Synthesis and Biological Activities of some Pyrimidine … · 2021. 1. 4. · ElkANzI., Orient.J. Chem., Vol. 36(6), 1001-1015 (2020) 1002 Fig. 1. Pyrimidine compounds that show pharmacological

ORIENTAL JOURNAL OF CHEMISTRY

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2020, Vol. 36, No.(6): Pg. 1001-1015

This is an Open Access article licensed under a Creative Commons license: Attribution 4.0 International (CC- BY).

Published by Oriental Scientific Publishing Company © 2018

Synthesis and Biological Activities of some Pyrimidine derivatives: (A-Review)

NAdIA ALI AHMEd ELkANzI1,2

1Chemistry Department , College of Science, Jouf University, P.O. Box: 2014, Sakaka, Saudi Arabia.2Department of Chemistry, Faculty of Science, Aswan University, P.O. box 81528, Aswan, Egypt.

*Corresponding author E-mail: [email protected]

http://dx.doi.org/10.13005/ojc/360602

(Received: September 01, 2020; Accepted: November 17, 2020)

ABSTRACT

Nitrogen containing synthetically and biologically important heterocyclic ring system namely pyrimidine possess both biological and pharmacological activities and defend as aromatic six heterocyclic with 1 and 3 nitrogen atom in ring. Preparation of pyrimidine via different methods offer its importance in fields of medicinal chemistry and Chemistry. Pyrimidines and their derivatives act as anti-inflammatory, anti-malaria, anti-tumor, cardiovascular agents, anti-neoplastic, anti-tubercular, anti-HIV, diuretic, anti-viral, anti-microbial, analgesic. This review give light up on biological and pharmacological activities of pyrimidine nucleus.

keywords: Antioxidant, Antibacterial, Antifungal, Antiviral, Pyrimidine derivatives.

INTROdUCTION

Because o f i t s d i f fe rent in t r ins ic biological proper ties Pyrimidine it become attractive for researcher in medicinal chemistry field1, pyrimidines are used as Mycobacterium tuberculosis2, antioxidants3, antidiabetics4. Heterocycles which contain pyrimidopyrimidine have therapeut ic proper t ies ant al lergic5, an t iox idant 6,7, an t iv i ra l 8, an t ih is tamin ic 9, cytostatic, immunomodulating10–12 herbicidal13, anticonvulsant14 activities. pyrimidines exhibit antimicrobial activities such as fungicidal15, antitoxoplasma16, antimalarial17,18, antibacterial19,20, anti f i ler ial21 anti leishmanial22,23, pyr imidine

(Fig. 1) broxuridine (I)-antiviral and brodimoprim (II)-respiratory tract and ear infections, trimethoprin (III)-antibacterial, antifungal flucytosine (IV),-liver disorder by orotic acid (V)24.

Pyrimidine nucleus act as antimicrobial agent25 so they are important chemicals in agricultural and drugs.

Pyrimidines comprise important interesting group of antibacterial drugs, which have made a major impact on the field of antibacterial chemotherapy particularly in the past few years. Pyrimidine nucleus act as chemotherapeutic agents and exhibit anticancer activities26.

1002ElkANzI., Orient. J. Chem., Vol. 36(6), 1001-1015 (2020)

Fig. 1. Pyrimidine compounds that show pharmacological activity

N

N NH2

NH2

OBr

O

N

N

O

Br

O

OH

OH

I

N

N NH2

NH2

OCH3

III

H3COC

H3COCN

HN O

NH2

F

IV

HN

HNO

O

OH

O

V

IIAntiviral

respiratory tract and ear infections

Antibacterial Antifungal Liver disorder

H

Synthesis and biological activities of pyrimidine derivatives Reaction of diazonium salt (1) and (2) in solution of NaOH yield the corresponding (3) which react with sulphonamide derivatives diazonium salt give compound (4 a-c) (Scheme 1)27, compounds (4b) and (4c) exhibit good results against anticancer and antifungal efficacies,

Gram-negative and gram positive respectively also both pyrimidine derivatives azo dyes and thiazolyl azo dyes derivatives displayed good properties on polyester fabrics, but thiazolyl azo dyes derivatives exhibit good properties than pyrimidine derivatives azo dyes27. sulphonamide-diazobenzene derivatives exhibit pharmacological activities so it used as nontextile27.

Scheme 1: Synthesis of diazobenzene dyes (4a-c), 4a (81%), 4b (77%), 4c (79%).

HO

HOOC NH2NaNO2/HCl

HO

HOOC N N ClOHHO

1 2

10%NaOH

HO

HOOC N N

OH

COOH

10%NaOH

3 (68%)

NNCl S NHO

O

HO

HOOC N N

OH

R

NN S NHO

O R

4a-c

4a:R= H

4b:R=N

S

4c:R=N

N

Treatment paracetamol(5) with 2,3-di chlorobenzaldehyde(6) in solution of kOH at 298k afford chalcones(7). Reaction of chalcones (7) with urea and potassium hydroxide in methyl alcohol yield the corresponding(8) Also treatment of chalcone(7) with Thiourea and kOH in methyl alcohol give compound(9), treatment of chalcone (7) and hydrazine monohydrate in AcOH provide the corresponding(10), the product recrystallized with ethanol28.

Reaction of triazole(11) with (12 a) by using different solvent such as methanol/HCl, ethanol, acetic acid, there is no reaction but the reaction of

mixture in DMF using reflux and heat in presence of potassium carbonate anhydrous provide triazolo pyrimidine(15a) or (18a).

The confirmation of (18a) was performed via reaction of (19) and malononitrile at the same condition provide the same sample of (18a). Treatment of triazole(11) with (12b) provide triazolo pyrimidine (18b). Also, mixing of (11) with (12c) give amino derivatives (18c). Another method for the preparation of (18b, c) is the reaction of benzyl cyanide and cyanoacetate with (19), compound (18d) was synthesized by reaction of (12) with


triazole (11). While reaction of (12e) with triazole (11) provide unsubstituted triazolo pyrimidine (18e).Triazolo pyrimidine (22) was synthesized via reaction of compound (20) with triazole (11), the reaction proceed by reflux in presence DMF/k2CO3 via cyclization of (21).

Refluxing of compound (22) with substituted 1, 4-benzoquinone and acetonitrile (3eq.) via refluxing provide triazolopyrimidine (23) (Scheme 3). Cyclocondensation of β-enaminones (24a–c) with 11 and acetic acid via reflux give substituted pyrimidines, when equimolecular amount from

compound (11) react with β-enaminones (24a) in presence of DMF/k2CO3 via refluxing for 2 h to provide isolated compounds (25a) and (26) in equal ratio29,30.

Compounds (25b,c) were prepared via treatment of (24b, c) with compound 11 (cf. Scheme 4). Pyrimidine derivatives (30a–n) (Table1)31 were prepared via treatment of three component (27), (28), (29) in ethanol.

HO NH

CH3

O ClClO

HO NH

CH

OKOH

CH3OHCH

ClCl

7

NH2CONH2/KOH,CH3OH

NN

HN OH

OH

Cl Cl

8

NN

HN OH

SH

Cl Cl

9

NH2CSNH2/KOH,CH3OH

NH2H4/CH3COH/C2H5OH

NH

10

HO

NHN Cl

Cl

5 6

Scheme 2: Synthesis of pyrimidine (8) and (9)

N NH

N NMe2R

X

N

NN

NH2OH

R N

NN

HN R

NH

N

NN

N R

NH2

1314 15

N

NNH

HN

R

CNN

NN

HNR

17NH16

N NH

NNMe2

DMFDM1112e

N

NN

1918e

Ph

CN

CN

N NH

N HN Ph

NCCN

N

NN

HN

NH2

CN

Ph

20

2122

DDQ,MeCN

50CN

NN

N

NH2

CN

Ph

23

12a,X=R=CN12,X=CN,R=COOEtc,X=CN,R=Phd,X=CN,R=He,X=CO,R=H

NH2

11 12a-d

N

NN

R

NH2

RCN

18a-d

Scheme 3: Synthesis of pyrimidine 22 and 23

N N

N

H

NH2 Ar NMe2

O

N

NN

N

ArN

NN

NPh

25a-c 2624a,R=Phb,R=2furylc,R=thienyl

11

Scheme 4: Synthesis of pyrimidine derivatives 25a-c and 26


Table 1: Synthese of pyrimidines (30a–n) (30a–n)31

Compound No Aldehyde Structure

30a CHOCl HN

NH

N

N

N

O

O

Cl

30b

O2N CHO

HN

NH

N

N

N

O

O

NO2

NC CHO

HN

NH

N

N

N

O

O

CN

30c

30d

Br CHO

CHO

Cl

HN

NH

N

N

N

O

O

Cl

30e

30f

CHO

O2N

HN

NH

N

N

N

O

O

NO2

30g

OHC

Cl

HN

NH

N

N

N

O

O

Cl

HN

NH

N

N

N

O

O

NO2

30h

O2N

Cl

30i

OHC Cl

HN

NH

N

N

N

O

S

Cl

30j

OHC NO2

HN

NH

N

N

N

O

S

NO2

30k

OHC CN

HN

NH

N

N

N

O

S

CN

30l

OHC

NO2

HN

NH

N

N

N

O

S

NO2

30m

OHC

HN

NH

N

N

N

O

O

30n

OHC

OH HN

NH

N

N

N

O

O

OH

HN

NH

N

N

N

O

O

Br


CHO

R

HN

NH

O

OX N

N

NH2

Ethanol

Reflux HN

NH

N

N

N

R

O

X

30,R=NO2,Cl,CN

27 28 X=O,S29

Scheme 5: Synthesis of pyrimidines (30a–n)

Scheme 6: mechanism for synthesized pyrimidines (30a–n).

NH

O

X OH

CHO

R

-H2O

NH

O

X O

R

N

NH2NNH

O

X O

R

N

NNH H

Michael Addition

NH

O

X O

R

N

NNH

Cyclization

NH

O

X

R

N

NNHH

-H2O

Air OxidationNH

O

X

R

N

NN

R= - NO2, -Cl, -CN

X= O,S

28 27 293132

33

3430a

The condensation of thioxopyrimidine (35) with substituted aromatic aldehydes and α chloroacetic acid afford the corresponding thiazolopyrimidine derivatives (36a–h) (Scheme 7) 32.

Treatment of 2-chloro-N-substituted-phenylacetamide (37a–c) with thioxopyrimidine 35 and dimethyl formamide, potassium carbonate,

provide (38a-c) and (39) obtained via reaction of compound (35) with p-toluene in presence of k2CO3 and DMF in stirring resulting N-alkylation product. treatment of (35) with ethylacetoacetate and potassium carbonate anhydrous afford compound (40) which react with hydrazine hydrate and ethanol provide the corresponding compound(41) (Scheme 7)32.

NH

NH

O

S

NC

H3CO

NH2NH2.H2O

NH

NH

O

NHNH2

NC

H3CO41

35

ClCH2COOH/Ar-CHO N

H

N

ONC

H3CO

S

OH

Ar

(36a-h)

Ar-NHCOCH2Cl

(37a-c)

NH

NH

O

S

NC

H3CO (38a,b) HN

OH

ArOCH3

N

N

NC

SO

HNAr

ClCl

OAr NH2

K2CO3/DMFAr N

H

ClO

37a-c37a,Ar= Cl

37b,Ar= SO2NH2

37c,Ar= ClCH3SClO

O NH

N

ONC

H3CO

S

S

CH3

O

O

ClCH2COOC2H5 NH

NH

ONC

H3CO

SCH2COOC2H5

39

40

NH2NH2.H2O41

38c

Scheme 7: Synthetic pathway of compounds (36-41)


Table 2: The syntheses of compounds (36a-h)32

Compound No. Ar Structure32

36a

OCH3

NH

N

ONC

H3CO

S

OH

OCH3

NH

N

ONC

H3CO

S

OH

C4H3S 36b C4H3S

36c

OCH3

OCH3

NH

N

ONC

H3CO

S

OH

OCH3

OCH3

36d

Cl

NH

N

ONC

H3CO

S

OH

Cl

36e

NO2

NH

N

ONC

H3CO

S

OH

NO2

36f

NH

N

ONC

H3CO

S

OH

36g

ClCl

NH

N

ONC

H3CO

S

OH

Cl

Cl

36h

OH

NH

N

ONC

H3CO

S

OH

OH

ClOH

O

N

O

SH

NC

H3CO 35

- HCl N

NH

O

S

NC

H3CO OH

O

-H2O

N

N

ONC

H3CO

S

OH

H

O

Ar

36N

N

ONC

H3CO

S

OH

H

N

N

ONC

H3CO

S

OH OH

HH-H2O

N

N

ONC

H3CO

S

OH

Ar

Scheme 8: Mechanism for synthesis of (36a-h)


NH

NH

ONC

H3CO35

S NH2 NH2

N

NH

ONC

H3CO

SHH

NNH2H

N

NH

ONC

H3CO

SO

O

NH2 NH2

N

NH

ONC

H3CO

S O

O

NH2 NH2

SN2 arom.

N

NH

ONC

H3CO41

NH

NH2

CH2COOEtSH

-H2S

40

Scheme 9: Mechanism for compound (41)

N

NH

ONC

H3CO41

NH

NH2

H3CO CN

CN

N

NH

ONC

H3CO

NH

N

OCH3

pyridine/Ref lux,8h

Ac2O/Ref ./2h.

N

NH

ONC

H3CO

NH

NH

42

43COCH3

N

NH

ONC

H3CO

NH

NO

ACOH,Ref .,8h.44

NHCOCH2Cl

Cl

DMF/K2CrO3Stirring r.t./5-8h.

N

NH

ONC

H3CO

NH

NHH2C

45

NH

O

Cl

Scheme 10: Conversion of (41) to pyrimidine derivatives (42–45)

N

NH

ONC

H3CO41

NH

NH2

Ar

H CN

CN

N

NH

ONC

H3CO

NH

NH

Ar

NC CN-CH2(CN)2

N

NH

ONC

H3CO42

NH

N

Ar

Scheme 11: Suggested mechanism for (42)


N

NH

ONC

H3CO41

NH

NH2

NaNO2/HCl

Stirring r.t./2h.

N

N

ONC

H3CO46

NH

NN

HCOOH,Ref/10h.N

N

ONC

H3CO47

NH

N

N

N

ONC

H3CO48

NH

N

COCl

K2CO3/DMF/Stirring

r.t./8h.

CS2

pyridine/Ref /8h.N

N

ONC

H3CO49

NH

NH

S

Scheme 12: Preparation of triazolo and tetrazolopyrimidinone derivatives (46–49)

N

NH

ONC

H3CO41

NH

NH2

C SS

N

NH

ONC

H3CO

NH

NH

SS

N

N

N

ONC

H3CO

NH

NH

H SS

HN

N

N

ONC

H3CO

NH

NH

S

49

Scheme 13: mechanism (49)

Treatment of (35) with hydrazine hydrate affords hydrazino derivative (41). Treatment of (41) and arylidene provide the corresponding (42) (Scheme 11).

Synthesis of compounds (42–45) appears in (Scheme 10). Compound (42) obtained via reaction of p-methoxybenzaldehyde with hydrazine derivative(41)32.

The acetyl derivatives 43 were obtained by reaction of compound (41) and acetic anhydride under reflux. Reaction of compound(41) with cyclopentanone in ethanol provide (44). Compound (45) was obtained by reaction of hydrazine derivative (41) with acetamide derivatives. Tetrazolopyrimidine (46) was obtained via diazotization of compound (41). Reaction of (41) with formic acid provide pyrimidines (47) (Scheme 6). Treatment of benzoyl chloride with compound (41) affords corresponding Triazolopyrimidone derivative (48). Reaction of

(41) and carbon disulfide in presence of pyridine provide triazolopyrimidone derivative(49)32. The synthesized compounds of cyanothiouracil derivatives (36–49) were obtained from cyanothiouracils and dihydropyrimidine carbonitriles derivatives. Some of these compounds exhibit Potent activities, anticancer and Antimicrobial32.

Synthesis of (54a-l) proceed via two-step (Scheme 14)33, the synthesis of (54a-I) via both methods microwave and conventional.in the conventional method substituted aldehydes (50a-l) treated with, malanonitrile (51), and 1, 3 dihydroxy benzene (52) afford the corresponding pyran derivatives (53a–l). Cyclization of pyrane derivatives (53a–l) by using nano catalyst provide (54a–l) this green method and highly efficient, Also the reaction occur without catalysts by using reflux for 8 hours.33.

The synthesized compounds exhibit antifungal, antioxidant and antibacterial effect33.

HR

OCN

CNO O N

N

R NH2

OH

R

CN

NH2

OH

OH

++

CH2COONH2

50 51 5253a

54a

HC(OEt)3

60C

Nano CUO-Ag

HO

DBU/50CEthanol

Scheme 14: synthesis of pyrano[2,3-d]pyrimidine (54a)


Table 3: Syntheses of pyrano pyrimidine derivatives (54a–l)33

Compound No. R Structure

54a

O N

N

NH2

OH

54b

H3CO

H3CO

O N

N

NH2

OH

OCH3

OCH3

54c

Br

O N

N

NH2

OH

Br

54d

Cl

O N

N

NH2

OH

Cl

54e

H3CO

O N

N

NH2

OH

OCH3

54f

C2H5O

O N

N

NH2

OH

OC2H5

54g

O2N

O N

N

NH2

OH

NO2

54h Cl

OH

O N

N

NH2

OH

Cl

HO

54i

OH

O N

N

NH2

OH

HO

54j

O

O

O N

N

NH2

OH

O

O

54k

HO

H3CO

54l

O N

N

NH2

OH

O

O N

N

NH2

OH

OH

OCH3

O


CHO

R R

+CN

CN

CN

CN

OH

OH R C

C

C

N

N

O

OH

DBU

CN

NHOH

R

H

+O

HI

CyclizationCN

NHOH

Cl

+O

CN

NH2HO

R

+O

53a

50 51

H

Scheme 15: mechanism for synthesis of compound (54a)

O

Ar

OH NH2

CN

C OEtOEt

OEt

CuO-Ag

+..

53a

H

C2H5OH

O

Ar

OH NH

CN

C OEtOEt

..

CuO-Ag

N HOOCCH3

H

HO N

H

C

NC

Ar

OH

N

HCuO-Ag

h

O NCH

NH

Ar

OH

NH

CuO-AgO N

CH

N

Ar

OH

NH2

CuO-Ag

O NCH

NH

Ar

HO

NH2

54a

-CH3COOH

-Et2OH

Pyr imid ine (58) was prepared by treatment of methylthiopyrimidinone (55) with bromomethylacetylene (56) in k2CO3/DMF at room temperature (Scheme 16)34.

Treatment of pyrimidine (57) and (59a)

in the absence of catalyst lead to there is no formation of product formed after 3 h the reaction give maximum of the yield when use CuI/Mg-Al-lDH catalyst [28, this method was easy, clean reaction, short reaction time and high yield34.

N

N OMeSN

NH

OBrH2C

MeS

N

N OMeS

OR N

NH

MeS OK2CO2

r.t.

55 5657 58

7 :3

Scheme 16: Synthesis of compound 57 and 58


N

N OMeS

N

N OMeS

+ [CuI-Mg-Al-LDH]

HI

Cu(I)-Mg-Al-LDH

N

N

SMeO

NNN

Ar

N

N

SMeON

N

SMeO

N

NN

ArCuI-Mg-Al-LDH

NN

Cu

N

ArMg-Al-LDH

59

(A)

60 (B)

HI ArN N NH

(C)

Scheme 17: Proposed mechanism for synthesis of pyrimidine derivatives (60)

Table 4: Syntheses of pyrimidine derivatives (60a-i)34

Compound No Azide Structure (60a-i)28

60a NO2N3 59a N

N OMeSN

N N

NO2

60b N3

NO3

59b N

N OMeSN

N N

NO2

60c N3

O2N

59c N

N OMeSN

N N

O2N

60d N3

O2N

Cl59d N

N OMeSN

N N

Cl

O2N

60e N3 Cl

NO2

59e N

N OMeSN

N N

Cl

NO2

60f N3 NO2

Cl

59f N

N OMeSN

N N

NO2

Cl

60g N3

Cl

59g N

N OMeSN

N N

Cl

60h N3

Cl

59h

60i N359h

N

N OMeSN

N N

Cl

N

N OMeSN

N N

Reaction of compound (63) with 64,66,68 afford the corresponding thioxypyrimidine (67) and pyridinethione (69) these compounds was

considered as a key for synthesis of different pyrimidine derivatives35. The formation of compound (63) indicated in (Scheme 18)36.


Compound (65) (Scheme 18)37 was prepared by treatment of chalcone (63) with thiourea (64) compound (67) was prepared via treatment of chalcone (63) and dihydropyrimidinone (66) (Scheme 18)38. the compound (69) was prepared by treatment of 2-cyanoethanethioamide (68) with chalcone (63) in diaoxane and piperidine catalyst at reflux the reaction proceed via cyclocondensation reaction (Scheme 18)39.

Reaction of (65) or (67) with the appropriate nitrilimines (71) afford the corresponding triazole compound, the nitrilimines (71) prepared by treatment of hydrazonoyl chlorides (70)40 With triethylamine (TEA). Triazolo pyrimidine (75a) (Scheme 19) was prepared by reaction of hydrazonylchloride (70a) with pyrimidine-2(1H)-thione (65) at reflux. In addition, reaction of hydrazonyl chlorides 70b-d with compound 65 provide triazolo pyrimidines (75b-d) (Scheme 19).

Init ial alkylation of (65) to provide thiohydrazonate (72) and then cyclization to provide the spiro-intermediate (73) and rearrangement occur41 provide corresponding (75) via (74) (Scheme 19).

Also treatment of thioxopyrido[pyrimidinone (67) with hydrazoe (70a-c) provide triazolopyrimidines

(76a-c) (Scheme 19)38, thienopyridine (78) (Scheme 20) was synthesized by treatment of 2-dihydropyridine-3-carbonitr ile (69) with 2-chloroacetamide (77) in sodium ethoxide at reflux42. thienopyrimidinone derivative (80) (Scheme 20)42 was prepared by reaction of thieno[2,3-b]pyridine-2-caboxamide derivative (78) with (79). Also, 2-carboxamide derivative (78) treated with both (81), (83a) and (83b) to give compounds (82) and (84a,b,) (Scheme 20). pyridotpyrimidinone (86)(Scheme 21)42 was synthesized by reaction of thienopyrimidinone (80) and iodomethane (85) in ethanolic sodium ethoxide. Preparation of fused triazole was proceed by treatment of (86) with hydrazonyl chlorides (70)43. triazolopyrimidinone derivative (88a) was synthesized by reaction of compound (86) with hydrazonyl chloride (70a) in dioxane and triethylamine at reflux, to provide (87) and then loss methane thiol provide (88a) (Scheme 21). Also, compound (86) treated with (70b-d) to provide triazolopyrimidinones (88b-d) (Scheme 21). Treatment of 2-thioxopyridothienopyrimidin-4(1H)-one derivative (80) with hydrazonyl chloride 70a in dioxane and triethylamine at reflux afford the corresponding compound (88a).

(Scheme 21)35. the newly pyrimidines was exhibit In vitro antimicrobial activities35.

O

O

CHO

S +

SO

KOH / ETOH

Strring, rt,1h, 82%

61 62

OO

O

H2N NH2

S

NH

NH

S

OO

KOH/EtOH,Ref lux,87%

S

N

OO

SNH

NH

SO

NH

HN S

O

H2N

ACOH,Reflux,8h,82%

H2N

CNS

EtOH/pip., Ref lux,5h,80%

63

64

65

66

67

68NH S

OO

S69

CN

Scheme 18: Preparation pyrimidinone (69)


N

R

X X

NHN

ClR

N

N

NS

O NN

R

OO

XTEA / DIOXANE

67

71 70 76

N

NH

S

OO

S N

R

NH

X

Dioxane,Ref lux,6h80-89%

NH

NH

OO

S N N

S

X

R NH

NH

OO

S N NH

X

R N

N

OO

S

S -H2S NN

R

X

7273 74 75

70-75a,R=COCH3 ,X=Hb,R=COCH3 X=CH3c,R=CO2C2H5, X=Hd,R=CO2C2H5, X=CH3

Et3N76a,R=COCH3 ,X=H

b,R=COCH3 X=CH3c,R=CO2C2H5, X=CH3

Scheme 19: Preparation] triazolopyrimidines (75) and (76)

Scheme 20: preparation pyrimidinones (80), (82) and (84a, b)

CONH2

N

OO

S

S

NaOEt / EtOHReflux, 3 h85-92% CONH2

NH2

78

77

84 a,R=Hb,R=CH3

Reflux ,4h87-89%

69 Cl CO(OEt)2

Ref lux ,4h86%

CS2 79

pyridine ,Ref lux ,12h91%

RCO2R/

83a,b83a,R=R1=H83b,R=CH3,R1=COCH3

81

N

OO

S

S

NHHN

S

O

80

N

OO

S

S

NHHN

O

O

82

N

OO

S

S

NHN

R

O

N

OO

S

S

NHNH

S

O

N

OO

S

S

NNH

SMe

O

Mel85

NaOEt/EtOHReflux 1h, 94%

N

OO

S

S

NN

NN

R

ON

OO

S

S

NN

NSMe

O

N

R

87

86

70

TEA / DioxaneReflux, 8h

83-89%

-MeSH

H

Ar

NN

HCl

R X

70,87,88a;R=COCH3,X=H;b;R=COCH3,X=CH3;c;R=CO2C2H5,X=H;d;R=CO2C2H5,X=CH3

O

70a

-H2S

80

88

Scheme 21: Preparation triazolopyrimidinones (88)


ethyl 3-amino-2-cyano-6-hydroxy-7, 12-dioxo-2, 7, 12, 12a-tetrahydro-1H-benzo[g]pyrimido [1, 2-a]quinoline-5-carboxylate 90 was prepared by reaction of alkylidenemalononitrile derivatives with

ethyl 2-amino-4-hydroxy-5, 10-dioxo-1, 5, 10, 10a-tetrahydrobenzo[g]quinoline-3-carboxylate 89, the pyrimido quinolone derivatives have photodiode applications44.

CONCLUSION

The current study gives a portrayal of the biological and natural significance of heterocyclic related pyrimidine nucleus, these pyrimidine unit exhibited significant and assorted organic properties, the examined pyrimidine derivatives prepared by cyclocondensation reaction, also through reaction of chalcone with different 1, 3-dinucleophiles. Pyrimidine

derivatives that have biological activities.

ACkNOwLEdgMENT

The author grateful to Jouf University, Saudi Arabia and Aswan University, Aswan, Egypt is gratefully acknowledged.

Conflicts of InterestThe author declares no conflict of interest.

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Documents

Synthesis and Biological Activities of some Pyrimidine … · 2021. 1. 4. · ElkANzI., Orient.J. Chem., Vol. 36(6), 1001-1015 (2020) 1002 Fig. 1. Pyrimidine compounds that show pharmacological