On the nature of intermediates in the reactions of carbanions of diethyl arylmalonates with isocyanates

Article abstract of DOI:10.1007/s11172-009-0139-7

A reaction of ethyl phenyl- and 4-nitrophenylmalonate carbanions with para-tolylsulfonyl isocyanate leads to stable addition products, the corresponding substituted para-tolyl-sulfonylacylamides.

Full text of DOI:10.1007/s11172-009-0139-7

Russian Chemical Bulletin, International Edition, Vol. 58, No. 5, pp. 1088—1090, May, 2009
1088
On the nature of intermediates in the reactions of carbanions
of diethyl arylmalonates with isocyanates
Yu. G. Gololobov, N. V. Slepchenkov, P. V. Petrovskii, and Yu. V. Nelyubina
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. Eꢀmail: Yugol@ineos.ac.ru
A reaction of ethyl phenylꢀ and 4ꢀnitrophenylmalonate carbanions with paraꢀtolylsulfonyl
isocyanate leads to stable addition products, the corresponding substituted paraꢀtolylꢀ
sulfonylacylamides.
Key words: ethyl phenylꢀ and 4ꢀnitrophenylmalonate carbanions, paraꢀtolylsulfonyl isoꢀ
cyanate, paraꢀtolylsulfonylacylamides.
During consideration of mechanism for the formation
of carbamates by the reaction of isocyanates with carbanꢀ
ions 1 based on phosphorusꢀcontaining zwitterions,1,2
phenylcyanacetic esters,3 and pyridinium ylides4, it was
suggested that Nꢀanion 2 is formed as an intermediate
(Scheme 1). The formation of the intermediate 2 was
confirmed by the data of quantum chemical calculations
for the reaction of pyridinium ylide, malonic ester derivaꢀ
tive, with phenyl isocyanate.4 At the same time, experiꢀ
we considered a model reaction of carbanions 5a,b with
tosyl isocyanate (Scheme 2). We presumed that if the
reactions with aryl isocyanates proceed according to
Scheme 1 through the formation of Nꢀanions 2, then the
analogous reaction with tosyl isocyanate according to
Scheme 2 will lead in the first step to the stable intermediꢀ
ate 6, the nucleophilicity of which should be extremely
low due to the strong electronꢀwithdrawing power of the
tosyl group.
1
ments using H NMR spectroscopy and kinetic data2 did
Scheme 2
not show formation of intermediate 2 as kinetically stable
species on the reaction coordinate.
To answer the question whether the intermediate
Nꢀanion 2 is formed in the transformations under study,
Scheme 1
R = R´ = H (a); R = NO2, R´ = H (b). Ts = SO2C6H4Meꢀp
R = Ph; Py(+)
;
; R´ P(+)CH2,
3
In fact, the reaction of tosyl isocyanate with carbanꢀ
ions obtained in the solution of THF from CH acid 5a,b
and NaH proceeds at room temperature and, after acidifiꢀ
R´ = Prn, Pri, Bun, Et2N;
X = O, S; Alk = Me, Et, allyl, CH≡CCH2; R″ = Me, cycloꢀC6H11, Ar.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1060—1062, May, 2009.
1066ꢀ5285/09/5805ꢀ1088 © 2009 Springer Science+Business Media, Inc.

Reactions of diethyl arylmalonates carbanions
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 5, May, 2009
1089
cation of the reaction mixture with dilute hydrochloric
acid, leads to the isolation of stable amides 7a,b in high
yields. The carrying out the reaction under consideration
at 65 °C does not lead to the formation of the correspondꢀ
ing carbamates of the type 3, which, no doubt, is due to
the low nucleophilicity of the Nꢀanion in the intermediꢀ
ate 6. The composition and structures of amides 7a,b were
inferred from the data of elemental analysis, IR and NMR
spectra. In contrast to carbamates obtained from malonic
ester derivatives and aryl isocyanates,3 which contain the
pared to the C—O(3) and C—O(6) bonds (1.2072(19)
and 1.1937(19) Å). The sixꢀmembered Hꢀbound cycle
has the chair conformation. In addition to the H bond
specified, in the crystal of 7a there also exist a number of
shortened contacts formed by the O(1), O(3), and O(7)
atoms with the distances 2.979(2) and 3.026(2) Å, which
...
is frequent enough phenomenon for the specific O
interactions in crystals.7
O
In conclusion, it was experimentally shown that the
reaction of carbanions, arylmalonic ester derivatives, with
isocyanates (using the reaction with tosyl isocyanate as an
example) indeed leads in the first step of the reaction to
the formation of Nꢀanions as the intermediates. It is quite
obvious that the reaction of carbanions with aryl isoꢀ
cyanates according to Scheme 1 initially also leads to
Nꢀanions 2, but due to their high nucleophilic activity, an
intramolecular attack N(–)→C(O)OEt takes place, which
is accompanied by a concerted cleavage of the C—C bond
and transfer of the ester group from the carbon atom to
the nitrogen atom.
1
signals of two different ethoxy groups in the H NMR
1
spectrum, the H NMR spectra of amides 7a,b exhibit
signals for the protons of the ethoxycarbonyl groups as a
single group. To study specificities in the spatial arrangeꢀ
ment of substituents in the molecule of amide 7a, we
performed its Xꢀray diffraction analysis (Fig. 1). The main
geometric parameters of amide 7a are close to the
expected values. Insignificant flattening (the sum of the
bond angles is 358(1)°) of the nitrogen atom, apparently,
is due to its conjugation with the C=O group. Statistical
analysis of the Cambridge Structural Database showed
that the arrangement of arylsulfone and amide groups
observed in 7a is quite rare. Direct analogs of compound
7a containing the fragment N(H)—C(O)—C(R)2C(O)OAlk
have not been earlier studied, and the only known analogs
are compounds, in which the nitrogen atom is in a heteroꢀ
cycle.5,6 Conformational analysis of the molecule showed
that the aromatic rings have a transoid arrangement with
respect to the central sulfonamide chain, whereas the
ester group O(6)C(10)O(7) is placed directly over
the plane of the tolyl substituent. Such an arrangement of
substituents is due to both the steric reasons and the presꢀ
ence of the intramolecular interactions. In the crystal, the
hydrogen atom of the NH group and O(4) atom of the
carboxylate fragment form an H bond (N...O 2.655(2) Å,
NHO 140(1)°), which, apparently, results in insignificant
elongation of the C—O(4) bond (1.2142(18) Å) as comꢀ
Experimental
1H NMR spectra were recorded on a Bruker AMХꢀ400
spectrometer in the solvent CDCl3. IR spectra were recorded on
a Nicolet MagnaꢀIRꢀ750 Fourierꢀspectrometer (KBr).
NꢀpꢀTolylsulfonyl[bis(ethoxycarbonyl)phenyl]acetamide (7a).
Diethyl phenylmalonate (1 g, 4.23 mmol) was added dropwise
to a suspension of NaH (0.15 g, 4.23 mmol) in THF (10 mL)
followed by stirring for 10 min. paraꢀTolylsulfonyl isocyanate
(1.70 g, 8.5 mmol) was added dropwise to the clear solution.
After 4 h, the reaction mixture was mixed with diethyl ether
(30 mL), The salt formed was filtered off, washed with diethyl
ether, and treated with dilute (1 : 10) hydrochloric acid in the
presence of benzene (50 mL). The organic layer was dried with
Na2SO4 for 12 h. Benzene was evaporated in vacuo and the
residue was twice crystallized from a mixture of light petroꢀ
leum—diethyl ether (1 : 1) to obtain colorless crystals (1.45 g,
79.2%), m.p. 93—94 °C. Found (%): C, 58.10; H, 5.25; N, 3.20;
S, 7.34. C21H23NSO7. Calculated (%): C, 58.19; H, 5.31;
N, 3.23; S, 7.39. 1H NMR, δ: 1.21 (t, 6 H, CH3CH2O,
JH,H = 10.5 Hz); 2.41 (s, 3 H, CH3—Ph); 4.27 (q, 2 H, CH3CHH´O,
JH,H = 10.5 Hz); 4.25 (q, 2 H, CH3CHH´O, JH,H = 10.5 Hz);
C(8)
C(20)
C(4)
C(21)
C(3)
O(7)
C(5)
C(6)
O(6)
O(3)
7.10 (d, 2 H, Harom, JH,H = 11.5 Hz); 7.84 (d, 2 H, Harom
,
C(19)
JH,H = 11.5 Hz); 7.22—7.3 (m, 6 H, HРh); 10.64 (s, 1 H, NH).
IR (ν/cm–1): 1706 (C(O)N), 1760, 1734 (COOEt), 3183 (NH).
NꢀpꢀTolylsulfonyl[bis(ethoxycarbonyl)ꢀ4ꢀnitrophenyl]acetꢀ
amide (7b). Colorless crystals (0.9 g, 53%) were obtained under
conditions of preceding experiment from diethyl 4ꢀnitroꢀ
phenylmalonate (1 g, 3.55 mmol), NaH (0.13 g, 3.55 mmol),
and paraꢀtolylsulfonyl isocyanate (1.40 g, 7.10 mmol).
M.p. 124—125 °C. Found (%): C, 52.68; H, 4.63; N, 5.82;
S, 6.64. C20H22N2SO9. Calculated (%): C, 52.71; H, 4.62;
N, 5.82; S, 6.65. 1H NMR, δ: 1.24 (t, 6 H, CH3CH2O,
JH,H = 7.20 Hz); 2.44 (s, 3 H, CH3—Ph); 4.31 (q, 2 H,
CH3CHH´O, JH,H = 7.20 Hz); 4.33 (q, 2 H, CH3CHH´O,
JH,H = 7.20 Hz); 7.29 (d, 2 H, Harom, JH,H = 8.0 Hz); 7.37 (d,
2 H, Harom, JH,H = 9.0 Hz); 7.87 (d, 2 H, Harom, JH,H = 8.02 Hz);
O(1)
C(2)
S(1)
C(15)
C(14)
C(1)
C(9)
C(7)
C(10)
C(13)
C(11)
N(1)
C(16)
O(5)
O(2)
C(12)
O(4)
C(17) C(18)
Fig. 1. General view of compound 7a. Hydrogen atoms, excluding
the atoms of the NH group, are not shown.

1090
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 5, May, 2009
Gololobov et al.
8.10 (d, 2 H, Harom, JH,H = 9.0 Hz); 10.71 (s, 1 H, NH).
IR (ν/cm–1): 1526, 1361 (NO2), 1703 (C(O)N), 1761, 1722
(COOEt), 3256 (NH).
2. V. I. Galkin, Yu. V. Bakhtiyarova, D. B. Mal´tsev, I. V.
Galkina, Yu. G. Gololobov, O. A. Linchenko, Izv. Akad.
Nauk, Ser. Khim., 2006, 850 [Russ. Chem. Bull., Int. Ed.,
2006, 55, 879].
3. O. A. Linchenko, I. Yu. Krasnova, P. V. Petrovskii, I. A.
Garbuzova, V. N. Khrustalev, Yu. G. Gololobov, Izv. Akad.
Nauk, Ser. Khim., 2007, 1608 [Russ. Chem. Bull., Int. Ed.,
2007, 56, 1671].
4. Yu. G. Gololobov, N. V. Kashina, O. A. Linchenko, P. V.
Petrovskii, N. P. Gambaryan, V. Fridrikhsen, Izv. Akad. Nauk,
Ser. Khim., 2003, 2141 [Russ. Chem. Bull., Int. Ed., 2003, 52,
2261].
5. Yu. G. Gololobov, I. R. Gol´ding, M. A. Galkina, B. V.
Lokshin, I. A. Garbuzova, P. V. Petrovskii, Z. A. Starikova,
B. B. Averkiev, Izv. Akad. Nauk, Ser. Khim., 2006, 854 [Russ.
Chem. Bull., Int. Ed., 2006, 55, 854].
Xꢀray diffraction data. Crystals 7a (C21H23NO7S,
M = 433.46) are monoclinic, space group is P21/n at 100 K,
a = 9.7338(6), b = 8.7805(6), с = 25.2144(16) Å, β = 92.021(5)°,
V = 2153.7(2) Å3, Z = 4 (Z´ = 1), dcalc = 1.337 g cm–3
,
μ(MoꢀKα) = 1.92 cm–1, F(000) = 912. Intensities of 23020
reflections were measured on a Bruker SMART 1000 CCD
diffractometer (λ(MoꢀKα) = 0.71072 Å, ωꢀscanning, 2θ < 58°)
and 5711 independent reflections (Rint = 0.0424) were used in
further refining. The structure was solved by the direct method
and refined using the fullꢀmatrix least squares method on F 2 in
anisotropicꢀisotropic approximation. The hydrogen atom of the
NH group was localized from the differential Fourier syntheses,
whereas positions of the C(H) protons were calculated geoꢀ
metrically. The final value of nonconfident factors for 7a:
wR2 = 0.1092 and GOOF = 1.002 for all the independent
reflections (R1 = 0.0458 were calculated on F for 3224 observed
reflections with I > 2σ(I)). All the calculations were performed
using the SHELXTL PLUS 5.0 program package.
6. N. Casamitjana, V. Lopez, A. Jorge, J. Bosch, E. Molins,
A. Roig, Tetrahedron, 2000, 56, 4027.
7. Yu. V. Nelyubina, K. A. Lyssenko, D. G. Golovanov, M. Yu.
Antipin, Cryst. Eng. Commun., 2007, 991.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 08ꢀ03ꢀ00196a).
References
1. Yu. G. Gololobov, M. A. Galkina, O. V. Dovgan´, T. I. Guseva,
I. Yu. Kuz´mintseva, N. G. Senchenya, P. V. Petrovskii, Izv.
Akad. Nauk, Ser. Khim., 1999, 1643 [Russ. Chem. Bull. (Engl.
Transl.), 1999, 48, 1622].
Received June 30, 2008;
in revised form December 29, 2008