Synthesis, spectral studies and antibacterial activity of 3-(4-phenyl-2,3-dihydro-1,5-benzodiazepin-2-yl)chromone

Article abstract of DOI:10.14233/ajchem.2014.16377

3-(4-Phenyl-2,3-dihydro-1,5-benzodiazepin-2-yl)chromone (PHBDC) has been synthesized by reacting 1-phenyl-3-(chromon-3-yl)-2- propene-1-one (chalcone) with o-phenylenediamine. Structures of chalcone as well as PHBDC were established on the basis of elemental analysis, IR and PMR spectral studies. 3-(4-Phenyl-2,3-dihydro-1,5-benzodiazepin-2-yl)chromone has been found to be antibacterial against bacillus bacteria some of which cause food poisoning, anthrax (a malignant boil), etc.

Full text of DOI:10.14233/ajchem.2014.16377

Asian Journal of Chemistry; Vol. 26, No. 13 (2014), 3992-3994
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.16377
Synthesis, Spectral Studies and Antibacterial Activity of
3-(4-Phenyl-2,3-dihydro-1,5-benzodiazepin-2-yl)chromone
*
VINAY PRABHA SHARMA and PRAVEEN KUMAR
Department of Chemistry, Meerut College, Meerut-250 001, India
*Corresponding author: E-mail: shambhavisharma98@hotmail.com
Received: 16 September 2013; Accepted: 16 January 2014;
Published online: 23 June 2014;
AJC-15390
3-(4-Phenyl-2,3-dihydro-1,5-benzodiazepin-2-yl)chromone (PHBDC) has been synthesized by reacting 1-phenyl-3-(chromon-3-yl)-2-
propene-1-one (chalcone) with o-phenylenediamine. Structures of chalcone as well as PHBDC were established on the basis of elemental
analysis, IR and PMR spectral studies. 3-(4-Phenyl-2,3-dihydro-1,5-benzodiazepin-2-yl)chromone has been found to be antibacterial
against bacillus bacteria some of which cause food poisoning, anthrax (a malignant boil), etc.
Keywords: IR, PMR, Synthesis, Antibacterial, 3-(4-Phenyl-2,3-dihydro-1,5-benzodiazepin-2-yl)chromone.
INTRODUCTION
Chromones as well as 2,3-dihydro-1H-1,5-benzodiaze-
pines are of immense biological importance. Chromones
possess medicinal activities like antimicrobial1-4, antiinfla-
mmatory5,6, diuretic7,8, coronary vasodialator9, antispasmodic10
and CNS-stimulant11. 2,3-Dihydro-1H-1,5-benzodiazepines
and related systems exhibit, anticonvulsant, antianxiety,
analgesic, sedative, antidepressant and hypnotic activities12,13
and are part of a number of drugs14. In the light of these obser-
vations it was thought worthwhile to synthesize compounds
incorporating these moieties with a view to test anti bacterial
activities in them and hence title compounds were synthesized
(Scheme-I).
EXPERIMENTAL
All melting and boiling points are uncorrected. Infrared
spectra were recorded on SPECTRUM BX SERIES in KBr.
Absorption frequency is recorded in cm-1. The PMR spectra
Scheme-I
were recorded in CDCl3 and /DMSO-d6 at BRUKERAVANCE
II 400 NMR SPECTROMETER. The chemical shifts are
Synthesis of 1-phenyl-3-(chromon-3-yl)-2-propene-1-
expressed in ppm units (δ) downfield from internal tetramethyl
silane (TMS) standard. Solvents and starting materials were
purified using standard procedures. The purity of compounds
one (3): To a solution of 3-formylchromone (0.01 mol) and
acetophenone (0.01 mol) in 40 mL of ethanol was added 15 mL
of 40 % KOH in portions with shaking and keeping the tempe-
was regularsly checked on TLC-plates coated with silica gel.
rature of reaction mixture below 10 ºC. The flask was kept at
room temperature for 48 h for the completion of reaction. Now
reaction mixture was acidified with glacial acetic acid and
Synthesis of 3-formylchromone (2): This compound was
synthesized starting with o-hydroxyacetophenone, dimethyl-
formamide (DMF) and phosphorus oxy chloride according
poured on crushed ice. Solid thus obtained was filtered, washed
to the procedure and conditions mentioned in the chemical
literature15.
with water and was crystallized from ethanol.

Vol. 26, No. 13 (2014)
Synthesis and Antibacterial Activity of 3-(4-Phenyl-2,3-dihydro-1,5-benzodiazepin-2-yl)chromone 3993
IR (KBr, pellets, nmax, cm-1): 3014 (=C-H str, aromatic),
1645 (C=O str of chromone and -CH=CH-CO-Ph moieties),
1603 (C=Cstr), 1220 (C-Ostr.) and 900 (=C-H def). PMR
(DMSO-d6) δ: 7.48-7.63 (6H, m, 5 protons of phenyl ring and
C6-H of chromone), 7.68 (1H, m, C8-H of chromone), 7.76
(2H, m, C7-H of Chromone and C3-CH=of propenone), 8.27
(1 H, d, = CH-CO of propenone), 8.54 (1H, dd, C5-H of
chromone) & 8.59 (1H, s, C2-H of chromone).
directly attached to C3 of chromone. Doublet at δ 8.23 can be
O
assigned to =CH-CO- proton of
moiety of
CH CH
C
chalcone which appeared downfield because of deshielding
effect of C=O group in neighbourhood. Signal visible at δ
8.54 may be assigned to C5-H of chromone and last signal, a
singlet at δ 8.59 in probably due to C2-H of chromone.
Infrared spectrum of 4, the title compound indicated the
condensation of chalcone with o-phenylenediamine, because
the broad absorption band at 1645 cm-1 got shifted to C=O
stretching of chromone only which was visible at 1618 cm-1.
IR-spectrum was devoid of 2-NH2 coupled vibrations and only
1-N-H stretching band was present at 3295 cm-1. Therefore,
-CH=CH-CO- moiety has condensed with o-phenylenediamine
to give 2,3-dihydro-1,5-benzodiazepin ring that contains 1-NH
group. Other usual bands for the system viz. aromatic = C-H
stretching, C=C and C=N stretching, C-N stretching and C-O
stretching were present in spectrum at 3051, 1603, 1532, 1321 and
1179 cm-1, respectively =C-H Bending was visible at 900 cm-1.
PMR-spectrum of this compound 4 showed its formation.
In PMR spectrum (CDCl3) eighteen protons showed up in 5
groups. Starting from highest field first to appear were -CH2-
protons of 2,3-dihydro-1,5-benzodiazepin moiety as a signal
located at δ 5.31. C2-H of 2,3-dihydro-1,5-benzodiazepine and
there aromatic protons appeared in the region δ 6.84-6.98 as a
multiplet. Third signal was ten proton multiplet in the region
δ 7.31-7.69 which may be accounted to C6-H, C8-H, C7-H and
C5-H of chromone ring and six other aromatic protons present
in two aromatic rings. Singlet at δ 7.90 may be ascribed to
C2-H of chromone and last signal present at δ 11.75 may be
assigned to -NH proton.
Synthesis of 3-(4-phenyl-2,3-dihydro-1,5-benzodiazepin-
2-yl)chromone (4): To a solution of chalcone [3; 0.01 mol] in
40 mL of ethanol, solution of o-phenylenediamine (0.012 mol)
in alcohol was added and refluxed for 6-7 h. The progress of
reaction was monitored onTLC.After the completion of reaction,
the reaction mixture was poured on crushed ice. The solid
separated was filtered, washed with ethanol and recrystallized
with 50 % ethanol m.p. 240-41 ºC, yield = 70 %; Found (%):
C = 78.69; H = 4.92; N = 7.65; calculated (%) C = 78.80; H =
5.00; N = 7.96 %]; IR (KBr, pellets, nmax, cm-1); 3295 (N-H str
of benzodiazepine ring), 3051 (=C-H str., Aromatic), 1618
(C=O str., chromone), 1532 (C=N str), 1321 (C-N str.), 1179
(C-O str). PMR [CDCl3] (δ): 5.31 [2H, d, -CH2 of 2,3 -dihydro
1,5-benzodiazepin ring]; 6.84-6.98 [4H, m, C-H of dihydro-
benzodiazepin and three aromatic protons], 7.31-7.69 [10 H,
m, C6-H, C8-H, C7-H, C5-H of chromone and six other aromatic
protons, 7.90 [1H, S, C2-H of chromone] and 11.15 [1H, S, N-
H proton of dihydrobenzodiazepin moiety].
RESULTS AND DISCUSSION
Chalcones react with o-aminothiophenol to give benzoaze-
pines16. Therefore, it was thought that chalcones of chromones
will react with bifunctional o-phenylenediamine to yield
dihydrobenzodiazepinyl chromones (title compound). Motivated
by this chalcone of chromone was condensed with o-phenylene-
diamine in ethanol by refluxing for 7 h to yield 3-(2,3-dihydro-
1,5-benzodiazepin-2-yl) chromone according to (Scheme-I).
Chalcone (3) required for this purpose was prepared starting
with o-hydroxyacetophenone (1). o-Hydroxy acetophenone
was converted into 3-formyl chromone (2) according to the
procedure described in literature15. 3-Formyl chromone was
condensed with acetophenone in ethanolic solution in presence
of 10 % aqueous solution of sodium hydroxide16.
A probable mechanism for the formation of present com-
pound from chalcone is given in Scheme-II.
Structuresofchalcone, 1-phenyl-3-(chromon-3-yl)-2-propene-
1-one (3) and of title compound 3-(4-phenyl-2,3-dihydro-1,5-
benzodiazepin-2-yl) chromone were brought about on the basis
of their elemental analysis, infrared spectrum as well as proton
magnetic resonance spectrum.
Infrared spectrum of chalcone exhibited characteristic
absorption band for C=O stretching of chromone nucleus &
α,β-unsaturated carbonyl moiety as a broad band around 1645
cm-1. Other usual bands were also present in this spectrum.
But, IR-spectrum gave no direct evidence for the formation of
chalcone. However, PMR-spectrum of the compound 3 comp-
letely revealed the structure of chalcone (3).
PMR-spectrum (in DMSO-d6) of 3 showed signals in five
groups for all twelve protons. Starting from highest field C6-
H of chromone & 5 aromatic protons appeared as multiplet
from δ 7.48 to 7.63. C8-H of chromone was visible at δ 7.68.
Third signal (δ 7.76) was a two proton multiplet which could
be assigned to C7-H of chromone and CH=C group proton
Scheme-II

3994 Sharma et al.
Asian J. Chem.
7. C. P. Garg, V. P. Sharma and R.P. Kapoor, Indian J. Chem., 24B, 1197
(1985).
Compound 4 was screened for antibacterial activity
against Bacillus bacteria. It showed 100 % inhibition of growth
at 1 % concentration (w/v) in DMF.
8. C.P. Garg, V.P. Sharma, V. Chhabra and R.P. Kapoor, Indian J. Chem.,
27B, 469 (1988).
9. G.S. Barsoum and M.R. Kenawy, Am. Heart, 47, 297 (1954);.
10. E. Kohlstaedt and K.H. Klinger, Ger. Patent, 1,018,874; Chem. Abstr.,
54, 5700 (1960).
REFERENCES
1. (a) V.P. Sharma, P. Kumar and M. Sharma, Asian J. Chem., 23, 4616
(2011); (b) V. B. Halnor, N. R. Dalvi, N. S. Joshi, C. H. Gill and B.K.
Karale, Indian J. Chem., 45 B, 288 (2006).
11. D. Molho, E. Boschetti and L. Fontiane, Fr. M. 2472; Chem. Abstr.,
61, 11975 (1964).
12. R.I. Fryer, Bicyclic Diazapines in Chemistry of Heterocyclic Com-
pounds, 50, E. Taylor, Ed. Wiley (1992), Chapter II, Chem. Abstr., 73,
100054 w (1970).
2. R. Purnik, Y. Jay Prakesh Rao and G.J. Kurupadam, Indian J. Chem.,
41B, 869 (2002).
3. S.M. Bhalekar and H.M. Prab, Indian J. Heterocycl. Chem., 17, 285
(2008).
13. L.H. Sternbach, J. Med. Chem., 22, 1 (1979).
14. T.L. Gilchrist, Heterocyclic Chemistry, John Wiley & Sons Inc., New
York, p. 346 (1991).
4. M. Yamada and K. Koyama, Japan Kokai Tokyo Koha Jp, 07,165,748
(1995); Chem. Abstr., 124, 7336a (1996).
15. A. Nohara, T. Umetani and Y. Sanno, Tetrahedron, 30, 3553 (1974).
16. A.G. Nikalje, R.D. Ingle, V.E. Bhingolikar and R.A. Mane, Indian J.
Heterocycl. Chem., 13, 37 (2003).
5. V. Gupta and U. Mishra, Indian J. Heterocycl. Chem., 17, 281 (2008).
6. R.G. Naik, S.L. Kattige, S.A.V. Bhat, B. Alreja, N.J. Desouza and R.H.
Rupp, Tetrahedron Lett., 44, 2081 (1988).