Synthesis of aromatic and heteroaromatic annelated [1,4]diazepines

4-Chlor-3-coumarincarbaldehyde 2 or 4-azido-3-coumarincarbaldehyde 3 are converted into 1,4-benzodiazepines 9 − 12 by nucleophilic substitution with diamines 4 − 7 and subsequent cyclization with good yields. Following the same methodologies, carbaldehydes 2 or 3 when treated with 2-aminophenol 8 afforded 4-(2'-hydroxyphenyl)-amino-3-coumarincarbaldehyde 13 in good yields.


Introduction
1,4-Benzodiazepines have been the object of intense studies since the early 1960s because of their value in psychotherapy.An impressive number of synthetic routes have thus been described. 1Recently the attention has been concentrated on the synthesis of analogs having heterocycles in place of the benzene ring and on compounds having additional fused heterocyclic rings.

Results and Discussion
The compound 2 was prepared from 4-hydroxycoumarin 1 under Vilsmeier conditions (POCl 3 /DMF).We studied three procedures described in the literature: chloroformylation of 1 carried out with an equimolecular mixture of POCl 3 and DMF in trichlorethylene (yield = 97%) 2 or in chloroform (65%) 3 or in a mixture of POCl 3 and excess of DMF (85%). 4iterature 2,4 claims high yields of carbaldehyde 2 and 4-chlorocoumarin without any indication of their ratio.Steinführer and al. 3 proved that the reaction mixture contained a mixture of 4-chlor-3-coumarincarbaldehyde 2 (65%) with 4-chlorocoumarin as a side product (20%).After further optimization, we could obtain up to 72% of the carbaldehyde 2, the undesired chlorocoumarin having been easily separated inside Soxhlet apparatus.
We prepared 4-azido-3-coumarincarbaldehyde 3 from the 4-chloro-3-coumarincarbaldehyde 2 by reaction with NaN 3 in aqueous acetone.In comparable reaction times, we could at room temperature achieve better yields (up to 87%) than those described in the literature. 3The compounds 3 could be separated from the reaction mixture by simple filtration.
We carried out the preparation of derivatives 9−12 starting from 4-chloro-3coumarincarbaldehyde 2, and treating it successively with diamines 4−7 under mild basic conditions (triethylamine in ethanol, method B).Method B (one step shorter than method A) leads to satisfactory yields of derivatives 9−12.When diamine 4 reacted with carbaldehyde 2 an intermediate 16 could be isolated.
TLC was used to monitor the progress of the reaction, the structures of products were assessed by MS, IR and/or NMR method.The spectroscopic data MS, IR and 1 H-NMR are in agreement with the structure of 4-chlorocoumarin. 5he reaction with 2-aminophenol 8 is a possible route to get the 1,4-oxazepine ring.The reaction failed to deliver the desired product 15, since the aminophenol 8 replaced the chlorine atom or azido group, giving access to 13 instead of the desired oxygen−bridged product 15 (Scheme 2).
In conclusion, new practical and efficient synthetic methodology of preparation of 6-oxo- 4]diazepine 12 have been described.The products could be prepared in appreciable yields using method A and method B. Finally, this study has contributed to finding an efficient production of new compounds belonging to the family of substituted 1,4diazepines.

Table 1 .
1ynthesis Flash chromatography was carried out on 0.04−0.063mm(Merck)silica gel, thin layer chromatography was carried out on aluminium backed silica plates by Merck and plates were revealed using a UV 254 light.1H-NMR(300 MHz) and 13 C-NMR (75 MHz) spectra were recorded on a Varian VXR 300 instrument at 293 °K in CDCl 3 or DMSO d-6.Spectra were internally referenced to TMS.Peaks are reported in ppm downfield of TMS.Multiplicities are reported as singlet (s), doublet (d), triplet (t), quartet (q), some combinations of these were made by DEPT editing of the spectra.The IR-spectra were recorded on a Philips Analytical PU 9800 spectrometer.The MS-spectra were recorded on a AEI MS 902 S electron ionization spectrometer (EI = 70 eV).The elemental analyses were recorded on a Perkin−Elmer 2400 spectrometer.