Kazi Mehraj AbukalamPharmaceutical Chemistry

Govt.college of Pharmacy,Aurangabad.

Guide Dr. V. K.Mourya

1

Synthesis and evaluation of some coumarines

ContentsNomenclatureCoumarins in natureBiological activities of coumarine comopundsLiterature survey

ArticlesPatents

Synthetic routesRole of catalystCurrent workFuture plan

2

Nomenclature

O O

2 or alpha pyrone

O

O

4 or gamma pyrone

O OCoumarin benzo 1,2-pyrone

O

O

Chromone benzo 1,2- pyrone

O O2

35

6

78 1

4

• Pyrones

• Benzopyrones

• Numbering

3

Biological activities of coumarines

AntimicrobialAntiinflammatoryAnticoagulantAntitumorAntiviralAntioxidantAntiallergicAntihypertensive

4

Naturally occuring CoumarinOccurs in plants like tonka bean & sweet

clover,richest source plants of Rutaceae & Umbelliferae

O O

Esculetin

O OOH

Umbilliferone

OO O

OH

(+) Decursinol5

Literature survey 4-Substituted coumarin posseses

antimicrobial,antiinflammatory,analgesic activity

7-Substituted coumarin having anticancer as well as antiviral activity

3-Substituted coumarin mainly posseses anticoagulant activity

Furocoumarin posseses antihypertensive activity

6

Catalyst used in Pechmann Condensation

PO/molecular sieves Gallium triiodide Metal (II) complexesBiCl3 Vanadium(III)chloride (VCl3) Heterogeneous recyclable

catalyst(HClO4•SiO2) Titanium(IV)chlorideCerium(III)salt Bmim ionic solventPhosphotungstic acid (H3PW12O40)7

Justification• Novelty

Coumarin : A new profile of biological Activity.Antimicrobial & Antimicrobial Activity

UsefulnessSynthesis of New Drug Molecules & their

derivativesTherapeutic activity against various disorders

8

Practicability

9

Synthetic route Synthesis of 4-Substituted methyl Coumarin f OH

R

+ BrCH2COCH2COOC2H5

Substituted Phenol Bromo ethylacetoacetate

O O

BrRConc.H2SO4

Substituted aniline135-138°c

O O

NHR

R2

Substituted 4-bromo coumarin

4-Substituted coumarin

R=7-OH, 7-CH3, 6-CH3,5,6-benz

R2= 4-Cl,3-nitro,2-carboxy,4-carboxy, 4-nitro,4-methyl10

room.temp.

11

OO

HN Cl

4-((4-chlorophenylamino)methyl)-7-methyl-2H-chromen-2-one

OO

HN

NO2

4-((3-nitrophenylamino)methyl)-7-methyl-2H-chromen-2-one

OO

HN COOH

4-((7-methyl-2-oxo-2H-chromen-4-yl)methylamino)benzoic acid

OO

HN

4-((p-toluidino)methyl)-7-methyl-2H-chromen-2-one

4-chloro aniline

3-nitro aniline

PABA

Anthranilic acid

O O

Br

H3C

4-(bromomethyl)-7-methyl-2H-chromen-2-one

8 hrs

8 hrs

10hrs

8 hrs

Toludine

9 hrs

Acetonitrile

OO

HN

COOH

2-((7-methyl-2-oxo-2H-chromen-4-yl)methylamino)benzoic acid

MK1

12

O O

Br

4-(bromomethyl)-6-methyl-2H-chromen-2-one

OO

HN Cl

4-((4-chlorophenylamino)methyl)-7-methyl-2H-chromen-2-one

OO

HN

NO2

4-((3-nitrophenylamino)methyl)-6-methyl-2H-chromen-2-one

OO

HN COOH

4-((6-methyl-2-oxo-2H-chromen-4-yl)methylamino)benzoic acid

OO

HN

4-((p-toluidino)methyl)-7-methyl-2H-chromen-2-one

4-chloro aniline

3-nitro aniline

PABA

Toludine

9 hrs

10 hrs

10 hrs

12 hrs

Acetonitrile

13

O O

Br

HO4-(bromomethyl)-7-hydroxy-2H-chromen-2-one

OO

HN NO2

HO4-((4-nitrophenylamino)methyl)-7-hydroxy-2H-chromen-2-one

4-nitro aniline

Anthranilic acid

7 hrs

14 hrsO

O

HN

HO

COOH

2-((7-hydroxy-2-oxo-2H-chromen-4-yl)methylamino)benzoic acid

Acetonitrile

14

O O

Br

4-(bromomethyl)-2H-benzo[g]chromen-2-one

OO

HN Cl

4-((4-chlorophenylamino)methyl)-2H-benzo[g]chromen-2-one

OO

HN

NO2

4-((3-nitrophenylamino)methyl)-2H-benzo[g]chromen-2-one

Acetonitrile

4-chloro aniline

3-nitro aniline

8 hrs

10 hrs

Sr. No.

Compound Name Molecular Formula

MolecularWeight

Melting Point

Rf % Yield

M1 4-(bromomethyl)-7-methyl-2H-chromen-2-one

C11H9O2Br 253 1300C 0.4 93.75%

M2 4-(bromomethyl)-6-methyl-2H-chromen-2-one

C11H9O2Br 253 1700C 0.86 90.76%

M3 4-(bromomethyl)-7-hydroxy-2H-chromen-2-one

C10H7O3Br 255 110 0.45 85%

M4 4-(bromomethyl)-2H-benzo[g]chromen-2-one

C14H9O2Br 289 1620C 0.9 85.71%

MK1 4-((4-chlorophenylamino)methyl)-7-methyl-2H-chromen-2-one

C17H14NO2Cl 300 1600C 0.8 40%

MK2. 4-((3-nitrophenylamino)methyl)-7-methyl-2H-chromen-2-one

C17H14N2O4 310 1800C 0.6 50%

MK3. 4-((7-methyl-2-oxo-2H-chromen-4-yl)methylamino)benzoic acid

C18H15NO4 309 2600C 1.7 80% 15

Physicochemical Properties

MK4. 4-((p-toluidino)methyl)-7-methyl-2H-chromen-2-one

C16H17NO2 279 188°C 0.72 76%

MK5. 2-((7-methyl-2-oxo-2H-chromen-4-yl)methylamino)benzoic acid

C18H15NO4 309 202°C 0.3 85%

MK6. 4-((4-chlorophenylamino)methyl)-6-methyl-2H-chromen-2-one

C17H14NO2Cl 300 220°C 0.9 90%

MK7. 4-((3-nitrophenylamino)methyl)-6-methyl-2H-chromen-2-one

C17H14N2O4 310 160°C 0.78 67%

MK8 4-((p-toluidino)methyl)-6-methyl-2H-chromen-2-one

C16H17NO2 279 218°C 0.79 64%

MK9 4-((6-methyl-2-oxo-2H-chromen-4-yl)methylamino)benzoic acid

C18H15NO4 309 260°C 1.2 68.85%

MK10. 4-((4-nitrophenylamino)methyl)-7-hydroxy-2H-chromen-2-one

C16H12N2O5 298 170°C 0.6 60%

MK11. 2-((7-hydroxy-2-oxo-2H-chromen-4-yl)methylamino)benzoic acid

C11H8ClNO 311 110°C 0.75 82%

MK12. 4-((4-chlorophenylamino)methyl)-2H-benzo[g]chromen-2-one

C20H14NO2Cl 335 210°C 0.8 61%

MK13. 4-((3-nitrophenylamino)methyl)-2H-benzo[g]chromen-2-one

C20H14N2O4 346 190°C 0.7 76%

Sr. No.

Compound Name Molecular Formula

MolecularWeight

Melting Point

Rf % Yield

17

M1

O O

Br

H3C

Sr. No. Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 761.04(785-540) -C-Br

3 1579.37(1690-1640) C-O

4 1547 (1600,1475) >C=C< (Aromatic)

5 690(690-710) Meta-substituted

6 1320(1375) -CH3

18

O O

Br

Sr. No. Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 761.04(785-540) -C-Br

4. 1579.37(1690-1640) C-O

5. 1547 (1600,1475) >C=C< (Aromatic)

6 (810-840) Para-substituted

7 (1375) -CH3

M2 4-bromo methyl, 6-methyl coumarin

19

M3 4-(bromomethyl),7-hydroxy coumarin

O O

Br

HO

Sr.

No.

Frequency (cm-1) Functional

Group

1 1712.78(1690-1750) C=O

2 646.04(785-540) -C-Br

4. 1631(1690-1640) C-O

5. 1580 (1600,1475) >C=C< (Aro.)

6 700(690-710) meta-substituted

7 3612(3610-3640) -OH

20

M4 4-(bromomethyl),5,6-benz coumarin

O O

Br

Sr. No. Frequency (cm-1) Functional

Group

1 1715.78(1690-1750) C=O

2 646.04(785-540) -C-Br

4. 1624.37(1690-1640) C-O

5. 1580 (1600,1475) >C=C< (Aro.)

21

MK1

OO

HN Cl

Sr. No. Frequency (cm-1) Functional Group

1 1705.78(1690-1750) C=O

2 724.04(530-730) -C-Cl

4. 1656(1690-1640) C-O

5. 1547 (1600,1475) >C=C< (Arom)

6 690.10(690-710) meta-substituted

7 1325(1375) -CH3

22

MK2

OO

HN

NO2

Sr. No. Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 761.04(1515-1560)-C-NO2

4. 1579.37(1690-1640) C-O

5. 1547 (1600,1475) >C=C< (Aromatic)

6 815 (810-840) Para-substituted

7 (1375) -CH3

23

MK3

OO

HN COOH

Sr. No. Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 761.04(2500-3000) -C-COOH

4. 1579.37(1690-1640) C-O

5. 1547 (1600,1475) >C=C< (Aromatic)

6 827 (810-840) Para-substituted

7 (1375) -CH3

24

MK4

OO

HN

Sr. No. Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 1579.37(1690-1640) C-O

3. 1547 (1600,1475) >C=C< (Aromatic)

4 820(810-840) Para-substituted

5 1380(1375) -CH3

25

OO

HN Cl

MK6

Sr. No. Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 761.04(730-530) -C-Cl

4. 1579.37(1690-1640) C-O

5. 1547 (1600,1475) >C=C< (Aromatic)

6 812(810-840) Para-substituted

7 (1375) -CH3

26

OO

HN

NO2

MK7

Sr.

No.

Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 761.04(1515-1560)-C-NO2

4. 1579.37(1690-1640) C-O

5. 1547 (1600,1475) >C=C< (Aromatic)

6 812(810-840) Para-substituted

7 1366(1375) -CH3

27

OO

HN

MK8

Sr. No. Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 1579.37(1690-1640) C-O

3. 1547 (1600,1475) >C=C< (Aromatic)

4 3400(3300-3500) N-H

5 (810-840) Para-substituted

5 (1375) -CH3

28

OO

HN COOH

MK9

Sr. No. Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 761.04(2500-3000) -C-COOH

4. 1579.37(1690-1640) C-O

5. 1547 (1600,1475) >C=C< (Aromatic)

6 (810-840) Para-substituted

7 (1375) -CH3

29

MK10

OO

HN NO2

HO

Sr. No. Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 1180-1360 -C-N

3 761.04(1515-1560)-C-NO2

4. 1579.37(1690-1640) C-O

5. 3420 (3300-3500) C-NH

6 815(810-840) Para-substituted

7 (3200-3400) -OH

30

MK12

OO

HN Cl

Sr. No. Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 730.04(530-730) -C-Cl

4. 1579.37(1690-1640) C-O

5. 1547 (1600,1475) >C=C< (Aromatic)

6 820(810-840) Para-substituted

31

MK13

OO

HN

NO2

4-((3-nitrophenylamino)methyl)-2H-benzo[g]chromen-2-one

Sr. No. Frequency (cm-1) Functional Group

1 1686.78(1690-1750) C=O

2 1234(1180-1360) -C-N

3 761.04(1515-1560) -C-NO2

4. 1579.37(1690-1640) C-O

5. 1547 (1600,1475) >C=C< (Aromatic)

6 705(690-710) Meta-substituted

Pending work Synthesis of 4-Substituted coumarin

derivative

Characterisation by UV,IR,MASS & NMR

Screening activity

Thesis writing

32

ReferencesS.S. Furniss,A.H.Honnaford, vogel’s Textbook of

Organic Synthesis,5 th edition,1192.O.P.Agrawal, Chemistry of Organic Natural

Product,volume II,goel publishing house,Meerut 2001,627-628,686-715.

Kulkarni G.M., Synthesis and biological activities of some new fluorinated coumarins and 1-aza coumarins, European Journal of Medicinal Chemistry, 20 (2007) 1-11

B.China Raju ,H3P12W40 catalysed efficient synthesis of

4-Substituted coumarin,Indian journal of chemistry vol.48B January 2009,120-123

33

M.V.Kulkarani,G.M.Kulkarani,C.H.Lin,C.M.Sun,Curr.Med.Chem.13(2006)2795-2818

M.V.Kulkarani,B.G.Pujar,V.D.Patil,Arch.Pharm.314(1983)15-23

Majunath Ghate,V.Kulkarani,R.Shobha,S.Y.Kattimani, European journal of medicinal chemistry38(2003)297-302

Imthyaz A.Khan,Manohar V. Kulkarani,Chung-Ming Sun European journal of medicinal chemistry 40(2005)1168-1172

35