http://www.rasayanjournal.com

Vol.3, No.3 (2010), 563-570

ISSN: 0974-1496

CODEN: RJCABP

STEROIDAL BENZOTHIAZEPINESAZHAR U. Khan et al.

MASS SPECTRAL STUDIES OF STEROIDAL

BENZOTHIAZEPINES

Azhar U. Khan*1 ,2

Geetesh Mudgal1, Mahboob Alam

1 and M. Mushfiq

1

1Steroidal Research Laboratory, Department of Chemistry,

Aligarh Muslim University, Aligarh-202002, India. 2Somany Institute of Technology and Management,Rewari-123401 Haryana INDIA.

*E-mail: azharukhan@rediffmail.com

ABSTRACT

The mass spectra of structurally related steroidal benzothiazepines [4α,6-bc] have been examined which show

strong resemblances by giving the same ion peak or corresponding peaks by similar fragmentation so much so that it

can be used as of diagnostic value. Common ion peaks at m/z 163 and m/z 95 or 93 can be taken as diagnostic

peaks. The fragmentations pathways have been suggested which are tentative in absence of deuterated analoges but

different substitutions at C3 compensate the difficiency to some extent.

Keywords: Steroidal ketones, benzothiazepines, mass fragmentation, heterocycles.

INTRODUCTION The benzothiazepines are important nitrogen and sulfur-containing seven-membered heterocyclic

compounds in drug research since they possess diverse bioactivities 1-3

. As should be expected, the fusion

of heterocycles to steroidal skeleton often led to a change in their physiological activities and the

appearance of new interesting biological behavior. As a result, various procedures have been worked out

for their synthesis and numerous derivatives have been published in the literature. The reaction of α,β-

unsaturated ketones and 2-aminothiophenol is an especially convenient and versatile method for their

preparation. As we know that mass spectroscopy has proved to be a powerful and commonly used tool in

the identification and structure elucidation of sterols. Detailed knowledge of the fragmentation triggering

behavior of the common functional groups on the steroid skeleton is essential, however, for reliable

structure assignments by this technique. In the present paper, we report the fragmentation4-7

routes of

steroidal benzothiazepines and their 3β-substituted derivatives.

X

C8H17

NS

Where, X = H (I), OCOCH3(II), OCOC2H5(III)

EXPERIMENTAL The mass spectra were measured on a JMSD-100 mass spectrometry at 70eV using direct insertation

technique at a source temperature 250C.The molecular formula of all the ions mentioned in the text were

established by accurate mass measurement relative to fragment ions of heptacosafluorotributylamine at

the resolving power of 15000.

Vol.3, No.3 (2010), 563-570

STEROIDAL BENZOTHIAZEPINESAZHAR U. Khan et al.

564

Compound I, II and III were prepared accordingly to the procedure describe in the literature8-13

.

RESULTS AND DISCUSSION The present study give the mass spectra of 5α- colestant [4α, 6]- 2′, 3′-dihydro- 1′, 5′-benzothiazepine

8-13

(I), 3β-ethanolyloxy -5α-cholestan [4α, 6-bc]-2′,3′-dihydro-1′,5′- benzothiazepine (II), 3β-propanoyloxy-

5α cholestan [4α, 6-bc]-2′,3′-dihydro-1′,5′-benzothiazepine (III).

The mass spectra 14-15

of all the free compounds have strong resemblances. The structure of the (I) (Fig.1)

is dealt with to explained the formation of important ion peaks, the mechanism of fragmentation is

tentative for want of suitably deuterated analogues but different substitution at C3-has to great extends

compensation the deficiency. Formation of characteristic fragment ions 458, 396, 95, 354, 243, 229, and

507 can be shown as given in scheme 1, 2, 3, 4, 5, 6 & schemer 6 are given to explain the formation of

some other important ion peaks from I which in others II-III (fig. 2 and 3) corresponding peaks are

observed. Alternatively the fragment ion m/z 458/456 can be shown to arise from the molecular ion as in

the following Scheme 1. It may be pointed out that ion peaks both at m/z 490 and 458 are very weak. The

fragment ion m/z 396 corresponds to the loss of mass unit 95 which may involve the loss of ring ‘A’ and

angular methyl group at C10 according to Scheme-2. The fragment ion peak at m/z 396 is very weak. It is

expected to be so in view of the ion structure (Ib) having two four membered strained rings. The loss of 2-

aminothiophenol moiety can be shown according to Scheme 3. Perhaps the most significant in peak in the

spectrum is m/z 243. Its formation can be shown to occur in more than one way. One of the possibilities

is the involvement of the ion m/z 244 (a small peaks which on one hydrogen loss can given rise to the ion

m/z 243 (Scheme 4).

These important ions m/z 230, 229 and 228 can be shown to arise according to (Scheme-5). These ions

along with the ion m/z 243 are of diagnostic value for [4α,6-bc] benzothiazepine (I-III) derivatives.

Alternatively the ion m/z 229 can be shown to arise without the involvement of ion m/z 230.

The presence of nitrogen and sulfur in the ion m/z 163 clearly indicates that the steroid frame work is lost

in a manner that three carbon i.e. C4- C6 remains with the fragment ion. This ion m/z 163 may be arising

according to fragmentation proposed in Scheme-6 and according to this Scheme-6, it can also be taken as

a characteristics fragmentations.

This fragment ion may occur as shown in Scheme- 7. The ion m/z corresponds to the loss of ketene

(CH2=C=0) from the molecular ion. The peak is common in all acetate derivatives and may be shown

according to Scheme-8.

ACKNOWLEDGEMENTS We are thankful to the chairman, department of chemistry, A.M.U., Aligarh for providing necessary

facilities. One of the authors (Azhar.U. Khan) is also thankful of the chairman of SITM for providing

computer lab.

Scheme-1

Vol.3, No.3 (2010), 563-570

STEROIDAL BENZOTHIAZEPINESAZHAR U. Khan et al.

565

Scheme-2

Scheme-3

Vol.3, No.3 (2010), 563-570

STEROIDAL BENZOTHIAZEPINESAZHAR U. Khan et al.

566

Fig.-1

Fig.-2

Vol.3, No.3 (2010), 563-570

STEROIDAL BENZOTHIAZEPINESAZHAR U. Khan et al.

567

Fig.-3

Scheme-4

Vol.3, No.3 (2010), 563-570

STEROIDAL BENZOTHIAZEPINESAZHAR U. Khan et al.

568

Scheme-5

Vol.3, No.3 (2010), 563-570

STEROIDAL BENZOTHIAZEPINESAZHAR U. Khan et al.

569

Scheme-6

Scheme-7

Scheme-8

Vol.3, No.3 (2010), 563-570

STEROIDAL BENZOTHIAZEPINESAZHAR U. Khan et al.

570

REFERENCES 1. L. H. Sternbach, Prog. Drug Res, 22, 229 (1978).

2. G. Roma, G. C. Grossi, B. M. Di, M. Ghia, and F. Mattioli, Eur. J. Med. Chem., 25,489 (1991).

3. J. X. Xu and S. Jin, Heteroatom Chem., 10, 35 (1999).

4. J.Xu, and Z.Gang, Rapid Communication in Mass Spectrometry, 14, 2373-2376 (2000).

5. F.L.Ansari, L.Hussain, S.Nasir and S.Sultana,Rapid Communication in Mass Spectrometry,19,

1200-1206(2005).

6. S.Lee and K.N.Fan, Journal of Raman Spectrometry, 39, 1568-1577(2008).

7. T.Mario, T.Andreas ,K.Maxie,B.Simon and W.Schanza, Journal of Mass Spectrometry, 44,442-

460 (2009).

8. M. S. Ahmad, G. Moinuddin and I. A. Khan, Org. Mass. Spectrom., 13, 382 (1978).

9. M. S.Ahamed, Z.H. Chowdhry, N. Z.Khan and S. K. Raza, Indian J. Chem., 23B, 171 (1984).

10. M. S. Ahmad, M. Mushfiq and Shafiullah, Steroids, 181 (1973).

11. M. S.Ahmad, M. Mushfiq, G.A.S Ansari and F. Waris, Org. Mass spectrom. 8, 1, (1974).

12. M. S. Ahmad and M. Mushfiq, Organic Mass Spectrom., 6, 1109 (1972).

13. M. S.Ahmad, S. A. Ansari, I. A. Ansari and G. Moinuddin, Org. Mass Spectrom., 19, 245 (1984).

14. M. S. Ahmad, M. Mushfiq and G.A.S. Ansari. J. Prakt. Chemia., 317 (1975).

15. H. Budzikiewicz and C. Djerassi J. Am. Chem Soc., 84, 1430 (1962).

(Received: 7 September 2010 Accepted: 25 September 2010 RJC-642)

ijCEPr______________________________________________ International Journal of

Chemical, Environmental and Pharmaceutical ResearchChemical, Environmental and Pharmaceutical ResearchChemical, Environmental and Pharmaceutical ResearchChemical, Environmental and Pharmaceutical Research www.ijcepr.com

______________________________________________________________________________

ijCEPr widely covers all fields of Chemical, Environmental and Pharmaceutical Research.

Manuscript Categories: Full-length paper, Review Articles, Short/Rapid Communications.

Manuscripts should be addressed to:

Prof. (Dr.) Sanjay K. Sharma Editor-in-Chief

23, ‘Anukampa’,Janakpuri, Opp. Heerapura Power Station,

Ajmer Road, Jaipur-302024 (India)

E-mail: ijcepr@gmail.com

Phone:0141-2810628(O), 09414202678(M)