Elsevier

Thermochimica Acta

Volume 354, Issues 1–2, 17 July 2000, Pages 107-115
Thermochimica Acta

Thermal behaviour of some spiro benzodiazepine derivatives

https://doi.org/10.1016/S0040-6031(00)00463-9Get rights and content

Abstract

The thermal behaviour of some benzodiazepine derivatives have been studied by differential thermal analysis (DTA) and thermogravimetry (TG). It was founded that pyrolytic decomposition accompanied melting of the compounds, some of which were hydrates. Dehydration is followed by total pyrolytic decomposition in two stage. GC–MS was used to identify the products of the pyrolytic decomposition.

Introduction

Benzodiazepines have been known to possess important medicinal properties for over 30 years. Some benzodiazepine derivatives have been found to be potent antagonists of the peptide hormones cholecystokinin (CCK) and gastrin [1], [2], [3]. The isolation from Aspergillus alliaceus of asperlicin (Scheme 1a) a potent non-peptide cholecystokinin (CCK) antagonist selective for peripheral tissues [4] initiated studies which led to the discovery of a benzodiazepine series of non-peptide CCK receptor antagonists such as the selective CCKA antagonist MK-329 (Scheme 1b) [5] and dual histamine H2-gastrin receptor antagonists [6], [7].

In this study, a series of spiro benzodiazepines derivatives (Spiro[2,3′-(1′methyl-1′,3′-dihydro-2′-oxo-5′-phenyl-(2′H)-1′,4′-benzodiazepinyl]-4-(2′-naphthyl)-3, 7-diaza-6, 8-dioxobicyclo[3.3.0]octane) (SBIN), Spiro[2,3′-(1′ methyl-1′,3′-dihydro-2′-oxo-5′-phenyl-(2′H)-1′,4′-benzodiazepinyl]-4-(N′-phenylsulphonyl)-indolyl]-3,7-diaza-6,8-dioxobicyclo[3.3.0]octane (SBII) and cyclocompounds (SBFN, SBFI)) as shown in Scheme 2 have been prepared [8], [9] and studied by differential thermal analysis (DTA) and thermogravimetry (TG) and the mechanism of thermal decomposition have been determined.

Section snippets

Experimental

The spiro benzodiazepine derivatives (SBIN, SBII, SBFN and SBFI) were synthesised using analytical pure reagents as described in [8], [9].

SBFI (C45H46N4O6S)

TG studies on SBFI using Electrothermal type mode 9200 showed that the sample first melted and was immediately accompanied by decomposition. The sample decomposed in two stages over the temperature range 440–1060 K (Fig. 1). The first decomposition occurs between 440 and 760 K with a mass loss of 49.5% and the second decomposition occurs between 760–1060 K with a 50.4% mass loss.

From the corresponding DTA analysis, one endotherm and two exotherms were observed with the endotherm between 439 and 448

Conclusions

Each of the spiro benzodiazepine derivatives show similar decomposition mechanisms. The decomposition mechanisms of the compounds are shown in Scheme 1, Scheme 2, Scheme 3, Scheme 4 and were derived from Arslan [10], Burakevich et al. [11] and Arslan et al. [12]. In spite of the fact that SBFI and SBII have the same indole moiety, they have different spiro groups and the last stage in the decomposition for each is the same (see Scheme 3, Scheme 6). Similarly, SBFN and SBIN have the same napthyl

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