A novel domino approach has been described for an easy access of the privileged nucleus of 5-carbomethoxy substituted 1,4-benzodiazepin-2-ones
Exploration of synthetic processes that lead to the development of small molecules of medicinal interest by telescoping the multicomponent operations into a single step or resorting to a process such as domino reactions is a rapidly emerging subject in medicinal chemistry. Ever since Koch et al. [
This communication reports the application of a novel domino process for an easy access of the privileged nucleus of 5-carbomethoxy substituted 1,4-benzodiazepin-2-ones
It is believed that Delepine reaction proceeded with the formation of the hexaminium ion. We surmise that it was the bulky nature of hexamine which hindered its formation from
Physical and spectral data of the compounds
Entry | Molecular formula | M.W. | M.P. (°C)a | Yield (%) | IR (KBr) cm−1 |
1H NMR (CDCl3-DMSO-d6) |
Elemental analysis | ||
---|---|---|---|---|---|---|---|---|---|
C |
H |
N | |||||||
|
C10H6ClNO3 | 223.61 | 210–12 | 91 | 1735, 1680, 1675 | 7.56–7.19 (m, 4H, ArH), 4.32 (s, 2H, CH2) | 53.71/53.67 | 2.70/2.65 | 6.26/6.18 |
|
C10H5ClFNO3 | 241.60 | 165–66 | 88 | 1755, 1725, 1700 | 7.81–7.23 (m, 3H, ArH), 4.33 (s, 2H, CH2) | 49.71/49.67 | 2.49/2.40 | 5.80/5.69 |
|
C10H5Cl2NO3 | 258.06 | 153–55 | 94 | 1785, 1740, 1720 | 7.81–7.53 (m, 3H, ArH), 4.32 (s, 2H, CH2) | 46.54/46.42 | 1.95/1.90 | 5.43/531 |
|
C10H5BrClNO3 | 302.51 | 178–79 | 90 | 1780, 1735, 1710 | 7.96–7.61 (m, 3H, ArH), 4.32 (s, 2H, CH2) | 39.70/39.62 | 1.67/1.56 | 4.63/4.59 |
|
C10H5ClINO3 | 349.51 | 206–07 | 89 | 1770, 1725, 1690 | 7.80–7.50 (m, 3H, ArH), 4.28 (s, 2H, CH2) | 28.95/28.89 | 1.21/1.17 | 3.38/3.27 |
|
C11H8ClNO3 | 237.64 | 185–86 | 92 | 1765, 1720, 1690 | 7.72–7.03 (m, 3H, ArH), 4.32 (s, 2H, CH2), 2.85 (s, 3H, CH3) | 55.60/55.51 | 3.39/3.28 | 5.89/5.80 |
|
C11H8ClNO4 | 253.64 | 223–25 | 90 | 1780, 1740, 1705 | 7.72–7.03 (m, 3H, ArH), 4.32 (s, 2H, CH2), 3.73 (s, 3H, OCH3) | 52.09/51.97 | 3.18/3.12 | 5.52/5.42 |
|
C10H5ClN2O5 | 268.61 | 130–32 | 91 | 1785, 1745, 1710 | 8.72–8.09 (m, 3H, ArH), 4.52 (s, 2H, CH2) | 44.71/44.56 | 1.88/1.71 | 10.43/10.37 |
|
C12H10ClNO3 | 251.67 | 168–70 | 92 | 1740, 1700, 1685 | 7.40–7.12 (m, 2H, ArH), 4.32 (s, 2H, CH2), 2.35 (s, 6H, CH3) | 57.27/57.19 | 4.01/3.97 | 5.57/5.46 |
|
C11H10N2O3 | 218.21 | 172–75 | 85 | 3190, 1725, 1675 | 8.0 (s, 1H, NH), 7.98–7.65 (m, 4H, ArH), |
60.55/60.48 | 4.62/4.52 | 12.84/12.79 |
|
C11H9FN2O3 | 236.20 | 198–200 | 87 | 3220, 1735, 1690 | 8.2 (s, 1H, NH), 8.08 (d, 1H, ArH), 7.78 (d, 1H, ArH), |
55.93/55.88 | 3.84/3.79 | 11.86/11.76 |
|
C11H9ClN2O3 | 252.65 | 176–78 | 84 | 3215, 1728, 1684 | 8.1 (s, 1H, NH), 7.90 (s, 1H, ArH), 7.81 (d, 1H, ArH), |
52.29/52.23 | 3.59/3.51 | 11.09/11.00 |
|
C11H9BrN2O3 | 297.98 | 243–45 | 86 | 3208, 1721, 1675 | 8.0 (s, 1H, NH), 7.90 (s, 1H, ArH), 7.75 (d, 1H, ArH), |
44.47/44.41 | 3.05/2.99 | 9.43/9.36 |
|
C11H9IN2O3 | 344.11 | 187–88 | 90 | 3200, 1710, 1670 | 8.0 (s, 1H, NH), 7.85 (s, 1H, ArH), 7.66 (d, 1H, ArH), |
38.39/38.29 | 2.64/2.59 | 8.14/8.07 |
|
C12H12N2O3 | 232.24 | 205–06 | 85 | 3188, 1723, 1672 | 8.0 (s, 1H, NH), 7.84 (s, 1H, ArH), 7.56 (d, 1H, ArH), |
62.60/62.52 | 5.21/5.17 | 12.06/11.96 |
|
C12H12N2O4 | 248.08 | 182–85 | 87 | 3202, 1728, 1677 | 8.0 (s, 1H, NH), 7.88 (d, 1H, ArH), 7.75 (d, 1H, ArH), |
58.06/57.98 | 4.87/4.79 | 11.29/11.19 |
|
C11H9N3O5 | 263.05 | 202–05 | 83 | 3228, 1735, 1698 | 8.0 (s, 1H, NH), 8.12 (s, 1H, ArH), 7.98 (d, 1H, ArH), |
50.20/50.13 | 3.45/3.34 | 15.96/15.89 |
|
C13H14N2O3 | 246.26 | 215–17 | 88 | 3185, 1720, 1670 | 8.0 (s, 1H, NH), 7.40 (s, 2H, ArH), 4.30 (s, 2H, CH2), |
63.40/63.31 | 5.73/5.69 | 11.38/11.33 |
M.W.: Molecular Weight; cald./exp.: calculated/experimental.
We suggest that this reaction proceeds with the base catalysed dehydrochlorination of
In view of the extremely weak nucleophilic character of isatinylamide nitrogen of
As the carbene was not likely to be trapped by the tertiary amine (hexamine) its reaction with hexamine was not examined.
All the melting points were taken in open capillaries and are uncorrected. The purity of all the compounds were checked by TLC using the solvent systems (benzene : methanol, 9 : 1 v/v) and silica gel G as adsorbent. IR spectra were recorded on Shimadzu FTIR-8400 infrared spectrometer using KBr, 1H NMR were recorded on Bruker AC 300F in CDCl3 + DMSO-d6 (2 : 1 v/v, TMS as internal reference and chemical shifts expressed in
Schematic presentation of the synthesis of the compounds.
5-Fluoroisatin (
5-Fluoro-1-chloroacetylisatin (
In summary, a high yielding n-butyl lithium catalysed one-pot domino process has been developed to the facile access of the privileged nucleus of methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one-5-carboxylates
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors are grateful to the Director of CDRI, Lucknow, India, for providing the spectral data of the compounds and to the Department of Science and Technology, DST, New Delhi, India, for providing the financial assistance to “Banasthali Centre for Education and Research in Basic Sciences,” under their CURIE (Consolidation of University Research for Innovation and Excellence in Women Universities) programme.