of 1-3 was
accomplished with a two-fold molar excess of silver carbonate in dry dioxane at 75°C in the presence of

Scheme 1
N
R
N
Cl
O
O
O
O
Ag2CO3
dioxane
NH N
R
Ph
O
Ph
Cl
Cl
1
R
1-3
Ph
O
N
O
R1
H H
B
C
N
N
N
S
N
O
H
A
O
N
O
S
O
R
11
O
O
7-9
N N
Ph
1
R
R
4-6
COOCH2Ph
N
O
N
N
N
S
O
1
1
1
7: R = H; 8: R = Me; 9: R = NO
2
1,4: R = H; 2,5: R = Me; 3,6: R = NO
2
12
R
Table 1. Base-promoted reaction between hydrazonoyl chlorides (1-3) and TFP (7-9).
_______________________________________________________________________________
Eluentb
Entry
R
R1 Time
(h)
Product and Yield
Ratio of
12/11
__________________________________________
7
8
9
11
12
_______________________________________________________________________________
__
__
__
__
__
__
__
__
__
H
Me
NO2
H
H
H
H
Me
Me
32
19
26
28
12
16
30
30
29
45
28
26
35
10
21
25
7
10
27
0.5a
12
12
10
7
0.46 AcOEt-hexane 2:1
0.34 Et2O-LP 2:1
a
b
c
d
e
f
g
h
i
25
1.0
Et2O-LP 2:1
__
40
10
0.33 Et2O-LP 2:1
0.04 Et2O-LP 2:1
__
__
__
__
__
1a
7
Me
NO2 Me
NO2
30
1.0
1.2
1.5
20
AcOEt-hexane 1:1
Et2O
Et2O
__
H
22
11
39
12
41
10
__
__
Me NO2
NO2 NO2
AcOEt-CH2Cl2 1:20
_______________________________________________________________________________
aNot isolated in the analytically pure state. bLP = light petroleum, bp 40-60°C.

Scheme 2
O
O
OMe
Ag2CO3
dioxane
NH N
N N
R
R
OMe
Cl
13-15
16-18
O
N
1
R
N
O
S
9,10
1
1
R
R
1
MeO
N
O
R
COOMe
N
O
N
O
N
N
N
N
MeO
O
N
COOMe
S
S
N
O
N
N
N
N
N
O
S
R
R
20
19
O
O
R
R
21
1
1
9: R =NO2; 10: R =Cl
13,16: R=Me; 14,17: R=Cl; 15,18: R=NO2
Table 2. Base-promoted reaction between hydrazonoyl chlorides (13-15) and TFP (9,10).
_________________________________________________________________________
Product and Yield (%)a
Entry
R
R1 Time
(h)
Eluent
__________________________________________
9
10
19
20
21
_________________________________________________________________________
__
Me
NO2 NO2
Cl Cl
NO2
11
40
24
10
12
15
20
10
15
20
10 AcOEt - Hexane 2:1
10 AcOEt - CH2Cl2 1:19
10 AcOEt - Hexane 1:2
a
b
c
__
20
__
10
_________________________________________________________________________
aIsolation yields.

equimolar amount of the appropriate FTP. Reaction times, products and eluants are collected in Table 1.
Structural assignment of products (11) and (12) are unambiguous and rely upon elemental analyses and
spectral data, including 1H-NMR, IR, and MS spectrometry (see experimental). As far as 1H NMR spectra
are concerned, the HA hydrogen of 11 resonates as a doublet in the range of δ 6.28-6.36. Those values are
fully coherent with the depicted regiochemistry, which requires that HA is linked on the carbon connected
with a nitrogen and a sulfur.2 The reversed regiochemistry must be rejected on this basis. Furthermore, HC
resonates as a singlet in the range of δ 5.96-6.03 ppm; such chemical shifts and spin multiplicity agrees
with those observed for structurally related tetracyclic pyrazolines.2 In fact, the stereochemical relationship
between HB and HC must be anti due to the apparent lack of vicinal coupling (Jvic< 1 Hz); the latter point is
substantiated by several literature examples concerning the same kind of disposition in strained policyclic
structures.3,4 IR spectra of 12 also show diagnostic evidence; higher frequencies appeared for the
unconjugated lactone carbonyl in comparison with the conjugated one of 11.
As can be inferred from Table 1, sizable amounts of the starting FTP were recovered, thus evidencing their
modest dipolarophilic reactivity. Furthermore, the extent of the cycloaddition depends upon the substituent
R placed on the phenyl ring of the nitrilimine counterpart; the electron-donating methyl group of 5
generally works better than the electron-withdrawing nitro group of 6. This behavior, as well as the
regiochemical outcome, may be accounted by assuming the HOMO-dipole (LUMO-dipolarophile)
controlled nature of the cycloaddition.3,5
The competition between the two dipolarophilic functionalities of FTP is fairly dependent on the R1
substituent placed on the phenyl ring of the FTP. The electron-withdrawing nitro group of 9 works to
favor the attack of the 1,3-dipolar intermediates to the C=N over the C=C bond, while the electron-
donating methyl group of 8 just reverts this preference. When R1=H, an intermediate behavior is operative.
Furthermore, for a given R1 on FTP, the site selectivity of the cycloaddition depends upon the electronic
features of the nitrilimines. So, with respect to the results obtained with unsubstituted nitrilimine (4)
(R=H), the nitro group of nitrilimine (6) somewhat facilitates the addition onto the C=N bond, while the
methyl group of nitrilimine (5) shows the reversed effect. This selectivity is clearly observedby the ratio of
12/11 in Table 1.
To this point, we perceived the opportunity studying whether steric encumbrance on the C-terminusof the
dipolar intermediates could have some influence on dictating the site-preference ofthe cycloaddition. Thus,
we synthesised the hydrazonoyl chlorides (13-15) and submitted them to the silver carbonate treatment in
the presence of equimolar amount of FTP (9) and (10) (Scheme 2). A lack of site selectivity was found,
giving cycloadducts (19) and (20) in 1:1 ratio. The formation of products (21) arising from a double
cycloaddition process is in line with this statement.

The cycloaddition outcomes of all the above reactions do not harmonise with the predictions based on the
FMO theory5,6 at the PM37 level (Figure 1). These calculations8 indicates that the C=N site of FTP,
although moderately sensitive to the R1 substituent, should be more reactive than the C=C site towards
electron-rich as well as electron-deficient nitrilimines.
5
8
9
6
N
N
S
N
S
N
E (eV)
0
+0.369
+0.314
-0.469
-0.964
-1.348
-1.635
-8.619
-9.110
-9.441
-9.428
-9.718
-9.718
Figure 1. FMO energies for nitrilimines 5,6 and FTP 8,9 calculated with the PM3 method.
It remains to be added that an attempted reaction between 9 and 2 by the standard triethylamine method
gave, besides some amounts of tarry material arising from the thermal decomposition of nitrilimine 5,
quantitatively unreacted 9. Such kind of behavior is not surprising, since the fast generation of the
nitrilimine intermediate, which occurs in the presence of triethylamine, can force intermolecular processes
leading exclusively to resinous material. The effectiveness of silver carbonate in a heterogeneous medium is
perhaps the consequence of a very slow generation of the nitrilimine.9 Furthemore, one can tentatively
suggest that the Ag+ cation, due to its known complexating ability towards double-bonded functionalities,10
might be involved in the transition state of the cycloaddition, so determining some kind of perturbation of
the molecular orbitals of the reactants.
In conclusion, on the basis of our experimental findings, the site preference in nitrilimine cycloadditions to
FTP seems to be dictated by a subtle interplay of electronic and steric factors. Notwithstanding, the

nitrilimine cycloaddition onto FTP constitutes an intriguing tool in the synthesis of fused tetra- and
pentacyclic heterocycles not easily accessible by other routes.
EXPERIMENTAL
Melting points were determined with a Büchi apparatus and are uncorrected. IR spectra were recorded on
an FT IR Perkin Elmer 1725 X spectrophotometer. MS spectra were determined with a VG-70EQ
1
apparatus. H-NMR spectra were taken with a Bruker AC 300 or AMX 300 instrument in CDCl3
solutions; chemical shifts are given as δ ppm from Me4Si and J values are given in Hz.
Benzyl 2-chloro-3-oxobutanoate11 as well as compounds (13,12 14,13 and 1512) was prepared according to
literature procedures.
Preparation of hydrazonoyl chlorides (1-3); General Procedure. A solution of the proper aniline (7.5
mmol) in 6M hydrochloric acid (6.5 mL) and methanol (8 mL) was treated with sodium nitrite (0.73 g,
10.5 mmol) under vigorous stirring and ice cooling. After 10 min, the cold mixture was adjusted to pH 5
with sodium acetate and cold benzyl 2-chloro-3-oxobutanoate (1.70 g, 7.5 mmol) in methanol (1.5 mL)
was added dropwise. The mixture was stirred under cooling for 2 h, then at rt for 15 h. The solvent was
partly removed under reduced pressure, and the residue was taken up with ether (70 mL). The organic
layer was washed firstly with 5% sodium hydrogencarbonate (25 mL), then with water (50 mL), and dried
over sodium sulfate. The solvent was evaporated and the residue was crystallised from diisopropyl ether
giving 1-3 in the analytically pure form.
Benzyl 2-Chloro-2-phenylhydrazonoacetate (1) (1.08 g, 50%) as pale yellow prisms having mp 116°C; IR
1
(nujol): 3260, 1710 (cm-1); H-NMR: 5.37 (2H, s), 7.00-7.50 (10H, m), 8.37 (1H, br s); MS: m/z 288
(M+). Anal. Calcd for C15H13N2O2Cl: C, 62.49; H, 4.55; N, 9.72. Found: C, 62.55; H, 4.51; N, 9.79.
Benzyl 2-Chloro-2-(4-tolylhydrazono)acetate 2 (1.22 g, 54%) as pale yellow prisms having mp 110°C; IR
1
(nujol): 3285, 1710 (cm-1); H-NMR: 2.32 (3H, s), 5.37 (2H, s), 7.05-7.50 (9H, m), 8.35 (1H, br s); MS:
m/z 302 (M+). Anal. Calcd for C16H15N2O2Cl: C, 63.56; H, 5.00; N, 9.27. Found: C, 63.60; H, 5.02; N,
9.33.
Benzyl 2-Chloro-2-(4-nitrophenyl-hydrazono)acetate (3) (1.40 g, 56%) as yellow prisms having mp
1
146°C; IR (nujol): 3270, 2250, 1735, 1640 (cm-1); H-NMR: 5.40 (2H, s), 7.20-7.45 (7H, m), 8.20-8.25
(2H, m), 8.58 (1H, br s); MS: m/z 333 (M+). Anal. Calcd for C15H12N3O4Cl: C, 54.05; H, 3.63; N, 12.61.
Found: C, 54.11; H, 3.68; N, 12.70.

Reaction of hydrazonoyl chlorides (1-3) with FTP (7-9) in the presence of silver carbonate; General
Procedure. A solution of the proper hydrazonoyl chloride (1,2 or 3) (5.0 mmol) and FTP (7,8 or 9) (5.0
mmol) in dry dioxane (250 mL) was treated with silver carbonate (2.76 g, 10.0 mmol). The mixture was
stirred in the dark at 75°C for the time indicated in Table 1. The insoluble material was filtered off, the
solvent was evaporated and the residue was chromatographed on a silica gel column. Eluents and isolation
yields are collected in Table 1; the order of elution was 11-12-unreacted FTP.
Compound (11a) (0.66 g, 26%) as white needles having mp 172°C (from diisopropyl ether); IR (nujol):
1
1765, 1700 (cm-1); H-NMR: 4.52 (1H, d, J=11.0), 4.60 (1H, d, J=11.0), 4.90 (1H, d, J=8.8), 5.38 (1H,
d, J=12.5), 5.44 (1H, d, J=12.5), 5.98 (1H, s), 6.30 (1H, d, J=8.8), 7.10-7.30 (15H, m); MS: m/z 510
(M+). Anal. Calcd for C28H22N4O4S: C, 65.86; H, 4.35; N, 10.98. Found: C, 65.92; H, 4.40; N, 11.06.
Compound (11b) (0.92 g, 35%) as white needles having mp 164°C (from diisopropyl ether); IR (nujol):
1
1765, 1700 (cm-1); H-NMR: 2.30 (3H, s), 4.54 (1H, d, J=11.2), 4.58 (1H, d, J=11.2), 4.89 (1H, d,
J= 8.5), 5.40 (1H, d, J=12.4), 5.45 (1H, d, J=12.4), 5.99 (1H, s), 6.28 (1H, d, J=8.5), 7.07-7.50 (14H, m);
MS: m/z 524 (M+). Anal. Calcd for C29H24N4O4S: C, 66.39; H, 4.61; N, 10.69. Found: C, 66.44; H, 4.68;
N, 10.77.
Compound (11c) (0.28 g, 10%) as pale yellow needles having mp 130°C (from diisopropyl ether-
methanol); IR (nujol): 1765, 1700 (cm-1); 1H-NMR: 4.56 (1H, d, J=10.1), 4.61 (1H, d, J=10.1), 5.00 (1H,
d, J=8.5), 5.45 (2H, s), 5.99 (1H, s), 6.31 (1H, d, J=8.5), 7.00-7.50 (12H, m), 8.22 (1H, d, J=9.1); MS:
m/z 555 (M+). Anal. Calcd for C28H21N5O6S: C, 60.53; H, 3.81; N, 12.61. Found: C, 60.48; H, 3.75; N,
12.69.
Compound (11d) (0.55 g, 21%) as white needles having mp 187°C (from hexane-benzene); IR (nujol):
1
1760, 1700 (cm-1); H-NMR: 2.33 (3H, s), 4.56 (2H, s), 4.88 (1H, d, J=8.5), 5.42 (2H, s), 5.96 (1H, s),
6.28 (1H, d, J=8.5), 7.05-7.50 (14H, m); MS: m/z 524 (M+). Anal. Calcd for C29H24N4O4S: C, 66.39; H,
4.61; N, 10.69. Found: C, 66.47; H, 4.60; N, 10.61.
Compound (11e) (0.67 g, 25%) as white needles having mp 157°C (from diisopropyl ether-methanol); IR
1
(nujol): 1760, 1700 (cm-1); H-NMR: 2.33 (3H, s), 2.37 (3H, s), 4.33 (2H, s), 4.88 (1H, d, J=8.5), 5.44
(2H, s), 5.97 (1H, s), 6.29 (1H, d, J=8.5), 7.00-7.55 (13H, m); MS: m/z 538 (M+). Anal. Calcd for
C30H26N4O4S: C, 66.89; H, 4.87; N, 10.41. Found: C, 66.96; H, 4.92; N, 10.51.
Compound (11f) (0.20 g, 7%) as yellow needles having mp 85°C (from diisopropyl ether-methanol); IR
1
(nujol): 1770, 1715 (cm-1); H-NMR: 2.33 (3H, s), 4.53 (1H, d, J=9.6), 4.59 (1H, d, J=9.6), 4.96 (1H, d,
J=8.5), 5.43 (2H, s), 5.97 (1H, s), 6.28 (1H, d, J=8.5), 6.95-7.50 (11 H, m), 8.18-8.29 (2H, m); MS: m/z
569 (M+). Anal. Calcd for C29H23N5O6S: C, 61.15; H, 4.07; N, 12.30. Found: C, 61.20; H, 4.02; N, 12.41.
Compound (11g) (0.28 g, 10%) as pale yellow solid having mp 154°C (from diisopropyl ether); IR (nujol):
1
1765, 1720 (cm-1); H-NMR: 4.62 (1H, d, J=10.0), 4.68 (1H, d, J=10.0), 4.91 (1H, d, J=8.6), 5.44 (2H,

s), 6.03 (1H, s), 6.34 (1H, d, J=8.6), 7.00-7.60 (12 H, m), 8.15-8.22 (2H, m); MS: m/z 555 (M+). Anal.
Calcd for C28H21N5O6S: C, 60.53; H, 3.81; N, 12.61. Found: C, 60.45; H, 3.72; N, 12.66.
Compound (11h) (0.77 g, 27%) as pale yellow solid having mp 205°C (from diisopropyl ether); IR (nujol):
1
1765, 1690 (cm-1); H-NMR: 2.37 (3H, s), 4.58 (1H, d, J=10.0), 4.67 (1H, d, J=10.0), 4.90 (1H, d,
J=8.3), 5.44 (2H, s), 5.97 (1H, s), 6.31 (1H, d, J=8.3), 6.90-8.35 (13 H, m); MS: m/z 569 (M+). Anal.
Calcd for C29H23N5O6S: C, 61.15; H, 4.07; N, 12.30. Found: C, 61.23; H, 4.12; N, 12.40.
Compound (11i) (15 mg, 0.5%) as oil; IR (nujol): 1780, 1720 (cm-1); 1H-NMR: 4.63 (1H, d, J=10.5), 4.72
(1H, d, J=10.5), 4.94 (1H, d, J=8.3), 5.46 (2H, s), 6.03 (1H, s), 6.36 (1H, d, J=8.3), 7.27-8.35 (13 H, m).
Compound (12a) (0.30 g, 12%) as white amorphous solid having mp 146°C (from diisopropyl ether); IR
1
(nujol): 1785, 1695 (cm-1); H-NMR: 4.40 (1H, d, J=10.5), 4.52 (1H, d, J=10.5), 5.24 (1H, d, J=12.0),
5.38 (1H, d, J=12.0), 5.56 (1H, dd, J=2.5, 1.5), 5.65 (1H, dd, J=6.6, 2.5), 6.16 (1H, dd, J=6.6, 1.5), 7.00-
7.40 (15H, m); MS: m/z 510 (M+). Anal. Calcd for C28H22N4O4S: C, 65.86; H, 4.35; N, 10.98. Found: C,
65.92; H, 4.40; N, 11.06.
Compound (12b) (0.31 g, 12%) as white amorphous solid having mp 134°C (from diisopropyl ether); IR
1
(nujol): 1785, 1695 (cm-1); H-NMR: 2.24 (3H, s), 4.37 (1H, d, J=10.6), 4.48 (1H, d, J=10.6), 5.28 (1H,
d, J=12.1), 5.37 (1H, d, J=12.1), 5.54 (1H, dd, J=2.3, 1.7), 5.61 (1H, dd, J=6.0, 2.3), 6.12 (1H, dd,
J=6.0, 1.7), 7.00-7.45 (14H, m); MS: m/z 524 (M+). Anal. Calcd for C29H24N4O4S: C, 66.39; H, 4.61; N,
10.69. Found: C, 66.44; H, 4.68; N, 10.77.
Compound (12c) (0.28 g, 10%) as pale yellow needles having mp 183°C (from diisopropyl ether-acetone);
IR (nujol): 1790, 1700 (cm-1); 1H-NMR: 4.40 (1H, d, J=10.5), 4.56 (1H, d, J=10.5), 5.32 (1H, d, J=12.5),
5.40 (1H, d, J=12.5), 5.65-6.22 (3H, m), 7.00-8.35 (14H, m); MS: m/z 555 (M+). Anal. Calcd for
C28H21N5O6S: C, 60.53; H, 3.81; N, 12.61. Found: C, 60.48; H, 3.75; N, 12.69.
Compound (12d) (0.18 g, 7%) as white amorphous solid having mp 137°C (from benzene-acetone); IR
1
(nujol): 1790, 1700 (cm-1); H-NMR: 2.30 (3H, s), 4.37 (1H, d, J=10.3), 4.49 (1H, d, J=10.3), 5.28 (1H,
d, J=7.9), 5.34 (1H, d, J=7.9), 5.51 (1H, dd, J=2.4, 2.0), 5.59 (1H, dd, J=6.0, 2.4), 6.09 (1H, dd, J=6.0,
2.0), 7.00-7.50 (14H, m); MS: m/z 524 (M+). Anal. Calcd for C29H24N4O4S: C, 66.39; H, 4.61; N, 10.69.
Found: C, 66.47; H, 4.60; N, 10.61.
Compound (12e) (27 mg, 1%) as oil; IR (nujol): 1785, 1700 (cm-1); 1H-NMR: 2.29 (3H, s), 2.33 (3H, s),
4.35 (1H, d, J=10.5), 4.50 (1H, d, J=10.5), 5.22 (1H, d, J=8.0), 5.33 (1H, d, J=8.0), 5.56-6.19 (3H, m),
7.00-7.35 (13H, m).
Compound (12f) (0.20 g, 7%) as pale yellow needles having mp 166°C (from diisopropyl ether); IR
1
(nujol): 1785, 1700 (cm-1); H-NMR: 2.33 (3H, s), 4.34 (1H, d, J=10.0), 4.46 (1H, d, J=10.0), 5.24 (1H,
d, J=8.2), 5.36 (1H, d, J=8.2), 5.53 (1H, dd, J=2.5, 2.0), 5.62 (1H, dd, J=6.0, 2.5), 6.11 (1H, dd, J=6.0,

2.0), 7.00-8.35 (13H, m); MS: m/z 569 (M+). Anal. Calcd for C29H23N5O6S: C, 61.15; H, 4.07; N, 12.30.
Found: C, 61.20; H, 4.02; N, 12.41.
Compound (12g) (0.33 g, 12%) as pale yellow amorphous solid having mp 140°C (from diisopropyl
1
ether); IR (nujol): 1785, 1720 (cm-1); H-NMR: 4.48 (1H, d, J=11.5), 4.56 (1H, d, J=11.5), 5.29 (1H, d,
J=12.1), 5.38 (1H, d, J=12.1), 5.62 (1H, dd, J=2.3, 1.6), 5.72 (1H, dd, J=6.2, 2.3), 6.29 (1H, dd, J=6.2,
1.6), 7.00-8.25 (14 H, m); MS: m/z 555 (M+). Anal. Calcd for C28H21N5O6S: C, 60.53; H, 3.81; N, 12.61.
Found: C, 60.45; H, 3.72; N, 12.66.
Compound (12h) (1.17 g, 41%) as pale yellow needles having mp 118°C (from diisopropyl ether); IR
1
(nujol): 1790, 1700 (cm-1); H-NMR: 2.26 (3H, s), 4.28 (1H, d, J=10.3), 4.38 (1H, d, J=10.3), 5.30 (1H,
d, J=12.1), 5.39 (1H, d, J=12.1), 5.62 (1H, dd, J=2.5, 1.5), 5.70 (1H, dd, J=6.3, 2.5), 6.30 (1H, dd,
J=6.3, 1.5), 7.00-8.25 (13H, m); MS: m/z 569 (M+). Anal. Calcd for C29H23N5O6S: C, 61.15; H, 4.07; N,
12.30. Found: C, 61.11; H, 4.00; N, 12.22.
Compound (12i) (0.30 g, 10%); as yellow prisms having mp 130°C (from diisopropyl ether-
1
dichloromethane); IR (nujol): 1790, 1700 (cm-1); H-NMR: 4.48 (1H, d, J=10.9), 4.52 (1H, d, J=10.9),
5.28 (1H, d, J=11.7), 5.39 (1H, d, J=11.7), 5.61 (1H, dd, J=3.0, 1.5), 5.70 (1H, dd, J=6.7, 3.0), 6.21 (1H,
dd, J=6.7, 1.5), 7.25-7.45 (9H, m), 8.05-8.25 (4H, m); MS: m/z 600 (M+). Anal. Calcd for C28H20N6O8S:
C, 55.99; H, 3.36; N, 14.00. Found: C, 60.05; H, 3.30; N, 13.91.
Reaction of hydrazonoyl chlorides (13-15) with FTP (9,10) in the presence of silver carbonate;
General Procedure. A solution of the proper hydrazonoyl chloride (13,14 or 15) (5.0 mmol) and FTP (9
or 10) (5.0 mmol) in dry dioxane (250 mL) was treated with silver carbonate (2.76 g, 10.0 mmol). The
mixture was stirred in the dark at 75°C for the time indicated in Table 2. The insoluble material was filtered
off, the solvent was evaporated and the residue was chromatographed on a silica gel column. Eluents and
isolation yields are collected in Table 2; the order of elution was 21-19-20-unreacted FTP.
Compound (19a) (0.29 g, 12%) as white needles having mp 114°C (from diisopropyl ether); IR (nujol):
1
1770, 1725 (cm-1); H-NMR: 2.30 (3H, s), 3.96 (3H, s), 4.63 (1H, d, J=9.9), 4.78 (1H, d, J=9.9), 4.91
(1H, d, J=8.4), 6.01 (1H, s), 6.35 (1H, d, J=8.4), 7.10-8.45 (8H, m); MS: m/z 493 (M+). Anal. Calcd for
C23H19N5O6S: C, 55.97; H, 3.88; N, 14.20. Found: C, 56.03; H, 3.82; N, 14.27.
Compound (19b) (0.39 g, 15%) as yellow prisms having mp 176°C (from diisopropyl ether-acetone); IR
1
(nujol): 1770, 1715 (cm-1); H-NMR: 4.05 (3H, s), 4.65 (1H, d, J=9.8), 4.80 (1H, d, J=9.8), 5.60 (1H, d,
J=8.0), 6.10 (1H, s), 6.35 (1H, d, J=8.0), 7.55-8.35 (8H, m); MS: m/z 524 (M+). Anal. Calcd for
C22H16N6O8S: C, 50.37; H, 3.08; N, 16.03. Found: C, 50.30; H, 3.11; N, 16.11.
Compound (19c) (0.50 g, 20%) as pale yellow needles having mp 176°C (from diisopropyl ether); IR
1
(nujol): 1765, 1710 (cm-1); H-NMR: 4.00 (3H, s), 4.62 (1H, d, J=10.1), 4.72 (1H, d, J=10.1), 4.88 (1H,

d, J=8.4), 6.02 (1H, s), 6.30 (1H, d, J=8.4), 7.10-7.40 (8H, m); MS: m/z 502 (M+). Anal. Calcd for
C22H16N4O4Cl2S: C, 52.59; H, 3.21; N, 11.16. Found: C, 52.53; H, 3.17; N, 11.23.
Compound (20a) (0.24 g, 10%) as white prisms having mp 106°C (from diisopropyl ether); IR (nujol):
1
1790, 1740 (cm-1); H-NMR: 2.30 (3H, s), 3.99 (3H, s), 4.63 (1H, d, J=10.4), 4.76 (1H, d, J=10.4), 5.64
(1H, dd, J=2.4, 1.6), 5.74 (1H, dd, J=6.1, 2.4), 6.33 (1H, dd, J=6.1, 1.6), 6.95-8.10 (8H, m); MS: m/z
493 (M+). Anal. Calcd for C23H19N5O6S: C, 55.97; H, 3.88; N, 14.20. Found: C, 55.92; H, 3.80; N, 14.23.
Compound (20b) (0.39 g, 15%) as yellow needles having mp 185°C (from diisopropyl ether); IR (nujol):
1787, 1735 (cm-1); 1H-NMR: 3.95 (3H, s), 4.50 (1H, d, J=8.6), 4.80 (1H, d, J=8.6), 5.65 (1H, dd, J=2.3,
1.9), 5.70-6.28 (2H, m), 7.20-8.30 (8H, m); MS: m/z 524 (M+). Anal. Calcd for C22H16N6O8S: C, 50.37;
H, 3.08; N, 16.03. Found: C, 50.27; H, 3.00; N, 15.99.
Compound (20c) (0.50 g, 20%) as yellow needles having mp 146°C (from diisopropyl ether); IR (nujol):
1
1790, 1730 (cm-1); H-NMR: 3.91 (3H, s), 4.47 (1H, d, J=10.6), 4.74 (1H, d, J=10.6), 5.53 (1H, dd,
J=2.4, 1.9), 5.64 (1H, dd, J=6.3, 2.4), 6.17 (1H, dd, J=6.3, 1.9), 7.02-7.27 (8H, m); MS: m/z 502 (M+).
Anal. Calcd for C22H16N4O4Cl2S: C, 52.59; H, 3.21; N, 11.16. Found: C, 52.66; H, 3.27; N, 11.20.
Compound (21a) (0.34 g, 10%) as white amorphous solid having mp 180°C (from methanol); IR (nujol):
1
1790, 1720, 1700 (cm-1); H-NMR: 2.30 (3H, s), 2.33 (3H, s), 3.95 (3H, s), 4.02 (3H, s), 4.41 (1H, d,
J=10.8), 4.53 (1H, d, J=7.9), 4.70 (1H, d, J=10.8), 5.80 (1H, s), 6.25 (1H, d, J=7.9), 7.07-8.11 (12H, m);
MS: m/z 683 (M+). Anal. Calcd for C33H29N7O8S: C, 57.96; H, 4.28; N, 14.35. Found: C, 58.03; H, 4.32;
N, 14.27.
Compound (21b) (0.37 g, 10%) as white amorphous solid having mp 204°C (from methanol); IR (nujol):
1
1790, 1735, 1730 (cm-1); H-NMR: 3.89 (3H, s), 3.96 (3H, s), 4.47 (1H, d, J=11.0), 4.60 (1H, d, J=7.6),
4.81 (1H, d, J=11.0), 5.88 (1H, s), 6.36 (1H, d, J=7.6), 7.28-8.45 (12H, m); MS: m/z 745 (M+). Anal.
Calcd for C31H23N9O12S: C, 49.42; H, 3.11; N, 16.91. Found: C, 49.47; H, 3.10; N, 17.00.
Compound (21c) (0.36 g, 10%) as white needles having mp 192°C (from methanol); IR (nujol): 1790,
1
1730, 1720 (cm-1); H-NMR: 4.00 (6H, s), 4.40 (1H, d, J=10.6), 4.45 (1H, d, J=8.0), 4.60 (1H, d,
J=10.6), 5.95 (1H, s), 6.26 (1H, d, J=8.0), 7.10-8.00 (12H, m); MS: m/z 712 (M+). Anal. Calcd for
C31H23N6O6Cl3S: C, 52.24; H, 3.26; N, 11.80. Found: C, 52.30; H, 3.27; N, 11.72.
Reaction between 2 and FTP (9) in the presence of triethylamine. A solution of 2 (0.68 g, 3.0 mmol)
and 9 (1.04 g, 3.0 mmol) in dry dioxane (150 mL) was added with triethylamine (1.52 g, 15.0 mmol). The
mixture was refluxed in the dark at for 48 h. The solvent was evaporated and the residue was
chromatographed on a silica gel column with diethylether as eluant. Besides some amount of tarry material,
unchanged 9 were recovered.

ACKNOWLEDGEMENTS
We thank MURST and CNR for financial support.
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