recent heterocyclic compounds from (1,3-dioxo-2,3-dihydro-1 h ...

Month 2014 Recent Heterocyclic Compounds
from (1,3-Dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile Alaa A. Hassan* and Sara M. Mostafa
This

Chemistry Department, Faculty of Science, Minia University, El-Minia 61519, Egypt
*E-mail: [email protected]
Received June 10, 2012DOI 10.1002/jhet.1821

Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).

review summarizes the literatures dealing with the synthesis of some important nitrogen or nitrogen/
heterocyclic, and fused heterocyclic compounds. sulfur heterocyclic, spiro
J. Heterocyclic Chem., 00, 00 (2014).

INTRODUCTION

Chemistryof 2-(dicyanomethylene-1,3-indandione). Selectivecombination of two or more different electron acceptors intoone molecule leads to a series of new electron acceptorswith unique properties [1,2]. Such a composite acceptor is(1,3-dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile1, also referred to as 2-(dicyanomethylene-1,3-indanedione);CNIND may be considered to be analogous toethenetetracarbonitrile 2 (TCNE) in its reactions. Like thelatter, it readily adds N-nucleophiles such as secondaryaliphatic [3] and primary aromatic amines [4–11] at thedicyanomethylene carbon atom with release of hydrogencyanide, analogous to the corresponding reaction of 2[12,13]. Tertiary aromatic amines (such as N,N-dimethylaniline) are prone to attack with their p-carbonatom, followed by release of HCN [1,4,14].Like 2, acceptor 1 [15] is also able to generate iminium ions

6 from tertiary cyclic amines 4a and 4b in ethanol or acetoni-trile solutions [16]. Cyanide ion released from anion 5 in turnintercepts 6 to generate a-cyanated amines 7 [16] (Scheme 1).It was reported earlier that 1 is isomerized to 2,3-

dicyano-1,4-naphthoquinone 3 when brought in contactwith electron donors [17] (Figure 1). Additionally, the reac-tion of 1 with arylazoaminopyrazoles [18,19], 2-mercapto-benzazoles [20], thiocarbohydrazides, and thiocarbazones[21] as well as N-arylisoindolines [22] has been reported.2-Dicyanomethylene-1,3-indanedione 1 is the weakest

acceptor in the series of related organic p-acceptors suchas TCNE 2 and tetracyanoquinodimethane 9, which alsoreadily form addition products with organic nucleophiles.Its EA is 2.45 eV, as compared with 2.75 and 2.85 eV

for tetracyanoethylene 2 and tetracyanoquinodimethane 9,respectively [23].

© 2014 HeteroC

Methods of preparation. Chatterjee [15] and Bespalov[23] prepared CNIND 1 from indane-1,2,3-trione andmalononitrile. CNIND 1 has also been synthesized from thereaction of indane-1,3-dione 10with TCNE 2 [5] (Scheme 2).

REACTIONS OF 2-DICYANOMETHYLENE-1,3-INDANDIONE

Synthesis of imidazolidine derivatives. Compound 1reacted with bisbenzalethylene diamine 11 to give 2-(indan-1,3-dionyl)imidazolidine derivative 15 via the formation ofintermediates 12–14 (Scheme 3) [24].

Synthesis of thiazolidine derivative. Considerable attention has been drawn to the condensation reaction between3-aminothiazolidine-2-thion-4-one (3-aminorhodanine, 16)and both aldehydes and ketones to give 3-alkylideneand/or arylidene rhodanines [25–28]. The reaction of 1with 16 afforded the condensation product 2-(3-amino-4-oxo-2-thioxothiadi-azolidine-5-ylidene)-1,3-indanedione17 via a nucleophilic attack of the rhodanine methylenefunction on the dicyanomethylene carbon atom of 1,followed by elimination of a molecule of malononitrile(Scheme 4) [29].

Synthesis of triazole derivatives. Amidrazone derivativesare an important class of amidines [30] because they oftenhave pharmacological and medicinal value [31–35]. Thereaction of 1 with amidrazones 18a–f afforded a veryconvenient one-step synthesis of 1,2,4-triazoles 19a–f(Scheme 5) [36].

Synthesis of oxadiazole derivatives. The reaction ofcompound 1 with substituted carbohydrazides 20a–e in amolar ratio of 2:1 in DMF gave several products. One was2-(5-substituted-1,3,4-oxadiazol-2(3H)-ylidene)-1H-indene-1,3,2(H)-diones 23a–e (Scheme 6) [37].

Synthesis of thiadiazole derivative. Addition of 1moleof thiadiazole 24 to twofold molar amounts of 1 in ethylacetate or DMF at room temperature afforded the

orporation

Scheme 1

O

O

CN

CN

+NAr

1 4a,b

O

O

CN

CNH

NAr

5 6a,b

- CN + CN

O

O

H

CN

N

ArCN

7a,b

+

4, 6, 7a 1,8-naphthalenediylb 2,2`-biphenyldiyl

8

Ar= R-C6H4 with R= H, 4-Me, 4-OMe, 4-Cl

Scheme 2

O

O

H

H

+

O

O

CCN

CN

110

2

Scheme

1 + CH

Ph NH2C

H2C N CH

Ph

O

ONH

HN

11

15 (57 %)

1

O

ONH

CN

H2C CH2

14

i) +H2O

ii) - PhCHOiii) - HCN

Figure 1. 2-(Dicyanomethylene-1,3-indanedione) (1), tetracyanoethylene(2), and 2,3-dicyano-1,4-naphthoquinone (3).

A. A. Hassan and S. M. Mostafa Vol 000

Journal of Heterocyclic Chemi

predominant products 2-(indane-1,3-dionyl)-3H-5-methyl-1,3,4-thiadiazoles 25 and 1,3-dihydroxy-2H-(inden-2-ylidene)malonodinitrile (13%) (Scheme 7) [38].

Synthesis of isoindole derivatives. N-arylisoindolines,featuring reactive benzylic hydrogens in a nearly planarfive-membered ring, show a different behavior towardsCNIND (1) and deviating from the behavior of ter-arylamines or indole. The reactions of N-arylisoindolineswith the p-deficient dicyanomethylene moiety have been

Scheme 4

1 +

S

N

O

O

16

- H2C(CN)2

O

OS

N

ONH2 NH2

S17 (71 %)

Scheme 5

+

R 1

R2HN

NPh

NH2

O

ON

NHN

R1R2

Ph

18a-f

18, 19 R1 R2

a H Hb H CH3c H OCH3d H Cle CH3 Hf Cl H

- 2HCN

19a-f (69-77%)

1

3

1 + 1

O

O

CN

N

NC

HC

CH2

Ph

H2C N CH

Ph

12

+ H2O

O

O

CN

N

NC

HC

H2C Ph

H2C N CH

Ph

OH

H

13

- HCN

- PhCHO

N CH

Ph

stry DOI 10.1002/jhet

Scheme 7

N

S

NH

SH3C+ 1

O

O

S

NHN

CH3

24 25 (56 %)

i) - S2

ii) + H2

iii) - CH2(CN)2

Scheme 8

N Ar + 1 Step 1

N Ar

26a-f 26-f

+

O

O

CN

CN

1

26a-f pyridineN Ar

26

1

Step 2

Step 3

O

OStep 4

28

Step 5

O

O

NC

NC

3

3 + 26Step 6

NO

NCNC

O

Step 7

N

O

O

NC

30a-f

- CN

O

O

NO

O

Ar

NC

NC

32a-f (25-61%)

26-32 Ara C6H5b C6H4-2-Mec C6H4-4-Med C6H4-3-Mee C6H4-2-OMef C6H4-4-OMe

30a-f repeat steps

1-7N Ar

O

O

NC

O

O

NC

H

H

- 2H

- H

N

NC

27

ONC

NCO

H H

31a-f

CT-complex

Ar Ar

29a-f

Scheme 6

R C

O

HN NH2 + 1

20a-e

O

O

CN

CN

HN

HN C

OR

21a-e

- HCN

O

O

CN

HNHN C

OR

22a-e

- HCN

O

OO

NHN

R

23a-e (51-57 %)

20-23 a b c d e

RS O N N

H

Scheme 9

1 +

R2H2N

H2N R1

OH

CCN

CNHN

O

H2N

R1

R2

O

ONH

HN R1

R2

33a-d 34a-d

35a-d (36-70 %)

33-55 R1 R 2

a H Hb CH3 Hc Cl Hd CH3 CH3

- 2 HCN

Month 2014 Recent Heterocyclic Compounds from (1,3-Dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile

reported [13,39,40]. When 1mole of 2-aryl-2,3-dihydro-1H-isoindoles 26a–f was added dropwise to 2moles of 1in pyridine and the mixtures were gently warmed to50–60 �C, a complex mixture containing a deep blue maincomponent and numerous colored byproducts (each insmall quantities) were formed. Chromatographic separationafforded 3,30-[2-(substituted)-2H-isoindol-1,3-ylidene]-di(1,4-naphthoquinone-2-carbonitriles) 32a–f (Scheme 8). Thestructure of 32c was unambiguously confirmed by X-raycrystallography [22].

Synthesis of benzimidazole derivatives. The interaction of1with o-phenylenediamines 33a–d gave 2-(1,3-dioxo-2-(1,3-dioxo-2-indanylidene)benzimidazolines 35a–d. Compounds35a–d can be regarded as isomers of indigo with respect tothe C═O and NH functions (Scheme 9) [41].

Synthesis of pyrimidine derivative. The reaction of 1,8-diaminonaphthalene 36 with 1 and the formation of2-(1H,3H-perimidin-2-ylidene)indan-1,3-dione 37 has beenreported (Scheme 10) [42].

Synthesis of spiro compoundsSynthesis of spiroindenocyclopropane derivative. In ethanolsolution at room temperature, the reaction between 1 and 2-(4-methyl-phenyl)-2,3-dihydro-1H-benz[d,e]isoquinolines 38was carried out. It gave intermediates 39 and 40 and theformation of cyanated product 41. Then, 40 reacted withanother molecule of 1 to give 1,100,3,300-tetraoxo-[indan-2-spiro-10-cyclopropane-200-indane]-30,30-dicarbonitrile 43,which has been unambiguously confirmed by singlecrystal X-ray crystallography (Scheme 11) [16].

Synthesis of spiroindenepyrazole derivatives. Solutions of1 and substituted thiosemicarbazides 44a–f in ethyl acetatewith a molar ratio of 1:1 were refluxed for 3–6h. Theconcentration of the reaction mixture yielded reddish browncrystals of N-substituted-50-amino-40-cyano-1,3-dioxo-1,3-

Journal of Heterocyclic Chemistry DOI 10.1002/jhet

dihydrospiro[indene-2,30-pyrazole]-20(10H)-carbothioamides46a–f. The formation of 46 indicates that thiosemicarbazides44a–f react with 1 through a nucleophilic attack of terminalamino group of 44a–f to the C�N triple bond of 1 to formintermediate 45; the latter exerts its nucleophilic characterby intramolecular attack of the NH to the C═C double

Scheme

R CO

NH NH2+ 1

O

ONH

HN20a-e

47a-

20, 47, 48 a b c d e

RS O N N

H

Scheme

+ 1O

4

HNR C

SHN NH2

44a-f

44-46 Ra C6H5b C6H5-CH2c CH2=CH-CH2d C6H4-4-CFe C6H3-3,5-Ff C6H4-4-F

Scheme 11

NAr

+ 1

NAr

+

O

OCN

CNH

38 39 40

NAr

NC

+

O

OCN

H

41 (19-30 %) 8 (4 %)

O

OCN

CNH

+ 1

40

O

OCN

CN

O

O

O

O

CNNC O

O

42 43 (46-60 %)

- H2C(CN)2

Ar = H-CH3-C6H4

Scheme 10

1 +

NH2 NH2 O

OHN

HN

3637 (67 %)

- 2HCN



bond, facilitated by the electron-withdrawing groups (twocarbonyl and one nitrile groups), to form products 46a–f(Scheme 12) [43].

Synthesis of spiroindenoxadiazole derivatives. The reactionof 1 with substituted carbohydrazides 20a–e in a molar ratioof 2:1 in DMF solution gave 50-substituted-spiro(indeno-2,20-[1,3.4]oxadiazole)-1,3-dione 48a–e (Scheme 13) [37].

Synthesis of spiroindenethiazine derivatives. Solutions of(substituted) alkenylidene-hydrazinecarbothioamides 49a–ein dry ethyl acetate were added to a solution of 1,followed by reflux for 4–6 h with admission of air.Chromatographic separation of the residue affordednumerous colored products, from which product 51 wasisolated. The presumed mechanism for the formation ofthese spirodioxo(indene-2,60-[1,3]thiazine derivatives (51a–e,Scheme 14) is the nucleophilic attack of N2 of 49a–e onone of the cyano groups of 1, followed by intramolecularattack of SH group on C-2 of the indanedione skeletonof 50 [44].

Synthesis of fused heterocyclic compoundsSynthesis of indenopyrrole derivativesFrom 1-substituted-2,5-dithiobiureas. The reaction

of 1 with 1-substituted-2,5-dithiobiureas 52a–c in ethylacetate afforded N-substituted (oxoindenopyrrolylidene)hydrazinecarbothiamides 53a–c (Scheme 15) [45].

13

CNH

CN

CO

R

- H2C(CN)2

O

ONH

N

OR

e 48a-e (13-17%)

12

OCN

NHNH

HNC

S NH

R

5a-f46a-f (63-71%)

N NH

O C

SNH

R

NH2CNO


Scheme 15

RHN C

SHN

HN C

SNH2 R

HN C

S HN N C

SHNH2

52a-c

52a-c + 1 52a-c + - CN

O

O

CN

H

8

+ 8i ) - H2 S

i i) - H 2O

O

N

CN

NHN C

S

HN R

53a-c (7-11 %)52, 5 3; R , a= C6 H 5-

b= C6 H5 CH 2-c= C H2 =CH -CH 2 -

52a-c

1 -H

Scheme 14

O

O

CN

C NHN

NCN

CHR

50a-e

+ 1

HS

O

OS

N

CN NH2

N

NCHR

51a-e (41-53%)

C6H5 NH

49a-e

S

NH

NCHR

49-51 R

a C6H5-CH=CH (trans)b o-OCH3-C6H4-CH=CH (trans)c CH3-(CH2)2-CH=CH (trans)d CH(CH)3e CH3-CH=CH

C6H5

C6H5

Scheme 16

R CO

HN

HN C

SNH2

54a-d

+ 1

O

HN N

CNCN

HN C

OR

55a-d (56-63%)

O

N N

CN

HN C

OR

56a-d (29-33%)

54-56, R: a= CH3b= C6H5c= C6H4-4-OHd= Br -C6H4-CH2

i) - S2ii) - H2O

i) - S 2ii) - HCNiii) - H2O


From acyl thiosemicarbazides. On the other hand,the treatment of acyl thiosemicarbazides 54a–d with twomolar equivalents of 1 in ethyl acetate as solvent at roomtemperature resulted in a yellow coloration of the reactionmixture ultimately yielded a brown precipitate identified asstructures 55a–d. 1H NMR spectrum of 55b showed thepresence of two separate broad signals centered at d 11.12and 11.28 ppm because of the amide–NH and pyrrole–NH,respectively. In the 13C NMR spectrum, the carbonylgroups of benzohydrazide and oxoindeno-C-4 resonated atd =174.12 and 182.12 ppm, respectively, and 116.11 (CN),155.63 (pyrrole, C-2), and 60.12 ppm (pyrrole, C-3) werealso observed. The remaining soluble materials weresubjected to preparative layer chromatography. The yellowzone of this chromatography corresponded to N0(3-cyano-4-oxoindeno[1,2-b]pyrrol-2(4H)-ylidene)-substituted hydra-zides 56a–d (Scheme 16). The 13C NMR spectrum of 56bshowed the carbonyl groups at d 172.63 (amide) and d



183.12 ppm (oxoindeno-C-4). Additional key resonancesobserved were 118.47 (CN), 156.12 (pyrrole, C-2), 124.17(pyrrole, C-3), 183.12 (pyrrole, C-4), and 164.35 ppm(pyrrole, C-8b). The 1H NMR spectrum showed onebroad signal at d 11.10 ppm (NH) in addition to thearomatic protons [46].

Synthesis of indenopyrazole derivativesFrom substituted carbohydrazides. The reaction of 1

with substituted carbohydrazides 20a–e in DMF afforded1-substituted-4-oxoindeno[1,2-c]pyrazolo-3-carbonitriles57a–e (Scheme 17). Isomeric structures 58a–e are excludedby the presence of acryl–CO signals in the 13C NMR spectrain the isolated products [37].From 2-substituted-N-phenylhydrazinecarbothioa-

mides. Addition of a solution of 2-substituted-N-phenylhydrazinecarbothioamides 49f–j in dry pyridine to asolution of 1 gave, upon chromatography of the residue,numerous zones. The 3-cyano-4-oxo-phenylindeno[1,2-c]pyrazole-1(4H)-carbothioamides 61 (Scheme 18) wasisolated [47].

Scheme 17

R CO

NH NH2+ 1

20a-e

O

O

CCN

CN

HN

HN C

OR

- HCN- H2O

O

NN

CN

ROC

21a-e

57a-e (11-15 %)

20, 21, 57, 58 a b c d eR

S O N NH

O

NNO

R

CN

58a-e

- HCN- H2O

Scheme

- -

HN CPh

SHN N C

HR

49f- j

+ 1

O

O

59

N N

O

CS NH

61

49 R 59-61

f C6H5 ag C6H4-p-Cl bh C6H5-p-OCH3 ci 2-Thienyl dj 2-Furyl e


Synthesis of indenoimidazolone derivatives. A mixtureof 49a–d and 1 in dry ethyl acetate were refluxed for>4–6 h under an air atmosphere. Chromatographic separa-tion of the residue afforded numerous colored zones, fromwhich products 62 and 64 were isolated. Starting material 1is partially reduced to 62. (Ylidene)hydrazinecarbothioa-mides 49 could serve as the reducing agents. Nucleophilicattack of N2 of 49a–d on the C═C of 62 with the elimina-tion of a molecule of malononitrile and another of H2Ofrom adduct 63 gives rise to 64a–d. The alternative option,namely nucleophilic attack by the thione sulfur atom onC-3 of 63, is not observed because a product correspondingto structure 65 is not found (Scheme 19) [44].

Synthesis of indenopyrimidine derivative. On react-ing compound 1 with 1-phenylbiguanide 66 in EtOH,2-amino-4,4-dicyano-5-oxo-N-phenyl-4,5-dihydroindeno[1,2-d]pyrimidine-3-carboxamidine 67 was obtained(Scheme 20) [48].

Synthesis of indenothiazine derivatives. The reaction of 1with 1-substituted-2,5-dithiobiureas 52a–c in ethyl acetateafforded N-substituted-2-(4,4-dicyano-5-oxoindeno[1,2-d][1,3]thiazine-2-(1H,4H,5H)-ylidene)hydrazinecarbothioamides68a–c and N-substituted-2-(4-cyano-5-oxoindeno[1,2-d][1,3]thiazine-2-(5H)-ylidene)hydrazinecarbothioamids 69a–c(Scheme 21) [45].

Synthesis of indenotriazine derivatives. Solutions of 1and substituted thiosemicarbazides 44a–e in ethyl acetatewith a molar ratio of 1:1 were refluxed for 3–6 h. Thesoluble materials were subjected to preparative layerchromatography to give 4-substituted-3-thioxo-3H-indeno[1,2-e]triazine-9(4H)-ones 72a–e. The first step in themechanism for this transformation is nucleophilic attackof 44a–e to the C═C double bond of 1 and elimination amolecule of malononitrile to form intermediate 70.Intramolecular nucleophilic attack of NH to the carbonylgroup to give 71 is followed by elimination of H2O toprovide thioxoindenotriazines 72a–e (Scheme 22) as thefinal products [43].

18

NC

N

CN

CH

HN CS

RHN Ph

a-e

+ H2O

O

OH

CN

HNCNN C

S

HN Ph

60

CN

Ph

(24-28 %)

- RCHO

- HCN

- H2O

H


Scheme 20

HN

NH

HN

NH

NH2+ 1

O

NN

NC

NH2NH

HN

66 67 (30 %)

CN- H2O

Scheme 21

CS H

NHN C

SNH2 R

HN C

SHN N C

SHNH2

52a-c

52a-c + 1- H2O

O

S

HN

CNNC

NHN C

S HN R

68a-c (44-49 %)

i) - H2Oii) - HCN

O

S

N NHN C

S HN R

CN69a-c (29-31 %)

52, 68 and 69; R, a= C6H5b= C6H4-CH2c= CH2=CH-CH2

HNR

Scheme 19

1 + 2H

from 49

OH

OH

CN

CN

62 (8-12 %)

62+

OH

OHN

CNHCN

N CHRC

SHNPh

O

N

N

PhS

N CHR

63

64a-d (27-53 %)

i) - H2C(CN)2ii) - H2O

O

S

NN CHR

NR

65a-d

PhNH

49a-d

S

NH

NCHR

49, 63-65 R

a C6H5-CH=CH (trans)b o-OCH3-C6H4-CH=CH (trans)c CH3-(CH2)2-CH=CH (trans)d CH(CH3)2

i) - H2C(CN)2ii) - H2O



Synthesis of indenoxadiazine derivatives. Chromatographicevaluation of the product mixture resulting fromthe reaction of the 2-substituted-N-phenylhydra-zinecarbothioamides 49f–j with 1 in dry pyridineunder gentle heating afforded numerous zones, fromwhich 4a-hydroxy-3-(substituted)-indeno[2,1-e]-[1,3,4]-oxadiazine-9(4aH)-ones 78a–e could be isolated(Scheme 23) [47].

Synthesis of indenoazepine derivatives. N1,N2-diarylacetamidines 79a–d reacted with 1 in ethyl acetateat room temperature, to give indenoazepine-6-ones80a–d as major products (21–61%) and 2-arylamino(1,3-dioxo-2-indanylidene)acetonitrile 81a–d as minorproduct (3%) [49].

The formation of indenoazepine-6-ones 80a–d can berationalized. An initial nucleophilic attack by N2 ofdiaryl-acetamidines 79a–d on the cyano group of 1gives 82a–d, which are in equilibrium with 83a–d.The acetamidine then exerts its nucleophilic characterat the a-carbon atom, attacking C-1 of 1 and forming80a–d. The formation of 81a–d may be assumed toarise from a minor fraction of the amidine 79a–d thatundergoes the Michael addition–elimination sequencegiving 81a–d [49]. On the other hand, the possibility


Scheme 23

HNPh C

SHN N C

HR + 1

O

O

CN

CNH

N N

C

CH

R

S NH

Ph

49f-j

73-e

O

O

N N CH

R

74a-e

O

O

N NHC RO

HH

O

O

NHN

HC ROH

75a-e76a-e

O

O

N N C ROH

77a-e

O

ON

N

RHO

78a-e (58-67 %)

i) - PhNCSii) - H2C(CN)2

+ H2O

+ 1

- 2H

73-78 R 49

a C6H5 fb C6H4-p-Cl gc C6H5-p-OCH3 hd 2-Thienyl ie 2-Furyl j

Scheme 22

44, 70-72 R

a C6H5b C6H5-CH2c CH2=CH-CH2d C6H4-4-CF3e C6H3-3,5-F

HNR C

SHN NH2

44a-e

+ 1 - CH2(CN)2

O

O

NHN C

S

HN R

70

O

NNH

N

SRHO

71

NN

N

S

O

R

72a-e ( 17-26 %)

- H2O


exists that CNIND (1) in the presence of electrondonors as 79a–d underwent an electron transfer rear-rangement to the 2,3-dicyano-1,4-naphthoquinone 3[17,50]. Consequently, the reaction between 1 and 79awas carried out under the same conditions as earlier.In contrast to the reaction of 1 with 79, all that wasobtained as green precipitate, which was assigned as asolid charge–transfer complex of DCNQ (3) and 79.This result supports a mechanism for the formation of80a–d as originating from the reaction of 79a–d withCNIND (1) without prior isomerization of 1(Scheme 24) [49].


Synthesis of indenothiadiazepine derivative. The reactionof 1 with ethyl dithiocarbazate 85 gave 3-ethyl sulfanyl-6-oxo-6H-indeno[2,3-e]-1,3,4-thiadiazepine-5-carbonitrile 86(Scheme 25) [51].

Synthesis of indenoxadiazocine derivative. 3-Benzoyldithiocarbazate 87 reacted with 1 to give 5-ethyl sulfanyl-7-oxo-2-phenyl-4,7-dihydroindeno[2,3-g]-1,3,4-oxodiazocine-6-carbonitrile 89 as illustrated in (Scheme 26) [51].

Synthesis of indenoquinoxaline derivatives. The reaction of 1 with o-phenylenediamine 33 gives the7-substituted-11H-indeno[1,2-b]quinoxaline-11-ones 90a–d(Scheme 27) [41].


Scheme 25

H2NHN C

S

SEt + 1(i) - HCN

(ii) - H2O S

NN

O

SEt

CN

85

86 (55 %)

Scheme 26

CO

PhHN

HN C

SSEt C

OH

Ph N N C

SH

SEt87

87 + 1COH

Ph N N CS

SEt +

O

OHCN

CN

87 1-H

2 X 87 (i) - S2

(ii) + 1-H

O

OH

CN CN

C SEt

NNC

Ph(i) + 2H(ii) - HCN

(iii) - H2O

88O

NHNO

CNSEt

Ph

89 (57 %)

HO

Scheme 27

1 +

R2H2N

H2N R1

33a-d 90a-d (69-71 %)

O

N

N R1

R2

33, 90 R1 R2

a H Hb CH3 Hc Cl Hd CH3 CH3

i) - CH2(CN)

ii) - H2O

Scheme 24

CN

HN Ar

Ar+ 1

79a-d

O

NAr

CN

HONH

N Ar

80a-d

+

O

O

CN

HN Ar

81a-d

H3C

79a-d + 1 Micheal addition

elimination sequence

O

O

CN

HN Ar

81a-d (3 %)O

O

CNNH

N

NH3C

Ar

Ar

O

O

CNNH

N

NH

H2C

Ar

Ar

82a-d 83a-d

O

N

O HN

NHNC

Ar

Ar

84a-d

O

N

OH N

NHNC

Ar

Ar80a-d

79-84 Ar

a C6H4-4-CH3b C6H4-4-OCH3c C6H4-4-Cld C6H4-4-NO2

(21-61 %)

Scheme 28

1 +

XH

NH2

i) - HCN

ii) - H2O

91a,bO

N

X

CN

92a,b (80-82 %)91 and 92, X; a= Ob= S



Scheme 32

R R


Synthesis of indenobenzoxa(thia)zepine derivatives. Asolution of 2-amino(thio)phenols 91a,b in dry ethyl acetateadded dropwise to a solution of 1 in dry ethyl acetateand then stirred at room temperature for 72h gives indeno-10-one-yl[b]-1,4-benzoxa(thia)zepine-11-carbonitriles 92a,b(Scheme 28) [52].

Synthesis of indenocyclopentathiadiazole derivative.Addition of 1mole of thiadiazole 24 to twofoldmolar amounts of 1 in ethyl acetate or DMF atroom temperature afforded as predominant productsindenocyclopentathiadiazole 93 and other products(Scheme 29) [38].

Synthesis of indenopyrroloimidazole derivative. 1H-benzo[d]imidazole-2-thiol 94 as electron donor reactedwith 1 to give 10,11-dihydro-10-oxabenzo[d]-indeno[2,1:4,5]pyrrolo[1,2-a]imidazole-11,11-dicarbonitrile 95(Scheme 30) [20].

Synthesis of pyridoxazine derivative. The reaction ofequimolar amounts of 3-amino-2-hydroxypyridine 96 with1 furnished the formation of 2-(2-aminopyrid[2,3-b]-1,4-oxazine-3-ylidene)indan-1,3-dione 97 (Scheme 31) [52].

Synthesis of indenopyrazolopyridine derivatives. Treatmentof 3-substituted 5-amino-1-phenylpyrazole 98a,b with 1afforded 6-oxo-3,6-dihydro-1H-indeno[1,2-d]pyrazolo[3,4-b]pyridine-5-carbonitrile 99a and 1-methyl-6-oxo-3-phenyl-3,6-

Scheme 29

N

S

NH

SH3C+ 1

O2493 (11 %)

NS

N

CH3

i) - S2ii) - HCN

iii) - H2O CN

Scheme 30

1 +

NH

N

SHO

N

NCNNC

94 95 (68%)

i) - H2 S

ii) - H2O

Scheme 31

1 +

N OH

NH2

N

ON

H2N96 97 (65%)

O

O

- HCN


dihydroindeno[1,2-d]pyrazolo[3,4-d]pyridine-5-carbonitrile99b (Scheme 32) [3b].

Synthesis of indenopyrazolopyrimidine derivativesFrom3-substituted-5-amino-1H-pyrazolocarbonitrile. However

on mixing both 1 and 3-substituted-5-amino-1H-pyrazolocarbonitriles 100a–e in pyridine, an initialcharge–transfer complex was formed. Upon heating themixture, a slow reaction (completed in a few hours)gave 5-oxo-3a,5-dihydro-3H-indeno[2,1-d]pyrazolo[1,5-a]pyrimidine-3,10-dicarbonitriles 103a–e (Scheme 33) asproducts [53].

From 4-(aryldiazenyl)-1H-pyrazol-3,5-diamines. Anothermethod for preparation of pyrazolo[1,5-a]pyrimidinederivatives is by reaction of 1 with 4-(aryldiazenyl)-1H-pyrazole-3,5-diamines 104a–e to give 2-amino-9-oxo-3-(substituted-diazenyl)-9H-indeno[1,2-d]pyrazolo[1,5-a]pyrimidine-10-carbonitriles 106a-e (Scheme 34) [18].

Synthesis of indenopyrazolopyridazine derivative.Thiocarbohydrazide 107 reacted with 1 to give

O

N

CN

NN

C6H5R

1 +

NN

H2N

C6H5

NN

HN

C6H598a,b

98a,b - HCN

- H2O

99a,b (80-83 %)98 and 99; R, a = Hb= C H3

Scheme 33

N NH

NH2

CN

R+ 1 CT-complex

100a-e

O

O

CN

CN

N NH

NH2

CN

R+

100a-epyridine

py H

1

O

O

CN

CNN

NR

CN

101a-e

py H

- CN

O

O

CN

N N

R

CNH2N

102a-e

N

N

CN

N

CN

R

100-103; R, a= NH-C6H4-p-CH3b= NH-C6H4-p-OCH3c= NH-C6H4-p-Cld= NH2

103a-e (64-75 %)e=

- H2O

H2N

O

HN O


Scheme 35

2 XHN CH2N

SHN NH2+ 1

- S2 N CH

H2NHN NH22

107 108

108 + 1- HCN

- H2O

O

N N

NH

N

H2N

109 (71%)

Scheme 34

NNH

H2N

Ar-N=N NH2

+ 1 CT-complex

NN

H2N

Ar-N=N NH2

C

CN

CN

O

O

105a-e104a-e

NN

H2N

Ar-N=N N

OCN

106a-e (52-89 %)

104-106; R, a= C6H4-4-OCH3b= C6H4-4-CH3c= C6H5d= C6H5-4-Cle= C6H4-4-NO2

- HCN- H2O

Scheme 37

HN NH

O O

S

112

+ 1i) + H2

ii) - HCN

OH

O

CN

NHHN

O

S

114 (69%)

CN

NH

HN

O

SOH

OH

O

113- H2O

OH

SN

CN

NHO

O

115


1-aminoindeno[1,2-c]pyrazolo[4,3-e]pyridazin-10(1H)-one109 via the formation of 108 as an intermediate(Scheme 35) [21].

Synthesis of indenotriazolopyrimidine derivatives.Considerable interest in the synthesis of fusedheterocycles containing the pyrazole or 1,2,4-triazolemoiety has increased because they were used as seedfungicides [54], as well as anti-inflammatory agents [55].Much attention has focused on the synthesis of triazolo[1,5-a]pyrimidine [56] ring systems. 3-Substitut-edaminotriazoles 110a–d react with 1 in DMF to form the

Scheme

N

N

NH

NH2R

+ 1 CT-comlex

110a-d

100 and 111; R, a= Hb= NH2c= NH-C6H4-p-CH3d= NH-C6H4-p-OCH3


substituted 1,2,4-indenotriazolo-[1,5-a]pyrimidine 111a–d(Scheme 36) [57].

Synthesis of indenopyranopyrimidine derivative. Thereaction of 1 with compounds containing an activemethylene such as thiobarbituric acid 112 gave 6-hydroxy-4-oxo-2-thioxo-1,2,3,4-tetrahydroindeno[20,10-:5,6]

36

O

N

N

CN

N

NR

111a-d (65-78 %)

- HCN

- H2O


Scheme 38

N

N

N

SH

NH2

R+ 1 pyridine

CT-comlex

116a,b

N

N

N

S

NH2

RCN

CN

O

O117a,b

py H- CN- H2O

S

NN

O CN

NN

R

118a,b (16-19%)

116-118; R, a= CH3b= C6H5


pyrano[2,3-d]pyrimidine-5-carbonitrile 114 not 115(Scheme 37) [58].

Synthesis of indenotriazolothiadiazepine derivatives.5-Substituted-4-amino-1,2,4-triazolo-3-thiols 116a,b havebeen used for the synthesis of 10H-indeno[1,2-e][1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine 118a,b by the reactionwith 1 in dry pyridine (Scheme 38) [59].

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