Synthesis of flavanones using methane sulphonic acid as a greencatalystand comparision under different conditions

Article abstract of DOI:10.13005/ojc/300264

Flavonoids are an important class of natural products with wide range activities. Flavonoids includes flavone, flavanone, flavane & flavanol. The synthetic route invovles synthesis of chalcone followed by ring closing to give flavanone. So many catalysts were mentioned in past literature. But most efficient catalyst is methane sulphonic acid.It is easy to handle,less reaction time &easily available. Flavanones were synthesized from chalcone using methane sulphonic acid under thermal condition, microw wave and ultrasound condition.Flavanones are syntheisized in very less time compared to other conditions.

Full text of DOI:10.13005/ojc/300264

ISSN: 0970-020 X
CODEN: OJCHEG
014, Vol. 30, No. (2):
Pg. 857-862
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
2
www.orientjchem.org
Synthesis of Flavanones using Methane Sulphonic Acid as
a Greencatalystand Comparision under Different Conditions
1
1
R.B. KSHATRIYA , J.K. Machhi and G.M. NAZERUDDIN *
1
Department of Organic Chemistry & Research Centre, Poona College of Arts,
Science and Commerce, (Affiliated to University of Pune). Camp, Maharashtra, India.
*
Corresponding author E-mail: rbkshatriya123@gmail.com
http://dx.doi.org/10.13005/ojc/300264
(Received: March 02, 2014; Accepted: March 31, 2014)
ABSTRACT
Flavonoids are an important class of natural products with wide range activities. Flavonoids
includes flavone, flavanone, flavane & flavanol. The synthetic route invovles synthesis of chalcone
followed by ring closing to give flavanone. So many catalysts were mentioned in past literature. But
most efficient catalyst is methane sulphonic acid.It is easy to handle,less reaction time &easily
available. Flavanones were synthesized from chalcone using methane sulphonic acid under
thermal condition, microw wave and ultrasound condition.Flavanones are syntheisized in very
less time compared to other conditions.
Key words: Flavanone, Methanesulphonic acid, Thermal, Micro wave, Ultrasound.
INTRODUCTION
Flavonoids are mainly classified as
flavone,flavanone and flavane etc .Human interest
1
Natural products includes alkaloids,
terpenoids, coumarins, amino acid derivatives and
flavonoids.Flavonoids are found in plant as a
secondary metabolite acts as defence from bacteria
and viruses.They also acts as coluring agent in
flowers to attract insect,honeybees and butterfy
toward flower.Due to which pollination occurs easily
in plants.Flavonoids are also important for human
health as it present in fruits,vegetables and
flowers.Initially it isnamed as Vitamin P.But due to
its yellow colour it is named as flavonoids.
is to isolate and synthesize flavone skeleton having
pharmacological activity.From past literature we
found that flavonoid skeleton (C6-C3-C6 & two
oxygen atoms) have wide range of activities.
Synthetic and naturallly occuring flavonoids
i.e.flavanone have interesting pharmaceutical
1
2
activity
like
anticancer ,anti-estrogen ,
3
4
5
antimycobacterial , antimicrobial , anti-lungcancer ,
anti-bacterial , anti-viral , anti-tuberculosis ,
antifungal , anti-oxidant , anti-arrhythmic ,
6
7
8
9
10
11
1
2
13
antihypertensive , anti-proliferative etc.

8
58
KSHATRIYA et al., Orient. J. Chem., Vol. 30(2), 857-862 (2014)
Flavonoids aresynthesized by various Spectral Data
methods like Clause-Schmidt,Baker-Venkatraman, 2-phenylchroman-4-one (2a)
1
3
Ganguly’s method and Robinson’smethod etc.
Armoatic aldehydes and ketones gives chalcone
which on cyclization gives flavanone.In past system- Hex+E.A.(7:3),Soluble – CHCl
Colour
0
light yellow/white powder,M.P.-76 C,TLC
3
-
1
methods chalcone are cyclized to flavanone by I / IR (KBr) Vmax/cm 1720,1675,1616-1500,1300,
2
15
16
4
17
DMSO , AcOH/H SO , silicagel , poly phosporic 750, 690.
2
1
8
19
20
acid , TFA ,N-methyl imidazole ,alkali metal
2
1
22
23
24
1
carbonates , KOH/MeOH , pyridine , DBU/MW ,
H NMR (CDCl ) 
3
2
5
26
HBr/AcOH , pottasium ferricynide etc.We
5.51(d,1H,J = 7 Hz),3.20(d,2H,J=7 Hz),
synthesized flavanone by using methane sulphonic 7.40 (dd,1H,J = 7.5,1.5 Hz), 7.0(1H,m,J= 7.5,1.5
acid under different conditions.
Hz),7.50(dd,1H,J = 7.5,1.5 Hz),7.15(dd,1H,J =
.5,1.5 Hz),7.32 (dd,2H,J = 7.5,1.5 Hz),7.25 (dd,1H,
J= 7.5,1.5 Hz),7.22(m,1H,J= 7.5,1.5 Hz)
7
EXPERIMENTAL
All material purchased from Sigma-Aldrich 2-(4-hydroxyphenyl)chroman-4-one (2b)
and solvents from Merck Chemical India.Melting Colour
1
0
points determined in parafin bath. IR & HNMR
spectra gives structure of compound.
Light yellow powder,M.P.-180 C,TLC
system-Hex+E.A.(7:3),Soluble – DMSO
-
1
IR (KBr) Vmax/cm : 3480,1700,1692, 1608,
Representative procedure
1514,754,697.
Thermal condition
A mixture of substituted 2- hydroxy
chalcone (1mole) was added in RBF.Then arrange
1
H NMR (DMSO) 
5.53(d,1H,J=7Hz),3.28(d,2H,J=7
the apparatus with thermometer in oil bath.Place Hz),9.79(s,1H,-OH),6.78(d,2H, J= 7.5,1.5 Hz), 7.33
apparatus on digital hot plate.Add through neck of (dd,2H,J = 7.5,1.5 Hz),7.34(d,1H,J = 7.5,1.5 Hz),
RBF acetic acid and then add dropwise MSA (15 7.046 (m,1H, J=7.5,7.2,1.5 Hz),7.55(dd,1H,J =
mole %).Maitain temperature 105-115°C till 7.5,1.5 Hz),7.76(m,1H,J=7.2,7.2,1.5 Hz),7.76(m,1H
completion of reaction.Reaction was monitored by J = 7.6,7.2,1.5 Hz).
TLC.Pour the reaction mass in water,filter to get
solid.Recrystalise with suitable solvent.Calculate 2-(3-hydroxyphenyl)chroman-4-one(2c)
yeild, M.P.After checking solubility in suitable Colour
solvent it was given for spectral analysis.
0
White powder,M.P.-134 C,TLC system-
Hex+CHCl +Acetone.(6:3:1),Soluble– DMSO
3
-
1
Ultra sound condition
IR (KBr) Vmax/cm 3400, 1711, 1656, 1610, 1515,
A mixture of substituted 2- hydroxy 750, 690.
chalcone (1mole) and methane sulphonic acid was
added(15 mole %) in RBF. Add acetic acid minimum
1
H NMR (DMSO)  5.70(d,1H,J=7Hz),3.17(d,1H,J =
to dissolve the reaction mass.Then keep RBF in a 7Hz),6.75(dd,1H,J = 1.5,1.5 Hz),6.92(m,1H,J= 7.5,
0
water bath with ultrasound. Maintain temp. 95 C. 1.5, 1.4 Hz), 7.09(m,1H,J =7.6,1.5,1.5), 7.21 (m,1H,
Carry out reaction for 30 minute under ultrasound. J = 7.5,1.5,1.5 Hz),7.57(dd,1H,J = 7.5,1.5 Hz),7.60
Check TLC.Carry out work up as above.
(dd,1H,J = 7.5,1.5 Hz), 7.76(dd,1H,J = 7.5,1.5
Hz),7.78(m,1H,J = 7.5,1.5,1.5 Hz)
Under micro-wave condition
A mixture of substituted 2- hydroxy 2-(3,4-dimethoxyphenyl)chroman-4-one (2d)
chalcone (1mole) and methane sulphonic acid was Colour
added (15 mole %) in RBF.Add acetic acid minimum
0
light yellow powder,M.P.-134 C,TLC
to dissolve the reaction mass.Then RM subjected system-Hex+E.A.(7:3),Soluble– DMSO.
-
1
to micro-wave.Check TLC.Carry out work up as IR (KBr) V /cm 1700,1656,1600,1512,740.
above.
max
1
H NMR (DMSO) d 5.42(d,1H,J = 7 Hz),3.14(d,2H,J

KSHATRIYA et al., Orient. J. Chem., Vol. 30(2), 857-862 (2014)
859
Scheme 1: Synthesis of flavanone from chalcone
Fig. 1: Molecules with biological activity

8
=
60
KSHATRIYA et al., Orient. J. Chem., Vol. 30(2), 857-862 (2014)
1
7 Hz),3.92(s,3H,-OMe) 3.90(s,3H,-OMe), 6.90
H NMR (CDCl ) 
3
(d,1H,J =7 Hz),7.008(d,1H,J=7Hz),7.027(d,1H,J =
5.50 (d,1H,J = 7 Hz),3.19(d,2H,J = 7
1
7
.5 Hz), 7.15(dd,1HJ = 7.5,1.5 Hz),7.52(dd,1H,J =
.5,1.5 Hz),7.94(m,1H,J= 7.5,1.5,1.5,1.5 Hz)
Hz),2.80(s,3H), 6.72(2H,d,J = 7.5 Hz),7.50(d,1H,J
= 7.5 Hz),7.35(s,5 H)
5
-methoxy-2-phenylchroman-4-one (2e)
7-hydroxy-2-phenylchroman-4-one (2f)
Colour
Yellow powder,M.P.-188 C,TLC system-
Hex+E.A.(7:3),Soluble–CHCl3.
Colour
0
0
Yellow powder,M.P.-141 C,TLC system-
Benzene+E.A.(9.5+0.5),Soluble–CHCl3.
-
1
-1
IR (KBr) Vmax/cm 1720,1654, 1600, 1500,
300, 980.
IR (KBr) Vmax/cm 3500, 1717, 1660, 1500, 1300,
980.
1
Table 1.Synthesis of flavanones under thermal microwave and ultrasound conditions

KSHATRIYA et al., Orient. J. Chem., Vol. 30(2), 857-862 (2014)
861
1
H NMR (CDCl ) 
toluene sulphonic acid which solid at room
3
5
.51(d,1H,J = 7 Hz),3.40(d,2H,J = 7 temperature. MSA isconsidered asintermediate
Hz),6.46(dd,1H,J=7.5,
between sulphuric acid and methyl sulphonyl
H
1
.5 Hz),6.50(d,1H,J = 1.5 Hz),7.50(d,1H,J = 7.5 methane.It maintains P which is necessary to go
Hz),7.40(dd,2H,J=7.5,1.5 Hz),
reaction smoothly. So many acids like acetic acid,
sulphuric acid, pTSA,poly H PO ,Hydrochloric acid
7.35(m,3H,J = 7.5,1.5 Hz).
3
4
were used in previous method.Sometimes mixture
of acids,mixed solvents are used in previous
methods.So as per our opinion P isimportant for
5
,7-dimethoxy-2-phenylchroman-4-one (2g)
H
Colour
0
White powder,M.P.-144 C,TLC system- the acidic synthesis of flavanone from 2-hydroxy
CHCl + MeOH.(9:1),Soluble – CHCl
chalcones. We also comparedreaction under
various conditions like ultrasound,thermal and
microwave conditions.
3
3
-
1
IR (KBr) Vmax/cm
7021674, 1608, 1489,1300,943.
1
CONCLUSION
1
H NMR (CDCl ) 
3
5
.51(d,1H,J = 7 Hz),3.029(d,2H,J= 7Hz),
We found cheap,environmental friendly
2
6
7
1
.79 (s,3H),2.62 (s,3H),6.16(d,1H,J= 1.5 Hz), process for the synthesis of flavanones.Methane
.10(d,1H,J = 1.5 Hz),7.38(m,1H,J = 1.5,1.5 Hz), sulphonic acid is green catalyst compared to other
.41 (m,1H,J = 7.5,1.5,1.5 Hz),7.45(m,1H,J=7.5, 1.5, catalysts.We compare different conditions for the
.5, 1.5 Hz)
reaction.We concluded that reaction under MW will
complete in minimum time.
RESULTS AND DISCUSSION
ACKNOWLEDGMENT
Methane sulphonic acid is used as an acid
catalyst in organic reactions because it is a non-
We specially thanks to Dr.Rajeshwari Nair,
volatile, strong acid that is soluble in organic Vice Principal, S.S.R.College of Arts,Commerce &
solvents. Methanesulfonic acid is convenient for Science, Silvasa (Affiliated to University of Pune)
industrial applications because it is liquid at ambient to give lab fascility to carry research.
temperature, while the closely related to para
REFERENCES
1
.
(a)Abou, E.; Osama, S.; Ashraf, M. Ind. J.
Chem. 2005, 44: 1887.
4704.
6.
7.
Pandey,V.K.; Singh,V.K.; Tandon,M.;
Joshi,M.N.;Bajpai,S.K. Ind. J. Chem. 2004,
43B,1770.
Lin, Y.M.; Zhou, Y.; Flavin, M.T.; Zhou, L.
Weiguo, N.; Chen, F.C.Bioorg Med Chem.
2002,10, 2795.
Dandia,A.; Singh,R.; Khaturia,S. Bioorg Med
Chem. 2006,14,1303.
Tapas,A.; Sakarkar, D.; Kakde, R. J.Pharm.
and Tech. 2008,1(3)132.
(b)Kshatriya, R.B.; Machhi, J.K.; Nazeruddin,
G.M.OIIRJ 2014, IV,196.
Biddle, M.M.; Lin,M.; Sheidt,K.A. J.Am.
Chem.Soc.2007,129,3830.
2
.
.
3
Soizic, P.;Janin,Y.L.;Brigitte ,Saint-Joanis;
Priscille, B.; Sylvie, M.; Koch, M.; Cole,S.T.;
François, T.; Pierre-Etienne ,B. Bioorg. Med.
Chem. 2007,15,2177.
Sherif B Abdel Ghani;Louise W.; Zidan H. Z.;
Hussein M. Ali;-C.William-Keevil; Brown.
R.C.D.Bioorg. Med. Chem. 2008, 518.
Mughal,E.U.; Ayaz, M.; Hussain, Z.;
Hasan,A;Riaz,M; Malik,A.; Hussain,S.;
Choudhary.M.I. Bioorg Med Chem. 2006,14,
8.
9.
4
.
.
10.
Koufaki, M.; Kiziridi, C.; Papazafiri, P.;
Vassilopoulos, A.;Varro, A.;Zsolt, N.; Farkas,
A.; Makriyannis, A..Bioorg. Med. Chem. 2006,
14, 6666.
5
11.
Amit Tapas,Dinesh Sakarkar,Rajendra

8
62
KSHATRIYA et al., Orient. J. Chem., Vol. 30(2), 857-862 (2014)
Kakde, Res. J.Pharm and Tech.
008,1(3),132.
Agarwal,A.D. Int.J.Of Pharm. Science and
Nanotech. 2011, 4,1394.
Kshatriya,R.B.;Nazeruddin,G.M.;Shaikh,Y.I.
Orient. J. of Chem.2013, 29(4),1475.
Kshatriya, R.B.; Machhi, J.K.; Patil, M.S.; Patel,
York, U. S. A. 1995,4172.
Chaturvedi, R.; Patil, P. N.; Mulchandani, N.
B. ibid.1992,31B, 340.
Liu,B. K. , Wu, X. ;Qian,Q.; Lv,D.S. Lin, X. F.
Synthesis 2007,22,2653.
Mondal,R. Gupta, A.D.Mallik, A.K. Tet. Lett.
2011, 52, 5020.
2
19.
20.
21.
1
1
1
2.
3.
4.
A.C.; More, D.B. Int.-Multi. e – Journal 2013, 22.
II(X), 67.
Kshatriya,R.B.;Machhi,J.K. IJPRR, 2014, 3(2):
Vatkar, B.S.; Pratapwar, A.S.; Tapas, A.R.;
Butle, S.R.Tiwari,B.Int.J.of Chem.Tech Res.
2010, 21, 504.
1
1
1
1
5.
6.
7.
8.
4
7.
23.
24.
25.
Dutta, C. P.; Roy, L. P. K. Indian J. Chem.
1975,13, 425.
Patonay, T.; Varma, R. S.; Vass, A.; Levai, A.;
Dudas, J.Tet. Lett. 2001,42, 1403.
Lee,J.I ; Jung, M.G. Bull. Korean Chem. Soc.
2005, 26(12), 2045.
Lokhande,P.D.; Sakate,S.S.;Taksande,K. N.;
Navghare,B. Tet. Lett.2005, 46,1573.
Babber, S.;Chandra, S.;Aggarwal, A.K. Indian
J.Chem.1987,26B, 797.
Paquette, L. A. Encyclopedia of Reagents for
Organic Synthesis; John-Wiley & Sons: New 26.
Makrandi, J. K.; Bala, S.Syn. Comm.2000,30,
3
555.