Captodative Formyl- and Acyl(amino)alkenes Containing a Terminal Double Bond or a Weakly Basic Tertiary Amino Group

Article abstract of DOI:10.1023/A:1026096826472

Piperidine reacts with 3-bromo-3-buten-2-one to give a mixture of 3,4-dipiperidinobutan-2-one and 3-piperidino-3-buten-2-one. The latter is also formed by the action of a strong base (Et₃N in THF or MeONa in MeOH) on the dipiperidino derivative. Analogous reaction of 2-bromo-3-phenylpropenal with N-methylaniline affords 2-[methyl(phenyl)amino]-3-phenylpropenal which is the first captodative formyl-(amino)alkene having a weakly basic tertiary amino group.

Full text of DOI:10.1023/A:1026096826472

Russian Journal of Organic Chemistry, Vol. 39, No. 5, 2003, pp. 646 649. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 5, 2003,
pp. 691 694.
Original Russian Text Copyright
2003 by Rulev, Fedorov, Chuvashev, Voronkov.
Captodative Formyl- and Acyl(amino)alkenes
Containing a Terminal Double Bond or a Weakly Basic Tertiary
Amino Group
A. Yu. Rulev, S. V. Fedorov, Yu. A. Chuvashev, and M. G. Voronkov
Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: rulev@irioch.irk.ru
Received July 5, 2002
Abstract Piperidine reacts with 3-bromo-3-buten-2-one to give a mixture of 3,4-dipiperidinobutan-2-one
and 3-piperidino-3-buten-2-one. The latter is also formed by the action of a strong base (Et N in THF or
3
MeONa in MeOH) on the dipiperidino derivative. Analogous reaction of 2-bromo-3-phenylpropenal with
N-methylaniline affords 2-[methyl(phenyl)amino]-3-phenylpropenal which is the first captodative formyl-
(
amino)alkene having a weakly basic tertiary amino group.
Until recently, captodative carbonyl-containing
aminoalkenes remained terra incognita. However,
they now attract increasing attention and constitute
a specific group of organic compounds [1]. We pre-
viously developed a procedure for the synthesis of
chloropropene [3]. Methyl 2-piperidinoacrylate is
formed in a poor yield (5 10%) by the action of
piperidine on methyl 2-chloroacrylate in benzene,
whereas the major product is methyl-2,3-dipiperidino-
propionate [5].
1
-formyl-1-aminoalkenes on the basis of reaction of
We have found that the reaction of 3-bromo-3-
buten-2-one (I) with piperidine leads to a mixture of
di- and monopiperidino derivatives II and III. The
product ratio depends on the presence of another base
in the reaction mixture. In the reaction of piperidine
with bromoalkene I at a ratio of 2:1 in THF at room
temperature, a mixture of 3,4-dipiperidinobutan-2-one
(II) and 3-piperidino-3-buten-2-one (III) at a ratio
of 4:1 was obtained. When the reaction was carried
out with equimolar amounts of the reactants in the
presence of 2 equiv of triethylamine, the fraction of
monopiperidino derivative III increased to 45%
the corresponding haloalkenes with highly basic
secondary amines [2, 3]. Numerous examples of
the synthesis of captodative acyl(amino)alkenes by
nucleophilic substitution of the halogen atom in
geminal acyl(halo)alkenes have been reported [4].
However, it is considerably more difficult to obtain
in this way captodative formyl- or acyl(amino)alkenes
having a terminal double bond or a weakly basic
tertiary amino group. It is known that the predominant
pathway of the reaction of 2-chloropropenal with
secondary amines is formation of 1,3-diamino-2-
Scheme 1.
Base = Et N or MeONa/MeOH.
3
1
070-4280/03/3905-0646$25.00 2003 MAIK Nauka/Interperiodica

CAPTODATIVE FORMYL- AND ACYL(AMINO)ALKENES
647
(
Scheme 1). These results led us to presume that the
tion bands belonging to stretching vibrations of the
carbonyl group and double bond. In addition, NOE
analysis of the structure of aminoalkene V confirmed
the Z-s-trans conformation of its major isomer.
A fundamental problem in the chemistry of capto-
dative olefins is estimation of the donor and acceptor
effects of geminal substituents on the degree of p,
basicity of the deaminating agent (in the above case,
tertiary amine) should be increased to successfully
complete the process. This presumption was con-
firmed when triethylamine was replaced, e.g., by
an alcoholic solution of alkali metal alkoxide. In fact,
by the action of sodium methoxide in methanol, di-
aminoketone II loses piperidine at room temperature,
affording captodative acetyl(amino)alkene III. Amino-
enone III was also obtained by one-pot procedure
including successive treatment of bromoalkene I with
and
,
conjugation in such systems. In the first
approximation, these effects can be estimated from
the difference in the chemical shifts of the neigh-
boring olefinic carbon atoms. As a rule, the C
atom in captodative carbonyl-containing aminoalkenes
resonates in a stronger field than the -carbon atom
2
equiv of piperidine and a solution of sodium
methoxide in methanol.
[
1, 10]. The difference ( C
C ) reaches 25 to
We previously reported on unsuccessful attempts to
involve weakly basic secondary amines in reactions
with geminal formyl(halo)alkenes [3]. However, it
was recently showed that Michael addition of primary
and secondary amines to , -unsaturated carbonyl
compounds can be accelerated by microwave radiation
45 ppm and is comparable with that observed for
1
3
unsubstituted enamines. In the C NMR spectrum
of aminoenone III, the - and -sp -carbon signals
2
appear at
98.52 and 157.34 ppm, respectively.
C
These data indicate a strong polarization of the double
bond and predominant contribution of the enamine
structure to the ground state of the molecule. By
[
6] or by applying a high pressure [7 9]. Taking this
into account, we turned again to the synthesis of
captodative aminoalkenes having a weakly basic
amino group. We have found that the reaction of
contrast, the difference (C )
V having a formyl group ranges from 1.2 to
0.7 ppm, which is the result of reduced donor power
(C ) for aminoalkene
1
2
-bromo-3-phenylpropenal (IV) with N-methylaniline
of the disubstituted amino group.
(which is 4 to 7 orders of magnitude less basic than
Analysis of the two-dimensional (COSY, HMBC,
and NOESY) NMR spectra of 2-[methyl(phenyl)-
amino]-3-phenylpropenal (V) allowed us to assign
the secondary amines used so far) proceeds at a low
rate but with excellent selectivity. According to the
GC MS data, heating of a mixture of aldehyde IV
and N-methylaniline in an ampule for 30 h at 90 C
gave aminoalkenal V as the only product (Scheme 2).
In the microwave-activated reaction, the conversion
of substrate IV was 15% in 15 min.
1
13
unambiguously all its H and C signals. Our results
2
put in doubt the assignment of signals from the sp -
carbon atoms in the previously described acyl analog
of aminoalkene V, 3-(N-methylanilino)-3-hexen-2-
one. The authors [11] assigned the signals at
116.9
C
and 142.0 ppm to the olefinic and aromatic carbon
atoms, respectively; we believe it more reasonable
to interchange them. In this case, the disagreement
between the spectral data for N-methylanilinoalkenes
activated by alkoxycarbonyl, acyl, or formyl group
is eliminated [1].
Scheme 2.
The synthesis of captodative formyl- and acyl-
amino)alkenes having a terminal double bond or
(
a weakly basic tertiary amino group extends the scope
of application of the method based on nucleophilic
vinyl substitution of halogen in activated haloalkenes.
Undoubtedly, captodative aminoalkenes possessing
double bonds with considerably different polarities
attract specific interest; they will be the subject of
our further studies.
The formation of aminoalkenal V in a good yield
is the first example pf successful synthesis of geminal
formyl(amino)alkenes having a weakly basic tertiary
amino group.
Despite obvious similarity, there are considerable
differences in the structures of compounds III and V.
Acetyl(piperidino)ethene III has an s-trans conforma-
tion, while its formyl analog V is an s-cis conformer.
This follows, e.g., from the intensities of IR absorp-
EXPERIMENTAL
The IR spectra were recorded on a Specord 75IR
spectrophotometer from samples prepared as thin
1
13
films. The H and C NMR spectra were obtained
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 5 2003

6
48
RULEV et al.
on a Bruker DPX-400 instrument (400 and 100 MHz,
(III), bp 43 44 C (1 mm). IR spectrum, , cm 1:
1
respectively) from solutions in CDCl at room tem-
1585 (C C), 1698 (C O). H NMR spectrum,
,
3
perature. The 13C signals were assigned using the
DEPT sequence. GC MS data were acquired on
a Hewlett Packard HP 5971A mass selective-detector
coupled with an HP-5890 chromatograph (energy
of ionizing electrons 70 eV; Ultra-2 column, 5% of
phenylmethylsilicone).
ppm (J, Hz): 1.45 1.70 m (6H, , -CH , piperidine),
2
2.30 s (3H, CH CO), 2.70 2.75 m (4H, -CH2,
3
piperidine), 4.47 d (1H, CH , J = 0.9), 4.87 d (1H,
2
1
3
CH , J = 0.9). C NMR spectrum, C, ppm: 24.16,
2
25.68 ( , -CH , piperidine); 27.69 (CH ), 50.66
2
3
(NCH ); 98.52 ( CH ); 157.34 ( C N); 200.54
2
2
+
(
1
C O). Mass spectrum, m/z (I , %): 153 (41, M ),
-
Bromocinnamaldehyde (IV) was prepared by
rel
52 (34), 110 (100), 54 (44), 43 (42). Found, %:
successive bromination and dehydrobromination of
cinnamaldehyde [12]. 3-Bromo-3-buten-2-one (I)
was synthesized by a procedure analogous to that
reported in [13].
C 70.00; H 10.00; N 8.87. C H NO. Calculated, %:
9
15
C 70.55; H 9.87; N 9.14.
3,4-Dipiperidinobutan-2-one (II) was identified
1
13
by the H and C NMR spectra, as well as by the
3
-Bromo-3-buten-2-one (I). A solution of 16 g
GC MS data [in a mixture with 3-piperidino-3-buten-
(
10 mmol) of bromine in 15 ml of CHCl was added
3
1
2
-one (III)]. H NMR spectrum, , ppm (J, Hz): 1.30
over a period of 0.5 h at 0 C to a solution of 7.0 g
10 mmol) of methyl vinyl ketone in 20 ml of CHCl3.
1
.55 m (12H, , -CH , piperidine), 2.14 s (3H,
(
2
CH CO), 2.30 2.50 m (10H, NCH ), 3.08 d.d (1H,
When the addition of bromine was complete, the
mixture was allowed to warm up to room temperature
and was left to stand for 3 h. The solution was
evaporated, the residue was dissolved in 20 ml of
diethyl ether, the solution was cooled to 10 C, a solu-
tion of 12.1 g (10 mmol) of N,N -dimethylaniline in
3
2
1
3
CHN, J = 9.1, 5.1). C NMR spectrum, C, ppm:
2
2
4.46, 24.61, 26.20, 26.52 ( , -CH , piperidine);
2
8.27 (CH ); 52.01, 55.27 (NCH ); 210.22 (C O).
3
2
+
Mass spectrum, m/z (I , %): 238 (< 1, M ), 195 (1),
rel
98 (100), 41 (13).
2
0 ml of Et O was added, and the mixture was left to
(Z,E)-2-[Methyl(phenyl)amino]-3-phenylpro-
2
stand for 12 h at room temperature. The mixture was
treated with water and extracted with ether (2 50 ml),
the extracts were dried over MgSO , the solvent was
distilled off, and the residue was distilled under
reduced pressure. Yield 6.0 g (40%), bp 55 56 C
penal (V). a. A mixture of 1.1 g (10 mmol) of
N-methylaniline, 1.1 g (5 mmol) of -bromocinnam-
aldehyde (IV), and 0.6 g (5.5 mmol) of triethylamine
in 2 ml of anhydrous THF was heated for 30 min at
90 C in a sealed ampule. The precipitate of triethyl-
amine hydrobromide was filtered off, and the filtrate
was evaporated. The residue was subjected to column
chromatography on silica gel using hexane ether (1:1)
as eluent to isolate 0.6 g (51%) of (E,Z)-2-[methyl-
(phenyl)amino]-3-phenylpropenal (V) as a colorless
oil. Both isomers were isolated by column chromatog-
4
1
(
(
(
20 mm) (cf. [14]). IR spectrum, , cm : 1609
C C), 1697 (C O). H NMR spectrum, , ppm
J, Hz): 2.43 s (3H); 6.38 d (1H, J = 2.4), 6.76 d (2H,
1
1
3
J = 2.4). C NMR spectrum, C, ppm: 26.03 (CH3),
29.53 ( CH ), 131.96 ( CBr), 191.88 (C O). Mass
1
2
+
spectrum, m/z (I , %): 150, 148 (45, M ); 107, 105
rel
1
raphy. IR spectrum, , cm : 1592 (C C), 1684
(
27); 143 (100). Found, %: C 32.11; H 3.68; Br 53.66.
1
(
(
C O). H NMR spectrum, , ppm: Z isomer: 3.03 s
C H BrO. Calculated, %: C 32.25; H 3.38; Br 53.63.
4
5
3H, NMe); 7.28 s (1H, CH ); 6.65 7.55 m (10H,
Reaction of 3-bromo-3-buten-2-one (I) with
C H ); 9.50 s (1H, CHO); E isomer: 3.24 s (3H,
piperidine. A solution of 2.8 g (18 mmol) of
-bromo-3-buten-2-one in 30 ml of anhydrous THF
was added with stirring to a solution of 3.4 g
40 mmol) of piperidine in 40 ml of anhydrous THF.
6
5
NMe); 6.90 7.50 m (11H, CH , C H ); 9.81 s (1H,
3
6
5
CHO). 13C NMR spectrum, , ppm: Z isomer: 37.81
NMe); 113.78, 118.87, 129.05, 129.47, 130.28,
(
1
(
1
1
(
(
39.77, 133.40, 146.79 (C H ); 142.36 (CH ); 143.54
The mixture was kept for 24 h at room temperature,
the precipitate of piperidine hydrobromide was filtered
off, and the filtrate was evaporated. A solution of
sodium methoxide in methanol (prepared from 0.2 g
of sodium and 20 ml of methanol) was added to the
residue, and the mixture was left to stand for 24 h
at room temperature. The mixture was treated with
water (10 ml) and extracted with ether (5 50 ml),
6 5
C N); 192.39 (CHO); E isomer: 40.52 (NMe);
19.00, 121.23, 128.33, 128.49, 128.78, 129.66,
34.18, 148.42 (C H ); 135.41 (CH ); 146.10
6
5
C N); 189.57 (CHO). Mass spectrum, m/z (I , %):
rel
+
2
37 (37, M ), 208 (56), 193 (100), 165 (44), 77 (60).
Found, %: C 80.27; H 6.56; N 5.86. C H NO.
16 15
Calculated, %: C 80.98; H 6.37; N 5.90.
the extracts were dried over MgSO and evaporated,
and the residue was distilled under reduced pressure
to obtain 0.6 g (22%) of 3-piperidino-3-buten-2-one
b. The reaction mixture (prepared as described
above in a) was kept for 15 min in a sealed ampule
placed in a microwave oven at a power of 700 W.
4
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 5 2003

CAPTODATIVE FORMYL- AND ACYL(AMINO)ALKENES
According to the GC MS data, the conversion of 7. Jenner, G., New J. Chem., 1995, vol. 19, p. 173.
649
initial bromoaldehyde IV was 15%.
8
.
Rulev, A. and Maddaluno, J., Eur. J. Org. Chem.,
This study was financially supported by the Rus-
sian Foundation for Basic Research (project no. 02-
2001, p. 2569.
9. Rulev, A., Maddaluno, J., Ple, G., Plaquevent, J-C.,
03-32547).
and Duhamel, L., J. Chem. Soc., Perkin Trans. 1,
1
998, p. 1397.
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