A New Green Approach to 2,3–Dihydro-1H-1,5 –Benzodiazepines

Asieh Yahyazadeh¹*, Jafar Abbasi², Farshid Salimi and Mohamad Saeed Daneshmandi³

¹Department of Chemistry, University of Guilan, P.O. Box 1914, Rasht (Iran).

²Department of Chemistry, Research Centre Medicinal Plants, Islamic Azad University Ardabil (Iran).

³Department of Electrical and Computer Engineering, University of Tehran, Tehran (Iran).

ABSTRACT:

Reaction of some diamines and ketones in the presence of catalytic amount of dodecylbenzene sulfonic acid leads to the formation of 2,3–dihydro -1H-1,5-benzodiazepines in good yields. It seems that dodecylbenzene sulfonic acid has two roles: first it acts as a surfactant to dissolve starting materials in water, and second it acts as an acidic catalyst to activate carbonyl groups.

KEYWORDS: Benzodiazepine; Dodecylbenzene Sulfonic Acid; Imine–Enamine Cyclization

Copy the following to cite this article: Yahyazadeh A, Abbasi J, Salimi F, Daneshmandi M. S. A New Green Approach to 2,3–Dihydro-1H-1,5 –Benzodiazepines. Orient. J. Comp. Sci. and Technol;2(2)

Copy the following to cite this URL: Yahyazadeh A, Abbasi J, Salimi F, Daneshmandi M. S. A New Green Approach to 2,3–Dihydro-1H-1,5 –Benzodiazepines. Orient. J. Comp. Sci. and Technol;2(2). Available from: http://www.computerscijournal.org/?p=2132

Introduction

Benzodiazepines are very important compounds because of their pharmacological properties.¹ Despite their importance from a pharmacological point of view, comparatively few methods for the preparation of 1,5- benzodiazepines have been reported. These include condensation reaction of o-phenylenediamines with α,β-unsaturated carbonyl compounds or ketones in the presence of BF₃–OEt₂, NaBH₄, polyphosphoric acid, SiO₂, MgO and POCl₃.^2-6 Unfortunately, many of these processes suffer from one or other limitations such as drastic reaction conditions, low yields and co-occurrence of several side reactions.^7-9

In this work, we report a facile method for the synthesis of 2,3 – dihydro–1H–1,5– benzodiazepines by the condensation of o-phenylenediamine with ketones in the presence of a catalytic amount of dodecylbenzene sulfonic acid in water.

The reactions were carried out in water at room temperature for 12h by taking 1:202 mol ratio mixture of o-phenylenediamine and the ketone in the presence of 1 mol % dodecylbenzene sulfonic acid to give the desired products (Scheme 1).

It is noteworthy that starting from unsymmetrical ketone such as 2-butanone (entry 3), the ring closure occurs selectively only from one side of carbon skeleton yielding a single product. All products were characterized by comparison of their melting point and ¹H- NMR spectra with those of authentic samples.

Scheme 1 Click here to View figure

 

Table 1: Dodecylbenzene sulfonic acid catalyzed formation of 2,3 – dihydro-1H-1,5–benzodiazepines Click here to View figure

 

For example, in ¹H–NMR spectrum of 2, 2, 4–trimethyl-2,3–dihydro-1H- benzodiazepine (entry 1) in CDCl₃ , the CH₃ groups showed two singlet at δ=1.34 (6H) and 2.34 (3H) ppm. The CH₂ and NH groups appeared at δ= 2.26 (2H) and 3.46 (1H) ppm, respectively. The aromatic protons appeared at δ=6.61-7.28 (4H) ppm, as expected.

Scheme 2 Click here to View figure

 

The mechanism of the reaction 2-6 probably involves an intramolecular imine–enamine cyclization as shown in Scheme 2.

In conclusion, a mild and green method has been developed for the synthesis of 2,3–dihydro -1H -1,5–benzodiazepines.

References

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