185

CHAPTER - VI

Synthesis of Chromeno pyrimidines

6.1. Introduction

Chromenes and their structural analogues are of great interest because they

are frequently found in a number of natural products like alkaloids, flavonoids,

tocopherols, and anthocyanins as well as biologically active molecules like antibiotic

rhodomyrtone, a glycosidase inhibitor myrtucommulone-E and an apoptosis inducer

HA14-1.1

Their syntheses have attracted wide attention for their valuable biological

properties, such as anticonvulsant,2

antimicrobial,3

antitumor,4

anticoagulant,

diuretic, spasmolytic, and antianaphylactic activities.5

Moreover, functionally

substituted chromenes have played increasing roles in synthetic approaches to

promising compounds in the field of medicinal chemistry.6-8

Fig. 6.1 Natural products containing chromene analogues

Pyrimidine derivatives also are well-known9,10

for their biological activities

and the pyrimidine annelated heterocycles belong to an important class of

biologically active compounds. A molecular scaffold that contains chromene as well

as pyrimidine moieties might integrate the synergism of both the heterocyclic

186

moieties in a single nucleus may result in the formation of some worthwhile

molecules from the biological point of view. For example, the chromeno [2,3-d]

pyrimidine-2,4(3H)-diones (oxadeazaflavines), which are biomimetic models of the

5-deazaflavin coenzyme, have been shown to possess strong redox properties in the

conversion of alcohols to aldehydes or ketones.11-13

Numerous pyrimidine based

compounds have found application in medicine and therapeutics especially, some

are used in the chemotherapy of cancer14

and some are used against HIV and viral

diseases.15

Novel methods for preparing heterocycles containing pyrimidine moiety

have attracted much interest in recent years.16,17

Despite the available synthetic

methods, there still exists a need for developing more efficient procedures, which

allow the ready synthesis of pyrimidine polycyclic systems.

The two benzodeazaflavine derivatives,13,18

(1) and (2), already known in

literature as organic oxidants, were both prepared by condensation of the appropriate

barbituric acids and 2-chloro-1-arylaldheydes in ethanol in the presence of pyridine,

as described by Chen et al.,13

Fig. 6.2 Benzodeazaflavines

187

A new heteroaromatic system, an unsubstituted 5-oxo-5H-chromeno[2,3-

d] pyrimidine (5) was synthesized by the debenzylation of 1-carbobenzoxy-3-

benzyl-5-oxo-5H-1,2,3,4- tetrahydro chromeno[2,3-d] pyrimidine (3) to

5-oxo-5H-1,2,3,4-tetrahydrochromeno[2,3-d]pyrimidine (4) and subsequent

dehydrogenation.19

Scheme 6.1

A simple and one-pot synthesis of new chromeno[2,3-d] pyrimidine-triones

by a three-component condensation reaction of barbituric acids, aldehydes and

cyclohexane-1,3-diones in refluxing ethanol in the presence of p-toluenesulfonic

acid (p-TSA) for 3-10h has been reported.20

Scheme 6.2

The 10-substituted-9H- benzo[5,6] chromeno[2,3-d] pyrimidine-9,11(10H)-

dione derivatives were prepared by condensation of the appropriate

N-alkylbarbituric acids, synthesized by standard methods,21

with 2-hydroxy-1-

naphthaldehyde in dry ethanol at reflux temperature for 1h. The 3-substituted-2H-

chromeno[2,3-d] pyrimidine-2,4(3H)-dione compounds were obtained by

188

condensation of the corresponding barbituric acids with o-chlorobenzaldehyde in dry

ethanol in the presence of a catalytic amount of pyridine followed by the

intramolecular dehydrohalogenation of the crude mixture of E and Z 5-(2′-

chlorobenzylidene)barbituric acid intermediates by heating them in an oven at 240-

260 °C without solvent for 0.5h.22

Scheme 6.3

5-(o-Halobenzylidene)barbituric acids when heated to 220-260°C suffer

dehydrohalogenation affording 5-deaza-10-oxaflavins in 85-92% yield.13

Scheme 6.4

Chromenopyrimidine derivatives could be formed by heating

5-salicylidenebarbituric acids obtained from barbituric acids and salicylaldehydes.

23

Besides these compounds, barbituric acids with salicylaldehydes afford four more

types of substances: (1) 5-salicylidene derivatives (7) same as with the other

189

benzaldehydes;24

(2) 5,5’-salicylidenebisbarbituric acids (8);13

(3) 1,5-dihydro-5-[2-

oxo(thioxo)-4,6-dioxohexahydropyrimidin-5-yl]-2H-chromeno [2,3-d]-pyrimidine-

2,4(3H)-diones (9) in 83-85% yield24-26

and (4) 10a-hydroxy-2,3,4,10a-

tetrahydro1H-chromeno[2,3-d]pyrimidine-2,4-diones (10).24

Scheme 6.5

Chromeno pyrimidine derivatives were obtained when 5-

salicylidenebarbituric acids prepared from barbituric acids and salicylaldehyde are

subjected to intramolecular cyclization effected by acetic anhydride.27

Hydrogenation of chromenopyrimidines with sodium borohydride provides a

compound (12), that also arise at cyclization of 5-(o-hydroxybenzyl) barbituric acids

or directly at boiling barbituric acid and salicylaldehydes in alcoholic solution

containing methane sulfonic or p-toluenesulfonic acid.27

190

The 2H-chromeno[2,3-d]pyrimidine-2,4(3H)-diones or 10-oxa-5-deaza-

flavines are known as potential organic oxidizers.28-30

Up to 1990 the works of

Yoneda et al29

and Blythin et al30

were the only known general procedures for the

preparation of oxadeazaflavines. Thus, the reaction of barbituric acid with

salicylaldehyde in water at 25 °C gave an orange crystalline product which was

converted into 2H-chromeno[2,3-d]pyrimidine-2,4(3H)-dione by recrystallization

from an HOAc-Ac2O 9:1 mixture, in 50% overall yield. When the same reaction

was performed at 100 °C, the reaction product was the 1,5-dihydro-5-[5-pyrimidine-

2,4(1H,3H)-d-2,4(3H)-dione. The reaction of barbituric acid with the aldehydes at

room temperature gave the oxadeazaflavines in 50% yields. At 100 °C the

tetracyclic products were obtained in almost quantitative yield.

Scheme 6.6

Synthesis of some cambinol analogues has been achieved by condensation of

N-phenylbarbituric acid or N-phenyl-2-thiobarbituric acid with 2-hydroxy-1-

naphthaldehyde in dry ethanol, by using the synthetic methodology reported by Ridi

191

and Aldo.18

The expected products 5-(2-hydroxynaphthalen-1-ylmethylene)-1-

phenylbarbituric and -2-thiobarbituric acids were obtained in addition to the other

products.

Scheme 6.7

An ecofriendly, one-pot, three component ZnO nanoparticles-mediated

synthesis of 4H-chromene in water under thermal condition has been described.31

The highly product-selective three component electrophilic reaction of 2-

hydroxybenzaldehyde with an active methylene compound and another carbon-

based varied nature of nucleophile has been developed by a reversible alkylation

procedure using greener approach.

Scheme 6.8

A general, practical, and environmentally benign method has been developed

to construct densely functionalized 4H-chromenes via the three-component reaction

of salicylaldehydes and 1,3-cyclohexanediones by using L-proline as catalyst.32

All

the reactions were performed in ethanol under mild and metal-free conditions. The

192

reaction may proceed via an enolic hydroxy-assisted mechanism. Many carbon,

sulfur, and nitrogen-based nucleophiles could be successfully used to react with

salicylaldehyde and 1,3-cyclohexanediones.

OH O O

O HN NH

O HN NH +

O O

O O

L-Proline O

EtOH, 80 °C

O O

Scheme 6.9

A mild and efficient method for the synthesis of 1H-chromeno[2,3-

d]pyrimidine-5-carboxamide derivatives via a one-pot, three-component reaction of

an isocyanide, barbituric acid, and a salicylaldehyde in the presence of acetic acid in

ethanol/water mixture at 75 °C has been reported.33

This high atom economy

reaction led to the construction of one benzopyran ring, and one amide group in a

single synthetic step.

Scheme 6.10

A modified reaction of hydroxy aldehydes with 2 equiv amounts of

barbituric acid afforded a tetra cyclic product in good yields which upon treatment

193

with 42% aq. HBF4, underwent elimination reaction of barbituric acid to give

oxadeazaflavine borofluorate in good yields.34

Scheme 6.11

Benzylidene barbiturates were prepared by condensation of benzaldehydes

with barbituric acid in 95% ethanol and reflux for 30 min.35

When these reactions

were carried out under reflux with salicylaldehyde, 5-hydroxysalicyladehyde

and 5-chlorosalicylaldehyde, the respective 5-(2,4-dioxo-2,3,4,5-tetrahydro-

1H-chromeno[2,3-d]pyrimidin-5-yl)pyrimidine-2,4,6(1H,3H,5H)-triones have been

formed.26

In order to prepare their respective benzylidene barbiturates the reaction

was carried out at 25 °C, leading to the orange cationic intermediates, which were

converted to the respective benzylidene barbiturates by dissolution in polar solvents

like EtOH, MeOH and DMSO.

Scheme 6.12

194

Scheme 6.13

A highly efficient one-pot three-component regioselective synthesis of

4-aryl-3-aroyl-2-methylsulfanyl-4,6,7,8-tetrahydrothiochromen-5-ones has been

developed by annulation of β-oxodithioesters with aldehydes and cyclic 1,3-

diketones under solvent-free conditions promoted by P2O5.36

Scheme 6.14

A series of novel 5-(2,3,4,5-tetrahydro-1H-chromeno[2,3-d]pyrimidin-5-

yl)pyrimidione derivatives has been synthesized from substituted salicylaldehydes

and barbituric acid or 2-thiobarbituric acid in water catalyzed by phase transfer

catalysis of triethylbenzyl ammonium chloride (TEBA).37

195

Scheme 6.15

The conversion of o-haloaryl barbiturylidenes to oxadeazaflavines could be

carried out with success using microwaves as the activation energy source, the

cyclization reaction of the benzylidene from 6-bromopiperonal under conventional

and microwave heating conditions have been reported.38

Scheme 6.16

Heating of 6-chloro-3-methyluracil with appropriate phenols in

dimethylformamide in the presence of potassium carbonate under reflux gave the

corresponding 3-methyl-6-phenoxyuracils, which on further heating with

dimethylformamide and phosphorous oxychloride results in formylation which on

further treatment with polyphosphoric acid resulted in 2H chromeno[2,3-d]-

pyrimidine- 2,4-(3H)diones.31

196

Scheme 6.17

The 2H-chromeno[2,3-d]pyrimidine-2,4(3H)-diones (oxadeazaflavines),

which are biomimetic models of the 5-deazaflavine coenzyme, have been

shown to possess strong redox properties in the conversion of alcohols to

aldehydes or ketones.30,32

One of the simplest approach for the synthesis of oxadeazaflavines, i.e., the

direct condensation of barbituric acid with salicylaldehyde in boiling water

resulted a tricyclic compound.39

Later Pavohni40

showed that the ratio barbituric

acid : salicylaldehyde in 2:1 ratio resulted the tetracyclic product .

Scheme 6.18

197

The syntheses of oxadeazaflavine (2H-chromeno[2,3-d]pyrimidine-

2,4(3H)-dione) derivatives from barbituric acid and salicylaldehydes as starting

materials was shown to be possible using water as solvent at room temperature.

The orange intermediate formed, an anthocyanin-like precursor of the desired

products, gave reasonable yields of the oxadeazaflavines when treated with

acetic acid-acetic anhydride mixture. When the reaction was carried out at 100 °C

the corresponding 1,5-dihydro-5(5’-barbituryl)-2H-chromeno[2,3-d]pyrimidine-

2,4(3H)-diones were obtained.26

6.2. Results and Discussion

Scheme 6.19

The main reactivity of benzylidene barbiturates occurs at the benzylidine

double bond conjugated with two carbonyl groups of the barbituric acid ring, which

mainly leads to Michael or cycloaddition reactions. The electrophilicity parameters

of the benzylidene barbiturates have been shown to be correlated with their

reactivity as Michael acceptors and were used to predict other reactions.41

198

Fig. 6.3 Nature of benzylidine barbiturate

Scheme 6.20. General reaction for the synthesis of chromeno pyrimidine

derivatives

Benzylidene barbiturates are important materials for the synthesis of

heterocyclic compounds with potential for the development of new drugs. The

reactivity of benzylidene barbiturates is mainly controlled by their exocyclic carbon-

carbon double bond. The carbon-carbon double bond polarization depends on the

electronic characteristics of the double bond substituents, which have a stronger

influence on the pi-bond.

The exo-cyclic carbon-carbon double bond polarization of benzylidene

barbiturates is promoted by its conjugation with the two carbonyl groups from the

199

barbituric acid ring and with the benzene aromatic ring, which effect certainly can

be altered by the electronic properties and the position of the -R groups in the

aromatic ring. Benzylidene barbiturates with polarized carbon-carbon double bond

were found to be important intermediates for the synthesis of new heterocyclic

compounds.

Scheme 6.21. Plausible mechanism for the formation of chromeno pyrimidines

The cyclic 1,3-dicarbonyl compound (3) enolised in aqueous medium

undergoes addition reaction with the o-hydroxy benzylidine barbiturate (7) moiety

resulting in the formation of an enolic tricyclic compound (8). This on ketonization

provides a tricyclic compound (9). Proton addition on the free -OH group of the

tricyclic compound (9) leads to the hydronium ion formation (10). Removal of water

molecule from (10) resulted in the formation of an expected tetracyclic compound

(4), a chromeno pyrimidine derivative. Similar type of reaction has been expected

while using acyclic 1,3-dicarbonyl compounds, but a tetracyclic compound namely,

5-(2,4-dioxo-2,3,4,10a-tetrahydro-1H-chromeno[2,3-d] pyrimidin-5-yl)pyrimidine-

2,4,6 (1H, 3H, 5H)-trione (6a) has been formed, which was confirmed by the

200

spectral techniques. It may be due to the enolizing nature of dicarbonyl compounds.

From this reaction sequence, we found that the cyclic dicarbonyl compounds were

found to be enolized well and available for the further addition reactions, than the

acyclic dicarbonyl compounds.

Table - 6.1 Water catalyzed chromeno pyrimidine synthesis with compound 2a:

S.No

1a/1b

3a-3i

Time (h) Yieldb (%)

Product

1 1a 3a 1 84 4a

2

1a

3b

2

82

4b

3

1a

3c

1

81

5a

4

1a

3d

4

75

6a

5

1a

3e

4

74

6a

6

1a

3f

4

71

6a

7

1a

3g

4

75

6a

8

1a

3h

4

77

6a

9

1a

3i

4

75

6a

10

1b

3a

1

80

4c

11

1b

3b

1

82

4d

12

1b

3c

1

81

5b

13

1a

--c

1

72

6a

14

1a

--d

1

71

6a

aReactions were performed with 1:1:1 mmol of barbituric acid, salicylaldehyde and 1,3-

dicarbonyl compounds in 1:1 (10 ml) of water and ethanol at room temperature. bIsolated Yield.

c1+2 in 1:1molar ratio.

d1+2 in 2:1 molar ratio.

We have developed a general, practical, and environmentally benign method

to construct chromeno pyrimidine dione derivatives, via the three-component

201

reaction of salicylaldehydes, barbituric acid and 1,3-dicarbonyl compounds by using

water and ethanol under mild conditions.

Fig. 6.4 1H-

1H correlations in compound 4a

From the

1H-

1H COSY spectrum of compound 4a, we have observed the

interactions between the protons as shown in the Fig. 6.4. One of the two CH2

protons (Ha) is having the interaction with the other CH2 proton (Ha). Both CH2

protons (Ha and Hb) are in interaction among them. One of the Hb proton was found

to have the interaction with the Hc and Hd protons. Similarly, Hc proton is having

interaction with Hd proton. The aromatic protons were also having the interactions,

not shown here.

When the reaction was carried out with salicylaldehyde and thiobarbituric

acid followed by the addition of barbituric acid, provided a tetracyclic

compound 5-(4-oxo-2-thioxo-2,3,4,10a-tetrahydro-1H-chromeno [2,3-d] pyrimidin-

5-yl)pyrimidine-2,4,6(1H,3H,5H)-trione (6b). In the case of dimedone and other 1,3-

dicarbonyl compounds, chromeno pyrimidine dione derivatives were obtained in

good yields, but while using meldrum’s acid as 1,3-dicarbonyl compound, instead of

the usual chromeno pyrimidine dione derivative, dihydro chromeno pyrimidine

202

acetaldehyde derivatives were formed due to the removal of acetone and CO2

molecule from meldrum’s acid.

6.3. Conclusion

An environmentally benign protocol for the synthesis of chromeno

pyrimidine dione derivatives, via the three-component reaction of salicylaldehydes,

barbituric acid and 1,3-dicarbonyl compounds by using water and ethanol under

mild conditions favoured the products in good yield. Chromeno pyrimidine

derivatives have been easily isolated by filtration afford the compound in high

purity, avoiding the use of column chromatography.

6.4. Experimental methods

Salicylaldehyde, barbituric acid, thiobarbituric acid, dimedone, 1,3-

cyclohexadione, meldrum’s acid, ethyl aceto acetate, methyl acetoacetate, acetyl

acetone, diethyl malonate, dimethyl malonate, cyclohexanone and all the solvents

used were purchased from Sigma-Aldrich and used as such without further

purification. The melting points of all compounds were determined with an

electrothermal apparatus using capillary tube and are uncorrected. The purities of the

compounds were checked by TLC using precoated silica gel plates with hexane :

ethyl acetate (6:4) as eluent. 1H and

13C NMR spectra were recorded on a Bruker

Avance spectrophotometer at 400/100 MHz respectively using TMS as reference.

Elemental microanalyses were carried out on a Perkin-Elmer elemental analyzer

Model 240C and a Thermo Finnigan analyser series Flash EA1112.

203

6.4.1. General procedure for the synthesis of chromeno pyrimidines:

1mmol of salicylaldehyde was dissolved in 5ml of ethanol to which, 1mmol

of barbituric acid in 5ml of water was added where a yellow coloured solution was

formed. To this, 1mmol of 1,3-dicarbonyl compounds have been added and stirred at

room temperature for the appropriate time as mentioned in the table. A precipitate

formed was separated by filtration, washed with water and dried under vacuum.

Spectral data:

5-(4,4-dimethyl-2,6-dioxocyclohexyl)-1H-chromeno[2,3-d] pyrimidine-2,4(3H,10aH)

-dione (4a): Pale pink solid; mp: 204-206 °C; 1H NMR (400 MHz, DMSO-d6) δ:

11.23 (s, 1H); 10.93 (s, 1H); 7.30-7.07 (m, 4H’s); 4.62 (s, 1H); 3.68 (s, 1H); 2.61-

2.58 (d, 1H); 2.41-2.36 (m, 2H’s); 2.17-2.14 (d, 1H), 1.11 (s, 3H’s); 1.04 (s, 3H’s).

13

C NMR (100 MHz, DMSO-d6) δ: 197.20, 170.07, 169.37, 167.75, 151.03, 150.36,

129.27, 128.49, 125.49, 117.00, 109.29, 56.50, 54.40, 50.60, 33.90, 32.26, 32.07,

29.73, 26.79, 19.02. LCMS (ESI) m/z calcd for C19H18N2O5 (M+

+1): 354.46, found:

355. Anal calcd for C19H18N2O5: C, 64.40; H, 5.12; N, 7.91. Found: C, 64.28; H,

5.18; N, 8.07.

5-(2,6-dioxocyclohexyl)-1H-chromeno[2,3-d] pyrimidine-2,4(3H,10aH)-dione (4b):

Pale yellow solid; mp: 186-188 °C; 1H NMR (400 MHz, DMSO-d6) δ: 11.20 (s, 1H);

10.92 (s, 1H); 7.29-7.06 (m, 4H’s); 6.96 (s, 1H); 4.60 (s, 1H); 2.61-2.21 (m, 6H’s).

13

C NMR (100 MHz, DMSO-d6) δ: 197.23, 170.01, 169.46, 151.09, 150.32, 129.32,

128.66, 125.52, 121.59, 116.90, 110.18, 54.65, 36.88, 34.27, 27.87, 20.57. LCMS

(ESI) m/z calcd for C17H14N2O5 (M+

+1): 326.30, found: 327. Anal calcd for

C17H14N2O5: C, 62.57; H, 4.32; N, 8.59. Found: C, 62.45; H, 4.27; N, 8.65.

204

5,5-dimethyl-2-(4-oxo-2-thioxo-2,3,4,10a-tetrahydro-1H-chromeno[2,3-d]

pyrimidin-5-yl)cyclohexane-1,3-dione (4c): Pale pink solid; mp: 150-152 °C 1H

NMR (400 MHz, DMSO-d6) δ: 12.30-11.96 (two broad singlet, 2H’s); 7.14-7.01 (m,

4H’s); 4.99 (d, 1H); 2.49-2.07 (m, 5H’s (4CH2 H’s + SH)); 1.09-0.87 (d, 6H’s). 13

C

NMR (100 MHz, DMSO-d6) δ: 197.20, 170.07, 169.37, 167.75, 151.03, 150.36,

129.27, 128.49, 125.49, 117.00, 109.29, 56.50, 54.40, 50.60, 33.90, 32.26, 32.07,

29.73, 26.79, 19.02. LCMS (ESI) m/z calcd for C19H18N2O4S (M+

+1): 370.42,

found: 372. Anal calcd for C19H18N2O4S: C, 61.61; H, 4.90; N, 7.56. Found: C,

61.52; H, 4.81; N, 7.67.

2-(4-oxo-2-thioxo-2,3,4,10a-tetrahydro-1H-chromeno[2,3-d]pyrimidin-5-yl)

cyclohexane-1,3-dione (4d): Pale yellow solid; mp: 178-180 °C LCMS (ESI) m/z

calcd for C17H14N2O4S (M+

+1): 342.37, found: 341. Anal calcd for C17H14N2O4S:

C, 59.64; H, 4.12; N, 8.18. Found: C, 59.48; H, 4.18; N, 8.26.

(Z)-2-(2,4-dioxo-3,4-dihydro-1H-chromeno[2,3-d]pyrimidin-5(2H)-ylidene)

acetaldehyde (5a): Colourless solid; mp: 136-138 °C; 1H NMR (400 MHz, CDCl3)

δ: 13.25 (s, 1H); 9.81 (s, 1H); 7.89-7.87 (d, 1H); 7.69-7.25 (t, 1H); 7.41-7.38 (t,

2H’s), 7.36 (s, 1H). 13

C NMR (100 MHz, CDCl3) δ: 164.43, 157.18, 154.92, 148.82,

134.74, 130.63, 125.28, 118.79, 118.42, 116.57.

(E)-2-(4-oxo-2-thioxo-3,4-dihydro-1H-chromeno[2,3-d]pyrimidin-5(2H)-ylidene)

acetaldehyde (5b): Pale yellow solid; mp: 196-198 °C; 1H NMR (400 MHz, CDCl3)

δ: 12.1 (s, 1H); 8.95 (s, 1H); 7.81-7.76 (m, 2H’s); 7.51-7.49 (d, 2H’s); 7.47 (s, 1H).

LCMS (ESI) m/z calcd for C13H8N2O3S (M+

+1): 272.28, found: 273.

5-(2,4-dioxo-2,3,4,10a-tetrahydro-1H-chromeno[2,3-d] pyrimidin-5-yl)pyrimidine -

2,4,6 (1H,3H,5H)-trione (6a): Yellow solid; mp: 218-220 °C; 1H NMR (400 MHz,

205

DMSO-d6) δ: 11.96 (s, 1H); 11.28 (s, 1H); 11.16 (s, 1H); 10.98 (s, 1H); 7.33-7.08

(m, 4H’s); 4.71 (s, 1H); 3.85 (s, 1H). 13

C NMR (100 MHz, DMSO-d6) δ: 170.01,

169.35, 163.97, 159.41, 155.88, 150.98, 149.99, 149.61, 129.68, 128.50, 126.04,

121.37, 118.70, 116.92, 85.67, 53.77, 34.09. LCMS (ESI) m/z calcd for C15H10N4O6

(M+

+1): 342.26, found: 343. Anal calcd for C15H10N4O6: C, 52.64; H, 2.94; N,

16.37. Found: C, 52.76; H, 2.91; N, 16.25.

5-(4-oxo-2-thioxo-2,3,4,10a-tetrahydro-1H-chromeno[2,3-d]pyrimidin-5-

yl)pyrimidine-2,4,6(1H,3H,5H)-trione (6b): Pale yellow solid; mp: 222-224 °C;

1H NMR (400 MHz, DMSO-d6) δ: 11.95 (s, 1H); 11.32 (s, 1H); 11.17 (s, 1H); 10.99

(s, 1H); 7.34-7.06 (m, 4H’s); 4.72 (s, 1H), 3.9 (s, 1H). 13

C NMR (100 MHz, DMSO-

d6) δ: 170.01, 169.35, 163.97, 159.41, 155.88, 150.98, 149.99, 149.61, 129.68,

128.50, 126.04, 121.37, 118.70, 116.92, 85.67, 53.77, 34.09. LCMS (ESI) m/z calcd

for C15H10N4O5S (M+

+1): 359.33, found: 359. Anal calcd for C15H10N4O5S:

C50.28, H, 2.81; N, 15.64. Found: C, 50.38; H, 2.86; N, 15.52.

206

Some representative NMR spectra

Fig. 6.5 1H and

13C NMR of 4a

207

Fig. 6.6 1H and

13C NMR of 4b

208

Fig. 6.7 DEPT 13

C NMR spectrum of 4b

209

Fig. 6.8 1H NMR of 4c

210

Fig. 6.9 1H and

13C NMR of 5a

211

Fig. 6.10 1H NMR of 5b

212

Fig. 6.11 1H and

13C NMR of 6a

213

Fig. 6.12 DEPT 13

C NMR of 6a

214

Fig. 6.13 1H NMR of 6b

215

Fig. 6.14 1H-

1H COSY NMR of 4a

216

Fig. 6.15 1H-

13C COSY NMR of 4a

217

References

[01] (a) G. P. Ellis, I. M. Lockhart, The Chemistry of Heterocyclic Compounds:

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