Dipolarophilic behaviour of (arylsulfonyl)allenes towards nitrilimines

Article abstract of DOI:10.1039/b001947j

The dipolarophilic behaviour of 1-[2-(acetylamino)phenylsulfonyl]propa-1,2-diene 1 towards a series of nitrilimines is here described. Mechanistic possibilities for the formation of pyrazolic products 4-7 are discussed. The Royal Society of Chemistry 2000

Full text of DOI:10.1039/b001947j

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Dipolarophilic behaviour of (arylsulfonyl)allenes towards
nitrilimines
Gianluigi Brogginia and Giorgio Molteni*b
1
a Dipartimento di Scienze Chimiche, Fisiche e Matematiche, Università dell’Insubria,
via Lucini 3, 22100 Como, Italy
b Dipartimento di Chimica Organica e Industriale, Università di Milano, via Golgi 19,
20133 Milano, Italy
Received (in Cambridge, UK) 10th March 2000, Accepted 5th April 2000
Published on the Web 16th May 2000
The dipolarophilic behaviour of 1-[2-(acetylamino)phenylsulfonyl]propa-1,2-diene 1 towards a series of
nitrilimines is here described. Mechanistic possibilities for the formation of pyrazolic products 4–7 are
discussed.
the following considerations: (i) the allene → acetylene
isomerisation is suppressed under these conditions; (ii) room
temperature and heterogeneous reaction medium allow a
smooth generation of the nitrilimine, so minimising the
degradative processes of the 1,3-dipole.
Cycloaddition reactions were carried out by using different
proportions of the reactants, which are summarised in Table 1
along with reaction times, products, eluents and yields. When
using a 2:1 molar ratio between a hydrazonoyl chloride 2 and
the allene 1, shorter reaction times and yield enhancement of
cycloaddition products 4 and 5 were observed. Some quantity
of the starting allene 1 was always recovered.
Introduction
Owing to the presence of two cumulative unsaturations,
allenes1 are interesting dipolarophiles.2 In fact, both C᎐C bonds
᎐
are suitable positions for dipolar attack which can proceed with
two opposite orientations. Hence, both site- and regioselectivity
are involved in their cycloadditions.
The dipolarophilic behaviour of arylsulfonylallenes with
nitrilium betaines has been extensively investigated in the field
of nitrile oxide cycloadditions.3 Conversely, nitrile imines were
only the object of occasional reports,3c,4 as recently stated.2
Aiming to acquire a better understanding of this subject,
we examined the reaction between 1-[2-(acetylamino)phenyl-
sulfonyl]propa-1,2-diene 13b and a series of properly substi-
tuted nitrilimines.
The regioisomeric formulae of 4 and 5 were distinguished on
1
the basis of H NMR chemical shifts of the pyrazolic hydro-
gens,7 while the 1-aryl-4-hydroxymethyl-3-(methoxycarbonyl)-
pyrazole structure 7 was assigned based upon analytical and
spectral data. The sulfinic ester 6f, which was fully character-
ised, was shown to undergo a complete conversion to 7f under
mild hydrolytic conditions (aq. HCl–1,4-dioxane, rt). Such
lability plausibly justifies the lack of isolation of analogous
intermediates 6a–e in the other cases.
Results and discussion
Among the hydrazonoyl chlorides 2, which we devised as
precursors of the desired nitrilimines, substrates 2a,b,d,e were
synthesised as previously reported,5 while the new substrates
2c,f were synthesised in an analogous manner as depicted in
Scheme 1.
The in situ generation of nitrilimines was accomplished in the
presence of 1 by treating the appropriate hydrazonoyl chlor-
ide with a two-fold molar excess of silver carbonate in dry
1,4-dioxane at room temperature. The choice of such an
unconventional basic agent in the place of more common
organic bases, like triethylamine or DABCO,6 comes from
The experimental findings can be accounted for by two
independent mechanistic hypotheses. The first one, which is
outlined in Scheme 2, implies competitive cycloadditions of
nitrilimines 3 across the α,β and the β,γ positions, in analogy
with the behaviour of 1 towards 2,4,6-trimethyl-3,5-dichloro
benzonitrile oxide.3b According to this picture, the primary
cycloadducts A and B give pyrazoles 4 and 5, respectively, via
1,3-prototropic shift facilitated by the basic medium. Such a
Table 1 Reaction of hydrazonoyl chlorides 2 with the allene 1a
Molar
equiv.
of 2
Products and Yields (%)
α,β:β,γ
Entry
t/h
67
28
120
48
140
48
96
1
4
5
6
7
ratioa
Eluentb
a
b
c
1
2
1
2
1
2
1
1
1
44
30
54
32
47
27
70
80
40
18
22
16
26
18
26
8
8
23
7
20
11
12
1
20
8
12
43:57
15:85
34:66
0:100
38:62
28:72
25:75
Et2O
Et2O
Et2O–LP (9:1)
CH2Cl2–Et2O (4:1)
Et2O–LP (9:1)
Et2O
18
15
3
d
e
f
Et2O–LP (9:1)
170
160
12
14
17
40:60
Et2O–LP (9:1)
a At rt (20 ЊC). b In light of the mechanistic pathway outlined in Scheme 2. c LP = light petroleum (distillation range 40–60 ЊC).
DOI: 10.1039/b001947j
J. Chem. Soc., Perkin Trans. 1, 2000, 1685–1689
This journal is © The Royal Society of Chemistry 2000
1685

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Scheme 1
Scheme 2
mechanism, however, does not provide a convincing rationalis-
the expectations based upon early CNDO computations on
ation of the very variable α,β:β,γ ratio (Table 1), since the latter
was roughly constant in the case of nitrile oxide cyclo-
additions.3b
The second mechanistic pathway requires the α,β position as
the exclusive site for dipolar attack (see Scheme 3), and reflects
(methylsulfonyl)allene.8 By performing PM3 calculations9 on
the allene 1,10 we found that the LUMO atomic coefficients of
the α and β carbons are only slightly different (ϩ0.33 on the α
carbon and Ϫ0.43 on the β carbon, see Fig. 1), so allowing the
formation of both regioisomers C and D. Within this pathway,
1686
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Table 2 Elemental analyses of compounds 4, 5, 6f and 7
Found (%) (Required)
Compound
(Formula)
C
H
Cl
N
S
4a
58.03
(58.10)
59.09
(59.00)
56.80
(56.87)
53.74
(53.68)
59.88
(59.85)
58.15
(58.10)
59.01
(59.00)
56.92
(56.87)
53.73
(53.68)
59.88
(59.85)
59.85
(59.85)
63.02
(62.05)
63.43
(63.39)
59.33
(59.29)
54.10
(54.13)
64.62
(64.59)
4.61
(4.64)
4.91
(4.96)
4.77
(4.78)
4.04
(4.06)
5.22
(5.25)
4.66
(4.64)
4.96
(4.96)
4.81
(4.78)
4.07
(4.06)
5.23
(5.25)
5.21
(5.25)
5.23
(5.21)
5.69
(5.73)
5.75
(5.75)
4.15
(4.17)
6.22
(6.20)
10.11
(10.17)
9.78
(9.84)
9.44
(9.48)
9.43
(9.40)
9.50
(9.52)
10.15
(10.17)
9.88
(9.84)
9.51
(9.48)
9.41
(9.40)
9.49
7.69
(7.74)
7.56
(7.49)
7.16
(7.22)
7.21
(7.15)
7.32
(7.25)
7.78
(7.74)
7.56
(7.49)
7.14
(7.22)
7.21
(C20H19N3O5S)
4b
(C21H21N3O5S)
4c
(C21H21N3O6S)
4d
7.77
(7.82)
(C20H18ClN3O5S)
4f
(C22H23N3O5S)
5a
(C20H19N3O5S)
5b
(C21H21N3O5S)
5c
(C21H21N3O6S)
5d
7.93
(7.82)
(C20H18ClN3O5S)
(7.15)
7.20
(7.25)
7.32
5f
(C22H23N3O5S)
(9.52)
9.50
6f
(C22H23N3O5S)
(9.52)
12.11
(12.07)
11.41
(11.38)
10.71
(10.64)
10.57
(10.53)
10.84
(10.77)
(7.25)
7a
(C12H12N2O3)
7b
(C13H14N2O3)
7c
(C13H15N2O4)
7d
13.08
(13.14)
(C12H11ClN2O3)
7f
(C14H16N2O3)
Fig. 1 Frontier molecular orbitals of the allene 1 calculated by the
PM3 method.
electron-poor nitrilimines: recovery of considerable amounts of
unchanged allene 1 and very poor product yields were the rule
here. These disappointing results are, however, explained in the
light of the HOMO-dipole-controlled nature of these cyclo-
additions onto an electron-deficient dipolarophile.13
Experimental
Mps were determined with a Büchi apparatus and are uncor-
rected. IR spectra were recorded with a Perkin-Elmer 1725X
spectrophotometer. Mass spectra were determined with a VG-
1
70EQ apparatus. H NMR spectra were taken with a Bruker
AC 300 instrument for samples in CDCl3 solution; chemical
shifts are given as ppm from tetramethylsilane, J-values
are given in Hz. All new compounds 4–7 gave satisfactory
elemental analyses, which are given in Table 2.
General procedure for the preparation of hydrazonoyl chlorides
2c,f
Scheme 3
A solution of the properly substituted aniline (15 mmol) in a
mixture of water (25 cm3) and methanol (15 cm3) was treated
with hydrochloric acid (10 mol dmϪ3, 4.5 cm3) and then cooled
to 0 ЊC. Sodium nitrite (15 mmol) as a solution in water (5 cm3)
was added dropwise to the cooled and stirred reaction mixture.
After 30 min, the cold mixture was adjusted to pH 5 with
sodium acetate and then a solution of methyl 2-chloroaceto-
acetate (15 mmol) in methanol (15 cm3) was added with cooling
and stirring of the mixture, which was stirred overnight at room
temperature and then extracted with diethyl ether. The organic
layer was washed with aq. sodium hydrogen carbonate, dried
over sodium sulfate and evaporated. Recrystallisation from
diisopropyl ether gave the pure hydrazonoyl chloride in 67%
(2c) or 91% (2f) yield.
the final pyrazoles 4 and 5 would originate from C and D via
1,3-allylic shift of the sulfonyl group.3c,11 Such a mechanism
suggests that the ratio of 5 to 7 should be very sensitive to pH
and solvent, but it also predicts that the ratio of 4 to 5 ϩ 7
should be constant, and this is not the case.
Irrespective of the above mechanistic hypothesis, the form-
ation of the sulfinic esters 6 can be rationalised by invoking
a [2,3]sigmatropic rearrangement of cycloadduct C via a
sulfur-to-oxygen bond migration.12
As a final remark, it can be stated that the mechanistic pic-
tures outlined in Schemes 2 and 3 are only partly in accord with
experimental results. However, we note that the course of
cycloaddition is strongly dependent on the electronic nature
of the 1,3-dipole. While electron-rich nitrilimines gave good
results, the cycloaddition pathway appeared impervious with
Compound 2c (2.11 g, 67%), mp 102 ЊC (from diisopropyl
ether) (Found: C, 49.66; H, 4.62; Cl, 14.56; N, 11.65. C10H11-
J. Chem. Soc., Perkin Trans. 1, 2000, 1685–1689
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Table 3 Physical and spectral data of compounds 4, 5, 6f and 7a–d
Compd.
Mp/ЊC
νmax/cmϪ1
δH
m/z (Mϩ)
4a
4b
4c
4d
4f
152a
165b
125a
168a
160c
201b
187a
170c
208b
168a
104b
3370, 1730, 1705
3345, 1715, 1700
3350, 1730, 1700
3340, 1745, 1680
3370, 1730, 1710
3360, 1720, 1700
3380, 1715, 1700
3355, 1720, 1700
3370, 1720, 1700
3360, 1715, 1700
2.00 (3H, s), 3.90 (3H, s), 4.45 (2H, s), 6.95 (1H, s), 7.00–8.60 (9H, m), 9.25
(1H, br s)
2.05 (3H, s), 2.40 (3H, s), 3.95 (3H, s), 4.45 (2H, s), 6.95 (1H, s), 7.00–8.60
(8H, m), 9.25 (1H, br s)
2.05 (3H, s), 3.85 (3H, s), 3.90 (3H, s), 4.40 (2H, s), 6.90 (1H, s), 7.00–8.60
(8H, m), 9.25 (1H, br s)
2.10 (3H, s), 3.95 (3H, s), 4.45 (2H, s), 6.90 (1H, s) 7.10–8.60 (8H, m), 9.20
(1H, br s)
1.85 (3H, s), 2.05 (3H, s), 2.25 (3H, s), 3.92 (3H, s), 4.30 (2H, d, JAB 10.5),
6.92 (1H, s), 7.01–8.60 (7H, m), 9.30 (1H, br s)
2.20 (3H, s), 3.80 (3H, s), 4.80 (2H, s), 7.00–7.80 (8H, m), 7.95 (1H, s), 8.40–
8.65 (1H, m), 9.45 (1H, br s)
2.20 (3H, s), 2.40 (3H, s), 3.85 (3H, s), 4.80 (2H, s), 7.00–7.80 (7H, m), 7.90
(1H, s), 8.50–8.60 (1H, m), 9.48 (1H, br s)
2.18 (3H, s), 3.80 (3H, s), 3.85 (3H, s), 4.75 (2H, s), 6.80–7.80 (7H, m), 7.85
(1H, s), 8.45–8.65 (1H, m), 9.50 (1H, br s)
413
427
443
447
441
413
427
443
447
441
441
5a
5b
5c
5d
5f
2.20 (3H, s), 3.90 (3H, s), 4.80 (2H, s), 7.00–7.85 (7H, m), 7.90 (1H, s), 8.55–
8.60 (1H, m), 9.50 (1H, br s)
2.15 (3H, s), 2.28 (3H, s), 2.35 (3H, s), 3.85 (3H, s), 4.80 (2H, s), 6.95–7.80
(6H, m), 7.82 (1H, s), 8.45–8.60 (1H, m), 9.55 (1H, br s)
2.08 (3H, s), 2.20 (3H, s), 2.34 (3H, s), 3.94 (3H, s), 5.20 (2H, d, JAB 12.0),
6.90–7.80 (6H, m), 7.88 (1H, s), 8.15–8.35 (1H, m), 9.60 (1H, br s)
3.85 (1H, br s), 3.95 (3H, s), 4.75 (2H, s), 6.90–7.80 (5H, m), 7.85 (1H, s)
2.30 (3H, s), 3.45 (1H, br s), 3.95 (3H, s), 4.70 (2H, s), 6.80–7.60 (4H, m)
3.40 (1H, br s), 3.82 (3H, s), 3.98 (3H, s), 4.72 (2H, s), 6.90–7.70 (4H, m)
3.99 (3H, s), 4.10 (1H, br s), 4.75 (2H, s), 7.40–7.70 (4H, m), 7.88 (1H, s)
2.11 (3H, s), 2.22 (3H, s), 3.50 (1H, br s), 3.90 (3H, s), 4.72 (2H, s), 6.95–7.60
(3H, m), 7.82 (1H, s)
6f
3350, 1720, 1710,
1120
3370, 1715
3365, 1715
3355, 1720
3485, 1705
3370, 1715
7a
7b
7c
7d
7f
91a
84b
232
246
263
266
260
133a
95b
89a
a From diisopropyl ether. b From hexane–benzene. c From diisopropyl ether–propan-2-ol.
1
ClN2O3 requires C, 49.58; H, 4.58; Cl, 14.45; N, 11.57%);
νmax (Nujol)/cmϪ1 3260, 1700; δH 3.80 (3H, s), 3.90 (3H, s), 6.90–
7.20 (4H, m), 8.30 (1H, br s); m/z (EI) 242 (Mϩ).
Compound 2f (3.28 g, 91%), mp 112 ЊC (from diisopropyl
ether) (Found: C, 55.09; H, 5.49; Cl, 14.65; N, 11.60. C11H13-
ClN2O2 requires C, 54.89; H, 5.44; Cl, 14.73; N, 11.64%);
νmax (Nujol)/cmϪ1 3250, 1710; δH 2.25 (3H, s), 2.35 (3H, s), 3.95
(3H, s), 6.70–7.40 (3H, m), 8.25 (1H, br s); m/z (EI) 240 (Mϩ).
periodically monitored by H NMR. After 200 h the undis-
solved material was filtered off, the filtrate was dried over
sodium sulfate, and the solvent was evaporated under reduced
pressure. The unchanged allene was quantitatively recovered.
Acidic hydrolysis of 6f
A solution of 6f (0.2 g, 0.5 mmol) in 1,4-dioxane (5 cm3)
was treated under stirring with hydrochloric acid (10 mol
dmϪ3; 0.1 cm3) for 6 h at room temperature. The mixture was
dried over sodium sulfate and the solvent was removed under
reduced pressure. The residue was chromatographed on a silica
gel column with diethyl ether as eluent. First fractions gave
1-(2,5-dimethylphenyl)-4-hydroxymethyl-3-(methoxycarbonyl)-
pyrazole 7f (83 mg, 64%). Further elution gave 2-(acetyl-
amino)benzenesulfinic acid14 (35 mg, 35%).
General procedure for the reaction between the allene 1 and
hydrazonoyl chlorides 2 in a 1:1 molar ratio
A solution of the allene 1 (1.19 g, 5 mmol) and a hydrazonoyl
chloride 2 (5 mmol) in dry 1,4-dioxane (25 cm3) was treated
with silver carbonate (2.76 g, 10 mmol). The mixture was stirred
at room temperature in the dark for the time indicated in Table
1. The undissolved material was filtered off, the solvent
was evaporated under reduced pressure, and the residue was
chromatographed on a silica gel column. Products, eluents and
yields are collected in Table 1. Physical and spectral data of
compounds 4, 5, 6f and 7a–d,f are collected in Table 3.
Treatment of 4-hydroxymethyl-3-methoxycarbonyl-1-
phenyl]pyrazole 7a with silver carbonate in 1,4-dioxane
A solution of 7a (210 mg, 0.91 mmol) in dry 1,4-dioxane (5.0
cm3) was treated with silver carbonate (500 mg, 1.82 mmol).
The mixture was stirred at room temperature in the dark and
1
General procedure for the reaction between allene 1 and
hydrazonoyl chlorides 2a–c in a 1:2 molar ratio
periodically monitored by H NMR. After 240 h the undis-
solved material was filtered off, the filtrate was dried over
sodium sulfate, and the solvent was evaporated under reduced
pressure. Unchanged 7a was quantitatively recovered.
A solution of the allene 1 (1.19 g, 5 mmol) and hydrazonoyl
chlorides 2a–c (10 mmol) in dry 1,4-dioxane (25 cm3) was
treated with silver carbonate (2.76 g, 10 mmol). The mixture
was stirred at room temperature in the dark for the time indi-
cated in Table 1. The undissolved material was filtered off, the
solvent was evaporated under reduced pressure, and the residue
was chromatographed on a silica gel column. Products, eluents
and yields are collected in Table 1. Physical and spectral data of
compounds 4, 5 and 7 are collected in Table 3.
Acknowledgements
We thank MURST and CNR for financial support. We are
grateful to Prof. Luisa Garanti and to Prof. Gaetano Zecchi for
helpful suggestions.
References
Treatment of the allene 1 with silver carbonate in 1,4-dioxane
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The mixture was stirred at room temperature in the dark and
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