Vicarious nucleophilic substitution of hydrogen in aldehydes and Knoevenagel reaction of iminium salts with α-halocarbanions

Article abstract of DOI:10.1023/A:1015090426917

Iminium salts derived from aromatic aldehydes react with α-chlorocarbanions via two different pathways: reaction with secondary carbanion of halomethyl sulfones proceeds as the Knoevenagel condensation, while tertiary α-chlorocarbanions gave products of v

Full text of DOI:10.1023/A:1015090426917

2236
Russian Chemical Bulletin, International Edition, Vol. 50, No. 11, pp. 2236—2238, November, 2001
Brief Communications
Vicarious nucleophilic substitution of hydrogen in aldehydes
and Knoevenagel reaction of iminium salts with α-halocarbanions
M. Makoszaa« and D. N. Kozhevnikovb
aInstitute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland.
Fax: +48 (22) 632 6621. E-mail: icho-s@icho.edu.pl
bUrals State Technical University,
19 ul. Mira, 620002 Yekaterinburg, Russian Federation.
Fax: +7 (343 2) 74 0458
Iminium salts derived from aromatic aldehydes react with α-chlorocarbanions via two
different pathways: reaction with secondary carbanion of halomethyl sulfones proceeds as the
Knoevenagel condensation, while tertiary α-chlorocarbanions gave products of vicarious
nucleophilic substitution of hydrogen in parent aldehydes.
Key words: vicarious nucleophilic substitution, Knoevenagel condensation, aldehydes,
carbanions.
Carbanions containing the leaving group X at the
corresponding dialkyliminium perchlorates,4 which are
much more active electrophilic reactants than parent
aldehydes and form readily adducts with some C-nu-
cleophiles.5—8 The addition of α-halocarbanions to these
salts would give substituted trialkylamines, which show
much less tendency for intramolecular substitution than
analogous anionic adducts to aldehydes or imines, one
can therefore expect that base-induced β-elimination
would occur readily to give the VNS products.
carbanionic center react with nitroarenes via the forma-
tion of σH-adducts and the subsequent β-elimination of
HX to give products of the vicarious nucleophilic substi-
tution of hydrogen (VNS).1 A similar process was re-
ported to occur in electrophilic alkenes, although, in
these cases, the formation of cyclopropanes is a much
more common reaction.2 It could be of great interest
to expand the VNS reaction on electrophilic car-
bon—heteroatom double bonds, such as in aldehydes or
aldimines. However, the reaction of α-chlorocarbanions
with these electrophilic partners gave usually oxiranes
and aziridines. Recently we have reported that VNS
does occur in the reaction of some highly electrophilic
aldimines with carbanions of chloromethyl p-tolylsulfone
and chloroform.3
Results and Discussion
Indeed, the addition of pre-formed carbanions of
halomethyl tolylsulfones 1a,b to iminium salts 2 and 3
(Scheme 1) gave the expected adducts (4a, 5a,b), which
could be isolated and purified, for example, 5a,b. Treat-
ment of these adducts with a base resulted, however, in
the elimination of dimethylamine, not HX, to give
Aromatic aldehydes treated with perchlorates of sec-
ondary aliphatic amines in refluxing toluene form the
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2136—2138, November, 2001.
1066-5285/01/5011-2236 $25.00 © 2001 Plenum Publishing Corporation

Iminium salts reactions with α-halocarbanions
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 11, November, 2001 2237
Scheme 1
Y
R = H
Ar
–HNMe2
X
Me + Me
Me
Ar
Me
Y
X
ButOK
6a, 7a,b
N
N
–
C
R
H
+
ClO4
THF/DMF
Y
O
Ar
H
H
Me
Me
R
R
Y
N
H2O
1a—d
2, 3
X
R ≠ H
–HX
Ar
Y
4a,c,d, 5a,b
R
Ar
HNMe2•HClO4
8c, 9d
ArCHO
2, 4, 6, 8: Ar = Ph
3, 5, 7, 9: Ar = 4-MeOC6H4
1—9
X
Y
R
a
b
c
d
Cl
Br
Cl
Cl
Ts
Ts
H
H
Ts
COOMe
Cl
COOMe
added, and the reaction mixture was stirred for 1 h, while the
temperature was increased to –20 °C. For isolation of the
adducts, the mixture was poured into acidified water, and the
product was extracted with methylene chloride, purified via
column chromatography, and recrystallized. For direct conver-
sion of the adducts of tertiary carbanions into the VNS
products, additional potassium tert-butoxide (235 mg, 2.1 mmol)
in THF (3 mL) was added, the whole mixture was stirred at
–20 °C for 5 min and treated as above. Elimination of
dimethylamine from adducts 4a, 5a,b: the adduct (0.5 mmol)
was dissolved in a solution of sodium methoxide in methanol
(prepared from Na (50 mg) and methanol (20 mL)), and after
2—4 h the mixture was poured into water and extracted with
methylene chloride, and the product was purified via column
chromatography. The yields of the compounds obtained are
presented in Table 1. All compounds obtained gave satisfactory
spectral and analytical data, some of them are presented below.
2-Chloro-1-dimethylamino-1-(4-methoxyphenyl)-2-(p-tolyl-
sulfonyl)ethane (5a). M.p. 140 °C. Found (%): C, 58.69;
H, 6.11; N, 3.91. C18H22ClNO3S. Calculated (%): C, 58.77;
H, 6.03; N, 3.81. 1H NMR (CDCl3), δ: 1.98 (s, 6 H, NMe2);
2.45 (s, 3 H, C6H4—CH3), 3.81 (s, 3 H, OMe); 4.10 (d, 1 H,
J = 9.1 Hz); 5.23 (d, 1 H, J = 9.1 Hz); 6.87 (m, 2 H); 7.13
(m, 2 H); 7.32 (m, 2 H); 7.80 (m, 2 H).
1-aryl-2-X-2-tosylethenes 6a, 7a,b as single stereoiso-
mers of the Z-configuration.9 This Knoevenagel type
reaction of halocarbanions is of some interest because
the direct reaction of such carbanions with aldehydes
gives usually oxiranes via intramolecular substitution in
the initial adducts. Synthesis of the Knoevenagel type
products with halogens at the double bond requires
additional steps.9
At the same time, the addition of tertiary α-chloro-
carbanions generated from dichloromethyl p-tolyl sul-
fone (1c) or dimethyl chloromalonate (1d) to iminium
salts 2 and 3 produces the adducts which undergo the
expected base-induced β-elimination of HCl giving
enamines. These enamines hydrolyzed during the work-
up procedure gave the products of VNS of hydrogen in
aldehydes, viz., α-chloro-α-tosylacetophenone (8c) and
dimethyl (4-methoxybenzoyl)malonate (9d). According
to 1H NMR spectroscopy, compounds 8c and 9d exist in
a CDCl3 solution in the enolic form.
Thus, the general goal, vicarious substitution of hydro-
gen at the carbonyl group of aldehydes with α-chloro-
carbanions, was realized via this indirect way.
2-Bromo-1-dimethylamino-1-(4-methoxyphenyl)-2-(p-tolyl-
sulfonyl)ethane (5b). M.p. 124 °C (decomp.). Found (%):
Experimental
Table 1. Yields of obtained adducts and
elimination products
1
H NMR spectra were recorded on a Varian Gemini-200
(200 MHz) in CDCl3. Column chromatography was carried
out on silica gel (Merck, 70—230 mesh) using CH2Cl2 as an
eluent. Precursors of carbanions, chloro-10 and bromomethyl
(p-tolyl)sulfones11 and dichloromethyl (p-tolyl) sulfone,12 were
prepared by described procedures. Commercial dimethyl
chloromalonate (Fluka) was used.
Reactions of α-halocarbanions with iminium salts 2, 3 and
transformations of adducts formed. A solution of the corre-
sponding carbanion precursor 1a—d (2 mmol) in THF (5 mL)
was added to a stirred solution of potassium tert-butoxide
(235 mg, 2.1 mmol) in THF (4 mL) at –70 °C. To this
solution iminium salt 2 or 3 (2 mmol) in DMF (1 mL) was
Adduct Yielda
(%)
Elimination
product
Yielda
(%)
b
4a
5a
5b
4c
4d
—
81
64
—
—
6a
7a
7b
8c
9d
72
76
63
40
54
b
b
a Isolated yields.
b Not isolated.

2238
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 11, November, 2001
Makosza and Kozhevnikov
C, 52.38; H, 5.52; N, 3.38%. C18H22BrNO3S. Calculated (%):
C, 52.43; H, 5.38; N, 3.40. 1H NMR (CDCl3), δ: 1.88 (s, 6 H,
NMe2); 2.45 (s, 3 H, C6H4—CH3); 3.81 (s, 3 H, OMe); 4.14
(d, 1 H, J = 9.5 Hz); 5.34 (d, 1 H, J = 9.5 Hz); 6.87 (m, 2 H);
7.10 (m, 2 H); 7.31 (m, 2 H); 7.82 (m, 2 H).
Z-β-Chloro-β-(p-tolylsulfonyl)styrene (6a). M.p. 63—65 °C.
Found (%): C, 61.38; H, 4.59. C18H22ClNO3S. Calculated (%):
C, 61.54; H, 4.48. 1H NMR (CDCl3), δ: 2.48 (s, 3 H,
C6H4—CH3); 7.2—7.5 (m, 4 H); 7.6—7.8 (m, 5 H); 8.01
(s, 1 H, CH).
Z-β-Chloro-β-(p-tolylsulfonyl)-4-methoxystyrene (7a).
M.p. 94—95 °C (cf. Ref. 9: 92—94 °C). 1H NMR (CDCl3), δ:
2.46 (s, 3 H, C6H4—CH3); 3.86 (s, 3 H, OMe); 6.95 (m, 2 H);
7.36 (m, 2 H); 7.79 (m, 2 H); 7.87 (m, 2 H); 7.98 (s,
1 H, CH). 13C NMR (CDCl3), δ: 21.75, 55.43, 114.16,
123.83, 127.52, 128.82, 129.71, 132.34, 134.09, 134.55,
144.89, 161.55.
Z-β-Bromo-β-(p-tolylsulfonyl)-4-methoxystyrene (7b). M.p.
88—89 °C. Found (%): C, 52.18; H, 4.29. C16H15BrO3S.
Calculated (%): C, 52.33; H, 4.12. 1H NMR (CDCl3), δ: 2.47
(s, 3 H, C6H4—CH3); 3.83 (s, 3 H, OMe); 6.94 (m, 2 H); 7.37
(m, 2 H); 7.83 (m, 2 H); 7.88 (m, 2 H); 8.01 (s, 1 H, CH).
α-Chloro-α-(p-tolylsulfonyl)acetophenone (8c). M.p. 139 °C
(cf. Ref. 13: 139 °C). 1H NMR (CDCl3), δ: 2.49 (s, 3 H, Me);
6.21 (s, 1 H, CH); 7.38 (m, 2 H); 7.54 (m, 2 H); 7.69
(m, 1 H); 7.80 (m, 2 H); 8.05 (m, 2 H).
References
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Received January 31, 2001