Ring Transformation of Heterocycles

Adel M. Awadallah

Chemistry Department, Faculty of Science, Islamic University of Gaza, P. O. Box108,

Gaza, Palestine; Tel. +970-8-2823311, Fax: +970-8-2823310, e-mail: awada@iugaza.edu.ps

Ring Contraction

N

NN

N

O

CH3CH3N

O

CH3CH3Nlight

-N2

Quast et al 1975

• a) Transformation of 4-amino-4,5-oxadiazoles into the aromatic 1,3,4-oxadiazoles.

• Acylation of 4-amino-4,5-dihydro-1,2,4-oxadiazoles 1 in refluxing toluene or treatment of the acyl derivatives of these compounds 2 with trifluoroacetic anhydride brings up ring transformation to the aromatic 1,3,4-oxadiazoles 3 [1].

N

ON

Ar R"

R'

NH2

N

ON

Ar R"

R'

NH

X

O

O

NN

Ar XXCOCl (CF3CO)2O

r.t.

1 23

X = H, CH3, Ph, CH2Cl,

• Similarly, 4-amino-4,5-dihydro-1,2,4-oxadiazoles 4 are transformed into the corresponding 2-arylamino-1,3,4-oxadiazoles (6, X = O) or thiadiazoles (6, X = S) via reaction with phenylisocyanate or phenylisothiocyanate, followed by brief treatment of the resulting adducts 5 with trifluoroacetic anhydride at ambient temperature [2].

N

ON

Ar R"

R'

NH2

N

ON

Ar R"

R'

NH

NHPh

X

X

NN

Ar NHPh

C4

(CF3CO)2O

r.t.

PhNCX

X = O, S

4

5

6

• b) Ring contraction of 1,2,3,4-tetrahydro-1,2,4,5-tetrazines into 1H-1,2,4-triazoles.

• The reaction of nitrile oxides 7 with methylhydrazones 8 in chloroform was found to constitute a convenient synthetic route to the novel 4,5-dihydro-6H-1,2,4,5-oxatriazines 9 [3].

Cl

OHN

R

R"

R'NN

H

CH3 N NH

ON

RR'

R"

CH3

Et3N+CHCl3

7 89

• Risitano and coworkers obtained triazoles 10 directly from the appropriate monomethylhydrazones of aryl aldehydes in refluxing ether for 2 hours [4].

Cl

OHN

R

H

R'NN

H

CH3

N N

OH

N

RR'

H

CH3

N N

NR R'

CH3

+ether

reflux

10

• 1,2,3,4-tetrahydro-1,2,4,5-tetrazines 9 derived from methylhydrazones of aryl aldehydes underwent ring contaction, via elimination of H2O, to yield the respective 1H-1,2,4-triazoles 10. This transformation was envisaged to proceed via the ring-opened (E)-hydrazonoximes which then suffered dehydrative cyclization. The process is acid-catalyzed and was thermally induced. Apparently, the driving force for this transformation was linked to the aromaticity of the triazole product [5].

•

N NH

ON

RR'

H

CH3

N N

OH

N

RR'

H

CH3

N N

NR R'

CH3

or ACOH

9 10

• c) Transformation of dihydrotriazoles into 1-Aryl-3-acetyl-5-methyl-1H-1,2,4-triazole

NN

NH

Ac R

R

ArNN

NAc R

R

Ar

CH3O

NN

NAc

Ar

OCH3

R

R

NN

NAc

Ar

CH3

NN

NAc

Ar

CH3 R

RO

(CH3CO)2O ..

..

..

....

+

..

+ +

11 12

13

• d) Ring Expansion 1,2,4-triazoles into 1,2,3,6-oxatriazine

• Oximic 1,2,4-triazole ligands 15 were prepared from the reaction of triazoles 1 with hydroxylamine hydrochloride at room temperature. At higher temperatures, the reaction afforded, however, the novel ring transformation product 4-amino-2-(4-chlorophenyl)-5-methyl-2H-1,2,3,6-oxatriazine 16. The reaction of the ligands 15 with

• nickel(II) and palladium(II) acetates in ethanol at room temperature yielded the respective square planar complexes 18. X-ray structure determination of one of these complexes revealed that metallation led to unexpected ring transformation of the triazole ligand. It is probable that such ring transformation generated the imidazole-N-oxide intermediate 17 which coordinated to Ni(II) ion, and the 4N-donor set comprises both imidazole nitrogen and arylhydrazone nitrogen. [7]

NN

NH

O

CH3

RR

ArN

NNH

N

CH3

RR

Ar

OHN O

N

N

CH3

NH2

Ar

N

NH

R

R

OCH3

N

NH

Ar

M

N

N N

N

N

RR

OCH3

N

N

RR

OCH3

N

Cl

Cl

NH2OH.HCl

NaOAc

reflux

M(OAc)2

ring transformation

14

15 16

17

18

N

NH

N

CH3

Ar

OH

NNN

Ar

N

OH

CH3

NH

NO

NNNH2

Ar

CH3

N

NN

NH2

Ar

CH3

O

- CH3-CH=CH2

M. Wt = (42)

M.Wt = 266

+-

M.Wt = 224

2a

3

7

8

NN

NH

N

CH3

RR

Ar

OHN

NH

R

R

OCH3

N

NH

Ar

M

N

N N

N

N

RR

OCH3

N

N

RR

OCH3

N

Cl

Cl

M(OAc)2

1517

18

• 3-Acetyl-1,2,4-triazole hydrazones (19) gave Square planar nickel(II) complexes (21) upon reaction with Ni(OAc)2 in EtOH at room temperature in a 2:1 mole ratio. [8]

NN

NH

N

CH3

RR

ArNH2

NH

NH

N

N

NH

Ar

R

R

CH3

Ni

N

N

N

N

NH

N

N

Ar

R

R

CH3

NH

N

N

Ar

R

R

CH3

Ni(OAc)2.4H2Oring transformation

(19) (20)

(21)

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