synthesis and biological activities of some pyrimidine … · 2021. 1. 4. · elkanzi., orient.j....
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ORIENTAL JOURNAL OF CHEMISTRY
www.orientjchem.org
An International Open Access, Peer Reviewed Research Journal
ISSN: 0970-020 XCODEN: OJCHEG
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
1003ElkANzI., Orient. J. Chem., Vol. 36(6), 1001-1015 (2020)
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
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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
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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)
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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)
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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)
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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)
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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
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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
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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.
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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)
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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)
1014ElkANzI., Orient. J. Chem., Vol. 36(6), 1001-1015 (2020)
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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