Nghiên cứu tổng hợp và tính chất của một số glucopyranosyl thioure có chứa dị vòng pyrimidin tt152644

ĐẠI HỌC QUỐC GIA HÀ NỘI
TRƯỜNG ĐẠI HỌC KHOA HỌC TỰ NHIÊN





NGUYỄN THỊ THANH MAI



NGHIÊN CỨU TỔNG HỢP VÀ TÍNH CHẤT
CỦA MỘT SỐ GLUCOPYRANOSYL THIOURE
CÓ CHỨA DỊ VÒNG PYRIMIDIN





LUẬN ÁN TIẾN SĨ HÓA HỌC







HÀ NỘI – 2010

2

ĐẠI HỌC QUỐC GIA HÀ NỘI
TRƯỜNG ĐẠI HỌC KHOA HỌC TỰ NHIÊN


NGUYỄN THỊ THANH MAI



NGHIÊN CỨU TỔNG HỢP VÀ TÍNH CHẤT
CỦA MỘT SỐ GLUCOPYRANOSYL THIOURE
CÓ CHỨA DỊ VÒNG PYRIMIDIN

Chuyên ngành: Hóa Hữu cơ
Mã số: 62.44.27.01


LUẬN ÁN TIẾN SĨ HÓA HỌC



NGƯỜI HƯỚNG DẪN KHOA HỌC:
PGS. TS.NGUYỄN ĐÌNH THÀNH

HÀ NỘI – 2010




i
MỤC LỤC
MỞ ĐẦU 1
CHƯƠNG 1. TỔNG QUAN 2
1.2. TỔNG QUAN VỀ THIOURE 2
1.2.1. Cấu trúc và các liên kết trong phân tử [46,55] 2
1.2.2. Tính chất của thioure 2
1.2.3. Ứng dụng của thioure 5
1.2.4. Phương pháp điều chế của dẫn xuất thioure 7
1.3. TỔNG QUAN VỀ GLUCOSYL ISOTHIOXYANAT 13
1.3.1. Giới thiệu về glucosyl isothioxyanat 13
1.3.2. Tính chất hoá học của glycosyl isothioxyanat[70,71,83,84] 13
1.3.3. Phương pháp tổng hợp glycosyl isoxyanat và glucosyl isothioxyanat [83,101] 15
1.3. TỔNG QUAN VỀ DỊ VÒNG PYRIMIDIN 17
1.3.1. Tổng hợp vòng pyrimidin 17
1.3.2. Tính chất của pyrimidin [7,9,86,96] 20
1.4. ỨNG DỤNG LÒ VI SÓNG TRONG HOÁ HỌC CACBOHYDRAT [14,56,75,88] 22
1.5 MỐI LIÊN QUAN GIỮA CẤU TRÚC HÓA HỌCVÀTÁC DỤNG SINH HỌC 25
CHƯƠNG 2. THỰC NGHIỆM 30
2.1. TỔNG HỢP MỘT SỐ XETON α,β-KHÔNG NO 32
1. 1,3-Diphenylprop-2-en-1-on (hay benzylidenaxetophenon) (3a1) 33
2. 3-(4’-Fluorophenyl)-1-phenylprop-2-en-1-on [hay (4’-fluorobenzyliden)-axetophenon] (3b1) 33
3. 3-(4’-Clorophenyl)-1-phenylprop-2-en-1-on [hay (4’-clorobenzyliden)-axetophenon] (3c1) 33
4. 3-(3’-Clorophenyl)-1-phenylprop-2-en-1-on [hay (3’-clorobenzyliden)-axetophenon] (3d1) 33
5. 3-(4’-Bromophenyl)-1-phenylprop-2-en-1-on [hay (4’-bromobenzyliden)-axetophenon] (3f1) 33

6. 3-(4’-Metylphenyl)-1-phenylprop-2-en-1-on [hay (4-metylbenzyliden)-axetophenon] (3g1) 33
8. 3-(3’-Metoxyphenyl)-1-phenylprop-2-en-1-on [hay (3’-metoxybenzyl-iden)axetophenon] (3j1) 34
9. 3-(3’,4’-Dioxymetylenphenyl)-1-phenylprop-2-en-1-on [hay (3’,4’-dioxy-
metylenbenzyliden)axetophenon] (3l1) 34
10. 3-(4’-Hydroxyphenyl)-1-phenylprop-2-en-1-on [hay (4’-hydroxy-benzyliden)axetophenon] (3m1)34
11. 3-(3’-Hydroxyphenyl)-1-phenylprop-2-en-1-on [hay (3’-hydroxy-benzyliden)axetophenon] (3n1)34
12. 3-(2’-Hydroxyphenyl)-1-phenylprop-2-en-1-on [hay (2’-hydroxy-benzyliden)axetophenon] (3o1)34
13. 3-[4’-(Dimetylamino)phenyl]-1-phenylprop-2-en-1-on [hay (4’-dimetyl-
aminobenzyliden)axetophenon] (3p1) 34
15. 3-(4’-Clorophenyl)-1-(4-metoxyphenyl)prop-2-en-1-on [hay (4’-cloro-benzyliden)-4-
metoxyaxetophenon] (3c2) 35



ii
16. 3-(3’-Clorophenyl)-1-(4”-metoxyphenyl)prop-2-en-1-on [hay (3’-cloro-benzyliden)-4-
metoxyaxetophenon] (3d2) 35
17. 3-(2’-Clorophenyl)-1-(4”-metoxyphenyl)prop-2-en-1-on [hay (2’-cloro-benzyliden)-4-
metoxyaxetophenon] (3e2) 35
18. 3-(4’-Bromophenyl)-1-(4”-metoxyphenyl)prop-2-en-1-on [hay (4’-brom-obenzyliden)-4-
metoxyaxetophenon] (3f2) 35
19. 1-(4’-Metoxyphenyl)-3-(4”-metylphenyl)prop-2-en-1-on [hay (4’-metylbenzyliden)-4-
metoxyaxetophenon] (3g2) 35
20. 1-(4’-Metoxyphenyl)-3- [4”-(propan-2-yl)phenyl]prop-2-en-1-on [hay (4’-isopropylbenzyliden)-4-
metoxyaxetophenon] (3h2) 35
22. 3-(3’-Metoxyphenyl)-1-(4”-metoxyphenyl)prop-2-en-1-on [hay (3’-metoxybenzyliden)-4-
metoxyaxetophenon] (3j2) 36
23. 3- [4’-(Dimetylamino)phenyl]-1-(4”-metoxyphenyl)prop-2-en-1-on [hay (4’-
dimetylaminobenzyliden)-4-metoxyaxetophenon] (3p2) 36
24. 1-(4’-Bromophenyl)-3-(4”-fluorophenyl)prop-2-en-1-on [hay (4’-fluorobenzyliden)-4-

bromoaxetophenon] (3b3) 36
25. 1-(4’-Bromophenyl)-3-(4”-clorophenyl)prop-2-en-1-on [hay (4’-clorobenzyliden)-4-
bromoaxetophenon] (3c3) 36
26. 1-(4’-Bromophenyl)-3-(3”-clorophenyl)prop-2-en-1-on [hay (3’-clorobenzyliden)-4-
bromoaxetophenon] (3d3) 36
27. 1-(4’-Bromophenyl)-3-(2”-clorophenyl)prop-2-en-1-on [hay (2’-clorobenzyliden)-4-
bromoaxetophenon] (3e3) 36
29. 1-(4’-Bromophenyl)-3-(4”-metylphenyl)prop-2-en-1-on [hay (4-metylbenzyliden)4-
bromoaxetophenon] (3g3) 37
30. 1-(4’-Bromophenyl)-3- [4”-(propan-2-yl)phenyl]prop-2-en-1-on [hay (4’-isopropylbenzyliden)-4-
bromoaxetophenon] (3h3) 37
31. 1-(4’-Bromophenyl)-3-(4”-metoxyphenyl)prop-2-en-1-on [hay (4’-metoxybenzyliden)-4-
bromoaxetophenon] (3i3) 37
32. 1-(4’-Bromophenyl)-3-(3”-metoxyphenyl)prop-2-en-1-on [hay (3’-metoxybenzyliden)-4-
bromoaxetophenon] (3j3) 37
33. 1-(4’-Bromophenyl)-3-(2”-metoxyphenyl)prop-2-en-1-on [hay (2’-metoxybenzyliden)-4-
bromoaxetophenon] (3k3) 37
34. 1-(4’-Bromophenyl)-3- [4”-(dimetylamino)phenyl]prop-2-en-1-on [hay (4’-
dimetylaminobenzyliden)-4-bromoaxetophenon] (3p3) 37
A-Phương pháp đun hồi lưu truyền thống (QTA1) 37
B-Phương pháp sử dụng lò vi sóng (QTA2) 38
1. 2-Amino-4,6-diphenylpyrimidin (4a1) 39
2. 2-Amino-4-phenyl-6-(4”-fluorophenyl)pyrimidin (4b1). 39



iii
3. 2-Amino-4-phenyl-6-(4”-clorophenyl)pyrimidin (4c1). 39
4. 2-Amino-4-phenyl-6-(3”-clorophenyl)pyrimidin (4d1) 39
5. 2-Amino-4-phenyl-6-(4”-bromophenyl)pyrimidin (4f1) 39

7. 2-Amino-4-phenyl-6-(4”-metoxyphenyl)pyrimidin (4i1) 40
8. 2-Amino-4-phenyl-6-(3”-metoxyphenyl)pyrimidin (4j1) 40
9. 2-Amino-4-phenyl-6-(3”,4”-dioxymetylenphenyl)pyrimidin (4l1) 40
10. 2-Amino-4-phenyl-6-(4”-hydroxyphenyl)pyrimidin (4m1) 40
11. 2-Amino-4-phenyl-6-(3”-hydroxyphenyl)pyrimidin (4n1) 40
13. 2-Amino-4-phenyl-6-(4”-dimetylaminophenyl)pyrimidin (4p1) 41
14. 2-Amino-4-(4’-metoxyphenyl)-6-(4”- fluorophenyl)-pyrimidin (4b2) 41
15. 2-Amino-4-(4’-metoxyphenyl)-6-(4”-clorophenyl)pyrimidin (4c2) 41
16. 2-Amino-4-(4’-metoxyphenyl)-6-(3”-clorophenyl)-pyrimidin (4d2) 41
17. 2-Amino-4-(4’-metoxyphenyl)-6-(2”-clorophenyl)-pyrimidin (4e2) 41
19. 2-Amino-4-(4’-metoxyphenyl)-6-(4”-metylphenyl)-pyrimidin (4g2) 42
20. 2-Amino-4-(4’-metoxyphenyl)-6-(4”- isopropylphenyl)-pyrimidin (4h2) 42
21. 2-Amino-4,6-bis(4’-metoxyphenyl)pyrimidin (4i2) 42
22. 2-Amino-4-(4’-metoxyphenyl)-6-(3”-metoxyphenyl)-pyrimidin (4j2) 42
23. 2-Amino-4-(4’-metoxyphenyl)-6-(4”-dimetylaminophenyl)pyrimidin (4p2) 42
24. 2-Amino-4-(4’-bromophenyl)-6-(4”-fluorophenyl)pyrimidin (4b3) 42
26. 2-Amino-4-(4’-bromophenyl)-6-(3”-clorophenyl)pyrimidin (4d3) 43
27. 2-Amino-4-(4’-bromophenyl)-6-(2”-clorophenyl)pyrimidin (4e3) 43
28. 2-Amino-4,6-bis(4’-bromophenyl)pyrimidin (4f3) 43
29. 2-Amino-4-(4’-bromophenyl)-6-(4”-metylphenyl)-pyrimidin (4g3) 43
30. 2-Amino-4-(4’-bromophenyl)-6-(4”-isopropylphenyl)-pyrimidin (4h3) 43
31. 2-Amino-4-(4’-bromophenyl)-6-(4”-metoxyphenyl)-pyrimidin (4i3) 43
33. 2-Amino-4-(4’-bromophenyl)-6-(2”-metoxyphenyl)-pyrimidin (4k3) 44
34. 2-Amino-4-(4’-bromophenyl)-6-(4”-dimetylaminophenyl)-pyrimidin (4p3) 44
35. 2-Amino-4-(4’-isopropylphenyl)-6-phenylpyrimidin (Phản ứng ‘one-pot’ từ 3 cấu tử) (4h1) 44
2.3. TỔNG HỢP N-(2,3,4,6-TETRA-O-AXETYL-β-D-GLUCO-PYRANOSYL)-N’-(4’,6’-
DIARYLPYRIMIDIN-2’-YL)THIOURE 44
A-Phương pháp đun hồi lưu 44
B-Phương pháp không dung môi trong lò vi sóng 44
1. N-(2,3,4,6-Tetra-O-axetyl-


-D-glucopyranosyl)-N’-(4’,6’-diphenylpyrimidin-2’-yl)thioure (6a1) 45
2. N-(2,3,4,6-tetra-O-axetyl-

-D-glucopyranosyl-N’-[4’-phenyl-6’-(4”’-flurophenyl)pyrimidin-2’-
yl]thioure (6b1) 45
3. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-[4’-phenyl-6’-(4”’-clorophenyl)pyrimidin-2’-
yl]thioure (6c1) 45



iv
4. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-[4’-phenyl-6’-(3”’-clorophenyl) pyrimidin-2’-
yl]thioure (6d1) 45
5. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-[4’-phenyl-6’-(4”’-bromophenyl)pyrimidin-2’-
yl]thioure(6f1) 45
6. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-[4’-phenyl-6’-(4”’-metylphenyl)pyrimidin-2’-
yl]thioure (6g1) 45
7. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-[4’-phenyl-6’-(4”’-isopropylphenyl)pyrimidin-2’-
yl]thioure (6h1) 46

8. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-[4’-phenyl-6’-(-4”’-metoxyphenyl) pyrimidin-2’-
yl]thioure (6i1) 46
9. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-[4’-phenyl-6’-(3”’- metoxyphenyl)pyrimidin-2’-
yl]thioure (6j1) 46
10. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-phenyl-6’-(2”’-hydroxyphenyl)pyrimidin-
2’-yl]thioure (6o1) 46
11. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(4”-metoxyphenyl) - 6’-(4”’-
fluorophenyl)pyrimidin-2’-yl]thioure (6b2) 46
12. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(4”-metoxyphenyl)- 6’-(4’”-
clorophenyl)pyrimidin-2’-yl]thioure (6c2) 46
13. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(4”-metoxyphenyl)- 6’-(3’”-
clorophenyl)pyrimidin-2’-yl]thioure (6d2) 47
14. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-[4’-(4”-metoxyphenyl)- 6’-(2’”-
clorophenyl)pyrimidin-2’-yl]thioure (6e2) 47
15. N-(2,3,4,6-Tetra-O-axetyl-


-D-glucopyranosyl)-N’- [4’-(4”-metoxyphenyl) -6’-(4’”-
bromophenyl)pyrimidin-2’-yl]thioure (6f2) 47
16. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(4”-metoxyphenyl)- 6’-(4’”-
metyphenyl)pyrimidin-2’-yl]thioure (6g2) 47
17. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-[4’-(4”-metoxyphenyl)-6’-(4’”-isopropyl-
phenyl)pyrimidin-2’-yl]thioure (6h2) 47
18. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’,6’-bis(4”-metoxy-phenyl)pyrimidin-2’-
yl]thioure (6i2) 47
20. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-[4’-(4”-metoxyphenyl) 6’-(4’”-dimetylamino-
phenyl)pyrimidin-2’-yl]thioure (6p2) 48
21. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-[4’-(4”-bromophenyl)-6’-(4’”-
fluorophenyl)pyrimidin-2’-yl]thioure (6b3) 48
22. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(4”-bromophenyl)-6’-(4’”-
clorophenyl)pyrimidin-2’-yl]thioure (6c3) 48



v

23. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(4”-bromophenyl) -6’-(3’”-
clorophenyl)pyrimidin-2’-yl]thioure (6d3) 48
25. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’,6’-bis(4”-bromo-phenyl)pyrimidin-2’-
yl]thioure (6f3) 49
26. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(4”-bromophenyl) -6’-(4’”-
metylphenyl)pyrimidin-2’-yl]thioure (6g3) 49
27. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(4”-bromophenyl) -6’-(4’”-
isopropylphenyl)pyrimidin-2’-yl]thioure (6h3) 49
29. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(4”-bromophenyl) -6’-(3’”-
metoxyphenyl)pyrimidin-2’-yl]thioure (6j3) 49
2.4. DEAXETYL HÓA CÁC DẪN XUẤT N-(2,3,4,6-TETRA-O-AXETYL-β-D-GLUOPYRANOSYL)-
N’-(4’,6’-DIARYLPYRIMIDIN-2’-YL)THIOURE 50
2.4.1. Hoạt hoá nhựa trao đổi ion Wofatit KPS 50
2.4.2. Deaxetyl hoá một số dẫn xuất N-(2,3,4,6-tetra-O-axetyl-

-D-glucoyranosyl)-N’-(4’,6’-
diarylpyrimidin-2’-yl)thioure 50
1. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’-(4’,6’-diphenyl-pyrimidin-2’-yl)thioure (7a1) 50

3. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(3”-clorophenyl)-6’-phenylpyrimidin-2’-
yl]thioure (7d1) 51
4. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(4-bromophenyl)-6’-phenylpyrimidin-2’-
yl]thioure (7f1) 51
5. N-(2,3,4,6-Tetra-O-axetyl-

-D-glucopyranosyl)-N’- [4’-(-4”-metoxyphenyl) -6’-phenylpyrimidin-2’-
yl]thioure (7i1) 51
2.5. TỔNG HỢP 2-IMINOTHIAZOLIDIN-4-ON 51
1. (Z)-2- [4”- phenyl-6’’-(4’”-Fluorophenyl)pyrimidin]-2”-ylimino)-3-(2’,3’,4’, 6’-tetra-O-axetyl-β-D-
glucopyranosyl)thiazolidin-4-on (8b1) và (Z)-3- [4”-(4’”-fluorophenyl)-6”-phenylpyrimidin]-2”-yl)-2-
(2’,3’,4’,6’-tetra-O-axetyl-β-D-glucopyranosyl-1’-imino)thiazolidin-4-on (8b1 và 8’b1) 51
5. (Z)-2-[4”-phenyl-6”-(2’”’-Hydroxyphenyl)pyrimidin]-2”-ylimino)-3-(2’,3’, 4’,6’-tetra-O-axetyl-β-D-
gluco-pyranosyl)thiazolidin-4-on và (Z)-3-[4”-(2’”-hydroxyphenyl)-6”-phenylpyrimidin]-2”-yl)-3-
(2’,3’,4’,6’-tetra-O-axetyl-β-D-gluco-pyranosyl-1’-imino)thiazolidin-4-on (8o1 và 8’o1) 52
8. (Z)-2-[4”-(4’”- bromophenyl)-6”-(4””-Dimetylaminophenyl) 53
pyrimidin]-2”-ylimino)-3-(2’,3’,4’,6’-tetra-O-axetyl-β-D-gluco-pyranosyl)thiazolidin-4-on và (Z)-3- [4”-
(4’”-dimetylaminophenyl)-6”-(4””-bromophenyl)pyrimidin]-2”-ylimino)-3-(2’,3’,4’,6’-tetra-O-axetyl-β-
D-gluco-pyranosyl)thiazolidin-4-on (8p3 và 8’p3) 53
2.6. HOẠT TÍNH SINH HỌC CỦA DẪN XUẤT 2-AMINO-4,6-DIARYLPYRIMIDIN VÀ CÁC HỢP
CHẤT THIOURE TƯƠNG ỨNG 53
2.6.1. Các chủng khuẩn và nấm dùng thử nghiệm. 53
2.6.3. Phương pháp thử 54
1. Nguyên tắc 54

vi
Chương 3. KẾT QUẢ VÀ THẢO LUẬN 55
3.1. TỔNG HỢP CÁC XETON α,β-KHÔNG NO 55
3.2. TỔNG HỢP CÁC 2-AMINO-4,6-DIARYLPYRIMIDIN………………………………………… 58
3.2.2. Phổ IR 71
3.2.3. Phổ
1
H-NMR 71
3.2.3. Phổ MS 75
3.3 TỔNG HỢP CÁC N-(2,3,4,6-TETRA-O-AXETYL--D-GLUCOPYRANOSYL)-N’-(4’,6’-
DIARYLPYRIMIDIN-2’-YL)THIOURE 77
3.3.1. Tổng hợp N-(2,3,4,6-tetra-O-axetyl-

-D-glucopyranosyl)-N’-(4’,6’-diarylpyrimidin-2’-
yl)thioure. 77
3.3.2. Phổ IR 78
3.3.3. Phổ NMR 83
3.3.4. Phổ MS 105
3.4. VỀ PHẢN ỨNG DEAXETYL HÓA MỘT SỐ HỢP CHẤT N-(2,3,4,6-TETRA-O-β-D-
GLUCOPYRANOSYL)-N’-(4’,6’-DIARYLPYRIMIDIN-2’-YL)THIOURE 110
3.5. VỀ TỔNG HỢP MỘT SỐ DẪN XUẤT 2-IMINOTHIAZOLIDIN-4-ON 112
3.6. HOẠT TÍNH SINH HỌC CỦA DẪN XUẤT 2-AMINO-4,6-DIARYLPYRIMIDIN VÀ CÁC HỢP
CHẤT THIOURE TƯƠNG ỨNG 132
KẾT LUẬN……………………………………………………………………………………………… 139
DANH MỤC CÁC CÔNG TRÌNH LIÊN QUAN ĐẾN LUẬN ÁN…………………………………….140
TÀI LIỆU THAM KHẢO 142