International Journal of ChemTech Research -...

International Journal of ChemTech Research CODEN (USA): IJCRGG ISSN: 0974-4290

Vol.8, No.7, pp 297-317, 2015

Isoxazole—A Basic Aromatic Heterocycle : Synthesis,Reactivity And Biological Activity

S.S.Rajput1*, Dr. S.N.Patel2, Nilesh B. Jadhav3

1Department of Chemistry, SVS’s Dadasaheb Rawal College Dondaicha 425408,Maharashtra, India.

2Department of Chemistry, S.P.D.M.College, Shirpur 425405, Maharashtra, India.3Department of Chemistry, S.P.D.M. College, Shirpur425405, Maharashtra, India.

Abstract: This review summarizes the synthetic method , reactions and biological applicationof isoxazoles and summarizes recent development in their derivatives such as chalcone, 5-isoxazole penicillins,shiff base etc.over the last years.The biological activities of isoxazoles isalso briefly discussed .Formation of isoxazoles & fused heterocyclic isoxazoles derivativesconstitute an interesting class of heterocycles which have diverse biological activities.Keywords: Isoxazoles, biological activity, 5-isoxazole penicillin.

1. Introduction

Substituted Isoxazoles are important compounds of many drugs and drug candidates. It is one of themost fundamental objectives of organic and medicinal chemistry is the design and synthesis of moleculeshaving value human therapeutic agents. The diversity of biological activities and pharmaceutical uses havebeen attributed to them, such as isoxazole is a part of many active molecule possessing activities such as Anti-tubercular[1], Analgesic[2], Antipyretic[2], Anti-inflammatory[2][3], Antiplatelet[4], Anti-HIV[4], Antagonistactivity[4], CNS depressant[5], Antifungal[6][7], Antibacterial[6][7][8], Anti-oxidant[7], Anticancer[9][10] .

The Substituted isoxazole moiety 1 appears as an interesting precursor of many biologically active ofthe above class compounds.

ON

1

2

34

5

Isoxazole1

This review provides an overview of the synthesis and reactivity of isoxazole and its derivatives .In firstpart we intend to outline the general methods by which substituted isoxazole are prepared .The second and thirdparts are devoted to the chemical reactivity of substituted isoxazoles.

2. Synthetic Methods

There have been a number of practically important routes to synthesize isoxazoles.

S.S.Rajput et al /Int.J. ChemTech Res. 2015,8(7),pp 297-317. 298

2.1 From furfuraldehyde using NH2OH.HCl

A well established route for the synthesis of substituted isoxazole (4) was reported from chalconesby claisen- Schmidt condensation of aldehyde, acetophenone and NH2OH.HCl.[Scheme 1][11]

O CHOR COCH3

C2H5OH

O CH CH

O

R

NH2OH.HCl

CH3COONa

ON

ORNH2 Br,NO2,Cl,F,CH3

+40%NaOH

1 2 3

4

R= ,

Scheme 1

2.2 By Knoevenagel Condensation using Sod.Ethoxide

The convenient method was reported for synthesis of substituted isoxazoles in which Knoevenagelcondensation of ethyl acetoacetate (6) and 1,3 diaryl -2-propen-1-one(5)using sodium ethoxide took place.The intermediate (8) was react with ethyl formate and sodium ethoxide gives compound (9) which onreaction with NH2OH in acetic acid afforded substituted isoxazole (10)[Scheme 2][12]

Ar

O

Ar

O

CO2ETNaOET

O

Ar

CO2Et

Ar

O

Ar Ar

HCO2ETO

Ar

OH

Ar

NH2OH

ACOH

Ar

O N

Ar

+

Dry Benzene10%NaOMe,Dil.HCl

5 6 7

89

10

Scheme 2

2.3 Synthesis using Click Chemistry Approach

The method includes transition metal catalyzed 1,3-dipolar cycloaddition of nitrile oxides(12) toalkynes (11)gives substituted isoxazoles(13)[Scheme-3][13]

NH

Xn

N+

O

CAr

ONAr

NHPGn X

PG +Cu(I) Cat.

11 12

13CF3

CF3

Scheme 3


2.4 From Glutaric acid using SOCl2,DMF/POCl3 and NH2OH.HCl

Glutaric acid (14) treated with amine using SOCl2 gives N-substituted phenyl glutarimides(15) whichon diformylated using Vilsmeier –Haack Reaction afforded dihalovinyl aldehyde(16).The halovinylaldehydeon condensation with acetophenone gives chalcone (17)which underwent ring closer with NH2OH.HClfurnished isoxazoles(18)[Scheme-4][14]

COOHHOOC

SOCl2

NH2

NO ON

CHOOHC

ClCl

O

CH3

N ClCl

O

R'R'

O

R

NH2OH .HCl

CH3COONaCH3COOH

R

ON

N ClCl

NO

R'R'

RReflux R

DMF,POCl3

0-50C

R

R'--C

in

14

15 16

1718

Scheme 4

2.5 From Tetrazole derivative

Treatment of Benzonitrile (19), sodium azide (20) in presence of DMF & Ammonium chloridefurnished 5- phenyl tetrazole(21) .5-phenyl tetrazole treated with acetic anhydride resulting in the formation ofacetyl tetrazole(22) which was condensed with substituted aldehydes followed by cyclization usingNH2OH.HCl furnished isoxazoles(24) which exhibited anticancer activity.[Scheme-5][15]

CN

NaN3 NNNN

H

Acetic anhydride

H2SO4

NNNN

COCH3

a)substituted Aldehyde

b)KOHN

NNN

O

R

NH2OH.HCl

R

NNNN

N

O

+a)DMF

b)Ammonium chloride

19 20 21

22

23

24

Scheme 5


2.6 Using 2-acetyl thiophene

A convenient route for the substituted Isoxazole (28) is achieved by refluxing NH2OH.HCl withchalcone (27) in presence of ethanol.[Scheme-6][16].

SO

CH3 OHCR NaOH

EtOHS

O

R

NH2OH.HCl

EtOH

OS

NR

+

25 26 27

28

Scheme 6

2.7 Microwave assisted synthesis of Isoxazole

Microwave assisted synthesis of isoxazole (34) reported by author Kumudini Bhanat,Bharat Parasharand V.K.Sharma from Irradiation of Chalcone (33) with NH2OH.HCl.[Scheme-7][17]

NC CH2

O

OC2H5N C

O

NH NH2 N C

O

N N

NH2O

R'--C6H5--CHOCONC.HCl

N C

O

N N

NO

CH

OH

R'--C6H4--CHO

KOH

N C

O

N N

NO

CHCH

OH

R

NH2OH.HCl

KOH

N C

O

N N

NN

OR

CH

OH

+

29 30 31

32

33

34

Scheme 7

2.8 Synthesis via [3+2] cycloaddition


The [3+2] cycloaddition reaction between alkynyl dimethyl silyl ethers (35) and aryl or alkyl nitrileoxide (36) gives isoxazolyl silanols (37).[Scheme-8][18]

R' N+ O

EtO Si

Me

Me

ON

R

R

Si

OHMe

Me+

R2

1

2

1.HEAT

2.ACOH

36

35

37

Scheme 8

2.9 From cycloaddition of Azolylacetylenes to nitrile oxides

Isoxazoles (43) have been synthesized from cycloaddition of enamines (40) with nitrile oxide (41)through the intermediate (42) [Scheme-9][19]

Az MeMe2NCH(OMe)2

Az

NMe2

Cl

ArN OH N

+O

ON

NMe2

Az

H

Ar

ON

Az

Ar

N-Methyl Imidazole

--HCl[ Ar ]

Dioxane

-Me2NH

38

39

40

41

42

43

Scheme 9

2.10 From Benzofuran

The reaction of 5-bromo-2-acetyl Benzofuran (44) with a different aromatic aldehydes (45) inpresence of alkali gives chalcones (46) which on treatment with hydroxylamine hydrochloride affordedIsoxazole derivatives of Benzofuran(47)[Scheme-10][20]

Br

O

O

CH3

R--CHOEtOH

Br

O

O

R

NH2OH.HCl

aq.NaOH

Br

ON O

RC6H5,C6H4OH(P),C6H4Cl(P),C6H4OCH3(P),C6H4N(CH3)2

+

Where R=

[Analgesic,Antiinflamatory,Antimicrobial Activity]

44

45 46

47

Scheme 10


2.11 Synthesis via 1,3 dipolar cycloaddition of α,β unsaturated ester & nitrile oxides

The multistep synthesis of isoxazole (52)(53) have been reported via 1,3 dipolar cycloaddition ofα,β unsaturated ester and nitriles oxide by author W.Marek GOLEBIEWSKI .[Scheme-11][21]

R

R

RR

R

HO

NaOH

NH2OH.HClR

R

RR

R

N H

OH

NCS

DMF R

R

RR

R

NCl

OH

CH2 CH OEt

O

Et3N

R

R

RR

R

ON

O

OEt

NBS/DMF

CH3COOKCH3COOH

R

R

RR

R

ON

O

OEt

R

R

RR

R

ON

O

Cl

1

2

3

4

5

2

3

4

5 1

2

3

4

5 1

2

3

4

5 1

2

3

4

5 1

I)NaOH

II)(COCl)2

III) HX

2

3

4

5 1

4849 50

5152

53

Scheme 11

2.12 Synthesis from oxime using NCS, HCl, DCM & Et3N, DCM Reagents

The substituted aromatic aldehyde (54) treated with NH2OH.HCl , NaOAc gives oxime(55) whichundergoes [3+2] cycloaddition with other chiral compound gives isoxazoline intermediate (56) which onoxidation with MnO2 gives isoxazole derivatives (57)[Scheme-12][22]

X

O

HNH2OH.HCl,NaOAc

EtOH,H2O X

N

H

I) NCS,HCl,DCMII)Et3N,DCM

O

X O

ONMnO2

Toluene X O

ON

OH

Reflux 40 min

54 55

56

57

Scheme 12


2.13 Synthesis from different oxime with different olefins

An alternative , fast & clean method was reported for the synthesis of substituted isoxazole(63) &(67) from aromatic aldehyde (58) and carbomethoxy benzaldehyde (59).[Scheme-13][Scheme-14][23]

CHO

NH2OH.HCl

NaHCO3

N OH

O

H

O

OMe

CH3

O

OMeCHCl3 ,Py

NCS,TEA

NO

CO2R

CCl4NBS

NO

CO2R

P(Ph)3+Br-

NaH

+

5859

6061

6263

Scheme 13

CHO O

H

O

OMe

O

OMeN

CHCl3 ,Py

NCS,TEA

N

CO2R

OCCl4NBS

ON

CO2R

CH3

NH2OH.HCl

NaHCO3

OH

P(Ph)3+Br-

NaH

+

5859

6465

6667

Scheme 14

2.14 Aqueous one pot synthesis of isoxazole

A novel one pot synthesis of isoxazoles (71) has been accomplished under microwave irradiationof three component reaction of 1,3 diketone (68) dimethyl formamide dimethyl acetal (69) and NH2OH.HCl(70). [Scheme-15][24]


n

O

ON

MeO

MeO

Me

MeNH2OH n

O

ON

+ +

Where n=0 , 1,3- cyclopentanedione n=1, 1,3-cyclohexanedione n=2, 1,3-cycloheptanedione

68 69 7071

Scheme 15

2.15 Synthesis from tropolone

A mixture of 3-acetyl-5-bromo tropolone (72) and hydroxyl amine hydrochloride (73) in methanoland promoter was refluxed for 10 hrs to obtain isoxazole(74)[Scheme-16][25]

O

O

Br

OHNH2OH.HCl

MeOH

O

Br

ON+

Reflux,10 hrs

7273

74

Scheme 16

2.16 Synthesis from Curcumin using NH2OH.HCl

A novel one spot synthesis of isoxazole (77) was reported by refluxing a mixture of Curcumin (75),NH2OH.HCl (76) with catalytic amount of pyridine in ethanol. [Scheme-17][26]

O

OH

O

O

OH

O

py,EtOH

NH2OH.HCl

O

OH

O

OH

NO

Refluxed,18hrs,80%

+75

76

77

Scheme 17

2.17 Synthesis using p- chloro phenol

Multistep reaction on p-chloro phenol (78) provides the intermediate (85). The intermediate ontreatment with hydroxyl amine hydrochloride afforded isoxazole (86) in good yield.[Scheme-18][27]


OH

Cl

(CH3CO)2O

CH3COONaCl

OCOCH3 AlCl3

Cl

OH

COCH3

Cl2In ACETICACID

Cl

OH

COCH3

Cl

NaOH,

C6H5COClCl

OCOC6H5

COCH3

Cl

KOH/BVT

Pyridine

Cl COCH2COC6H5

Cl

OH R--CHO

EtOH,Py

O

Cl

Cl

O

R

COC6H5

I2

EtOH

O

Cl

Cl

O

R

COC6H5

NH2OH.HCl

EtOH,Py

OH

Cl

Cl

ORN

COC6H5

1200C

10%

78 79 80

8182

83 84

8586

Scheme 18

2.18 Using Cycloaddition reaction of Aromatic aldoximes & propiolonitrile

A mixture of aromatic aldoximes (88),3-(4-methoxy phenyl)propiolonitrile(87) and chloramine –Tin ethyl alcohol was refluxed afforded isoxazole derivatives (89)[Scheme-19][28]

MeO CN

RR

CH N OH

1

2

CAT

EtOH

ON

RR

MeO

CN

1

2

+

1000C ,3 hrs87

8889

Scheme 19

2.19 Synthesis using copper catalyst

The quinolene carbaldehyde (90) is mixed with NH2OH.HCl & chloramine-T trihydrate is catalyzedby CuSO4 with copper turnings afforded isoxazole derivatives(93)[Scheme-20][29]


N R

O

H a)NH2OH.HCl,KOH

b)TsN(Cl)Na.

N R

N+

O

O

ONH

R

O

O2

Cu/CuSO4O

ONH

R

O

O2

N R

ON

11

1

3H2O

+

90 91

9293

Scheme 20

2.20 Microwave induced synthesis of isoxazole

The p-amino acetophenone (94) on diazotization and coupling with N-methyl piperazine yield(95).In which Substituted aldehyde were added gives intermediate (96) which cyclised with hydroxylaminehydrochloride furnished isoxazole derivatives (97) by microwave assisted reaction.[Sheme-21 ][30]

NH2

O

CH3

HCl+NaNO2

NHNCH3

N N

O

CH3

N N CH3

CHOR

CH3N N

O

N N

R

NH2OH.HClKOH

CH3

NO

N NN N

R

,0-50C

40%KOH

Conventional 4-6 hrsmicrowave 2-3 min

Conventional 8 hrsmicrowave 5-6 min

94

95

96

97

Scheme 21

3. Chemical Reactions

3.1 Synthesis of bicyclic lactum of Isoxazoles

The synthesis of bicyclic lactum of isoxazoles (102) were reported by using alcohols of isoxazole(98) which on bromination , amination and by EDCI,DIEA , DMAP.[Scheme-22][31]


OHON

Ar CO2Me

PBr3, CH2Cl2, BrON

Ar CO2Me

R'NH2,Et3N,Anhydrous Benzne

ON

Ar CO2Me

NHR' KOH in MeOH:H2OO

N

Ar

NHR'

CO2H

EDCI , DIEA , DMAP ,CH2Cl2

N

ON

ArO

R' CH2Ph

00C,30 min Reflux 30min

R.T ,1 hrs R.T.45min

Where R'=

98 99

100 101

102

Scheme 22

3.2 Microwave assisted synthesis of Schiff base

Isoxazole Schiff bases (105) obtained from 3-amino-5-methyl isoxazole (103) with substitutedsalicylaldehyde (104) using microwave assisted method [Scheme-23][32]

ON

CH3

NH2

RR

R

OH

OHC

1

2

3

R

R

R

OHO

N

CH3

N CH

1

2

3

+M.W

103 104

105

Scheme 23

3.3 Synthesis of isoxazole Azepine

Synthesis of Azepine began with bromothiophene (106) & isoxazole boronic ester(107) condensedvia Suzuki reaction & which deprotected to primary alcohol (108) oxidation & imine formation with (s)-tert-butyl sulfinamide formed sulfinyl imine (109) which on addition of enolate of tert-butyl acetate givessulfinamine (110) which was deprotected in acid condition & treat with iPrMgBr gives Lactum(111) whichon treatment with PCl5 afforded imidoyl chloride(112) whichwas converted into Azepine(113) on deprotection& amide formation gives desired compound (114).[Scheme-24][33]


S Br

CO2Me

ON

B

OAc

O O

SCO2Me

ONOH

SCO2Me

ONN S

OtBu

S

CO2Me

ON

NH

O

CO2tBu

tBuS

S ON

ONH

CO2tBu

PCl5,CH2Cl2S O

N

N

CO2tBu

Cl

S ON

N

CO2tBu

Cl

S O

N

N

Cl

O

NH2

+i)Pd2(dba)3 ,Sphos,K3PO4,

n-BuOH,1000C

ii)MeONa,MeOH

i)Swern Oxidationii)Ti(OEt)4,(S)-t-butyl sulfinyl

amide

2-(tert-butoxy-2-oxo ethyl)Zinc(II)Chloride,

NMP,-100C

i)HCl,MeOHii)iPrMgBr ,THF

Pd(PPh3)4,K3CO4,

4-Chloro Phenyl boronic acid,Toluene / Water

i) TFA,CHCl3,360C

ii)HATU,NH4Cl,Et3N,CH2Cl2

106

107

108

109110

111 112

113114

Scheme-24

3.4 Synthesis of Novel Isoxazole derivatives

A Convenient synthesis of some isoxazole have been reported by the reaction ofisoxazole derivatives with some reagents such as NH2OH.HCl,hydrazine hydrate,thiosemicarbazide & thiaureavia Michael addition to gives compound (116-119).Compound(119) was reacted with p-chloro benzaldehyde& glucose afforded compound (120,121) while compound (118) react with different halo compounds togives (122-124).compound(115) reacted with malononitrile and acetoacetanilide to gives compounds(125,126).[Scheme-25][34]


ON O

ArCH3

NH2OH

NHO

NO

CH3 Ar

NH2NH2

NHN

NO

CH3 Ar

X

X=O,SNH

NHN

O

CH3

Ar

X

NH2NHCSNH2

NNO

CH3 Ar

NH

CS NH2

NNO

CH3 Ar

NH

CS NH2

GlucoseNN

O

CH3 Ar

NH

CS N CH

(CH2OH)4

CH2OH

ClOHC

NNO

CH3 Ar

NH

CS

Cl

N CH

NH2 NH2115

116

117

118

119

119

121

120


NH

NHN

O

CH3

Ar

S

ClCH2COOH

ClOHC N

NN

O

CH3

Ar

SO

CHC6H4Cl

Cl CH2

ON

NN

O

CH3

Ar

S

CH2

O

CH2

O

ClCH2CH2OCH2CH2Cl

N

NN

O

CH3

Ar

S

CH2CH2OCH2CH2Cl

CH2CH2OCH2CH2Cl

ON O

CH3 CH2(CN)2

ON

O

CH3

Ar

NH2

CN

Ac2O

ON

O

CH3

Ar

NHCOCH3

CN

AcetoacetanilideNO

CH3

N O

ArCOCH3

Ph

2 Moles

122

118 124

123

126115

125

127

Scheme 25

3.5 Synthesis of phenacyl - imidazoles

Synthesis of imine (130) by mixture of phenyl (s-phenyl isoxazol -3 -yl) methanamine (129) &aldehyde .Then Boulton-Katritzky rearrangement of imine gives isoxazoles (131).[Scheme-26][35]

ON O

Ph

PhNH2

Ph

ON

Ph

Ph

NH2

Ar CHO

ACOHO

NPh

N

Ar

Ph

tBuOKDMF/N2

NHN

ArO

Ph

Ph

Mont-K10 /Toluene600C

B.K128129 130

131

Scheme 26


3.6 Reduction

The isoxazole alcohols(132) is oxidized by Dess-Martin Periodinane ,CH2Cl2 gives isoxazolylaryl ketones(133) which on Corey-Bakshi-Shibata reduction using dimethyl sulfide borane furnished chiralisoxazole carbinols(134)[Scheme--27][36]

R ON

OHR R12

3

CH2Cl2

R ON

R R

O

12

3 BH3.DMS

(R)-diphenyl prolinol,, CH2Cl2

R ON

R R

OH H

12

3Dess-MartinPeriodinane

-450C

132133 134

Scheme 27

3.7 Synthesis of substituted pyrrolyl furans

Synthesis by Sadighi cross-coupling using ZnCl2 of 3-bromo isoxazole(135) gives pyrrolyl isoxazole(136). Which convert in triisopropyl silyl derivatives (137). & treated NCS/Pd(OAc)2 gives chlorinated pyrrol(138) hydrogenolysis of over Pd/C in MeOH gives enaminone (139) which react with acid affordedpyrrolyl furans(140)[Scheme-28][37]

ON

BrOBn

NH

NaH,ZnCl2 ,

Cat.PdN

R

ON

OBn

KH,TIPSOTf

N

ON

OBnNCS

PdN

ON

OBnCl

O

N

ClNH2 OH

O

O R

N

Cl

(0)

TIPS

(II)

TIPS

H2 (1 atm)10% Pd/CMeOH, RT

TIPS

Acid, R-OH

RT,1-4 hrsTIPS

UNSTABLE

135136

137138

139140

Scheme 28

3.8 Synthesis of new Lead structure in isoxazole

The reaction of 5-amino -3-methyl-4-isoxazole carboxylic acid hydrazide(141) with mixture of


isopropanol & (hexanedione-2,5),(pentanedione2,4) and cyanogen bromide gives new lead structures: 5-amino-3-methyl-4-(2,5-dimethyl pyrrol –amino carbonyl)-Isoxazole RM54(142),5-amino-3-methyl-4-(3,5-dimethyl pyrazole carbonyl)-Isoxazole RM55 (143), & 5-amino – methyl -4-[2-(5-amino-1,3,4-oxadiazole)] –Isoxazole RM56(144)[Scheme-29][38]

NH

NH2

NO

O

CH3

NH2

NN

O NH2

NO

CH3

NH2

N

CH3

CH3

NH

NO

OCH3

NN

CH3

CH3NO

O

CH3

NH2

RM56

RM55

RM54

RM-54RM-55RM-56

Imminological activity

142

141

144

143

Scheme 29

3.9 Synthesis of metal complexes

The hot methanolic solution of isoxazole ligand (145) and hot methanolic solution of copper chloride(146) were mixed together and refluxed to afforded Cu-Complex(147).[Scheme-30][39]

NO

R

R'

OH

NO

R

R'

O

NO

R

R'

OCu+ CuCl270-800C

2-3 hrs

WHERE R,R'= I R,R'=Br Structure Of Cu-complex

145146

147

Scheme 30

3.10 Synthesis of Novel Isoxazole Derivatives

Synthesis of novel isoxazole reported by reaction of 5-(methyl thio)-3,4-diphenyl isoxazole(148)with chlorosulfonic acid afforded compound (149) which treated with Conc.NH4OH furnished compound(150)[Scheme-31][40]


ON

SCH3

ClSO3HO

N

SCH3

ClO2S

Conc.NH4OH

ON

SCH3

H2NO2S

148

149

150

Scheme 31

4. Miscellaneous Reaction

4.1 Synthesis of novel Schiff base ligands and their metal complexes

Schiff bases are excellent ligands which are synthesized from condensation of primary amine withcarbonyl group like MSBPMA (153) , NINIHI (156) , NHIIMC (159). The Co(II) , Ni(II) , Cu(II) & Zn(II)metal complexes have been synthesized compounds- (160,161,162)[Scheme-32][41]


ON

CH3

SO

O

NH2

NH

OHC--H2O

NHON

CH3

SO

O

N CH

Sulphametoxazole

NH

NNH2

ON

OH

OHCH2O

ON

OH

CH

NH

NN

ON

OH

NH2

OO

OHC

H2O

OO

ON

OH

NCH

+

{4-[(5-Methyl isoxazole-3-yl)Sulfonyl Benzyl diene]-N-[(E)-1-(2-pyrrol) methyl diene)[MSBPMA] (L1)}

Fig.-1

+

Histamine 3-hydroxy-5-carbaldehydeisoxazole

{N-[(E)-1H-imidazole-3yl)-N-[(imino methylidine)-(3-hydroxy-3-isoxazole)]} [NINIHI] (L2)

Fig.-2

+

Muscinol Chromine-2-carbaldehyde

{N-[3-hydroxy-3-isoxazol imino]methyl 4-oxo-4H chromine}[NHIIMC](L3)

Fig.-3

151

152

153

154 155156

157 158

159


M

CH

OH2

OH2

R

ON

OH

ON

OH

N

N

R

CH

M

CH

OH2

OH2

R

N

OH

N

OH

N

N

R

CH

N

N

M=Co(II),Ni(II),Cu(II),Zn(II) ON

CH3

SO

O

M

CH

OH2

OH2

R

H

OO

O O

N

N

R

ON

OH

Where- R=

Complex M(II)(L1)2.2H2O

Where-R=

M=Co,Ni,Cu,Zn

Complex M(II)(L2)2.2H2O

Where- R=

M= Co,Ni , Cu ,ZnComplex M(II)(L3)2

.2H2O

(Complexes 160,161,162 have antimicrobial activity) .

160

161

162

Scheme 32

Conclusion

Isoxazoles are easily available and have high chemical reactivity. A series of heterocycliccompounds containing a five membered ring consisting of three carbon atoms united to first positionoxygen and second position nitrogen atom .Substituted Isoxazoles are important compounds of manydrugs & drug candidates .This survey was attempted to summarize the synthetic methods and reactionsof isoxazoles.

Reference:

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