Regioselective reactions of N1-alkyl-N2-(4- nitrophenyl)ethanediamide and acetylenic esters in the presence of tert-butyl isocyanide

Article abstract of DOI:10.1070/MC2005v015n04ABEH002078

The regioselective reactions of N¹-alkyl-N²-(4- nitrophenyl)ethanediamide with dialkyl acetylenedicarboxylates in the presence of tert-butyl isocyanide lead to dialkyl 2-{[2-(alkylamino)-2-oxoacetyl]-4- nitroanilino}-3-[(tert-butylim

Full text of DOI:10.1070/MC2005v015n04ABEH002078

, 2005, 15(4), 156–158
Regioselective reactions of N1-alkyl-N2-(4-nitrophenyl)ethanediamide and
acetylenic esters in the presence of tert-butyl isocyanide
Issa Yavari,* Loghman Moradi, Farough Nasiri and Hoorieh Djahaniani
Department of Chemistry, Tarbiat Modarres University, 14115-175, Tehran, Iran.
Fax: +98 21 800 6544; e-mail: yavarisa@modares.ac.ir
DOI: 10.1070/MC2005v015n04ABEH002078
The regioselective reactions of N1-alkyl-N2-(4-nitrophenyl)ethanediamide with dialkyl acetylenedicarboxylates in the presence of
tert-butyl isocyanide lead to dialkyl 2-{[2-(alkylamino)-2-oxoacetyl]-4-nitroanilino}-3-[(tert-butylimino)methylene]succinates in
good yields.
Multicomponent reactions are of interest to combinatorial chem-
istry, for example, versatile isocyanide-based Ugi and Passerini
reactions.1–4 In recent years, the synthetic applications of multi-
functional heteroallenes have been widely investigated.5,6 In
spite of extensive developments in the chemistry of modified
ketenes and isocyanates,7,8 little attention has been paid to the
synthesis of ketenimines.8–10
Ketenimines are transient intermediates in many interconver-
sions, especially, in elimination–addition processes and in the
formation of heterocyclic ring systems.11–14 We report a regio-
selective one-pot synthesis of highly functionalised ketenimines
3. Thus, the reaction of dialkyl acetylenedicarboxylates 1 with
N1-alkyl-N2-(4-nitrophenyl)ethanediamide 2 in the presence of
tert-butyl isocyanide leads to dialkyl 2-{[2-(alkylamino)-2-oxo-
156 Mendeleev Commun. 2005

, 2005, 15(4), 156–158
1
The H NMR spectrum of 3a (CDCl3) showed signals for
CO2R
C
O
tert-butyl (d 1.36 ppm), methoxy (d 3.69 and 3.80 ppm), methylene
(d 4.32 ppm, d, JHH 5 Hz), methine (d 5.58 ppm) and NH
H
3
N
N
C
O2N
N
R'
(d 7.48 ppm) protons together with aromatic protons at d 7.19–
8.22 ppm. The 13C NMR spectrum of 3a exhibited 20 sharp
signals in agreement with the proposed structure. The sp2-
hybridised carbon atom of the ketenimine residue appears at
d 59.1 ppm, as a result of strong electron delocalization. The
structural assignments of compounds 3a–e made on the basis of
their NMR spectra were supported by their IR spectra. These
compounds show strong absorption bands at about 2020 cm–1.
Mechanistically, it is conceivable that the reaction involves
the initial formation of 1:1 zwitterionic intermediate 4 between
tert-butyl isocyanide and the acetylenic ester.2,4 The protonation
of 4 by diamide 2 and the subsequent attack of the resulting
nucleophile on positively charged ion 5 afforded ketenimine 3.
In this reaction, the stronger NH acid of 2 acts as a source of
protons (Scheme 2).
H
C
O
CO2R
1a R = Me
1b R = Et
1c R = But
2a R' = Bn
2b R' = Allyl
O2N
O
H
N
R'
N
O
RO2C
C
N
CO2R
3a R = Me, R' = Bn
3a R = Me, R' = Bn
3b R = Et, R' = Bn
3b R = Et, R' = Bn
3c R = Butt, R' = Bn
CO2R
CO2R
3c R = Bu , R' = Bn
3d R = Me, R' = Allyl
3d R = Me, R' = Allyl
3e R = Butt, R' = Allyl
3e R = Bu , R' = Allyl
N
C
Scheme 1
4
2
acetyl]-4-nitroanilino}-3-[(tert-butylimino)methylene]succinates
3a–e in good yields (Scheme 1).†
CO2R
O
H
The reaction of tert-butyl isocyanide with electron-deficient
acetylenic esters 1 in the presence of NH acids 2 proceeded in
dichloromethane at room temperature and was complete within
Ar
CO2R
3
N
N
C
N
R'
O
1
24 h. The IR, H NMR and 13C NMR spectra of the crude pro-
5
6
ducts clearly indicated the formation of stable ketenimines 3
(Scheme 1).
Scheme 2
The three-component reaction of N1-alkyl-N2-(4-nitrophenyl)-
ethanediamide with dialkyl acetylenedicarboxylates in the pres-
ence of tert-butyl isocianide provides a simple, one-pot and
regioselective synthesis of polyfunctionalised ketenimines of
potential synthetic interest.
†
The 1H and 13C NMR spectra were measured with a Bruker DRX-500
AVANCE instrument in CDCl3 as a solvent at 500.1 and 125.7 MHz,
respectively. Mass spectra were recorded on a Finnigan-Matt 8430 mass
spectrometer operating at an ionization potential of 70 eV.
Preparation of N1-benzyl-N2-(4-nitrophenyl)ethanediamide 2a: benzyl-
amine (1.07 g, 10 mmol) was added to a stirred solution of ethyl
2-(4-nitroanilino)-2-oxoacetate (2.38 g, 10 mmol) in CH2Cl2 (20 ml). The
reaction mixture was stirred for 4 h. The product precipitated as a white
powder, which was filtered off and washed with Et2O. Product 2 was
obtained as a white powder; yield 2.93 g (98%), mp 169–170 °C.
General procedure for the preparation of dimethyl 2-{[2-(benzylamino)-
2-oxoacetyl]-4-nitroanilino}-3-[(tert-butylimino)methylene]succinate 3a:
to a stirred solution of 0.60 g N1-benzyl-N2-(4-nitrophenyl)ethanediamide
(2 mmol) and 0.28 g dimethyl acetylenedicarboxylate (2 mmol) in 6 ml
CH2Cl2, was added dropwise at 0 °C for 10 min 0.45 g tert-butyl iso-
cyanide (2 mmol) in 2 ml CH2Cl2. The reaction mixture was then allowed
to warm up to room temperature and stand for 24 h. The solvent was
removed under reduced pressure and the product was extracted with
n-hexane–EtOAc (5:1) and crystallised at –20 °C. Pale yellow crystals;
yield: 0.79 g (75%), mp 116–118 °C. 1H NMR (CDCl3, Me4Si) dH: 1.36
(s, 9H, CMe3), 3.69 and 3.80 (2s, 6H, 2OMe), 4.32 (d, 2H, NCH2, 3JHH
5 Hz), 5.58 (s, 1H, CH), 7.19–7.36 (m, 5H, Ph), 7.48 (br. s, 1H, NH),
7.54 and 8.22 (2d, 4H, C6H4, 3JHH 9 Hz). 13C NMR (CDCl3, Me4Si) dC:
30.1 (CMe3), 43.5 (NCH2), 51.9 and 53.0 (2OMe), 59.1 (C=C=N), 61.7
(N–CMe3), 62.4 (CH), 124.2, 127.8, 127.9, 128.8, and 129.0 (9CH), 136.7,
146.9 and 147.1 (3C), 158.7, 161.1, 161.5, 168.7 and 169.7 (C=C=N
and 4C=O). IR (KBr, n/cm–1): 3300 (NH), 2022 (C=C=N), 1738 and
1653 (C=O). MS, m/z (%): 524 (M+, 3), 299 (25), 91 (100), 65 (25).
Found (%): C, 59.5; H, 5.4; N, 10.7. Calc. for C26H28N4O8 (524.5) (%):
C, 59.54; H, 5.38; N, 10.68.
For 3c: pale yellow crystals; yield 1.10 g (90%), mp 140–142 °C.
1H NMR (CDCl3, Me4Si) dH: 1.36, 1.40 and 1.48 (3s, 27H, 3CMe3),
4.30 (d, 2H, NCH2, 3JHH 5 Hz), 5.48 (s, 1H, CH), 7.21–7.38 (m, 5H, Ph),
7.52 (br. s, 1H, NH), 7.56 and 8.22 (2d, 4H, C6H4, 3JHH 9 Hz). 13C NMR
(CDCl3, Me4Si) dC: 28.0, 28.3 and 30.0 (3CMe3), 43.5 (NCH2), 61.4 and
62.1 (C=C=N and N–CMe3), 61.9 (CH), 80.9 and 83.2 (2OCMe3),
124.4, 128.1, 128.3, 129.2 and 130.0 (9CH), 137.3, 147.1 and 147.5
(3C), 159.5, 161.9, 162.7, 167.9 and 169.1 (C=C=N and 4C=O). IR (KBr,
n
max/cm–1): 3290 (NH), 2023 (C=C=N), 1725, 1681 and 1652 (C=O).
MS, m/z (%): 608 (M+, 2), 299 (20), 91 (100), 57 (90). Found (%): C,
63.1; H, 6.6; N, 9.2. Calc. for C32H40N4O8 (608.7) (%): C, 63.14; H,
6.62; N, 9.20.
For 3d: pale yellow crystals; yield 0.87 g (92%), mp 112–114 °C.
1H NMR (CDCl3, Me4Si) dH: 1.35 (s, 9H, CMe3), 3.70 and 3.76 (2s,
6H, 2OMe), 3.82 (m, 2H, NCH2), 5.15 (m, 2H, =CH2), 5.57 (s, 1H, CH),
5.75 (m, 1H, =CH), 7.33 (br. s, 1H, NH), 7.52 and 8.21 (2d, 4H, C6H4,
3JHH 9 Hz). 13C NMR (CDCl3, Me4Si) dC: 30.1 (CMe3), 41.7 (NCH2),
51.9 and 52.9 (2OMe), 59.0 and 61.7 (C=C=N and N–CMe3), 62.4 (CH),
117.2 (=CH2), 124.1 (2CH), 129.0 (CH), 132.7 (2CH), 147.0 and 147.6
(2C), 158.5, 161.3, 163.3, 168.7 and 169.6 (C=C=N and 4C=O). IR (KBr,
n
max/cm–1): 3335 (NH), 2022 (C=C=N), 1734, 1679 and 1654 (C=O).
MS, m/z (%): 474 (M+, 3), 249 (100), 57 (20), 41 (30). Found (%): C,
55.7; H, 5.5; N, 11.8. Calc. for C22H26N4O8 (474.5) (%): C, 55.69;
H, 5.52; N, 11.81;
For 3b: pale yellow crystals; yield 0.94 g (85%), mp 125–127 °C.
1H NMR (CDCl3, Me4Si) dH: 1.28 and 1.36 (2t, 6H, 2Me, JHH 7 Hz),
For 3e: pale yellow crystals; yield 1.05 g (94%), mp 146–148 °C.
1H NMR (CDCl3, Me4Si) dH: 1.46, 1.47 and 1.54 (3s, 27H, 3CMe3),
3.80 (m, 2H, NCH2), 5.20 (m, 2H, =CH2), 5.34 (s, 1H, CH), 5.53 (m,
1H, =CH), 7.39 (br. s, 1H, NH), 7.58 and 8.25 (2d, 4H, C6H4, 3JHH 9 Hz).
13C NMR (CDCl3, Me4Si) dC: 28.4, 28.7 and 30.5 (3CMe3), 42.1 (NCH2),
61.7 and 62.2 (C=C=N and N–CMe3), 62.2 (CH), 81.0 and 83.3 (2OCMe3),
117.5 (=CH2), 124.3 (2CH), 129.9 (CH), 133.2 (2CH), 147.2 and 147.4
(2C), 159.2, 161.5, 161.9, 167.6 and 168.9 (C=C=N and 4C=O). IR (KBr,
3
1.40 (s, 9H, CMe3), 4.19 and 4.29 (2q, 4H, 2OCH2, 3JHH 7 Hz), 4.32 (d,
3
2H, NCH2, JHH 5 Hz), 5.52 (s, 1H, CH), 7.22–7.35 (m, 5H, Ph), 7.49
(br. s, 1H, NH), 7.59 and 8.26 (2d, 4H, C6H4, JHH 9 Hz). 13C NMR
3
(CDCl3, Me4Si) dC: 14.6 and 14.8 (2Me), 30.5 (CMe3), 43.8 (NCH2),
60.1 and 62.2 (C=C=N and N–CMe3), 60.9 and 62.5 (2OCH2), 62.6
(CH), 124.5, 128.2, 128.3, 129.1 and 129.4 (9CH), 137.4, 147.4 and
147.5 (3C), 159.2, 162.1, 162.8, 168.4 and 169.6 (C=C=N and 4C=O).
IR (KBr, nmax/cm–1): 3310 (NH), 2020 (C=C=N), 1730 and 1675 (C=O).
MS, m/z (%): 552 (M+, 2), 299 (28), 91 (100). Found (%): C, 60.9; H,
5.8; N, 10.1. Calc. for C28H32N4O8 (552.6) (%): C, 60.86; H, 5.84; N,
10.14.
n
max/cm–1): 3330 (NH), 2020 (C=C=N), 1730, 1680, and 1650 (C=O).
MS, m/z (%): 558 (M+, 2), 333 (25), 57 (100), 41 (35). Found (%): C,
60.2; H, 6.8; N, 10.0. Calc. for C28H38N4O8 (558.6) (%): C, 60.20;
H, 6.86; N, 10.03.
Mendeleev Commun. 2005 157

, 2005, 15(4), 156–158
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Received: 26th October 2004; Com. 04/2403
158 Mendeleev Commun. 2005