VIETNAM NATIONAL UNIVERSITY, HANOI HANOI UNIVERSITY OF SCIENCE FALCUTY OF CHEMISTRY ORGANIC CHEMISTRY DEPARTMENT

INITIAL SYNTHESIS OF SOME 4-COUMARIN-3(2,3,4,6-TETRA-O-ACETYL--D-GLUCOPYRANOSYL)2-[(4-SUBSTITUTED PHENYL METHYLENE)HYDRAZONO]-2,3-DIHIDROTHIAZOLES

Supervisor: Assoc.Prof. Nguyen Dinh Thanh M.Sc. Vu Ngoc Toan Student: Hoang Thi Thuy

Content
Introduction Experimental and discussion

Conclusion

Introduction
Thiosemicarbazone of carbohydrate, with glycozide groups, has variable biological activities such as anti-cancer, antivirus, anti-bacteria, protecting metal from corrosion

Thiazoles is the inhibitor of virus protease under clinical studies for the treatment of some infections

Derivatives of thiosemicarbazones and thiazoles have incredibly biological activities through glycozide radicals

Introduction

Synthesize 3-(-bromoacetyl) coumarin by SR reaction. Some thiosemicarbazones were synthesized using microwaveassisted method. The necessary time for reaction is just 5-10 minutes with the yields about 70-85%.

Studied on the initial synthesis of 4-coumarin-3-(4-(2,3,4,6-tetra-Oacetyl--D-glucopyranosyl)-2-[(4-substituted phenylmethylene) hydrazon]-2,3-dihidro-thiazoles.

Experimental and Discussion

1. Synthesis of 3-(-bromoacetyl) coumarin

2. Synthesis of (2,3,4,6-tetra-O-acetyl--D-glucopyranosyl) thiosemicarbazide 3. Synthesis of some substituted benzaldehyde (2,3,4,6-tetra-Oacetyl--D-glucopyranosyl) thiosemicarbazones 4. Synthesis some compounds derived from 4-(2,3,4,6-tetra-Oacetyl--D-glucopyranosyl)thiosemicarbazone and substituted 3-(-bromoacetyl) coumarin

Reaction Schemes

3-acetyl coumarin

3-(-bromoacetyl)coumarin

salicylaldehyde

MW oven 2,3,4,6-tetra-O-acetyl--Dglucopyranosyl isothiocyanate 2,3,4,6-tetra-O-acetyl--D-glucopyranosyl thiosemicarbazide Substituted benzaldehyde (2,3,4,6tetra-O-acetyl--D-glucopyranosyl) thiosemicarbazones

Substituted benzaldehyde (2,3,4,6-tetra-O-acetyl--Dglucopyranosyl) thiosemicarbazones

Ethanol/chloroform

3-(-bromoacetyl) coumarin

4-coumarin-3-(4-(2,3,4,6-tetra-O-acetyl--D-glucopyranosyl)2-[(4-substituted phenylmethylene)hydrazon]-2,3-dihidro-thiazoles

Synthesis of 3-(-bromoacetyl)coumarin

-Reflux for 3-4 hours.

-SR reaction
- Remove the solvent at reduced pressure. - Recrystallized by ethanol/chloroform. - Yield: 60-75%. - Melting point 162-165oC - Structure of product: IR.

IR SPECTRA OF 3-ACETYL COUMARIN AND 3(-BROMO ACETYL) COUMARIN

C=O

C=O

Synthesis of 2,3,4,6-tetra-O-acetyl--D-glucopyranosyl thiosemicarbazide

OAc AcO AcO O NCS OAc N2H4.H2O AcO AcO

OAc O NHCSNHNH OAc

2

CH2Cl2

- Reaction temperature: 10-15oC. - Remove the solvent at reduced pressure. - Wash by ethanol.

- Yield: 60-70%.
- Melting point 156-157oC - Structure of product: IR, 1H-NMR spectra.

IR SPECTRA OF THIOSEMICARBAZIDE
105 100

95

90

3322

75

2987

80

%T

3129

70

NH
1355

1437

85

65

OAc AcO AcO O OAc

3000

60

C=O
1752 1242

1043

912

55

NH C NH NH2
S
2000 Wavenumbers (cm-1)

50 4000

C=S

1532

C-O-C

1000

Compare IR Spectra of isothiocyanate and thiosemicarbazide derivatives

1 20 1 10

1 00

90

1319

70

N=C=S
2079 1381 1104

1146

%T

60

OAc

50

40

NH = 3129; 3322 cm-1

30 4 00 0

3 00 0

NCS = 2079 cm-1

2 00 0

1747

1240

1 00 0

Wa ven umb ers (cm-1)

1 05

1 00

95

90

3322

1038

75

OAc AcO AcO

70

2987

80

%T

3129

1355

O NH OAc
C S
2 00 0 Wa ven umb ers (cm-1)

1437

85

65

NH

60

NH2
1532

55

50 4 00 0 3 00 0

1752

1242

1 00 0

1043

912

916

605

80

AcO AcO

1428

987

414

Compared IR Spectra of isothiocianate OAc thiosemicarcazide derivatives

547

Synthesis of some substituted benzaldehyde 4-(2,3,4,6-tetra-Oacetyl--D-glucopyranosyl) thiosemicarbazones

R = H ; p- Cl ; p- OCH3 ; p- CH3

-Use microwave.

-Reaction time: 5-7 min.

- Acetic acid: catalyst. - Recrystallized by ethanol. - High yield. -Products: pure

Table 1. Yields, melting points and IR Spectrums of substituted benzaldehyde 4-(2,3,4,6-tetra-O-acetyl--D-glucopyranosyl) thiosemicarbazones
Spectra IR (cm1) N0 R T.f,C Yield, %
NH CH=N C=O ester COC ester C=S

p-CH3

215-216

81

3327

1608

1746

1227;1040

1356

183-184

73

3322

1632

1750

1227;1039

1355

p-Cl

209-210

79

3299

1625

1747

1227;1044

1355

p-OCH3

215-216

78

3311

1605

1746

1231;1039

1360

IR spectrum of 3-acetyl-6-bromocoumarin (2,3,4,6-tetra-Oacetyl--D-glucopyranosyl) thiosemicarbazone

C-O-C

C=O NH

N0

TC

Yield, %

Spectra IR (cm1)

NH

CH=N

C=O ester

COC ester

p-Cl

209-210

79

3299

1625

1747

1227;1044

Synthesis of some 4-coumarin-3-(4-(2,3,4,6-tetra-O-acetyl--D-glucopyranosyl) -2-[(4-substituted phenylmethylene)hydrazon]-2,3-dihidro-thiazoles

-Reflux 2-4 hours.

R = H ; p- Cl ; p- OCH3 ; p- CH3

-Chloroform/ethanol (2:1): solvent.

- Sodium acetate: catalyst. - Recrystallized by chloroform. -Low yield

C-O-C

C=O
C=N

Table 2. Yields,Melting points and IR spectrum 4-coumarin-3-(4-(2,3,4,6tetra-O-acetyl--D-glucopyranosyl)-2-[(4-substituted phenylmethylene) hydrazon]-2,3-dihidro-thiazoles

Spectra IR (cm1) N0 R T.f,C Yield, %

NH CH=N C=O ester COC ester C=S

p-CH3

280-285

35

3327

1608

1746

1227;1044

1355

265-270

40

3322

1632

1750

1227;1039

1360

p-Cl

287-290

45

3299

1625

1747

1227;1044

1357

p-OCH3

2273-275

35

3311

1605

1746

1231;1039

1355

CONCLUSION
3-(-bromoacetyl) coumarin have been successfully synthesized. 2,3,4,6-tetra-O-acetyl--D-glucopyranosyl thiosemicacbazide have been synthesized from 2,3,4,6-tetra-O-acetyl--D-glucosepyranosyl isothiocyanate. Some substituted benzaldehyde 4-(2,3,4,6-tetra-O-acetyl--Dglucopyranosyl) thiosemicarbazones have been synthesized from 2,3,4,6tetra-O-acetyl--D-glucosepyranosyl thiosemicarbazide. Some of 4-coumarin-3-(4-(2,3,4,6-tetra-O-acetyl--D-glucopyranosyl)-2[(4-substituted phenylmethylene) hydrazon]-2,3-dihidro-thiazoles have been synthesized by using the condensation reaction between substituted benzaldehyde 4-(2,3,4,6-tetra-O-acetyl--D-glucopyranosyl) thiosemicarbazones and 3-(-bromoacetyl)coumarin derivatives in solvent of ethanol/chloroform. The last step procedure is still investigated in lab.

Thanks for your attention!