Reversible C ? N migration of the ethoxycarbonyl group in the reactions of pyridinium and isoquinolinium ylides derived from malonic ester with isocyanates

Article abstract of DOI:10.1002/hc.1104

Pyridinium and isoquinolinium ylides (7 and 12) derived from malonic ester react in an unusual manner with isocyanates giving the new pyridinium ylide (9) and the new isoquinolinium ylide (14). C → N Migration of the COOEt group takes place at room temperature, but, at an elevated temperature, reverse N → C migration of the COOEt group proceeds and ylides 9 and 14 are reconverted into the starting ylides 7 and 12, respectively.

Full text of DOI:10.1002/hc.1104

Heteroatom Chemistry
Volume 13, Number 1, 2002
→
Reversible C N Migration of the
Ethoxycarbonyl Group in the Reactions of
Pyridinium and Isoquinolinium Ylides Derived
from Malonic Ester with Isocyanates
Yuri G. Gololobov, Olga V. Dovgan, Igor R. Golding, Pavel V.
Petrovskii, and Irina A. Garbuzova
A. N. Nesmeyanov Institute of Organo-Element Compounds, Russian Academy of Science,
V-334, Vavilov str. 28, 117813 Moscow, Russia
Received 18 March 2001; revised 4 June 2001
This type of behavior can be regarded as a gen-
ABSTRACT: Pyridinium and isoquinolinium ylides
eral method for the apparent insertion of RNCX into
(7 and 12) derived from malonic ester react in an
a carbon carbon bond and appears to have wide
unusual manner with isocyanates giving the new
applicability. Such behavior is, however, limited to
pyridinium ylide (9) and the new isoquinolinium
anions that do not contain other acidic protons, be-
ylide (14). C → N Migration of the COOEt group
cause, if these are present, self-protonation of the
takes place at room temperature, but, at an ele-
intermediate N-anion can occur leading to the for-
vated temperature, reverse N → C migration of the
mation of an N-monosubstituted amide.
COOEt group proceeds and ylides 9 and 14 are recon-
It was shown, for example, that pyridinium ylide
verted into the starting ylides 7 and 12, respectively.
(4) reacts with phenyl isocyanate to give the mono-
C
2002 John Wiley & Sons, Inc. Heteroatom Chem 13:36–
substituted amide 6, via self-protonation of the in-
termediated N-anion 5 [7] (Scheme 2).
45, 2002; DOI 10.1002/hc.1104
RESULTS AND DISCUSSION
INTRODUCTION
It was established by us that N-ylide 7, derived
from malonic ester [8,9], reacts with isocyanates
in an unexpected way. Because of the lack of a
mobile hydrogen, intermediate 8 was transformed
(via C → N migration of COOEt) into the new
N-ylide 9. This rearrangement in the reaction of the
pyridinium ylide (7) with each isocyanate occurs in
CH2Cl2 solution, at room temperature, to give the
corresponding carbamate (Scheme 3), which was ei-
ther obtained as a pure compound (9b,c,f) or else
its formation was detected in the reaction mixture
Although the reactions of carbanions with iso-
cyanates have been known for many years as a
route to monosubstituted amides [1], the carban-
ionic species 1 can behave in a novel way leading
to the formation of the carbamate 3 via rearrange-
ment of the initially formed nitrogen anion 2 [2–6]
(Scheme 1).
Correspondence to: Yuri G. Gololobov; e-mail: Yugol@ineos.
ac.ru.
Contract grant sponsor: Russian Foundation for Basic
Research.
1
by H NMR spectroscopy (9a,e,g). Crude 9d was
transformed into the corresponding salt 10 with
MeSO2OH (Scheme 4).
Contract grant numbers: 95-03-08200, 98-03-33117a.
2002 John Wiley & Sons, Inc.
c
36

Reactions of Pyridinium and Isoquinolinium Ylides Derived from Malonic Ester with Isocyanates 37
i
SCHEME
1
R = Pr3 P+CH2, Ph; Alk Me, Et; X O, S;
SCHEME 3 R = cyclohexyl (a), Ph (b), 2-Tolyl (c), 3,4-di-
chlophenyl (d), 2-nitrophenyl (e), 4-nitrophenyl (f) and
1-naphthyl (g).
R0 = Me or Ar = Ph, m-Tol, 1-naphthyl, p-ClC6H5, m,p-Cl2
C6H3, C6H5 NO2-p.
SCHEME 2
SCHEME
4
Ar = Ph (10b), 3,4-Cl2-phenyl (10d), p NO2
C6H4 (10f, 11f).
The degree of the rearrangement can easily be
1
followed by H NMR spectroscopy. Protons of the
pyridinium ring in the starting ylide 7 and the ylides
9 have differences in their chemical shifts. Groups
C2H5 in carbamates 9 are not equal in contrast to
the protons of the C2H5 groups in the starting ylide 7.
For instance, the relationships of the ylides 7 and 9f
in the respective reaction mixtures were established
by a comparison between the intensities of the ␣-H
signals of the pyridinium rings and the protons of the
CH3CH2 groups which belong to the ylide 7 (23–25%)
and 9f (75–77%) (Fig. 1).
The
signal of another COOEt group at nitrogen
C
O
1
is found at 1720 cm (Fig. 2).
Initially, adduct 8 seems to be formed. Since the
N-anionic intermediate 8 does not contain sufficient-
ly active hydrogen atoms that would be able to
protonate its N-anionic center, but does contain an
ethoxycarbonyl group, intramolecular transforma-
tions as depicted in Scheme 3 become possible. This
process is unusual, because a carbanion rather than
an ethoxy anion (as in the case of aminolysis of es-
ters) acts as the leaving group upon nucleophilic at-
tack by nitrogen on the carbonyl group. Perhaps this
unique situation in which cleavage of a C C bond
is preferred over cleavage of a C O bond is due to
According to the IR spectroscopic data, the neg-
ative charge in N-ylide 7 is delocalized with the par-
1
ticipation of both COOEt groups (
= 1658 cm )
C
O
but in the N-ylide 9f only one COOEt group is con-
1
jugated with the anionic charge (
= 1591 cm ).
C
O

38 Gololobov et al.
FIGURE 1 1H NMR spectrum of the reaction mixture of ylide 7 (upper picture) and the ylide 9f.
the efficient delocalization of the negative charge in
the resulting carbanions 9. The latter is indicated by
the data of IR spectroscopy; a change occurs in the
intensity and the position of the absorption bands
for the carbonyl group at the carbanion center in
the ylide 9f as compared with the absorption bands
for the carbonyl group at the carbanion center in
ylide 7 (Fig. 2).
The rate of formation of the ylides 9 depends
on electronic and spatial characteristics of the
isocyanates. The first step of the reaction (Scheme 3)
involves the nucleophilic attack of the carbanion
at the carbon of the isocyanate group and the rate
of this step is dictated by electronic factors mainly
(cf. [10]). The rate of the second stage should be
particularly sensitive to the electronic and also,

Reactions of Pyridinium and Isoquinolinium Ylides Derived from Malonic Ester with Isocyanates 39
mono-salt 10f, but introduction of the ylide 9f into
reaction with two equivalents of the same acid brings
about formation of the salt 11f, which contains two
equivalents of MeSO2OH. A special problem is the
structure of this double-salt 11f. Literature data [12]
regarding the protonation of bis-substituted amides
show that the place of the protonation is oxygen, not
nitrogen. As support for this statement the data of
the IR spectroscopy [13] can be cited, because the
protonation of the C O group leads to a change in
its intensity and the position of the
O band. In our
C
case, IR spectra of the mono- 10f and double- 11f
salts show no principal differences (Fig. 3).
However, it is interesting to note that all signals
in the 1H NMR spectra of the double salt 11f exhibit
higher field shifts compared with the corresponding
signals of the mono-salt 10f (Table 1).
FIGURE 2 IR spectrum of the starting ylide 7 and ylide 9f in
the region.
C
O
especially, to the spatial effects of the substitutents
in the nucleus of ArNCO [11]. Actually, the cyclo-
hexyl isocyanate (fivefold excess) reacts with the
ylide 7 very slowly, and within 1 month only 64% of
the compound 9a was revealed in the reaction mix-
ture by 1H NMR spectroscopy. Moreover, the ylide 7
reacts with phenyl or 4-nitrophenyl isocyanates (70%
excess) in CH2Cl2 during 24 h, being transformed
completely into carbamates 9b and 9f, respectively.
Steric effects of the substituents in the ortho po-
sition of ArNCO, whether of the donor or acceptor
type, decrease the rate of formation of the ylides 9.
For example, ylide 7 reacts with o-tolyl isocyanate
(fivefold excess) in CH2Cl2, and after 2 weeks at room
temperature, the reaction mixture consists of the
starting ylide 7 (7%) and carbamate 9c (93%). In
a similar manner, ylide 7 reacts with o-nitrophenyl
isocyanate (twofold excess). In this instance, after
2 weeks at room temperature, the reaction mixture
contains two main compounds: carbamate 9e (85%)
and ylide 7 (15%).
Rearrangement as depicted in Scheme 3 is re-
versible. While stable in the crystal state at room tem-
perature, ylides 9 transform back into ylide 7 and an
isocyanate polymer at elevated temperatures or after
several weeks at room temperature in CDCl3 or ace-
tone. For example, crystalline 9f is transformed in
solution in CDCl3 to the starting ylide 7 in 28% yield
in 2 days and in 35% yield in a week (1H NMR data).
In a similar manner, ylide 9c is transformed into the
starting ylide 7 in 8% yield in a day and in 50% yield
in 16 days in a solution in CDCl3. The reversible equi-
librium situation is reached after 3 weeks: 70% of the
ylide 7 and 30% of the ylide 9c.
In the case of the protonation of any one of
the atoms of compound 10f, one would expect that
all the protons in the H NMR spectra of the bis-
1
salt 11f should undergo a downfield shift. From
the results obtained it may be concluded that 11f
is an adduct of the salt 10f and MeSO2OH, in
which a proton of the latter is not located in the
cationic part of 11f but is rather connected with
both MeSO2O anions. Also, the distance between
the positive charge of the pyridinium ring and the
anion center of 11f is evidently very short because
the signal of the proton in N+ CH in 11f has a
high field shift compared with that of the mono-salt
10f.
An isoquinolinium ylide derived from malonic
ester (12) [8] reacts with aryl isocyanates similarly
to the pyridinium ylide (7) (Scheme 5). Starting ylide
12 enters into reaction with 4-nitrophenyl isocyanate
(twofold excess) completely during 24 h with the for-
mation of the new ylide 14a.
It is particularly remarkable that, in the 1H
NMR spectrum of the CH2 groups, only those of
the ylide 14b reveals complex multiplets at room
The yellow compounds 9 react in CH2Cl2 with
MeSO2OH to form the corresponding stable salts 10
(Scheme 4).
It is interesting to note that the reaction of the
ylide 9f with one equivalent of MeSO2OH leads to the
FIGURE 3 IR spectrum of the salts 10f and 11f.

40 Gololobov et al.
TABLE 1 Comparison 1H NMR Data of Mono-Salt 10f Bis-Salt 11f
Compound
CH COOCH2CH3
N COOCH2CH3
CH3SO2O
a
10f
= 9.27
= 7.99
= 7.68
= 8.25
= 2.78
H
H
H
H
H
H
H
CH2
H2
H3
CH3
a
= 8.02
= 1.31
a
CH2
CH3
= 8.52
= 1.18
a
CH3
11f
= 9.02 (1
= 8.11 (1
= 8.53 (1
= 0.25)
= 0.09)
= 0.01)
= 7.69 (1 = 0.30)
= 7.58
= 2.88
H
H
H
H
H
CH2
H2
H3
CH3
(1
= 1.30
(1
= 0.10)
= 0.10)
CH2
CH3
CH3
= 1.17
(1
= 0.01)
=H82.25
CH3
(1
CH3
= 0.01)
1
= 0.00
CH3
H3
am. 4.25–4.45 ppm.
SCHEME 6
SCHEME 5 Ar = 4-O2NC6H4 (a), 1-naphthyl (b).
( ppm, internal reference TMS and CDCl3 for 1H and
13C spectra respectively). IR spectra were recorded
on an IR-Fourier-spectrometer Magna-750 (KBr).
The reactions were performed under a nitrogen or
argon atmosphere.
temperature. However, in contrast, at +55 C this
unexpected effect disappears and the 1H NMR spec-
tra of the ylide 14b shows no evidence of mag-
netic nonequivalence of the CH2 protons. Perhaps
this indicates that there is some unexpected asym-
metry in the molecule 14b, the effect of which is
visible at room temperature. Asymmetry in the re-
gion of the nitrogen atom seems most likely, possibly
owing to the strong impedance of rotation around
the N Ar bond. Apparently, this is an example of
atropisomerism. A result of a similar nature was
noted for the carbamate derived from 1-naphthyl iso-
cyanate and a phosphorus containing zwitter ion [5].
Isoquinolinium carbamate (14a) is transformed
into the corresponding double salt 15a by action of
two equivalents of MeSO2OH (Scheme 6).
Yields, analytical and spectral data (1H NMR, IR)
of products are given in Tables 2–5.
Pyridinium ylide (7) was prepared according to
[8]. 13C NMR : 14.22 (OCH2CH3), 58.12 (OCH2 CH3),
96.82 (C ), 125.35 (C␤ (Py)), 141.11 (C␥ (Py)), 149.41
(C␣ (Py)), 164.18 (COOEt).
N-(Diethoxycarbonylmethyl)pyridinium
Methosulfate
MeSO2OH (0.1 g, 1.05 mmol) was added dropwise
to the ylide 7 (0.25 g, 1.05 mmol) in CH2Cl2 (10 ml).
The colorless solution that formed was evaporated
to dryness under reduced pressure. The residue
was washed with ethyl ether, dried under reduced
pressure, and recrystallized from acetone. White
powder. Yield 67%, mp 103 C. 1H NMR : 1.29 (t, 6H,
CH2CH3, J = 6.8 Hz), 2.70 (s, 3H, CH3SO2O ), 4.29
EXPERIMENTAL
NMR spectra were recorded on a Bruker (AMX-400)
1
spectrometer, H (400.26 MHz), 13C (100.68 MHz),

Reactions of Pyridinium and Isoquinolinium Ylides Derived from Malonic Ester with Isocyanates 41
TABLE 2 Characterization Data of the Pyridinium Ylides and Their Salts
Elemental Analysisa (%)
Molecular
Formula
Molecular
Weight
Yield
(%)
mp
( C)
Compound
C
H
N
S
7
C12H15NO4
237.26
356.38
452.48
370.41
82
73
96
40
176
60.96
(60.75)
63.84
(64.04)
52.70
(53.09)
65.11
(64.85)
–
6.21
(6.37)
5.69
(5.66)
5.25
(5.35)
5.86
(5.99)
–
5.91
(5.90)
7.72
(7.86)
6.06
(6.19)
7.61
(7.56)
–
–
9b
C19H20N2O5
C20H24N2O8S
C20H22N2O5
108–109b
135–137
60–62b
–
10b
9c
7.05
(7.09)
–
9a
9d
10d
C
C
C
S
C
C
19H26N2O5
19H18Cl2N2O5
20H22Cl2N2O8
362.43
425.27
521.37
57c
86c
95
–
–
–
–
–
–
–
128–129
46.11
(46.07)
–
56.97
(56.86)
47.47
(48.29)
42.49
(42.63)
–
4.46
(4.25)
–
4.73
(4.77)
4.72
(4.66)
4.68
(4.58)
–
5.37
(5.37)
–
10.44
(10.47)
7.93
(8.45)
7.15
(7.08)
–
6.10
(6.15)
–
9e
9f
19H19N3O7
19H19N3O7
401.38
401.38
84c
62
–
58–60b
–
10f
11f
9g
C
C
C
20H23N3O10
S
497.48
593.58
406.44
70
95
120–122
130–132
–
6.64
(6.44)
10.77
(10.80)
–
21H27N3O13S2
23H22N2O5
92c
aValues found are followed by the calculated values (in parentheses).
bDecomposition.
c1H NMR Data.
(q, 2H, CH2CH3, J = 6.8 Hz), 4.36 (q, 2H, CH2CH3,
J = 6.8 Hz), 7.28 (s, 1H, CH), 8.11 (t, 2H, H␤ (Py), J =
7.2 Hz), 8.67 (t, 1H, H␥ (Py), J = 7.6 Hz), 9.32 (d, 2H,
H␣ (Py), J = 5.6 Hz). 13C NMR : 13.36 (OCH2CH3),
39.18 (CH3S), 64.03 (OCH2CH3), 71.48 (CH), 127.56
(C␤ (Py)), 146.36 (C␥ (Py)), 147.72 (C␣ (Py)), 162.18
(COOEt). IR (cm ) : 1751 (COOEt). Found: C,
46.73: H, 5.87; N, 4.19; S, 9.61. For C13H19N1O7S: C,
46.84; H, 5.74; N, 4.20; S, 9.62.
was removed under reduced pressure without heat-
ing. The residue was dissolved in a minimum of
acetone at room temperature and the solution was
left to stand overnight at 20 C. Yellow crystals 9b
were filtered off. 13C NMR : 10.66 (OCH2CH3), 55.61
(OCH2CH3), 57.60 (OCH2CH3), 103.40 (C ), 121.76–
122.23 (Ph), 124.70 (C␤ (Py)), 135.78 (N C (Ph)),
138.49 (C␥ (Py)), 145.14 (C␣ (Py)), 150.01 (C(O)N),
159.01 (NCOOEt) 160.21 (COOEt).
1
Reaction Between the Ylide 7 and Cyclohexyl
Isocyanate
Pyridinium (N-Ethoxycarbonyl-N-2-
tolylcarbamoyl)ethoxycarbonylmethylide (9c)
A solution of the ylide 7 (0.02 g, 0.08 mmol) in CDCl3
was placed in a 5-mm NMR tube and treated at room
temperature with cyclohexyl isocyanate (0.05 g,
A mixture of ylide 7 (0.5 g, 2.11 mmol) and 2-TolNCO
(0.6 g, 4.88 mmol) in CHCl3 (5 ml) was left for 17 days
at room temperature Dry hexane (3 ml) was added
to the reaction mixture; and precipitated powder
(0.15 g, mp 170–174 C, starting ylide 7) was filtered
off. The filtrate was dried under reduced pressure
without heating.
1
0.42 mmol). After 25 days, the H NMR spectrum
showed the signals in the reaction mixture: 7.62 and
8.04 ppm (ylide 7, H␤ and H␥ (Py)); 7.69 and 8.11
ppm (9a, H␤ and H␥ (Py)). There exist ylides 7 (38%)
and 9a (62%).
Reaction of Ylide 7 with 3,4-Dichlorophenyl
Isocyanate
Pyridinium (N-Ethoxycarbonyl-N-phenyl-
carbamoyl)ethoxycarbonylmethylide (9b)
A mixture of ylide 7 (1 g, 4.20 mmol) and 3,4-
dichlorophenyl isocyanate (1.2 g, 6.63 mmol) in
CHCl3 (25 ml) was left for 24 h at room tempera-
A mixture of the ylide 7 (2 g, 8.44 mmol) and PhNCO
(1.5 g, 12.66 mmol) in CHCl3 (25 ml) was left for
24 h at room temperature, and then the solvent
1
ture. The H NMR spectrum showed the signals in

42 Gololobov et al.
TABLE 3 The 1H NMR and IR Spectral Data of the Synthesized Compounds
--1
IR (
cm
)
max
C
O
C
O
C O
Compound
1H NMR
(C(O)OEt) ( C(O) N) (N C(O)OEt)
7
1.24 (t, 6H, CH2CH3, J = 7.1 Hz), 4.14 (q, 4H, CH2CH3,
J = 7.1 Hz), 7.66 (t, 2H, H (Py), J = 7.2 Hz),
1658
–
–
–
8.07 (t, 1H, H (Py), J = 7.6 Hz),
8.53 (d, 2H, H (Py), J = 5.6 Hz) (cf. [6])
9a
1.20 (t, 3H, CH2CH3, J = 7.2 Hz), 1.27 (t, 3H, CH2CH3,
J = 7.2 Hz), 1.55–1.98 (m, 10H, C6H11), 3.86–3.92
(m, 1H, C6H11), 4.08 (q, 2H, CH2CH3, J = 7.2 Hz),
4.15 (q, 2H, CH2CH3, J = 7.2 Hz), 7.42 (t, 2H, H (Py),
J = 7.2 Hz), 8.15 (t, 1H, H (Py), J = 8.0 Hz),
–
–
8.57 (d, 2H, H (Py), J = 5.2 Hz)
9b
1.21 (t, 3H, CH2CH3, J = 7.2 Hz), 1.26 (t, 3H, CH2CH3,
J = 7.2 Hz), 4.14 (q, 2H, CH2CH3, J = 7.2 Hz),
4.22 (q, 2H, CH2CH3, J = 7.2 Hz), 7.25–7.30 (m, 5H, Ph)
7.21 (t, 2H, H (Py), J = 7.2 Hz), 8.15 (t, 1H, H (Py),
J = 7.6 Hz), 8.56 (d, 2H, H (Py), J = 5.6 Hz)
1594
1748
1586
–
1594
1707
1586
–
1708
1748
1712
–
10b
9c
1.15 (t, 3H, CH2CH3, J = 7.2 Hz), 1.29 (t, 3H, CH2CH3,
J = 7.2 Hz), 2.77 (s, 3H,CH3S), 4.20–4.40 (m, 4H, CH2CH3),
7.31–7.40 (m, 5H, Ph), 7.78 (s, 1H, CH),
7.95 (t, 2H, H (Py), J = 7.6 Hz), 8.43 (t, 1H, H (Py),
J = 7.6 Hz), 9.13 (d, 1H, H (Py), J = 5.6 Hz)
1.23 (t, 3H, CH2CH3, J = 7.2 Hz), 1.26 (t, 3H, CH2 CH3,
J = 7.2 Hz), 2.34 (s, 3H, CH3), 4.14–4.21 (m, 4H, CH2CH3,
7.13–7.32 (m, 4H, Ar), 7.68 (t, 2H, H (Py), J = 7.6 Hz),
8.09 (t, 1H, H (Py), J = 8.0 Hz),
8.64 (d, 2H, H (Py), J = 5.6 Hz)
10c
1.17 (t, 3H, CH2CH3, J = 7.2 Hz), 1.29 (t, 3H, CH2CH3,
J = 7.2 Hz), 2.23 (s, 3H, CH3), 2.76 (s, 3H, CH3S), 4.20–4.40
(m, 4H, CH2CH3), 7.18–7.27 (m, 3H, Ar), 7.53 (d, 1H, Ar,
J = 7.6 Hz), 7.78 (s, 1H, CH), 7.97 (t, 2H, H (Py), J = 7.2 Hz),
8.45 (t, 1H, H (Py), J = 7.6 Hz),
9.22 (d, 2H, H (Py), J = 6.4 Hz)
9d
1.10 (t, 3H, CH2CH3, J = 7.2 Hz), 1.18 (t, 3H, CH2CH3,
J = 7.2 Hz), 4.02 (q, 2H, CH2 CH3, J = 7.2 Hz), 4.13
(q, 2H, CH2CH3, J = 7.2 Hz), 7.28–7.29 (m, 2H, Ar), 7.54
(bs, 1H, Ar), 7.68 (t, 2H, H (Py), J = 7.2 Hz), 8.10
(t, 1H, H (Py), J = 8.0 Hz), 8.50 (d, 2H, H (Py), J = 5.6 Hz)
1.20 (t, 3H, CH2CH3, J = 7.2 Hz), 1.29 (t, 3H, CH2CH3,
J = 7.2 Hz), 2.74 (s, 3H, CH3S), 4.23–4.43 (m, 4H, CH2CH3),
7.36 (m, 2H, H2,6 (Ar)), 7.45 (d, 1H, H5 (Ar), J = 8.4 Hz), 7.88
(s, 1H, CH), 7.99 (t, 2H, H (Py), J = 6.8 Hz), 8.50 (t, 1H,
–
1746
–
–
1704
–
–
1746
–
10d
9e
H
(Py), J = 7.6 Hz), 9.22 (d, 2H, H (Py), J = 4.0 Hz)
1.15 (t, 3H, CH2CH3, J = 7.2 Hz), 1.17 (t, 3H, CH2CH3,
J = 7.2 Hz), 4.08 (q, 2H, CH2CH3, J = 7.2 Hz), 4.13 (q, 2H,
CH2CH3, J = 7.2 Hz), 7.36 (t, 1H, Ar, J = 8.0 Hz), 7.50
(t, 1H, Ar, J = 8.0 Hz), 7.70 (t, 2H, H (Py), J = 7.2 Hz), 7.87
(d, 1H, Ar, J = 8.0 Hz), 8.05 (d, 1H, Ar, J = 8.0 Hz), 8.13 (t, 1H,
H
(Py), J = 7.6 Hz), 8.53 (d, 2H, H (Py), J = 5.6 Hz)
9f
1.12 (t, 3H, CH2CH3, J = 7.2 Hz), 1.30 (t, 3H, CH2CH3,
J = 7.2 Hz), 4.05 (q, 2H, CH2CH3, J = 7.2 Hz), 4.28 (q, 2H,
CH2CH3, J = 7.2 Hz), 7.71 (d, 2H, Ar, J = 9.2 Hz), 7.85 (t, 2H,
1591
1750
1591
1711
1720
1750
H
H
(Py), J = 7.6 Hz), 8.17 (d, 2H, Ar, J = 9.2 Hz), 8.26 (t, 1H,
(Py), J = 8.0 Hz), 8.63 (d, 2H, H (Py), J = 5.6 Hz)
10f
1.18 (t, 3H, CH2CH3, J = 7.2 Hz), 1.31 (t, 3H, CH2CH3,
J = 7.2 Hz), 2.78 (s, 3H, CH3S), 4.25–4.45 (m, 4H, CH2CH3),
7.68 (d, 2H, Ar, J = 8.8 Hz), 7.99 (s, 1H, CH), 8.02 (t, 2H, H
(Py), J = 7.2 Hz), 8.25 (d, 2H, Ar, J = 8.8 Hz), 8.52 (t, 1H,
H
(Py), J = 7.6 Hz), 9.27 (d, 2H, H (Py), J = 6.0 Hz)
(Continued)

Reactions of Pyridinium and Isoquinolinium Ylides Derived from Malonic Ester with Isocyanates 43
TABLE 3 Continued
--1
IR (
cm
)
max
C
O
C
O
C O
Compound
1H NMR
(C(O)OEt) ( C(O) N) (N C(O)OEt)
11f
1.17 (t, 3H, CH2CH3, J = 7.2 Hz), 1.30 (t, 3H, CH2CH3,
J = 7.2 Hz), 2.88 (s, 6H, CH3S) 4.27–4.42 (m, 4H, CH2CH3),
7.58 (d, 2H, Ar, J = 6.8 Hz), 7.69 (s, 1H, CH), 8.11 (bs, 2H, H
(Py)), 8.25 (d, 2H, Ar, J = 7.2 Hz), 8.53
1750
1711
–
1750
(bs, 1H, H (Py)), 9.02 (bs, 2H, H (Py)), 13.34 (bs, 1H, H+)
1.17 (t, 3H, CH2CH3, J = 6.8 Hz), 1.29 (t, 3H, CH2CH3,
J = 7.2 Hz), 4.17 (q, 2H, CH2CH3, J = 6.8 Hz), 4.25 (q, 2H,
CH2CH3, J = 7.2 Hz), 7.40–7.48 (m, 3H, Nf), 7.53–7.58 (m, 3H, Nf)
7.78 (t, 2H, H (Py), J = 8.6 Hz), 7.93 (t, 1H, Nf, J = 8.0 Hz),
8.25 (bs, 1H, H (Py)), 8.55 (d, 2H, H (Py), J = 6.0 Hz)
9g
–
–
the reaction mixture: 7.61 and 8.02 ppm (ylide 7,
H␤ and H␥ (Py)), 7.70 and 8.13 ppm (9d, H␤ and
H␥ (Py)). This corresponds to ylides 7 (15%) and
9d (85%).
(Py)), 152.77 (C(O)N), 161.28 (NCOOEt) 163.41
(COOEt).
Reaction of Ylide 7 with 1-Naphthyl Isocyanate
A mixture of ylide 7 (0.4 g, 1.69 mmol) and
1-naphthyl isocyanate (0.7 g, 4.14 mmol) in CH2Cl2
(5 ml) was left for 13 days at room temperature. The
1H NMR spectrum of the reaction mixture showed
the signals in the reaction mixture: 8.50 ppm (ylide
7, H␣ (Py)), 8.55 ppm (9g, H␣ (Py)). These correspond
to ylides 7 (8%) and 9g (82%).
Reaction of Ylide 7 with 2-Nitrophenyl
Isocyanate
A mixture of ylide 7 (0.5 g, 2.11 mmol) and 2-
nitrophenyl isocyanate (1 g, 6.04 mmol) in CH2Cl2
(10 ml) was left for 16 days at room temperature.
The 1H NMR spectrum showed the signals in the re-
action mixture: 8.49 ppm (ylide 7, H␣ (Py)), 8.53 ppm
(9e, H␣ (Py)). These correspond to ylides 7 (25%) and
9e (75%).
N-[(N-Ethoxycarbonyl-N-phenylcarbamoyl)
ethoxycarbonylmethyl]pyridinium Methosulfate
(10b)
Pyridinium (N-Ethoxycarbonyl-N-4-nitro-
phenylcarbamoyl)ethoxycarbonylmethylide (9f)
MeSO2OH (0.135 g, 1.40 mmol) was added drop-
wise to a stirred yellow solution of the crude 9b
(0.5 g, 1.40 mmol) in CH2Cl2 (2 ml). A color-
less solution that formed was evaporated to dry-
ness under reduced pressure, and the residue was
recrystallized (acetonitrile/hexane) to obtain white
crystals.
Compound 9f was prepared similarly to 9b. 13C
NMR : 14.29 (OCH2CH3), 59.63 (OCH2CH3), 62.01
(OCH2CH3), 107.34 (C ), 122.59 (C2,6 (Ar)), 123.93
(C3,5 (Ar)), 126.29 (C␤ (Py)), 142.66 (C␥ (Py)),
143.45 (C NO2), 145.58 (N C (Ar)), 148.88 (C␣
TABLE 4 Characterization Data of Isoquinolinium Ylides and Bis-Salt 15a
Elemental Analysisa (%)
Molecular
Formula
Molecular
Weight
Yield
(%)
mp
( C)
Compound
C
H
N
S
12
14a
C16H17NO4
287.32
451.44
70
68
191–193
90–91b
–
–
4.48
(4.69)
4.54
(4.69)
–
9.48
(9.31)
6.56
(6.53)
–
–
C
C
C
23H21N3O7
60.99
(61.19)
47.42
(46.65)
70.75
(71.04)
15a
14b
25H29N3O13S2
27H24N2O5
643.64
456.50
93
81
134–136
79–80b
10.07
(9.96)
–
5.49
(5.30)
5.83
(6.14)
a
Values found are followed by the calculated values (in parentheses).
Decomposition.
b

44 Gololobov et al.
TABLE 5 The 1H NMR and IR Spectral Data of the Synthesized Compounds
--1
IR (
cm
)
max
C
O
C
O
C O
Compound
1H NMR
(C(O)OEt) ( C(O) N) (N C(O)OEt)
12
1.29 (t, 6H, CH2CH3, J = 7.2 Hz), 4.19 (q, 4H, CH2CH3,
J = 7.2 Hz), 7.82 (m, 1H, Is), 7.94 (d, 1H, Is, J = 6.8 Hz),
7.99 (d, 2H, Is, J = 4.0 Hz), 8.12 (d, 1H, Is, J = 8.0 Hz),
8.30 (t, 1H, Is, J = 7.2 Hz), 9.27 (s, 1H, H1 (Is))
1658
1591
–
–
14a
15a
1.13 (t, 3H, CH2CH3, J = 7.2 Hz), 1.35 (t, 3H, CH2CH3, J = 7.2 Hz),
4.08 (q, 2H, CH2CH3, J = 7.2 Hz), 4.32 (q, 2H, CH2CH3,
J = 7.2 Hz), 7.76 (d, 2H, Ar, J = 9.2 Hz), 7.90 (m, 1H, Is), 8.08
(m, 3H, Is), 8.18 (d, 2H, Ar, J = 9.2 Hz), 8.16–8.23 (m, 1H, Is),
8.33 (d, 1H, Is), J = 6.8 Hz), 9.34 (s, 1H, H1 (Is))
1591
1714
1.21 (t, 3H, CH2CH3, J = 7.2 Hz), 1.32 (t, 3H, CH2CH3,
J = 7.2 Hz), 2.95 (s, 6H, CH3S), 4.23–4.48 (m, 4H, CH2CH3),
7.61 (d, 2H, Ar, J = 8.8 Hz), 7.87 (s, 1H, CH), 7.95 (t, 1H, Is,
J = 7.2 Hz), 8.07–8.17 (m, 2H, Is), 8.24 (d, 1H, Is, J = 6.4 Hz),
8.25 (d, 2H, Ar, J = 8.8 Hz), 8.41 (d, 1H, Is, J = 6.8 Hz), 8.60
(d, 1H, Is, J = 8.4 Hz), 10.29 (s, 1H, H1 (Is)), 10.77 (bs, 1H, H+)
(1H NMR at +20 C) 1.20 (t, 3H, CH2CH3, J = 7.2 Hz),
1.33 (t, 3H, CH2CH3, J = 7.2 Hz), 4.15–4.24 (m, 2H, CH2CH3),
4.25–4.34 (m, 2H, CH2CH3), 7.37–8.39 (m, 13H, Harom),
9.36 (s, 1H, H1 (Is))
1751
1583
1715
1583
1751
1712
14b
(1H NMR at +55 C) 1.30 (t, 3H, CH2CH3, J = 7.2 Hz),
1.33 (t, 3H, CH2CH3, J = 7.2 Hz), 4.21 (q, 2H, CH2CH3,
J = 7.2 Hz), 4.31 (q, 2H, CH2CH3, J = 7.2 Hz), 7.37–8.39
(m, 13H, Harom), 9.37 (s, 1H, H1 (Is))
Is = isoquinoline.
N-[(N-Ethoxycarbonyl-N-3,4-dichlorophenyl-
carbamoyl)ethoxycarbonylmethyl]pyridinium
Methosulfate (10d)
N-[(N-Ethoxycarbonyl-N-4-nitrophenyl-
carbamoyl)ethoxycarbonylmethyl]pyridinium
bis-methosulfate (11f)
MeSO2OH (0.83 g, 8.68 mmol) was added dropwise
to a stirred yellow solution of 9d (3.69 g, 8.68 mmol)
in CH2Cl2 (20 ml). The colorless solution that formed
was evaporated to dryness under reduced pressure.
The residue was washed by ethyl ether and re-
crystallized from acetone to obtain white crystals.
13C NMR : 13.63 (OCH2CH3), 39.31 (CH3S), 64.10
(OCH2CH3), 64.50 (OCH2CH3), 75.79 (CH), 127.82–
127.04 (C2,6 (Ar)), 130.25 (C5 (Ar)), 130.65 (C␤ (Py)),
132.53 (C Cl), 132.91 (C Cl), 135.75 (N C (Ar)),
146.16 (C␥ (Py)), 147.59 (C␣ (Py)), 152.98 (C(O)N),
162.84 (NCOOEt) 164.64 (COOEt).
MeSO2OH (0.05 g, 0.50 mmol) was added dropwise
to a stirred yellow solution of 9f (0.10 g, 0.25 mmol)
in CH2Cl2 (2 ml). A colorless solution that resulted
was evaporated to dryness under reduced pressure.
The residue was washed by ethyl ether and recrys-
tallized from THF to obtain white crystals. 13C NMR
: 9.87 (OCH2CH3), 35.11 (CH3S), 60.86 (OCH2CH3),
60.90 (OCH2CH3), 71.93 (CH), 120.07–124.06 (Ar),
125.83 (C␤ (Py)), 137.75 (N C (Ar)), 141.95 (C␥ (Py)),
143.79 (C␣-(Py)), 148.68 (C(O)N), 158.62 (NCOOEt)
160.36 (COOEt).
Thermolysis of (9b)
N-[(N-Ethoxycarbonyl-N-4-nitrophenyl-
carbamoyl)ethoxycarbonylmethyl]pyridinium
Methosulfate (10f)
Ylide 9b (1 g, 0.28 mmol) was heated (130 C) un-
der N2 for 1 h. The resulting mixture was cooled to
room temperature and extracted with boiling ace-
tone. Evaporation of the solvent gave a powder,
which was recrystallized from acetone. Yield 60%,
mp 174 C. The 1H NMR spectrum gave the signals of
the starting ylide 7.
MeSO2OH (0.024 g, 0.25 mmol) was added dropwise
to stirred yellow solution of 9f (0.10 g, 0.25 mmol) in
CH2Cl2 (2 ml). A colorless solution that resulted was
evaporated to dryness under reduced pressure. The
residue was washed by ethyl ether and recrystallized
(ether/THF) to obtain white crystals.
Isoquinolinium ylide (12) was obtained by the
literature method [5].

Reactions of Pyridinium and Isoquinolinium Ylides Derived from Malonic Ester with Isocyanates 45
from acetone to obtain white crystals. 13C NMR
:
Isoquinolinium (N-Ethoxycarbonyl-N-4-
nitrophenylcarbamoyl)ethoxycarbonylmethylide
(14a)
9.93 (OCH2CH3), 35.44 (CH3S), 60.52 (OCH2CH3),
61.07 (OCH2CH3), 71.74 (CH), 120.59–148.74
(Carom), 148.94 (C(O)N), 159.19 (NCOOEt) 161.06
(COOEt).
A mixture of ylide 12 (2 g, 6.96 mmol) and 4-nitro-
phenyl isocyanate (2.3 g, 14.02 mmol) in CHCl3
(25 ml) was left for 24 h at room temperature. The
reaction mixture was filtered, and petroleum ether
was added dropwise to the filtrate. The precipitate
that formed was filtered off and dried under reduced
pressure without heating to obtain orange powder.
REFERENCES
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Russ Chem Bull 1995, 44, 181.
[3] Krylova, T. O.; Shishkin, O. V.; Struchkov, Yu. T.;
Kolomnikova, G. D.; Gololobov, Yu. G. Russ J Gen
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[4] Gololobov, Yu. G.; Pinchuk, V. A.; Thonnessen, H.;
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[5] Gololobov, Yu. G.; Kardanov, N. A.; Khroustalyov, V.
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McGraw-Hill Intern Book Company: Bucharest, New
York, 1976; p. 396.
Isoquinolinium (N-Ethoxycarbonyl-N-1-
naphthylcarbamoyl)ethoxycarbonylmethylide
(14b)
A mixture of ylide 12 (2 g, 6.96 mmol) and 1-naphthyl
isocyanate (2.4 g, 14.20 mmol) in CH2Cl2 (25 ml)
was left for 8 days at room temperature. Completion
of the reaction was monitored by 1H NMR spec-
troscopy. The reaction mixture was filtered, and
petroleum ether was added dropwise to the filtrate.
An oil that formed was stirred in the mixture of ethyl
ether and petroleum ether. An orange powder 14b
that formed was filtered off and dried under reduced
pressure without heating.
[8] Kro¨hnke, F. Chem Ber 1937, 70, 543–547.
[9] Zaslona, A. T.; Hall, C. D. JCS Perkin I 1981, 12,
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Krasnova, I. Yu.; Petrovskii, P. V.; Antipin, M. Yu.;
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[13] Pimentel, G. C.; McClellan, A. L. The Hydrogen Bond;
W. H. Freeman and Company: New York, 1960;
p. 47.
N-[(N-Ethoxycarbonyl-N-4-nitrophenylcar-
bamoyl)ethoxycarbonylmethyl]isoquinolinium
bis-methosulfate (15a)
MeSO2OH (0.42 g, 4.43 mmol) was added dropwise
to a stirred yellow solution of 14b (1 g, 2.21 mmol) in
CH2Cl2 (10 ml). A colorless solution that resulted was
evaporated to dryness under reduced pressure. The
residue was washed by ethyl ether and recrystallized