INTRODUCTION
1. The necessity of the study
Heterocyclic chemistry plays a very important role in organic chemistry. Currently, the
increase in the number of organic compounds is mainly due to heterocyclic compounds. Researches on
heterocyclic compounds synthesized from natural compounds in plant essential oils have attracted
much attention of scientists. These heterocyclic compounds have both specific structural parts of
natural compounds and new structural components. Therefore, they could be highly bioactive, and
could be applied in pharmacy and medicine.
Furoxan heterocyclic compounds (1,2,5-oxadiazole-2-oxide) have NO-releasing properties
when they enter the human body. NO molecules have effects on the nervous system that controls blood
vessel elasticity. Therefore, they are promising in treatment of cardiovascular diseases. Currently,
several compounds that can release NO, including either monocyclic compounds or heterocyclic
compounds associated with the furoxan ring, have been used in clinical trials such as NO-aspirin, NOsteroid and NO-ursodeoxycholic acid.
Compounds containing quinoline heterocycle have a wide range of bioactive activities. Many
of those have been used as antibiotics, antibacterial drugs, antimalarial drugs, and some other
derivatives have been used as anti-tuberculosis drugs. Moreover, quinoline-containing compounds also
have many applications in analytical chemistry metal analysis by photometric and fluorescent methods.
Quinazoline and quinazolinone compounds have gained many attentions in medicine due to
their wide range of biological activities. Numerous quinazoline- and quinazolinone-contaning
compounds have antihypertensive, anti-inflammatory, anti-HIV, antiviral and anticancer activity due to
their inhibitory effects on thymidylate synthase, poly- (ADP-ribose) polymerase (PARP) and thyrosine
kinase. Currently, some antihypertensive drugs such as (1- (4-Amino-6,7-dimethoxy-2-quinazolinyl) 4- (1,4-benzodioxan-2-ylcarbonyl) -piperazine monomethane-sul fonate with brand name
doaosinemesylate), obesity medication such as ((RS) -dimethoxy-2- [4- (tetra hydrofuran-2-ylcarbonyl)
piperazin-1-yl] -quinazolin-4-amine brand name terazosine) and blood pressure medication, such as (
2-[4- (2-furoyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine with the commercial name prazosin)
having a quinazoline structure have been brought to market.
The previous furoxan, quinoline, and quinazoline heterocyclic compounds were mostly
synthesized from products of the chemical industry, mainly from petrochemical technology. The
synthesis of those heterocyclic compounds from plant essential oil resources, which are renewable
materials, is consistent with the green chemistry. Current research directions still attract a little
attention, therefore, the studies on heterocyclic compounds synthesized from plant essential oils are

- Providing accurate data sources on IR, NMR, MS spectra of complex heterocyclic compounds for
scientific research and chemistry teaching.
- Several synthetic quinazoline compounds have shown high cytotoxicity. Their structures help guide
the search for more active compounds.
5. New contributions of the study
5.1. Synthesis:
* Starting from eugenol in basil essential oil, a total of 64 new compounds have been synthesized
corresponding to 5 series of compounds including: Chain of compounds containing heterocyclic
furoxan (A series, 18 substances), series of compounds containing both furoxan and quinoline
heterocyclic rings (series B, 18 substances), series containing quinazoline heterocyclic ring (range D,
12 substances), Chain of compounds containing heterogeneous quinoline ring group (range E, 8
substances), the compound sequence which are derivative of quinoline-5,6-dione (G series, 8
substances).
* Some abnormal reactions have been investigated whose reaction mechanisms were proposed, leading
to a new synthesis method. They are: Synthesis of quinazoline ring (compound D1) by transforming


furoxan ring and acetamido group at the positions 1 and 2 of the benzene ring; Creation a carbonyl
ketone group (compound D2) by reducing the nitro group at the same position at the branch;
Preparation of diazo compound G8 by reaction in the reversed order of normal diazoni salt preparation.
5.2. Structural study:
* The structures of 64 new compounds have been determined by combining IR, 1H NMR, 13C NMR,
HMBC, NOESY, X-RAY and MS spectra.
* Identify the structures and explain the formation of many new and unexpected compounds obtained
from unprecedented reactions, namely: 4- (1-chloro-1-nitroethyl-6,7-dimethoxy-2-methylquinazoline
(D1); 5,6-dimethoxy-2-methyl-3-H-indole-3-one (D4) from the hydrolysis reaction of D1; isoquinoline
D12 compound from quinazoline D2 compound; magnetic??? G3 compound additive
thiosemicarbazide reaction to quinolin-5,6-dione G0; molecular complexes G6 and G7 from diamine
reaction with G0; diazo G8 compound from reaction of diazoni salt with amine.
5.3. Bioactive tests: The micro-antibiotic activity of some new compounds was moderate and weak.

3.1.1. Synthesis of A-range compounds
a. Synthetics scheme:
Comment [H1]: acetonitrile

Scheme 3.1. Summary scheme of range A compounds


b. Synthesis
Microwave oven were used to perform the reactions: radiate the reaction mixtures with microwave for
1 minute each time, use TLC to monitor the reactions, and repeat the radiation. After every 2 minutes, check the
TLC until all the starting materials have been consumed, then stopped the reactions. Spectral analysis showed
that the products had the expected structures.
A15 compound: The reaction of Ao with maleic anhydride was performed in ethanol in the presence
of concentrated H2SO4 as catalyst. The progress of the reaction was monitored by TLC which shown that the
amount of product increased gradually. After 8 h, there were no starting materials. Let the reaction mixture cool
down to room temperature. The desired product was obtained as yellow needles,
The double bond in A15 has trans configuration which is different from the original cis configuration
of maleic anhydride. This can be explained as followed: the carbonium cation rotates freely around the single
bond, which helps the acylium ion to have a more stable trans configuration and it is more convenient to attack
the NH2 group right next to the bulky furoxan group of A0.
We expected the A15 amide reaction mechanism to be as follows:

Scheme 3.2. Mechanism of the reaction that produced amide A15
A16-A18 compounds: For succinic anhydride, there was no product formed when the reaction was carried out
in ethanol or pyridine solvents. Therefore, PhOMe was used instead of ethanol that allowed to increase the
reaction temperature. The results showed that when the reaction was conducted at 120°C for 5 h, the product was
amide A16, and when the reaction was conducted at 140°C, a mixture of two imide isomers of position N → O,
when a reaction of 120 °C for 7 h, the product was imide and the N → O group was not isomerized to the A17
position. The causes of the formation of imides and amides from A0 and succinic anhydride are explained in the
following scheme:

Ethanol
Dioxane
Dioxane : water
1:1
Ethanol: water
1:1

A9
A10

A12
A13
A14

Ethanol

A15

Ethanol

A16

Ethanol

A17

Ethanol

A18



Colour and shape

Small yellowish brown
crystals
Orange-yellow crystals
orange red crystals
Yellow needle-shaped
crystals
Yellow needle shaped
crystals
white needle-shaped
crystals
Brown needle shaped
crystals
Brown needle shaped
crystals

Yield
%

210 - 211

85

195 - 196

81

200 - 201


82

195- 196
191-192

80
80

185-186

80

178-179

74

168-169

54

173-174

65

166-169

60

Analyzed spectrum

IR spectrum of A1-A18 are given in tables 3.3, 3.9 and 3.11 of the thesis.1H NMR spectra data of A1-A18
substances are summarized in Table 3.2.
Table 3.2. 1H NMR spectral data of A1-A18 substances
H3
H6
6.81 s
6.50 s

H7a
H7b
3.75 s
3.67 s

H10
OH/NH(H11)
2.17 s
5.34 s

H12
H13
-

A1

7.37 s
7.81 s

4.03 s
3.92 s


7.88d;
J=9
6.70
dd;J=2.0;7

H16
H17
7.50 t;J=7.5
7.66 t;
J = 7.5
7.31 d;
J=8.0
2.61 s

H18
-

8.69 d
J = 8.5

-


A3

7.26 s
7.63 s

3.99 s
3.91 s

6.75 d J=8.5

7.62 d (che)
7.65 d (che)

8.19 d
J=8.0

6.94 dJ=8.5

7.22 d
J = 1.5; 8.0
-

7.30 d;
J = 1.5
2.02 s

-

2.01 s
10.74 s

7.1 d;J = 9

7.42 d;J =
2.5;9.5
-

7.30 d;

7.98 dd
J=7.0; 2
-

8.01 s

2.50

A8

7.25 s
7.47 s

3.91 s
3.90 s

1.96 s
-

7.63 dJ=8.5
6.82 dJ=8.5

6.82 d J=8.5

7.63 dJ=8.5
3.04 s

-

A9

8.40 s

7.76 dJ=9.0
6.72 d J=7.5

-

8.72 s
7.57 dd
J=8;3.5

9.14 d
J=8.5

A11

7.22 s
7.46 s

3.88 s
3.90 s

1.96 s
-

7.93 s
-

6.48 s


3.83 s

2.07 s
8.79 s

8.32 d J=1.5

-

7.26d;J=9.0
7.97 dd
J =2.0;9.0

-

A14

7.15 s
7.18 s

3.99 s
3.91 s

2.08 s
8.77 s

8.15 dd
J=3.0;1.0

7.43 dd

7.08 s
7.31 s

3.84 s
3.73 s
3.85 s
3.82 s

2.80 m
3.01 m
2.73 m
2.73 m

-

-

-

-

-

6.89 s
6.33 s

3.67 s
3.66 s

2.30 s

to the phenyl group.
In A0, the chemical shift of the C4 is smaller than that of the C6 but in the azo compounds, the
opposite was found. This is due not only to the different electronic effects of the NH2 and –N = N- groups, but
also to the bulky azo component that caused the furoxan ring to be perpendicular to the plane of the benzene ring
which makes the effect of the +C effect of furoxan to the C4 position of the azo compound is no longer the same
as in A0.
In the 1H NMR spectrum of the amide A15, synthesized from A0 and maleic anhydride, there are two
doublets with splitting constants of JH12,H13 = 12.0 Hz, showing that the acrylamito group has trans configuration
which differs from the original cis configuration of maleic anhydride.
- The 13C NMR spectroscopic data of the series A are given in the tables 3.5, 3.6 and 3.13. All the spectroscopic
data were in accordance with the expected structures of the synthesized compounds.
- The ESI MS spectra of the four compounds A1, A4, A5 and A6 give pseudo-molecular peaks suitable for
calculated molecule weights.
3.2. SYNTHESIS AND STRUCTURAL STUDY OF THE SERIES B
3.2.1. Summary of the compounds in series B
a. General scheme:

Scheme 3.4. Synthetic scheme of the series B
b. Synthesis
The quinoline B1 was synthesized from A0 following the Döebner – Miler method. The procedure
was improved from the traditional method as follows: the reaction was performed in toluene – HCl
heterogeneous system in which the actetaldehyde was replaced with paraldehyde. The desired product B1 was


obtained with 85% yield as white crystals. B1 is insoluble in water but well soluble in common organic solvents.
This is an important key substance, opening up a diverse synthesis of the derivatives containing both furoxan and
quinoline heterocycles.
The mechanism of the Döebner – Miler reaction is as follows: Paraldehyde is the trimer of
acetaldehyde. In acidic medium, paraldehyde is gradually decomposed into acetaldehyde which underwent the
aldol condensation to yield crotonaldehyde. Crotonaldehyde then took part in the reaction with amine and was

Toluene

B10

Toluene

B11
B12
B13

Toluene
Ethanol
Ethanol

B14

Ethanol

B15
B16
B17
B18

Ethanol
Ethanol
Ethanol
Ethanol

Melting
temperature

71
78
80
75
68

224

70

Dark yellow needle-shaped crystals
Light yellow needle-shaped crystals
Light yellow needle-shaped crystals
Light yellow needle-shaped crystals

220
230-231
202

60
80
80

217-218

80

Light yellow needle-shaped crystals
Light yellow needle-shaped crystals
Light yellow needle-shaped crystals

IR, 1H , 13C
IR, 1H , 13C, HMBC, HSQC,
MS
IR, 1H, 13C
IR, 1H, 13C
IR, 1H, 13C
IR, 1H, 13C

3.2.2. Structure of compounds in series B
- Main IR absorption bands of B1-B18 are given in tables 3.17, 3.20 and 3.24. The IR spectrum of B1 no longer
has absorption band of the NH2 group. The IR spectrum of B2 has the absorption band of the aldehyde carbonyl
group, substances B3 - B7 have the typical absorption bands for the acid and ester C = O groups (C = O ester >
C = O acid), the α, β-unsaturated ketones B12 - B18 have absorption band for C = O group in conjugation with
the C = C ethylenic group


- The 1H NMR spectrum of B1 has three downfield protons with chemical shift greater than 7.0 ppm, while in
amine A0 there are only two aromatic protons in the benzene ring with smaller chemical shifts. The upfield
range in the spectrum of B1 differs from that in A0 which has an additional signal with an intensity of 3H at δ=
2.61 ppm, proving that the ring reaction according to Doebner - Miller method has occurred, affording 2methylquinoline.
- The 1H NMR spectrum of B2 has the signal integrating for one hydrogen of the aldehyde proton at =10.01
ppm and no longer has the proton signal at = 2.61 ppm with the intensity of three protons.
Table 3.4. 1H NMR signal of compounds B1 - B7; δ, ppm; J, Hz
Compound

X
2a

B1



H14
H15

H16
H17

8.05 d;J=9.0
8.18 s

8.74 d; J=8.5
2.11 s

4.09 s
4.05 s

10.01 s
-

-

-

8.19 d;J=9.0
8.14 s

8.70 d;J=9.0
2.14 s

4.09 s


B5

13 14
2a OCH
2CH3
C
O

8.18 d;J=9.0
8.15 s

8.74 d;J=9.0
2.16 s

4.08 s
4.05 s

4.39 m

1.34 t
-

-

B6

13 14 15 16
2a OCH
2CH2CH2CH3

8.17 d;J=9.0
8.15 s

8.72 d;J=9.0
2.13 s

4.08 s
4.05 s

4.37 t

1.62 m
1.75 m

0.93 m
0.93 m

- The 1H NMR spectra of the alkenes from B8 to B11 showed that in the sp2 range, the number of protons is not
three as in the key substance B1 but at least 3 more protons appear, in which two peaks with coupling constants
of 15 - 16,5 Hz corresponding to a trans C-C double bond.
Table 3.5. 1H NMR signal of compounds B8 - B11; δ, ppm; J, Hz
H3
H7
7.50 d;J=8.5
7.92 s

H4
H12a
8.42 dJ=9.0
2.06 s

4.08 s
4.06 s

7.62 dJ=16
7.80 dJ=16.5

8.24 d J=9.0
7.98 d J=9.0

7.98 d J=9.0

8.24 dJ=9.0
-

B9

8.00 d; J=9.0
7.97 s

8.56 dJ=9.0
2.12 s

4.07 s
4.05 s

7.60d J=16.5
7.82d J=16.5

8.50 t J=1.5
-

B11

8.01 d; J=9.0
7.98 s

8.56 dJ=8.5
2.10 s

4.04 s
4.03 s

7.62d J=16.5
7.77d J=16.5

8.00 d J=2.0
-(3.98 s)

-

7.89 d J=2.0
2.35 s

KH
B1

X


- The 1H NMR spectra of the compounds from B12 - B18 showed no signal of the aldehyde proton (typically at
about 10 ppm), and there were 10 signals of aromatic protons in accordance with the number of aromatic protons

-

H14/
H18
-

H15/
H17
-

B12

8.30 d;J=8.5
8.05 s

8.61 d;J=9.0
2.08 s

4.06 s
4.05 s

7.69 d J=15.5
8.22 d J=16

8.14 d
J=9.0

7.12 d
J=8.5



4.06 s
4.05 s

7.43 d; J = 16
8.21 d;J =16

8.12 d;
J=8.5

7.61 t;
8.5

7.72 t
J=8.0
-

B15

8.30 d;J=8.5
8.06 s

8.61 d;J=9.0
2.08 s

4.06 s
4.05 s

7.72 d J=15.5
8.18 d J=16

1.38 tJ=7

B17

8.22 d;J=8.5
8.04 s

8.61 d;J=9.0
2.09 s

4.08 s
4.07 s

7.72 d;J=15
8.10 d;J=15

8.11 d;
J=9.0

7.65 d
J=8

-

8.04 d;J=8.5
8.04 s

8.58 d;J=9.0
2.06 s


- The ESI-MS spectra of the three compounds B1, B5 and B6 give pseudo-molecular peaks suitable for the
calculated molecular weights.


3.3. SYNTHESIS AND STRUCTURAL STUDY OF SERIES D
3.3.1. Summary of series D
a. Synthetic Scheme :

Scheme 3.5. Summary scheme of series D
b. Synthesis
Acetylation A0 produced 3-methyl-4- (2-acetamido-4,5-dimethoxy-phenyl) furoxan Am. The reaction between
Am and DMF-POCl3 (Wilsmeier-Haack agent) did not give quinoline type compounds as expected by Wilsmeier-Haack
method but heterocyclic quinazoline D1 was obtained. The formation of D1 was explained as in scheme 3.6.

Scheme 3.6. Explanation of the quinazolin D1 ring formation from Am.
The quinazoline ring as shown in the scheme 3.6 above is an unprecedented reaction. The right
conditions for this abnormal reaction were found to become a synthetic method of quinazoline D1 with the yield
of 64 %. Interestingly, the reaction of quinazoline D1 with Na2S2O4 did not stop at reduction of nitro group into
amino group, as soon as it wasconverted to methylketone D2 as shown in scheme 3.7. The structure of D2 is
determined on the basis of analyzing its spectra, in addition, its structure was further confirmed by the reaction
of D2 with C6H5NHNH2HCl to create phenylhydrazone D3.


Scheme 3.7. The formation of D2 from D1
Interestingly, a yellow needle-shaped D4 compound was obtained by boiling D1 with 10%
NaOH solution in 95% ethanol after crystallizing . The spectral analysis showed that D4 was 5,6-dimethoxy-2methyl-3H-indol-3-one. On the other hand, when boiling D1 with KClO3 in a solution of HCl at 50 °C, oxidation
product D5 as a white needle-shaped crystal wasobtained indicating that branch was oxidized .
Because 4-acetyl-2-methyl-6,7-dimethoxyquinazoline (D2) is a new ketone, it was further investigated
its reaction to aldehyde


D2

Ethanol

D3

Ethanol
Ethanol :
nước 1:1

D4
D5

Ethanol

D6

Ethanol

D7

Ethanol

D8

Ethanol

D9

Ethanol

yellow
Yellow needle-shaped
crystals

Yellow needle-shaped
crystals

Melting
temperature
(oC)

Yield
%

Analyzed spectrum

167 - 168

60

IR, 1H , 13C, HMBC, HSQC,
NOESY, ESI MS

185- 186

60

IR, 1H , 13C, HMBC

151


80

IR, 1H , 13C.

186 - 187

75

IR, 1H , 13C

190-191

78

IR, 1H , 13C, HMBC

187-188

79

IR, 1H , 13C, HMBC,

288

55

IR, 1H , 13C, HMBC, HSQC,
MS


H NMR spectrum,
 (ppm)
-/7.08 / - / 7.44
-/2.76 s
- / 2.64
3.86 / 3.99

C NMR spectrum,
 (ppm)
106.4 / 157.3
100.3 / 150.0
155.9 / 107.3
150.1 / 113.2
25.5
104.0 / 29.8
55.7 / 56.4

In the IR spectrum of D2, the difference compared to that of D1 is a strong absorption range at 1691
-1

cm , which characterizes the stretching vibration of the C = O group connected with aromatic ring, however,
vibration of the NH group does not appear. Unlike the IR spectrum of D1, the IR spectrum of D4 is characterized
by the strong absorption at 1671 cm-1, which is typical for the conjugated carbonyl C = O group, while in the D5
spectrum, the absorption at 3450 cm-1 is indicated for hydrogen bonded OH group. IR spectra data of D1-D5
compounds are given in table 3.29 of the dissertation.
An important the difference of the

13

C NMR spectra between of D2 and D1 is the appearance of


H4b
2.64 s
2.74 s

H12/16
-

H13/15
-

H14
-


7.29 s
7.38 s
7.46 s

D3
D4
D5
13

7.93 s
7.04 s
7.35 s

3.89 s
3.84 s

formulae.
The IR spectrum of the D12 at 2500 - 3500 cm-1 range is enhanced, indicating that the compound D12
exists of intramolecular hydrogen bonds. The two peaks are sharp at 3514 and 3239 cm-1 corresponding to the
valence stretching of the OH and NH groups. The typical IR spectrum of D12 is shown in table 3.36 of the
dissertation. Analysis of 1H,

13

C and HMBC spectra (Figure 3.2) shows that D12 is an isoquinoline type

compound.
Table 3.10. 1H NMR signal of compounds D6– D12; δ, ppm; J, Hz
Compound

-X

D2
D6
D7

11
12
13

D8

16
15
14 14a
N(CH3)2


16
15

14
Cl

H5
H8
7.95 s
7.34 s
7.84 s
7.39 s

H6a
H7a
3.90 s
3.98 s
4.00 s
3.91 s

H4b
H2a
2.76 s
2.74 s
7.80 d; J=15.5
2.81 s

H4c
H14

7.67 d; J=15.5
-

7.61d;
J=7.0

6.74 d; J=7.0

3.00 s
-

7.89 s
7.39 s

3.99 s
3.92 s

7.91 d J = 16
2.81 s

8.07 d; J = 16
-

8.08 d
J = 9.0

8.28 d
J=9

-


8.10 d; J=16
7.74 d; J=8.0

7.54 d
J= 9

8.12 dd; J=8.0;1
7.85 td; J=8.0;1

4.18 m
1.41 t

7.84 s
7.40 s

4.00 s
3.91 s

7.81 d J=16
2.81 s

7.91 d J=16
-

8.11 d;
J=9.0

7.86; d
J =9

conditions with either a dilute alkaline or a dilute acid condition. In addition, E0 was also stirred with
acetophenone under the same conditions but the condensation reaction did not occur. To explain the observation,
it is assumed that in the phenolic HO group at position 6 of E0 is deprotonized into O-group in alkaline
environment, which pushes the electron to reduce the reactivity of the CH=O group, so condensation in a strong


acidic environment as described in section 2.6 of the dissertation. In the first 5 cases in Table 3.39, α, βunsaturated ketones were obtained in about 68-75% yield. In the following three cases, it is necessary to increase
the heating time from15 to 20 h to obtain a product of 1,5-diketone with 30-38% yield.
c. General results
Table 3.11. Composite results data of E1-E8
Compound

Aryl methyl
ketone

Decomposition
temperature
(oC)/
Time (h)

Crystalline solvent

Colour and Shape

E1

MeCOPh

80/12


70/8

DMF:H2O:EtOH
1:4:1

E6

p-MeCOPhBr

80/15

DMF:H2O:EtOH
2:1:1

E7

p-MeCOPhNO2

80/20

DMF:H2O:EtOH
1:2:1

E8

p-MeCOPhCl

80/15

DMF:H2O:EtOH

IR, 1H , 13C, HMBC

35

IR, 1H , 13C, HSQC,
HMBC, MS

30

IR, 1H,

Red needleshape crystals,
red
Yellow needleshape crystals, Orange eedleshape crystal,
Orange
yellowish
needle shape
crystals
Light yellow
needleshapecrystals
Light yellow
needle- shape,
crystals
Light yellow
needle- shape,
crystals

38

1

9.00 s

10.72s

E1

9.16 d
J =2
9.16 s

E2

9.00s

8.78s

E3

9.13 s

8.96 s

E4

9.15s

8.99s

E5


H8

5.11 s

7.63 s

5.09 s

7.53 s

5.06s

7.48 s

5.08 s

7.51s

5.09 s

7.53 s

5.09s

7.53 s

H12
H16

H13

1.37
tJ=7

Table 3.12 shows that the chemical shifts of proton H5a of compounds E1-E5 is much lower than that
of E0; the H4 signal of E0 is in weaker field than H2; in the α, β-unsaturated products, the opposite pattern is
found (this is confirmed through HMBC spectrum analysis); The proton signals of E1-E5 are similar because of
the same types of α, β-unsaturated compounds with trans configuration as predicted.
Results of 13C NMR spectral analysis of E1-E5 compounds are listed in Table 3.42 of the dissertation.
The number of none-equivalent Cs and their chemical shift are completely consistent with the formula of each
compound, Table 3.42.
Spectrum MS
The molecular formula of E2 is C21H17NO8S with M = 443 au. In its MS spectrum, the peak at 444 au
has very small intensity, only about 5% compared to the base peak at 364 au, whosethe intensity is 100%. Thus,
unstable pseudo-ion [M + H]+ molecules have been formed and decomposed as follows:

In E2 -MS spectral, there was no peak at 442 au (M-H+), but peak at 362 au is 100% intensity. Thus,
similar to the spectra + MS, the unstable pseudo-molecular ions [M-H] - were formed and decomposed as
follows:

Comment [H3]: thiếu J=?


The results of 13CNMR spectrum analysis of E1-E5 compounds are listed in Table 3.42. The chemical
shift of none-equivalent Cs is listed in Table 3.42. These is completely consistent with the formula of each
compound.
Table 3.12. Table of signals 13C NMR of E1-E5, δ (ppm)

E0
E1
E2

115.4
140.0
115.3

C5a
C5b
191.2
134.6
128.4
134.8
127.6
133.4
128.5
133.8
128.5
133.6
128.4

C5c
C6
157.3
189.6
149.4
189.2
148.8
187.5
148.9
187.7
149.1
187.6

104.0

C9
C10
136.5
122.0
137.2
123.2
140.8
122.4
137.7
127.9
137.0
123.1
137.0
123.0

C11
C14
137.6
133.4
135.2
143.7
129.0
162.4
130.4
163.4
130.1
162.2


63.6
14.4

3.4.3. Structure of compounds E6-E8.
Some key absorption bands on the IR spectrum of E6 –E8 are listed in Table 3.43 of the dissertation.

Figure 3.3. A part of 1H NMR spectrum and structure of E6
1

H NMR spectra of E6 - E8 are quite similar but different from that of E1-E5. The two interesting


anomalies in the proton spectrum of E6 (Figure 3.3) are as follows: Firstly, the signal of 4 methylene protons (2
CH2 groups) is represented by two doublets of doublet while these 2 methylene group only gives 1 signal in the
13

C NMR spectrum and cross peaks on the HSQC spectrum. Secondly, the singlet (singlet) at  = 7.94 ppm (1H),

 = 2.87 ppm (3H) and  = 2.71ppm (3H) proves that there is a DMF molecule attached to a diketone. The strong
infrared absorption band at 1632 cm-1 (Table 3.44) is suitable for that observation. On the HMBC spectrum
(Appendix E) of E6, the H17 signal of DMF has a cross peak with C12 of phenyl group. This can only be
explained by the assumption that the π-π interaction between the electron systems π of the 2 phenyl groups and
the C = O group of DMF helped to create the molecular complex E6. On 1H spectrum of E7, there is a signal of
DMF similar to that of E6, indicating that it is also a complex molecule. On the 1H spectrum of E8, there is no
signal of DMF, proving that it does not form complex molecules. The results of NMR spectroscopy analysis of
E6, E7 and E8 are listed in Table 3.13.
Table 3.13. 13C NMR and 1H NMR signals of E6 - E8 (ppm, Hz).
1

Location

J= 16; 9
3.83 dd;
J= 16; 6
- / 7.87 s
4.99 s / -/-/-/8.09 d; J= 9
8.09 d; J= 9
8.27 d; J= 9
8.27 d; J= 9
2.90 s / 2.75 s

5b
5b’
7/17
7a/7b
9/10
11/14
11’/14’
12+16
12’+16’
13+15
13’+15’
18/19

3.5. SYNTHESIS AND STRUCTURE OF SERIES G
3.5.1. Synthesis of G1 - G7 compounds
a. General scheme

13

E8

46.5

-

-

153.5/162.3
65.8/168.9
134.4/124.7
135.4/127.4
-/129.8
-/131.8
-/35.8/30.8

151.6/65.7/169.1
135.0/120.6
138.3/128.8
133.5/128.5
130.1
126.1
128.7
128.6
-/-

138.7/137.7


Scheme 3.10. Synthetic scheme of G series compounds
b. Synthesis
When G0 reacts with semicarbazide hydrochloride in methanol, the semicarbazone G2 is not obtained

Ethanol :
water 1:1
Ethanol :
water 1:1
Ethanol :
water 2:1
Ethanol :
water 1:1

G1
G2
G3
G4
G5
G6
G7

Ethanol

G8

Ethanol :
water 1:1

Colour and Shape

Decomposition
temperature
(oC)


250

55

IR, 1H , 13C, HMBC

250

35

IR, 1H , 13C

280

87

IR, 1H, 13C, MS

-

64

IR, 1H , 13C, X-ray

Dark yellow crystals
Pale brown crystals
pale yellow crystals
Dark brown crystals
Pale green crystals
Blue crystals

J= 2
8.42 d;
3
J= 2
8.68 d;
3
J= 2
9.01 d;
3
J= 2
9.45 s

G6

9.16 d;
3
J= 2

G7

9.26 d;
3
J= 2

Compound
G0
G1
G2
G3
G4

6.88 s

4.85 s

-

-

-

4.86 s

5,84 s
NH
5,84 s
NH
8.81 s
NH

-

4,87 s

8.81 s
NH

5.04
NH

6.76 s

14.09 s
NH
10.46 s
OH
9.12 d;
3
J= 2
9.13 s

-

-

9.59 d;
3
J= 2

7.46 s

5.20 s

3

8.42 dd;
J= 8; 4J= 2

8.06 m

8.10 m



Comment [H4]: các bảng khác nên theo kiểu
của bảng này


Table 3.16. 13C NMR spectral data of G1-G7 compounds; δ, ppm

C2
C3
C4
C5
C6
C7
C7a
C7b
C8
C9
C10
C11
C12
C13
C14
C15
C16

G1

G2

G3

169.4
102.6
155.2
121.6
159.5
-

147.0
139.6
126.6
144.0
136.2
155.0
69.8
167.2
102.7
141.8
117.9
171.7
-

148.4
135.9
130.1
1389.9
134.9
154.1
67.6
174.8
107.1

109.1
149.7
121.1
142.1
129.5
131.3
131.7
129.3
141.8

146.6
141.1
132.1
140.5
137.2
155.9
65.6
169.2
105.8
147.2
120.2
142.0
129.6
131.9
132.2
129.3
141.9

3.5.3. Structure of G8
In order to confirm the structure of G8, which was elucidated by the single crystal X-ray diffraction

with MIC value of 50 µg/ml. Compound A6 exhibited moderate activity against B. subtilis with MIC value of 50
µg/ml. The antibacterial ability of Gram+ of compound E3 is weak with MIC value of 112 g/ml for B.subtillis
and MIC = 124.3 g/ml with S.aureus.
3.6.2. Cytotoxic activity
Three out of the synthesized compoundswere screened cytotoxic test: D5 (symbol of sample Q1), D6
(symbol of symbol QN2) and D8 (model of symbol QN5). Celllines tested include: Hep-G2: liver cancer; LU-1:
lung cancer; KB: carcinoma and MCF-7: breast cancer. Results are shown in table 3.51.
Table 3.17. Results of exploration of cytotoxic activity
No.
1
2
3
4
5
6

Compound

Label

D3
Qhy(Y4)
D4
B2
D5
Q1
D6
QN2B
D8
QN5

32
0.54

1.84
94.95
4.41
0.41