synthesis of novel heterocycles of -...

Chapter 5

Facile three-component sequential

synthesis of amino-1,4-naphthoquinone-appended triazoles and triazole-chromene

hybrids: A click chemistry approach

Chapter 5 Introduction ___________________________________________________________________________

83

5.1. Abstract

A general method for the synthesis of a library of hitherto unreported amino-1,4-

naphthoquinone-appended triazoles was accomplished via a sequential three-component

reaction of substituted N-propargylaminonaphthoquinones with variously substituted alkyl

bromides/2-bromonaphthalene-1,4-dione and sodium azide in the presence of Et3N/CuI in

water. In this protocol, the formation of organic azides via substitution and the subsequent

click reaction furnishing triazole-naphthoquinone hybrid occurs efficiently in a sequential

one-pot operation in water affording, in general, a very high yield of the product and the

overall transformation is experimentally simple. Aminonaphthoquinone-appended

iminochromene-triazole hybrid heterocycles were also synthesized from the amino-

1,4-naphthoquinone-appended 1,2,3-triazolylacetonitriles.

5.2. General aspects

Development of new methodologies for the combinatorial synthesis of heterocyles with

promising medicinal properties is of great importance to organic chemists.1 1,2,3-Triazoles

derived from Huisgen’s 1,3-dipolar cycloaddition2 of azides and alkynes is one of the most

prevailing click reactions. 1,2,3-Triazoles have gained tremendous amount of attention as they

find utility as agrochemicals, dyes, photographic materials and photostabilizers.3 Triazoles are

also attractive as important heterocyclic pharmacophore for developing several therapeutic

agents including anti-HIV,4 antimicrobial,5 antiviral,6 anticancer,7 antifungal,8 antiallergic,9

antibiotic,10 selective 3-adrenergic receptor agonists11 and Src-kinase inhibitors.12 Hence

[1] (a) Li, C.; Mu, X.-Y.; Li, Y.-L.; Liu, Y.; Wang, X.-S. ACS Comb. Sci. 2013, 15, 267; (b) Wang, H.-

Y.; Shi, D.-Q. ACS Comb. Sci. 2013, 15, 261; (c) Pradhan, K.; Paul, S.; Das, A. R. Tetrahedron Lett.

2013, 54, 3105.

[2] Huisgen R.; Szeimies, G.; Möbius, L.Chem. Ber. 1967, 100, 2494.

[3] Fan, W. Q.; Katritzky, A. R. 1,2,3-Triazoles In Comprehensive Heterocyclic Chemistry II;

Katritzky, A. R.; Rees, C. W.; Scriven, E. F. Eds.; Pergamon Press: Oxford, 4: 1-126.

[4] Velaquez, S.; Alvarez, R.; Perez, C.; Gago, F.; De Clercq, E.; Balzarini, J.; Camarasa, M. J. Antivir.

Chem. Chemother. 1998, 9, 481; (b) Lazrek, H. B.; Taourirte, M.; Oulih, T.; Barascut, J. L.; Imbach, J.

L.; Pannecouque, C.; Witrouw, M.; De Clercq, E. Nucleos. Nucleot. Nucleic Acids 2001, 20, 1949.

[5] (a) Holla, B. S.; Mahalinga, M.; Karthikeyan, M. S.; Poojary, B.; Akberali, P. M.; Kumari, N. S.

Eur. J. Med. Chem. 2005, 40, 1173; (b) Banday, A. H.; Shameem, S. A.; Ganai, B. A. Org. Med. Chem.

Lett. 2012, 2, 13.

[6] Cho, J. H.; Bernard, D. L.; Sidwell, R. W.; Kern, E. R.; Chu, C. K. J. Med. Chem. 2006, 49, 1140.

[7] Bathula, S. N. P.; Vadla, R. Asian J. Pharm. Clin. Res. 2011, 4, 66.

[8] (a) Fung-Tomc, J. C.; Huczko, E.; Minassian, B.; Bonner, D. P. Antimicrob. Agents Chemother.

1998, 42, 313; (b) Pfaller, M. A.; Messer, S. A.; Hollis, R. J.; Jones, R. N.; Doern, G. V.; Brandt, M.

E.; Hajjeh, R. A. Antimicrob. Agents Chemother. 1998, 42, 3242.

[9] (a) Buckle, D. R.; Rockell, C. J. M.; Smith, H.; Spicer, B. A. J. Med. Chem. 1984, 27, 223; (b)

Buckle, D. R.; Rockell, C. J. M.; Smith, H.; Spicer, B. A. J. Med. Chem. 1983, 26, 251.

[10] Romero, A.; Liang, C.-H.; Chiu, Y.-H.; Yao, S.; Duffield, J.; Sucheck, S. J.; Marby, K.; Rabuka,

D.; Leung, P. Y.; Shue, Y.-K.; Ichikawa, Y.; Hwang, C.-K. Tetrahedron Lett. 2005, 46, 1483.


84

synthesis of triazole conjugated compounds accessed through click chemistry reaction

continues to attract the attention of chemists in a bid to identify molecules with enhanced

pharmacological properties.13

Antiallergicactivity

Trypanocidalactivity

O

O

N N

N

R

O

O

N

N

HN

R

O

O

N

N

N

R

Me

Antibacterialactivity

Figure 5.1. Structures of previously reported 1,2,3-triazole

linked/fused-1,4-naphthoquinones14-16

Buckle et al. reported the synthesis of naphtho[2,3-d]- -triazoles and their antiallergic

activity. 4,9-Dihydro-4,9-dioxo-lH-naphtho[2,3-d]- -triazoles inhibit the IgE-mediated

passive cutaneous anaphylaxis (PCA) reaction in rats and hence constitute a potent class of

antiallergic compounds.14 1,2,3-Triazolic para-naphthoquinones were evaluated against the

infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease and

found to be more active than the anti-T.cruzi drug benznidazole.15 1-Alkyl-1H- and 2-alkyl-

2H-naphtho-[2,3-d]triazole-4,9-diones manifest high potency and selectivity against Gram

positive (G+) pathogens including methicillin-resistant Staphylococcus aureus (MRSA).16

Due to the biological significance of triazoles and 1,4-naphthoquinones as well as their

hybrids, in this chapter, we report a facile three-component sequential synthesis of hitherto

unreported functionalized 1,2,3-triazolylmethylamino-1,4-naphthoquinones from the reaction

[11] Brockunier, L. L.; Parmee, E. R.; Ok, H. O.; Candelore, M. R.; Cascieri, M. A.; Colwell Jr, L. F.;

Deng, L.; Feeney, W. P.; Forrest, M. J.; Hom, G. J.; MacIntyre, D. E.; Tota, L.; Wyvratt, M. J.; Fisher,

M. H.; Weber, A. E. Bioorg. Med. Chem. Lett. 2000, 10, 2111.

[12] Kumar, D.; Reddy, V. B.; Kumar, A.; Mandal, D.; Tiwari, R.; Parang, K. Bioorg. Med. Chem.

Lett. 2011, 21, 449.

[13] Siddiqui, N.; Ahsan, W.; Alam, M. S.; Alia, R.; Jain, S.; Azad, B.; Akhtar, J. Int. J. Pharm. Sci.

Rev. Res. 2011, 8, 161.

[14] Buckle, D. R.; Smith, H.; Spicer, B. A.; Tedder, J. M. J. Med. Chem.1983, 26, 714.

[15] da Silva Jr, E. N.; de Melo, I. M. M.; Diogo, E. B. T.; Costa, V. A.; de Souza Filho, J. D.; Valenca,

W. O.; Camara, C. A.; de Oliveira, R. N.; de Araujo, A. S.; Emery, F. S.; dos Santos, M. R.; de

Simone, C. A.; Menna-Barreto, R. F. S.; de Castro, S. L. Eur. J. Med. Chem. 2012, 52, 304.

[16] Zhang, J.; Redman, N.; Litke, A. P.; Zeng, J.; Zhan, J.; Chan, K. Y.; Chang, C.-W. T. Bioorg.

Med. Chem. 2011, 19, 498.


85

of N-propargylaminonaphthoquinones, alkyl bromides/2-bromonaphthalene-1,4-dione and

sodium azide. Hence a brief review of literature reports on the synthesis of triazoles follows.

5.3. Synthesis of triazoles

A microwave-assisted three-component reaction was reported by Appukkuttan et al.17 to

prepare a series of 1,4-disubstituted 1,2,3-triazoles 4 from the corresponding alkyl halides 1,

sodium azide 2 and alkynes 3 in a 1:1 mixture of t-BuOH and water.

Quan et al.18 synthesized N-functionalized 1,2,3-triazoles linked with 3,4-dihydropyrimidione

7 via the 1,3-dipolar cycloaddition between azide functionalized DHPMs 5 with

phenylacetylene 6 in water and in the presence of 10 mol % of CuI.

1,4-Disubstituted 1,2,3-triazoles 10 were obtained by a convenient one-pot procedure from

aromatic and aliphatic halides 8, sodium azide and terminal alkynes 9 without isolating the

unstable organic azide intermediates.19

N N

I

N

N

NN

N

NaN3, CuSO4.5H2O

sodium ascorbate

L-Proline, Na2CO3

DMSO:H2O 9:1

60 oC8 9 10

Elamari et al.20 reported the synthesis of bis-akyne amides 11 derived from propiolic acid.

The bis-alkynes 11 were transformed into their mono-1,2,3-triazole analogs 13 on the amide

side due to their greater reactivity by a catalyst-free Huisgen’s reaction. Then the

[17] Appukkuttan, P.; Dehaen, W.; Fokin, V. V.; Van der Eycken, E. Org. Lett. 2004, 6, 4223.

[18] Quan, Z.-J.; Xu, Q.; Zhang, Z.; Da, Y.-X.; Wang, X.-C. Tetrahedron 2013, 69, 881.

[19] Feldman, A. K.; Colasson, B.; Fokin, V. V. Org. Lett. 2004, 6, 3897.

[20] Elamari, H.; Slimi, R.; Chabot, G. G.; Quentin, L.; Scherman, D.; Girard, C. Eur. J. Med. Chem.

2013, 60, 360.


86

monotriazoles 13 in the presence of polymer-supported catalyst, Amberlyst A-21, underwent

CuI-catalyzed Huisgen’s cycloaddition to afford the bis-triazoles 14.

A series of 4'-[1,2,3]triazole-2'-deoxy-2'-fluoro- -D-arabinofuranosylcytosines 16 were

prepared by Cu(I)-mediated [3+ 2] cycloaddition reactions of 1-(4'-azido-2'-deoxy-2'-fluoro-

-D-arabinofuranosyl)cytosine 15 with appropriate alkynes 3 in good yields.21

Li et al.22 described a synthetic protocol for the 1,3-dipolar cycloaddition of azides 18 with

electron-deficient alkynes 17. Alkynes with at least one neighbouring electron-withdrawing

group proceeds with the cycloaddition successfully without any catalyst at room temperature

in water.

Dialkyne substituted 2-aminobenzothiazole 20 upon reaction with various substituted aryl

azides 21 afforded benzothiazole 1,2,3-triazole analogs 22 in presence of

CuSO4.5H2O/sodium ascorbate catalyst.23

[21] Wu, J.; Yu, W.; Fu, L.; He, W.; Wang, Y.; Chai, B.; Song, C.; Chang, J. Eur. J. Med. Chem. 2013,

63, 739.

[22] Li, Z.; Seoa, T. S.; Ju, J. Tetrahedron Lett. 2004, 45, 3143.

[23] Singh, M. K.; Tilak, R.; Nath, G.; Awasthi, S. K.; Agarwal, A. Eur. J. Med. Chem. 2013, 63, 635.


87

A variety of 3-triazolyl-2-iminochromenes 25 were synthesized by Qian et al.24 using one-pot,

three-component Cu(I)-catalyzed reaction between 2-azidoacetonitrile 24, acetylenes 3 and

substituted salicylaldehydes 23. This reaction proceeds via triazole formation-an aldol

reaction-cyclization-dehydration sequence.

A one-pot protocol for the synthesis of 1,2,3-triazoles 27 has been developed by Alonso

et al.25 starting from inactivated alkenes 26 via two click reactions, (i) the azidosulfenylation

of the carbon-carbon double bond and (ii) the copper-catalyzed azide-alkyne Cycloaddition.

They have also demonstrated the versatility of the methylsulfanyl group through a series of

synthetic transformations, including direct access to 1-vinyl and 4-monosubstituted triazoles

28 and 29.

Ph

Ph , 70 oC, 12 h

NN

N

Ph

Ph

SMe

NN

N

Ph

Ph

NN

NH

Ph

26 27

29

28

a) CuNPs/C, Me2SSMeBF4, NaN3, MeCN, rt, 1 h; b)

a

b

Alkynes 3 undergo a copper(I)-catalyzed cycloaddition with sodium azide 2 and

formaldehyde 30 to yield 2-hydroxymethyl-2H-1,2,3-triazoles 31, which can be readily

converted to polyfunctional molecules. The hydroxymethyl group can also be removed

providing a convenient access to NH-1,2,3-triazoles.26

[24] Qian, W.; Amegadzie, A.; Winternheimer, D.; Allen, J. Org. Lett. 2013, 15, 2986.

[25] Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, M. J. Org. Chem. 2013, 78, 5031.

[26] Kalisiak, J.; Sharpless, K. B.; Fokin, V. V. Org. Lett. 2008, 10, 3171.


88

1,2,3-Triazolic para-naphthoquinone derivatives 34 were obtained from the

azidonaphthoquinone 33 via Huisgen cycloaddition with alkyne 3 using a Cu(I) catalyst.15

These compounds were, in turn, obtained by the reaction of 2-bromo-1,4-naphthoquinone 32

with sodium azide in DMF.

O

O

Br

32

O

O

N3

O

O

N

N N

R

R

NaN3

DMF CuICH3CN

33 34

3

Chapter 5 Results and Discussion ___________________________________________________________________________

89

5.4. Facile three-component sequential synthesis of amino-1,4-naphthoquinone-

appended triazoles and triazole-chromene hybrids: A click chemistry approach-The

present work

A facile three-component sequential synthesis of hitherto unreported functionalized 1,2,3-

triazolylmethylamino-1,4-naphthoquinones 36-41 from the reaction of

N-propargylaminonaphthoquinones 35, alkyl bromides/2-bromonaphthalene-1,4-dione 1 and

sodium azide 2 (Scheme 5.1) has been performed.

Scheme 5.1 Three-component sequential synthesis of 1,2,3-triazolyl-

methylamino-1,4-naphthoquinones 36-41

N-Propargylaminonaphthoquinones were synthesized by our earlier method.27 For

optimization, initially we examined the model two-component reaction of

2-((4-chlorophenyl)(prop-2-ynyl)amino)naphthalene-1,4-dione and benzyl azide (Scheme

5.2) in toluene at ambient temperature in the presence of CuI/Et3N, which furnished the

expected triazole, 39c in 84% yield in 1 h (Table 5.1). This reaction in nitromethane afforded

O

O

N

N

NNO

O

N

Bn

Bn N3

ClCl

39c35c

Scheme 5.2. Two-component synthesis of 1,2,3-triazolyl-

methylamino1,4-naphthoquinones 39c

[27] Devi Bala, B.; Muthusaravanan, S.; Perumal, S. Tetrahedron Lett. 2013, 54, 3735.


90

81% of 39c in 30 min, whilst it proceeded less efficiently in dichloroethane, dichloromethane,

THF and DMF, affording the product in lower yields of 74%, 70%, 71% and 34%

respectively (Table 5.1). In DMSO, the reaction failed to give the product. To our delight, we

found that the reaction either under solvent-free conditions or in water proceeded very well

and afforded an excellent yield of 39c, 90% and 96% respectively (Table 5.1).

Table 5. 1. Optimization of reaction conditions for the synthesis of

1,2,3-triazolylmethylamino-1,4-naphthoquinones 39ca

Entry Solvent Catalyst Yield of

39c (%)b

Two- component reaction

1 Toluene rt, 1 h 84

2 Dichloroethane rt, 1 h 74

3 Dichloromethane rt, 40 min 70

4 Nitromethane rt, 30 min 81

5 THF rt, 2 h 71

6 DMF rt, 2 h 34

7 DMSO rt, 3 h -c

8 Water rt, 30 min 96

9 --d rt, grinding, 1 min 90

Three-component reaction

10 --d (one pot) rt, grinding, 10 min 39

11 --d (one pot) 70 ûC, 10 min 47

12 --d (sequential)e 70 ûC, 2 min then rt, grinding 1 min 52

13 Water (one pot) rt, grinding, 7 min 44

14 Water (one pot) 70 ûC, 5 min 71

15 Water (sequential)e 70 ûC, 2 min then rt, grinding 1 min 96 aAll the reactions were performed in the presence of 5 mol%

of CuI and Et3N (1 mmol); bYield after filtration through a pad of silica gel.; cReaction failed to occur; dSolvent-free reaction; eThese reactions performed first at 70 ûC for 2 min and then

35 added and ground at rt for 1 min.

Further, we also examined the efficacy of the three-component reaction in a one-pot manner

under neat conditions as well as in water. In our preliminary experiment, equimolar amounts

of 2-((4-chlorophenyl)(prop-2-ynyl)amino)naphthalene-1,4-dione, benzyl bromide and

sodium azide (each 1 mmol) were taken together with the catalyst CuI (5 mol%) and base

Et3N (1 mmol) (Scheme 5.3) and the mixture ground at room temperature. After completion


91

Scheme 5.3. Three-component sequential synthesis of

1,2,3-triazolylmethylamino-1,4-naphthoquinones 39c

of the reaction under solvent-free conditions and in water, we have obtained only 39% and

44% of triazole 39c respectively (Table 5.1), whilst the reaction under these conditions at

70 ûC afforded 47% and 71% of triazole (Table 5.1) respectively. To our delight, we found

that the triazole 39c was obtained in near quantitative yield by performing the reaction

sequentially in water at 70 ûC. In this method, equimolar amounts of benzyl bromide and

sodium azide (each 1 mmol) together with 1 ml of water were taken in a reaction vial and

heated for 2 min at 70 ûC. To this reaction mixture, 2-((4-chlorophenyl)(prop-2-ynyl)-

amino)naphthalene-1,4-dione (1 mmol) was added and the reaction mixture was ground for

additional 1 min in the presence of CuI/Et3N at ambient temperature. After completion of the

reaction (TLC), the reddish brown solid formed was separated and purified by filtration

through a short pad of silica gel using 7:3 n-hexane–ethyl acetate to obtain pure compound

39c in near quantitative yield, 96% (Table 5.1).

Encouraged by the efficiency of the reaction protocol described above, the substrate scope

was probed next with a variety of substituted alkyl bromides/2-bromonaphthalene-1,4-dione,

sodium azide and substituted N-propargylaminonaphthoquinones, which afforded a library of

functionalized 1,2,3-triazolylmethylamino-1,4-naphthoquinones (Table 5.2). In the case of

allyl bromide, the reaction was found to be more facile, the initial grinding for 2 min in water

and subsequent reaction with N-propargylaminonaphthoquinones in the presence of CuI/Et3N

occurred efficiently at room temperature affording the product, in contrast to heating at 70 oC

required for the first step in the case of other organic halides.


92

Table 5.2. Sequential three-component synthesis of 1,2,3-triazolyl-

methylamino-1,4-naphthoquinones 36-41

O

O

N

N

NN

CN

O

O

N

N

NN

CN

O

O

N

N

NN

CN

O

O

N

N

NN

CN

O

O

N

N

NN

CN

O

O

N

N

NN

EtOO

O

O

N

N

NN

EtOO

O

O

N

N

NN

EtOO

O

O

N

N

NN

EtOO

O

O

N

N

NN

EtOO

Me

Br Cl F

OMe

O

O

N

N

NN

EtOO

Cl

O

O

N

N

NN

O

O

N

N

NN O

O

N

N

NN

Cl

F

OMe

O

O

N

N

NN O

O

N

N

NN

Me Cl

O

O

N

N

NN

O

O

N

N

NN

Ph

Cl

O

O

N

N

NN

Ph

Br

O

O

N

N

NN

Ph

Me

FOMe

Me Cl

36a90%

36c93%

36d91%

36e94%

36b91%

37b95%

37d90%

37e88%

37f91%

37c92%

38b92%

38d91%

38e92%

38f90%

38c89%

39b94%

39c94%

37a96%

38a94%

39a96%

O

O

N

N

NN

Ph

O

O

N

N

NN

Ph

O

O

N

N

NN

Ph

O

O

N

N

NN

Ph

CF3

OMe

Cl Cl

Cl

39d90%

39e91%

39f95%

39g89%

O

O

N

N

NN O

O

N

N

NN

PhO

PhO

ClMe

Cl

O

O

N

N

NN

Me

O

O

O

O

N

N

NN

Br

O

O

O

O

N

N

NN

Cl

O

O

40c88%

41a75%

41b80%

40b90%

41c77%

O

O

N

N

NN

F

PhO

40a93%

The structure of 1,2,3-triazolylmethylamino-1,4-naphthoquinones 36-41 was deduced from

elemental analysis and one- and two-dimensional NMR spectroscopic and mass spectral data

and elemental analysis. As a representative case, the structural assignment of 37a is described

below (Figures 5.2 and 5.3). The 1H NMR spectrum of 37a has two singlets appearing at 5.11

and 5.17 ppm, each accounting for two protons assignable to the hydrogens of the two

methylene groups, other than that of ethyl group, which were distinguished by the fact that the


93

former gives a HMB correlation with C-2 of the naphthoquinone ring, whilst the latter gives a

HMB correlation with the ester carbonyl (Figure 5.3). Among the two singlets at 6.07 and

7.69 ppm each integrating for one proton, the first one shows HMB correlations with C-1 and

C-4 carbonyls of naphthoquinone ring assigning it to H-3, whilst that at 7.69 ppm was due to

H-5' of the triazole ring. The two doublets of doublets occurring at 7.91 and 7.99 (1H, J=7.5,

1.4 Hz) ppm are due to H-5 and H-8 and the two triplets of doublets at 7.61 and 7.66 ppm

(1H, J=7.5, 1.4 Hz) have been assigned to H-6 and H-7. The chemical shifts of the hydrogens

and C,H-COSY correlations helped in the assignment of the hydrogen-bearing carbons.

Figure 5.2. 1H and 13C NMR assignments of compound 37a

Figure 5.3. Selected HMB correlations of compound 37a

A plausible mechanism for the formation of 1,2,3-triazolylmethylamino-1,4-naphthoquinones

36-41 is depicted in Scheme 5.4. Presumably, the copper (I) species forms a complex with

the triple bond of N-propargylaminonapthoquinone 35 to form 43. The alkyne proton of the

complex 43, being acidic, is abstracted by the base forming the carbanion, which forms a

Cu-acetylide intermediate 44. This Cu atom activates the azide function by coordination to


94

form intermediate 45. This intermediate 45 undergoes annulation furnishing the copper

complex 46, which furnishes the products 36-41 via elimination of Cu and protonation.

NaN3R Br R N3

1 2 42

[Cu]

O

O

N

N

N

N

36-41

R

R'

-BH

O

O

N

O

O

N

R'

[Cu]

H

BH

42RN N N

R'

O

O

N

R'

[Cu]

O

O

N

R'

NN

NR[Cu]

[Cu]

Cu

O

O

N

N

NN

R

R'

O

O

N

H

B

Cu

R'

43

35

44

45

46

47

B

Scheme 5.4. Plausible mechanistic pathway for the synthesis of

1,2,3-triazolylmethylamino-1,4-naphthoquinones 36-41

As triazolylcoumarins,28 2-iminochromenes29 and toddacoumaquinone (coumarin-

naphthoquinone dimer)30 are known to possess significant biological activities, we have now

synthesized the amino-1,4-naphthoquinone-appended iminochromene-triazole hybrid

herocycles 49 (Scheme 5.5) adopting the method of Quain et al.24 Initially, the

[28] Stefani, H. A.; Gueogjan, K.; Manarin, F.; Farsky, S. H. P.; Zukerman-Schpector, J.; Caracelli, I.;

Rodrigues, S. R. P.; Muscará, M. N.; Teixeira, S. A.; Santin, J. R.; Machado, I. D.; Bolonheis, S. M.;

Curi, R.; Vinolo, M. A. Eur. J. Med. Chem. 2012, 58 117.

[29] Huang, C.- K.; Wu, F.-Y.; Ai, Y.-X. Bioorg Med Chem. Lett. 1995, 5, 2423.

[30] Ishikawa, T.; Kotake, K.-I.; Ishii, H. Chem. Pharm. Bull.1995, 43, 1039.


95

1,2,3-triazolylacetonitriles 36 required for this synthesis were obtained from the

three-component sequential reaction of 2-(prop-2-ynyl(p-tolyl)amino)-naphthalene-1,4-dione,

bromoacetonitrile and sodium azide in presence of CuI/Et3N in water (Scheme 5.1).

Subsequently, 1,2,3-triazolylacetonitriles 36, without isolation, were treated with

salicylaldehyde and Et3N and the reaction at room temperature for 24 h afforded 49a in 54%

yield. To our delight, the transformation of intermediate 36 to 49 occurs more efficiently

under microwave irradiation at 60 oC in 3 min. furnishing 89% of 49a. Employing these

reaction conditions, nine compounds in series 49 could be obtained in moderate to good

yields (Table 5.3), which discloses the generality of this protocol.

Scheme 5.5. Sequential one pot synthesis of aminonaphthoquinone appended

iminochromene-triazole hybrid heterocycle 49

Table 5.3. Sequential one pot synthesis of 49

Entry Comp R' X Yield (%)a

1 49a 4-Me H 89

2 49b 4-F H 76

3 49c 3-OMe H 77

4 49d 2-Cl H 93

5 49e 2,4-(Me)2 H 82

6 49f H H 79

7 49g 4Me Br 81

8 49h 4F Cl 88

9 49i H Me 90

aYield after filtration through a pad of silica gel


96

The structure of 49 was deduced from elemental analysis, one- and two-dimensional NMR

spectroscopic and mass data. As a representative case, the structural assignment of 49a is

described below (Figures 5.4 and 5.5). The 1H NMR spectrum of 49a has a 2H singlet

appearing at 5.28 ppm readily assignable to the hydrogens of the methylene group. These

methylene hydrogens and a 1H singlet at 8.60 ppm due to H-5' show HMB correlations with

C-4', whilst H-4'' of the chromene ring gives another singlet at 8.56 ppm. The other protons of

chromene ring appear as multiplets in the region 7.37-7.44 and 7.61-7.68 accounting for two

protons each. The remaining protons were also assigned similarly.

Figure 5.4. 1H and 13C NMR assignments of compound 49a

O

O

NN N

NO

HN

Me

5

6

78 1

2

34

1'

2'

4'

5'

1''2''

3''

4''

5''6''

7''

8''

H HH H H

Figure 5.5. Selected HMB correlations of compound 49a

A plausible mechanism for the formation of 49 is described below. The initially formed 1,2,3-

triazolylacetonitriles 36 via the mechanism shown in Scheme 5.4, in the presence of base

undergoes aldol condensation with salicyaldehyde affording the intermediate 50 (Scheme

5.6). Subsequent intramolecular annulation of intermediate 50 and concomitant dehydration

furnishes aminonaphthoquinone appended iminochromene-triazole hybrid heterocycle.


97

1

NaN3

2

"in situ"

Br

O

O

N

N

NN

O

NH

OH

CHONC

48

R'

49

click

O

O

N

N

NN

36

R'

CN

O

O

N

R'

35

aldol

O

O

N

N

NN

50

R'

OHN

HOO

O

N

N

NN

51

R'

HO

O

NH

cyclization dehydration

N3NC

Scheme 5.6. Mechanism for the synthesis of aminonaphthoquinone appended

iminochromene-triazole hybrid heterocycle 49

5.5. Conclusions

This work describes a facile synthesis of a library of hitherto unreported functionalized

1,2,3-triazolylmethylamino-1,4-naphthoquinones via a sequential three-component reaction of

N-propargylaminonaphthoquinones with variously substituted alkyl bromides/

2-bromonaphthalene-1,4-dione and sodium azide in the presence of Et3N/CuI in water.

Formation of organic azide and its concomitant reaction with alkynes takeplace efficiently in

one-pot and the reaction is experimentally simple. A series of aminonaphthoquinone-

appended iminochromene-triazole hybrid heterocycles have also been synthesized.

Chapter 5 Experimental section ___________________________________________________________________________

99

5.6. Experimental section

5.6.1. General methods

Melting points were measured in open capillary tubes and are uncorrected. The 1H-NMR, 13C-

NMR, DEPT, H,H-COSY and C,H-COSY, HMBC were recorded on a Bruker (Avance) 300

MHz NMR instrument using TMS as internal standard and CDCl3 as solvent. Standard Bruker

software was used throughout. Chemical shifts are given in parts per million ( -scale) and the

coupling constants are given in Hertz. Silica gel-G plates (Merck) were used for TLC analysis

with a mixture of petroleum ether (60–80 °C) and ethyl acetate as eluent. Elemental analyses

were performed on a Perkin Elmer 2400 Series II Elemental CHNS analyzer. Mass spectra

were recorded in LCQ Fleet mass spectrometer, Thermo Fisher Instruments Limited, US.

Electrospray ionisation mass spectrometry (ESI-MS) analysis was performed in the positive

ion mode on a liquid chromatography ion trap. Microwave reactions have been carried out in

a Biotage Microwave synthesizer.

5.6.2. General procedure

(a) Synthesis of 1,2,3-triazolylmethylamino-1,4-naphthoquinones 36-41

A mixture of substituted bromide 1 and sodium azide 2 (each 1 mmol) together with 1 ml of

water was taken in a reaction vial and heated for 2 min at 70 ûC. To this reaction mixture,

N-propargylaminonaphthoquinone 35 (1 mmol) was added and the reaction mixture ground

for additional 1 min in the presence of CuI (5 mol%) and Et3N (1 mmol) at ambient

temperature. After completion of the reaction (TLC), the product was extracted with ethyl

acetate and washed with water (2 X 20 mL), the organic layer separated and dried over

anhydrous sodium sulfate and the solvent was removed under reduced pressure. The resulting

crude product was purified by filtration through a short pad of silica gel using 7:3 n-hexane–

ethyl acetate to obtain pure compounds 36-41.

(b) Synthesis of aminonaphthoquinone appended iminochromene-triazole hybrid

heterocycles 49

1,2,3-Triazolylacetonitrile 36 was synthesized according to the procedure described above.

This intermediate 36 in situ without isolation was treated with salicyaldehyde 48 (1 mmol)

and Et3N (1 mmol) in a vial and subjected to microwave irradiation at 100W, 60 ûC and 1 bar

pressure. After a period of 1–2 min, the temperature reached a plateau, 60ûC, and remained


100

constant. After completion of the reaction (TLC), the reaction mixture obtained was extracted

with ethyl acetate and washed with water (2 X 20 mL). The organic layer was separated, dried

over anhydrous sodium sulphate, the solvent removed under reduced pressure and purified by

filtration through a short pad of silica gel using 8:2 n-hexane–ethyl acetate to obtain pure 49.

5.6.2.1. 2-(4-(((1,4-Dioxo-1,4-dihydronaphthalen-2-yl)(4-fluorophenyl)amino)methyl)-

1H-1,2,3-triazol-1-yl)acetonitrile (36a)

Red solid; Yield: 90%; m.p 106 oC; 1H NMR (300 MHz, CDCl3) H: 1H NMR (300 MHz,

CDCl3) H: 5.16 (s, 2H), 5.34 (s, 2H), 6.00 (s, 1H), 7.07-7.12 (m, 2H), 7.16-7.21 (m, 2H),

7.62 (td, 1H, J=7.5, 1.2 Hz), 7.69 (td, 1H, J=7.5, 1.2 Hz), 7.85 (s, 1H), 7.92 (dd, 1H, J=7.5,

1.2 Hz), 7.98 (dd, 1H, J=7.5, 1.2 Hz). 13C NMR (75 MHz, CDCl3) C: 37.5, 49.8, 112.4,

113.0, 116.9, 123.1, 125.5, 126.6, 128.0, 132.1, 132.2, 132.6, 134.1, 141.3, 145.1, 151.2,

161.2, 182.9, 183.5. Anal. Calcd. for C21H14FN5O2: C, 65.11; H, 3.64; N, 18.08%. Found

C, 65.23; H, 3.57; N, 17.97%.

5.6.2.2. 2-(4-(((1,4-Dioxo-1,4-dihydronaphthalen-2-yl)(3-methoxyphenyl)amino)methyl)-

1H-1,2,3-triazol-1-yl)acetonitrile (36b)

Red semi-solid; Yield: 91%; 1H NMR (300 MHz, CDCl3) H: 3.78 (s, 3H), 5.19 (s, 2H), 5.30

(s, 2H), 6.10 (s, 1H), 6.74-6.84 (m, 3H), 7.30 (t, 1H, J=7.8 Hz), 7.63 (td, 1H, J=7.5, 1.5 Hz),

7.70 (td, 1H, J=7.5, 1.5 Hz), 7.79 (s, 1H), 7.94 (dd, 1H, J=7.5, 1.5 Hz), 8.01 (dd, 1H, J=7.5,

1.5 Hz). 13C NMR (75 MHz, CDCl3) C: 37.5, 49.6, 55.4, 111.9, 112.3, 112.5, 113.7, 118.0,

123.1, 125.5, 126.6, 130.6, 132.2, 132.3, 132.6, 134.1, 145.3, 146.5, 151.3, 160.8, 182.9,

183.6. Anal. Calcd. for C22H17N5O3: C, 66.16; H, 4.29; N, 17.53%. Found C, 66.23; H, 4.18;

N, 17.63%.

5.6.2.3. 2-(4-(((1,4-Dioxo-1,4-dihydronaphthalen-2-yl)(o-tolyl)amino)methyl)-1H-1,2,3-

triazol-1-yl)acetonitrile (36c)

Red solid; Yield: 93%; m.p 106 oC; 1H NMR (300 MHz, CDCl3) H: 2.10 (s, 3H), 5.03

(br s, 2H), 5.33 (s, 2H), 5.67 (s, 1H), 7.06-7.09 (m, 1H), 7.23-7.29 (m, 3H), 7.61 (td, 1H,

J=7.5, 1.2 Hz), 7.68 (td, 1H, J=7.5, 1.2 Hz), 7.94-7.99 (m, 3H). 13C NMR (75 MHz, CDCl3)

C: 17.5, 37.4, 49.1, 110.5, 112.6, 123.6, 125.4, 126.5, 127.3, 127.8, 128.3, 131.8, 132.2,

132.3, 132.4, 134.1, 134.7, 143.1, 145.2, 150.6, 183.2, 183.4. Anal. Calcd. for C22H17N5O2:

C, 68.92; H, 4.47; N, 18.27%. Found C, 69.01; H, 4.59; N, 18.16%.

5.6.2.4. 2-(4-(((2-Chlorophenyl)(1,4-dioxo-1,4-dihydronaphthalen-2-yl)amino)methyl)-

1H-1,2,3-triazol-1-yl)acetonitrile (36d)

Orange solid; Yield: 91%; m.p 119 oC; 1H NMR (300 MHz, CDCl3) H: 5.12 (s, 2H), 5.34


101

(s, 2H), 5.91 (s, 1H), 7.27-7.34 (m, 3H), 7.46-7.50 (m, 1H), 7.63 (td, 1H, J=7.5, 1.5 Hz), 7.67

(td, 1H, J=7.5, 1.5 Hz), 7.93-7.95 (m, 2H), 8.00-8.03 (m, 1H). 13C NMR (75 MHz, CDCl3)

C: 37.5, 49.1, 111.5, 112.5, 123.6, 125.5, 126.6, 128.4, 128.9, 129.0, 130.9, 131.5, 132.0,

132.2, 132.6, 134.1, 142.1, 144.6, 150.1, 182.3, 183.7. Anal. Calcd. for C21H14ClN5O2:

C, 62.46; H, 3.49; N, 17.34%. Found C, 62.38; H, 3.38; N, 17.43%.

5.6.2.5. 2-(4-(((1,4-Dioxo-1,4-dihydronaphthalen-2-yl)(phenyl)-amino)methyl)-1H-1,2,3-

triazol-1-yl)acetonitrile (36e)


(s, 2H), 6.07 (s, 1H), 7.17-7.20 (m, 2H), 7.29-7.32 (m, 1H), 7.39-7.44 (m, 2H), 7.64 (td, 1H,

J=7.5, 1.5 Hz), 7.70 (td, 1H, J=7.5, 1.5 Hz), 7.78 (s, 1H), 7.95 (dd, 1H, J=7.5, 1.5 Hz), 8.02

(dd, 1H, J=7.5, 1.5 Hz). 13C NMR (75 MHz, CDCl3) C: 37.3, 49.5, 112.7, 113.2, 123.2,

123.5, 125.8, 126.4, 126.7, 129.7, 132.1, 132.2, 132.4, 133.8, 144.7, 145.4, 151.2, 182.6,

183.3. ESI-MS: m/z. Calcd.: 369.12; Found: 370.17 (M+H)+, 392.17 (M+Na)+. Anal. Calcd.

for C21H15N5O2: C, 68.28; H, 4.09; N, 18.96%. Found, C, 68.34; H, 4.19; N, 18.89%.

5.6.2.6. Ethyl 2-(4-(((1,4-dioxo-1,4-dihydronaphthalen-2-yl)(p-tolyl)amino)methyl)-1H-

1,2,3-triazol-1-yl)acetate (37a)

Red solid; Yield: 96%; m.p 114 oC; 1H NMR (300 MHz, CDCl3) H: 1.25 (t, 3H, J=7.2 Hz),

2.35 (s, 3H), 4.22 (q, 2H, J=7.2 Hz), 5.11 (s, 2H), 5.18 (s, 2H), 6.07 (s, 1H), 7.05 (d, 2H,

J=8.4 Hz), 7.18 (d, 2H, J=8.4 Hz), 7.61 (td, 1H, J=7.5, 1.4 Hz), 7.66 (td, 1H, J=7.5, 1.4 Hz),

7.69 (s, 1H), 7.91 (dd, 1H, J=7.5, 1.4 Hz), 7.99 (dd, 1H, J=7.5, 1.4 Hz). 13C NMR (75 MHz,

CDCl3) C: 13.9, 21.0, 50.0, 50.8, 62.2, 112.6, 124.0, 125.4, 125.9, 126.5, 130.4, 132.3, 132.4,

132.5, 133.8, 136.7, 143.0, 144.1, 151.5, 166.0, 183.0, 183.3. ESI-MS: m/z. Calcd.: 430.16;

Found: 431.25 (M+H), 453.25 (M+Na). Anal. Calcd. for C24H22N4O4: C, 66.97; H, 5.15;

N, 13.02%. Found C, 66.90; H, 5.05; N, 13.14%.

5.6.2.7. Ethyl 2-(4-(((4-bromophenyl)(1,4-dioxo-1,4-dihydronaphthal-en-2-yl)amino)-

methyl)-1H-1,2,3-triazol-1-yl)acetate (37b)


4.23 (q, 2H, J=7.2 Hz), 5.12 (s, 2H), 5.14 (s, 2H), 6.22 (s, 1H), 7.08 (d, 2H, J=8.4 Hz), 7.49

(d, 2H, J=8.4 Hz), 7.62 (td, 1H, J=7.5, 1.5 Hz), 7.65 (s, 1H), 7.69 (td, 1H, J=7.5, 1.5 Hz),

7.92 (dd, 1H, J=7.5, 1.5 Hz), 8.01 (dd, 1H, J=7.5, 1.5 Hz). 13C NMR (75 MHz, CDCl3)

C: 13.9, 49.6, 50.8, 62.3, 114.1, 119.9, 124.0, 125.4, 126.5, 127.5, 132.2, 132.3, 132.5, 132.8,

133.9, 143.4, 144.9, 150.9, 165.9, 182.4, 183.4. Anal. Calcd. for C23H19BrN4O4: C, 55.77;

H, 3.87; N, 11.31%. Found C, 55.90; H, 3.78; N, 11.25%.


102

5.6.2.8. Ethyl 2-(4-(((4-chlorophenyl)(1,4-dioxo-1,4-dihydronaphthalen-2-yl)amino)-

methyl)-1H-1,2,3-triazol-1-yl)acetate (37c)


4.23 (q, 2H, J=7.2 Hz), 5.12 (s, 2H), 5.15 (s, 2H), 6.20 (s, 1H), 7.08 (d, 2H, J=8.7 Hz), 7.49

(d, 2H, J=8.7 Hz), 7.63 (td, 1H, J=7.5, 1.5 Hz), 7.65 (s, 1H), 7.70 (td, 1H, J=7.5, 1.5 Hz),

7.91-7.94 (m, 1H), 8.01-8.04 (m, 1H). 13C NMR (75 MHz, CDCl3) C: 13.9, 49.7, 50.7, 62.3,

113.7, 124.0, 125.4, 126.5, 127.1, 129.8, 132.0, 132.1, 132.2, 132.5, 133.9, 143.4, 144.2,

150.8, 166.0, 182.4, 183.4. Anal. Calcd. for C23H19ClN4O4: C, 61.27; H, 4.25; N, 12.43%.

Found C, 61.36; H, 4.19; N, 12.35%.

5.6.2.9. Ethyl 2-(4-(((1,4-dioxo-1,4-dihydronaphthalen-2-yl)(4-fluorophenyl)amino)-

methyl)-1H-1,2,3-triazol-1-yl)acetate (37d)


4.24 (q, 2H, J=7.2 Hz), 5.12 (s, 2H), 5.16 (s, 2H), 6.06 (s, 1H), 7.05-7.12 (m, 2H), 7.15-7.20

(m, 2H), 7.62 (td, 1H, J=7.5, 1.2 Hz), 7.66-7.72 (m, 2H), 7.92 (dd, 1H, J=7.5, 1.2 Hz), 8.01

(dd, 1H, J=7.5, 1.2 Hz). 13C NMR (75 MHz, CDCl3) C: 13.9, 50.0, 50.8, 62.3, 112.7, 116.7,

124.2, 125.4, 126.5, 128.0, 132.2, 132.3, 132.5, 134.0, 141.5, 143.7, 151.2, 161.0, 166.0,

182.7, 183.4. ESI-MS: m/z. Calcd.: 434.14; Found: 435.17 (M+H)+, 457.17 (M+Na)+. Anal.

Calcd. for C23H19FN4O4: C, 63.59; H, 4.41; N, 12.90%. Found, C, 63.47; H, 4.48; N, 12.99%.

5.6.2.10. Ethyl 2-(4-(((1,4-dioxo-1,4-dihydronaphthalen-2-yl)(3-methoxyphenyl)amino)-

methyl)-1H-1,2,3-triazol-1-yl)acetate (37e)


3.78 (s, 3H), 4.23 (q, 2H, J=7.2 Hz), 5.11 (s, 2H), 5.20 (s, 2H), 6.15 (s, 1H), 6.73-6.83

(m, 3H), 7.27-7.31 (m, 1H), 7.62 (td, 1H, J=7.5, 1.2 Hz), 7.65 (s, 1H), 7.69 (td, 1H, J=7.5, 1.2

Hz), 7.94 (dd, 1H, J=7.5, 1.2 Hz), 8.02 (dd, 1H J=7.5, 1.2 Hz). 13C NMR (75 MHz, CDCl3)

C: 13.9, 49.9, 50.8, 55.3, 62.3, 111.8, 112.3, 113.4, 118.1, 124.0, 125.5, 126.6, 130.4, 132.3,

132.4, 132.5, 133.9, 144.1, 146.8, 151.4, 160.7, 166.0, 182.8, 183.5. Anal. Calcd. for

C24H22N4O5: C, 64.57; H, 4.97; N, 12.55%. Found C, 64.46; H, 4.91; N, 12.67%.

5.6.2.11. Ethyl 2-(4-(((2-chlorophenyl)(1,4-dioxo-1,4-dihydronaphthal-en-2-yl)amino)-

methyl)-1H-1,2,3-triazol-1-yl)acetate (37f)

Red semi-solid; Yield: 91%; 1H NMR (300 MHz, CDCl3) H: 1.27 (t, 3H, J=7.2 Hz), 4.24

(q, 2H, J=7.2 Hz), 5.11 (s, 2H), 5.14 (s, 2H), 6.00 (s, 1H), 7.26-7.32 (m, 3H), 7.45-7.48 (m,

1H), 7.60 (td, 1H, J=7.5, 1.2 Hz), 7.68 (td, 1H, J=7.5, 1.2 Hz), 7.82 (s, 1H), 7.92 (d, 1H,

J=7.5 Hz), 8.01 (d, 1H, J=7.5 Hz). 13C NMR (75 MHz, CDCl3) C: 13.8, 49.0, 50.7, 62.2,

111.0, 124.5, 125.3, 126.4, 128.1, 128.6, 129.0, 130.5, 131.3, 131.9, 132.1, 132.3, 133.8,


103

142.3, 143.1, 150.1, 166.0, 182.0, 183.5. Anal. Calcd. for C23H19ClN4O4: C, 61.27; H, 4.25;

N, 12.43%. Found C, 61.18; H, 4.36; N, 12.36%.

5.6.2.12. 2-(((1-Allyl-1H-1,2,3-triazol-4-yl)methyl)(4-chlorophenyl)amino)naphthalene-

1,4-dione (38a)

Red solid; Yield: 94%; m.p 148 oC; 1H NMR (300 MHz, CDCl3) H: 4.93 (dt, 2H, J=6.0,1.2

Hz), 5.12 (s, 2H), 5.24 (dq, 1H, J=16.8, 0.9 Hz), 5.32 (dq, 1H, J=10.2, 0.9 Hz), 5.91-6.04

(m, 1H), 6.19 (s, 1H), 7.13 (d, 2H, J=8.7 Hz), 7.34 (d, 2H, J=8.7 Hz), 7.49 (s, 1H), 7.62

(td, 1H, J=7.5, 1.5 Hz), 7.70 (td, 1H, J=7.5, 1.5 Hz), 7.91 (dd, 1H, J=7.5, 1.5 Hz), 8.02

(dd, 1H J=7.5, 1.5 Hz). 13C NMR (75 MHz, CDCl3) C: 49.8, 52.6, 113.8, 120.1, 122.3, 125.5,

126.5, 127.1, 129.8, 131.0, 132.0, 132.1, 132.2, 132.6, 134.0, 143.3, 144.4, 150.9, 182.5,

183.5. ESI-MS: m/z. Calcd.: 404.10; Found: 405.17 (M+H)+, 427.17 (M+Na)+. Anal. Calcd.

for C22H17ClN4O2: C, 65.27; H, 4.23; N, 13.84%. Found C, 65.37; H, 4.29; N, 13.71%.

5.6.2.13. 2-(((1-Allyl-1H-1,2,3-triazol-4-yl)methyl)(4-fluorophenyl)amino)naphthalene-

1,4-dione (38b)



(m, 1H), 6.07 (s, 1H), 7.04-7.11 (m, 2H), 7.14-7.20 (m, 2H), 7.52 (s, 1H), 7.62 (td, 1H, J=7.5,

1.5 Hz), 7.70 (td, 1H, J=7.5, 1.5 Hz), 7.93 (dd, 1H, J=7.5, 1.5 Hz), 8.02 (dd, 1H J=7.5, 1.5

Hz). 13C NMR (75 MHz, CDCl3) C: 50.0, 52.6, 112.8, 116.6, 120.0, 120.1, 122.4, 125.4,

126.5, 127.9, 131.0, 132.3, 132.4, 133.9, 141.7, 143.5, 151.3, 161.0, 182.7, 183.4. Anal.

Calcd. for C22H17FN4O2: C, 68.03; H, 4.41; N, 14.43%. Found C, 68.09; H, 4.30; N, 14.52%.

5.6.2.14. 2-(((1-Allyl-1H-1,2,3-triazol-4-yl)methyl)(3-methoxyphenyl)amino)naphtha-

lene-1,4-dione (38c)


(dt, 2H, J=6.0,1.2 Hz), 5.17 (s, 2H), 5.22 (dq, 1H, J=17.1, 0.9 Hz), 5.31 (dq, 1H, J=10.2, 0.9

Hz), 5.90-6.04 (m, 1H), 6.16 (s, 1H), 6.73-6.82 (m, 3H), 7.25-7.30 (m, 1H), 7.48 (s, 1H), 7.62

(td, 1H, J=7.5, 1.4 Hz), 7.69 (td, 1H, J=7.5, 1.4 Hz), 7.94 (dd, 1H, J=7.5, 1.4 Hz), 8.02

(dd, 1H J=7.5, 1.4 Hz). 13C NMR (75 MHz, CDCl3) C: 49.9, 52.6, 55.3, 111.8, 112.2, 113.4,

118.1, 120.0, 122.3, 125.5, 126.5, 130.4, 131.1, 132.3, 132.4, 132.5, 133.9, 143.8, 146.8,

151.4, 160.6, 182.8, 183.5. Anal. Calcd. for C23H20N4O3: C, 68.99; H, 5.03; N, 13.99%.

Found C, 69.07; H, 5.15; N, 13.92%.


104

5.6.2.15. 2-(((1-Allyl-1H-1,2,3-triazol-4-yl)methyl)(o-tolyl)amino)naphthalene-1,4-dione

(38d)

Red solid; Yield: 91%; m.p 91 oC; 1H NMR (300 MHz, CDCl3) H: 2.11 (s, 3H), 4.93-5.96

(m, 4H), 5.23 (d, 1H, J=17.1 Hz), 5.32 (d, 1H, J=10.2 Hz), 5.72 (s, 1H), 5.91-6.05 (m, 1H),

7.07-7.10 (m, 1H), 7.22-7.27 (m, 3H), 7.63-7.71 (m, 3H), 7.96-8.02 (m, 2H). 13C NMR

(75 MHz, CDCl3) C: 17.5, 49.3, 52.6, 110.3, 120.0, 122.8, 125.4, 126.4, 127.3, 127.6, 128.1,

131.4, 131.6, 132.2, 132.3, 132.5, 134.0, 134.7, 143.3, 143.9, 150.8, 183.3, 183.4. Anal.

Calcd. for C23H20N4O2: C, 71.86; H, 5.24; N, 14.57%. Found C, 71.79; H, 5.15; N, 14.70%.

5.6.2.16. 2-(((1-Allyl-1H-1,2,3-triazol-4-yl)methyl)(2-chlorophenyl)amino)naphthalene-

1,4-dione (38e)



(m, 2H), 7.25-7.31 (m, 3H), 7.44-7.48 (m, 1H), 7.62 (td, 1H, J=7.5, 1.2 Hz), 7.64 (s, 1H),

7.70 (td, 1H, J=7.5, 1.2 Hz), 7.93 (dd, 1H, J=7.5, 1.2 Hz), 8.03 (dd, 1H J=7.5, 1.2 Hz). 13C

NMR (75 MHz, CDCl3) C: 49.4, 52.7, 111.2, 120.1, 122.8, 125.5, 126.5, 128.3, 128.7, 129.1,

130.7, 131.1, 131.5, 132.1, 132.3, 132.5, 134.0, 142.5, 143.1, 150.3, 182.3, 183.7. Anal.

Calcd. for C22H17ClN4O2: C, 65.27; H, 4.23; N, 13.84%. Found C, 65.16; H, 4.16; N, 13.94%.

5.6.2.17. 2-(((1-Allyl-1H-1,2,3-triazol-4-yl)methyl)(phenyl)amino)naphthalene-1,4-dione

(38f)

Red semi-solid; Yield: 90%; 1H NMR (300 MHz, CDCl3) H: 4.92 (dt, 2H, J=6.0,1.2 Hz),

5.18 (s, 2H), 5.20-5.25 (m, 1H), 5.31 (dq, 1H, J=10.2, 0.9 Hz), 5.90-6.03 (m, 1H), 6.14

(s, 1H), 7.16-7.19 (m, 2H), 7.24-7.29 (m, 1H), 7.36-7.41 (m, 2H), 7.49 (s, 1H), 7.62 (td, 1H,

J=7.5, 1.4 Hz), 7.69 (td, 1H, J=7.5, 1.4 Hz), 7.92 (dd, 1H, J=7.5, 1.4 Hz), 8.02 (dd, 1H J=7.5,

1.4 Hz). 13C NMR (75 MHz, CDCl3) C: 49.9, 52.5, 113.1, 119.9, 122.3, 125.3, 125.8, 126.5,

126.6, 129.7, 131.0, 132.2, 132.3, 132.4, 133.8, 143.7, 145.6, 151.3, 182.7, 183.4. Anal.

Calcd. for C22H18N4O2: C, 71.34; H, 4.90; N, 15.13%. Found C, 71.22; H, 4.97; N, 15.04%.

5.6.2.18. 2-(((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)(p-tolyl)amino)naphthalene-1,4-

dione (39a)


(s, 2H), 5.48 (s, 2H), 6.06 (s, 1H), 7.01 (d, 2H, J=8.4 Hz), 7.15 (d, 2H, J=8.4 Hz), 7.17-7.20

(m, 2H), 7.31-7.34 (m, 3H), 7.39 (s, 1H), 7.59 (td, 1H, J=7.5, 1.2 Hz), 7.67 (td, 1H, J=7.5, 1.2

Hz), 7.89 (dd, 1H, J=7.5, 1.2 Hz), 8.00 (dd, 1H, J=7.5, 1.2 Hz). 13C NMR (75 MHz, CDCl3)

C: 21.0, 50.0, 53.9, 112.5, 122.6, 125.3, 125.8, 126.4, 127.6, 128.5, 128.9, 130.3, 132.3,


105

133.8, 134.6, 136.6, 142.9, 144.0, 151.4, 182.9, 183.3. Anal. Calcd. for C27H22N4O2: C, 74.64;

H, 5.10; N, 12.89%. Found C, 74.56; H, 5.23; N, 12.96%.

5.6.2.19. 2-(((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)(4-bromophenyl)amino)naphtha-

lene-1,4-dione (39b)


(s, 2H), 6.20 (s, 1H), 7.02 (d, 2H, J=8.7 Hz), 7.18-7.35 (m, 6H), 7.45 (d, 2H, J=8.7 Hz),

7.59-7.72 (m, 2H), 7.88 (d, 1H, J=7.2 Hz), 8.01 (d, 1H, J=7.2 Hz).13C NMR (75 MHz,

CDCl3) C: 49.7, 54.1, 114.4, 120.0, 122.6, 125.6, 126.6, 127.5, 127.8, 128.7, 129.1, 132.2,

132.6, 132.8, 134.0, 134.4, 143.5, 144.8, 151.0, 182.5, 183.6. Anal. Calcd. for C26H19BrN4O2:

C, 62.54; H, 3.84; N, 11.22%. Found C, 62.45; H, 3.95; N, 11.28%.

5.6.2.20. 2-(((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)(4-chlorophenyl)amino)naphtha-

lene-1,4-dione (39c)


(s, 2H), 6.18 (s, 1H), 7.09 (d, 2H, J=8.7 Hz), 7.15-7.18 (m, 2H), 7.28-7.36 (m, 6H), 7.62

(td, 1H, J=7.5, 1.5 Hz), 7.70 (td, 1H, J=7.5, 1.5 Hz), 7.87-7.90 (m, 1H), 8.01-8.04 (m, 1H).

13C NMR (75 MHz, CDCl3) C: 49.7, 54.1, 113.9, 122.6, 125.5, 126.6, 127.2, 127.7, 128.7,

129.0, 129.8, 132.1, 132.2, 132.3, 132.6, 134.0, 134.4, 143.5, 144.3, 151.0, 182.5, 183.5.

ESI-MS: m/z. Calcd.: 454.12; Found: 455.25 (M+H)+, 477.25 (M+Na)+. Anal. Calcd. for

C26H19ClN4O2: C, 68.65; H, 4.21; N, 12.32%. Found C, 68.73; H, 4.33; N, 12.21%.

5.6.2.21. 2-(((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)(4-(trifluoromethyl)phenyl)amino)-

naphthalene-1,4-dione (39d)


(s, 2H), 6.37 (s, 1H), 7.14-7.18 (m, 2H), 7.25 (d, 2H, J=7.2 Hz), 7.31-7.34 (m, 4H), 7.57

(d, 2H, J=8.4 Hz), 7.63 (td, 1H, J=7.5, 1.5 Hz), 7.71 (td, 1H, J=7.5, 1.5 Hz), 7.89 (dd, 1H,

J=7.5, 1.5 Hz), 8.03 (dd, 1H, J=7.5, 1.5 Hz). 13C NMR (75 MHz, CDCl3) C: 49.5, 54.2,

116.4, 122.4, 123.9 (1JC,F = 270.4 Hz, CF3), 125.3, 125.7, 126.7, 127.7 (2JC,F =32.5 Hz), 127.8,

128.7, 129.1, 132.2, 132.3, 132.8, 134.1, 134.5, 144.3, 149.1, 150.9, 182.2, 183.6. Anal.

Calcd. for C27H19F3N4O2: C, 66.39; H, 3.92; N, 11.47%. Found C, 66.29; H, 3.99; N, 11.56%.

5.6.2.22. 2-(((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)(3-methoxyphenyl)amino)naphtha-

lene-1,4-dione (39e)


CDCl3) H: 3.73 (s, 3H), 5.14 (s, 2H), 5.47 (s, 2H), 6.13 (s, 1H), 6.70-6.79 (m, 3H), 7.14-7.33

(m, 6H), 7.40 (s, 1H), 7.59 (td, 1H, J=7.5, 1.2 Hz), 7.67 (td, 1H, J=7.5, 1.2 Hz), 7.88 (dd, 1H,


106

J=7.5, 1.2 Hz), 8.00 (d, 1H, J=7.5, 1.2 Hz). 13C NMR (75 MHz, CDCl3) C: 49.8, 54.0, 55.3,

111.8, 112.3, 113.4, 118.2, 122.6, 125.4, 126.5, 127.7, 128.6, 129.0, 130.3, 132.2, 132.3,

132.4, 133.9, 134.5, 144.0, 146.7, 151.4, 160.6, 182.8, 183.5. Anal. Calcd. for C27H22N4O3:

C, 71.99; H, 4.92; N, 12.44%. Found C, 72.08; H, 4.81; N, 12.36%.

5.6.2.23. 2-(((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)(2-chlorophenyl)amino)naphtha-

lene-1,4-dione (39f)

Yellow solid; Yield: 95%; m.p 107 oC; 1H NMR (300 MHz, CDCl3) H: 1H NMR (300 MHz,

CDCl3) H: 5.08 (s, 2H), 5.47 (s, 2H), 6.20 (s, 1H), 7.17-7.28 (m, 5H), 7.33-7.43 (m, 4H),

7.53 (s, 1H), 7.60 (td, 1H, J=7.5, 1.4 Hz), 7.69 (td, 1H, J=7.5, 1.4 Hz), 7.90 (dd, 1H, J=7.5,

1.4 Hz), 8.02 (dd, 1H, J=7.5, 1.4 Hz). 13C NMR (75 MHz, CDCl3) C: 49.2, 54.1, 111.3,

123.0, 125.5, 126.5, 127.3, 128.2, 128.6, 129.0, 129.2, 130.6, 131.5, 132.0, 132.3, 132.4,

133.9, 134.5, 142.3, 143.3, 150.2, 182.2, 183.6. Anal. Calcd. for C26H19ClN4O2: C, 68.65;

H, 4.21; N, 12.32%. Found C, 68.78; H, 4.11; N, 12.26%.

5.6.2.24. 2-(((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)(2,4-dichloro-phenyl)amino)naph-

thalene-1,4-dione (39g)

Red solid; Yield: 89%; m.p 77 oC; 1H NMR (300 MHz, CDCl3) H: 5.00 (s, 2H), 5.49 (s, 2H),

6.06 (s, 1H), 7.17-7.23 (m, 4H), 7.32-7.42 (m, 4H), 7.49 (s, 1H), 7.60 (td, 1H, J=7.5, 1.2 Hz),

7.68 (td, 1H, J=7.5, 1.2 Hz), 7.88 (dd, 1H, J=7.5, 1.2 Hz), 8.01 (dd, 1H, J=7.5, 1.2 Hz).

13C NMR (75 MHz, CDCl3) C: 48.8, 54.0, 111.5, 122.9, 125.4, 126.4, 127.6, 128.3, 128.6,

128.9,130.0, 130.2, 131.8, 132.0, 132.3, 132.4, 133.4, 133.9, 134.4, 141.1, 142.6, 149.8,

181.8, 183.5. Anal. Calcd. for C26H18Cl2N4O2: C, 63.81; H, 3.71; N, 11.45%. Found C, 63.90;

H, 3.60; N, 11.37%.

5.6.2.25. 2-((4-Fluorophenyl)((1-(2-oxo-2-phenylethyl)-1H-1,2,3-triazol-4-yl)methyl)-

amino)naphthalene-1,4-dione (40a)


(s, 2H), 6.09 (s, 1H), 7.04-7.10 (m, 2H), 7.16-7.21 (m, 2H), 7.48-7.53 (m, 2H), 7.57-7.69

(m, 3H), 7.71 (s, 1H), 7.88-8.00 (m, 4H). 13C NMR (75 MHz, CDCl3) C: 50.1, 55.4, 112.6,

116.7, 124.7, 125.4, 126.6, 128.0, 128.1, 129.1, 132.2, 132.3, 132.4, 133.8, 133.9, 134.5,

141.6, 143.6, 151.2, 161.1, 182.8, 183.5, 190.1. Anal. Calcd. for C27H19FN4O3: C, 69.52;

H, 4.11; N, 12.01%. Found C, 69.59; H, 4.01; N, 12.14%.


107

5.6.2.26. 2-(((1-(2-Oxo-2-phenylethyl)-1H-1,2,3-triazol-4-yl)methyl)(o-tolyl)amino)-

naphthalene-1,4-dione (40b)

Red solid; Yield: 90%; m.p 164 oC; 1H NMR (300 MHz, CDCl3) H: 2.12 (s, 3H), 5.26 (br s,

2H), 5.74 (s, 1H), 5.83 (s, 2H), 7.09-7.12 (m, 1H), 7.22-7.27 (m, 3H), 7.51 (t, 2H, J=7.8 Hz),

7.58-7.70 (m, 3H), 7.82 (s, 1H), 7.95-8.01 (m, 4H). 13C NMR (75 MHz, CDCl3) C: 17.6,

49.4, 55.4, 110.2, 125.1, 125.4, 126.5, 127.4, 127.7, 128.0, 128.1, 129.1, 131.7, 132.2, 132.4,

132.5, 133.8, 133.9, 134.5, 134.9, 143.1, 144.2, 150.8, 183.4,* 190.1. ESI-MS: m/z. Calcd.:

462.17; Found: 463.25 (M+H)+, 485.33 (M+Na)+. Anal. Calcd. for C28H22N4O3: C, 72.71;

H, 4.79; N, 12.11%. Found C, 72.60; H, 4.72; N, 12.20%.*Two carbonyls are merged

together.

5.6.2.27. 2-((2,4-Dichlorophenyl)((1-(2-oxo-2-phenylethyl)-1H-1,2,3-triazol-4-yl)methyl)-

amino)naphthalene-1,4-dione (40c)

Red semi-solid; Yield: 88%; 1H NMR (300 MHz, CDCl3) H: 5.06 (s, 2H), 5.84 (s, 2H), 6.11

(s, 1H), 7.22-7.29 (m, 2H), 7.45-7.54 (m, 3H), 7.57-7.70 (m, 3H), 7.80 (s, 1H), 7.89 (d, 1H,

J=7.5 Hz), 7.94-8.00 (m, 3H). 13C NMR (75 MHz, CDCl3) C: 49.0, 55.5, 111.4, 125.0, 125.5,

126.6, 128.0, 128.5, 129.1, 130.2, 130.4, 131.9, 132.2, 132.4, 132.5, 133.6, 133.8, 134.0,

134.5, 141.3, 142.7, 149.9, 182.0, 183.7, 190.0. Anal. Calcd. for C27H18Cl2N4O3: C, 62.68;

H, 3.51; N, 10.83%. Found, C, 62.59; H, 3.63; N, 10.89%.

5.6.2.28. 2-(4-(((1,4-Dioxo-1,4-dihydronaphthalen-2-yl)(p-tolyl)-amino)methyl)-1H-1,2,3-

triazol-1-yl)naphthalene-1,4-dione (41a)


(s, 2H), 6.12 (s, 1H), 6.48 (s, 1H), 7.13 (d, 2H, J=8.1 Hz), 7.20 (d, 2H, J=8.1 Hz), 7.56-7.79

(m, 4H), 7.93 (d, 1H, J=7.5 Hz), 7.98 (d, 1H, J=7.5 Hz), 8.07 (d, 1H, J=7.5 Hz), 8.14 (d, 1H,

J=7.5 Hz), 8.67 (s, 1H). 13C NMR (75 MHz, CDCl3) C: 21.1, 50.1, 112.5, 125.4, 126.6,

126.1, 126.5, 126.7, 127.0, 129.5, 130.6, 132.1, 132.4, 132.5, 132.9, 133.9, 135.5, 136.9,

141.1, 142.5, 143.2, 151.5, 175.6, 180.5, 182.9, 183.6. Anal. Calcd. for C30H20N4O4: C, 71.99;

H, 4.03; N, 11.19%. Found C, 72.05; H, 4.13; N, 11.06%.

5.6.2.29. 2-((4-Bromophenyl)((1-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)-1H-1,2,3-

triazol-4-yl)methyl)amino)naphthalene-1,4-dione (41b)


CDCl3) H: 5.24 (s, 2H), 6.27 (s, 1H), 6.51 (s, 1H), 7.16 (d, 2H, J=8.7 Hz), 7.53 (d, 2H, J=8.7

Hz), 7.51-7.73 (m, 3H), 7.81 (t, 1H, J=7.5 Hz), 7.95 (d, 1H, J=7.4 Hz), 8.03 (d, 1H, J=7.8

Hz), 8.11 (d, 1H, J=7.4 Hz), 8.18 (d, 1H, J=7.8 Hz), 8.70 (s, 1H). Anal. Calcd. for

C29H17BrN4O4: C, 61.61; H, 3.03; N, 9.91%. Found C, 61.52; H, 2.91; N, 9.98%.


108

5.6.2.30. 2-((4-Chlorophenyl)((1-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)-1H-1,2,3-

triazol-4-yl)methyl)amino)naphthalene-1,4-dione (41c)


(s, 1H), 6.49 (s, 1H), 7.21 (d, 2H, J=8.7 Hz), 7.38 (d, 2H, J=8.7 Hz), 7.59-7.71 (m, 3H), 7.79

(t, 1H, J=7.5 Hz), 7.94 (d, 1H, J=7.5 Hz), 8.01 (d, 1H, J=7.5 Hz), 8.10 (d, 1H, J=7.5 Hz),

8.16 (d, 1H, J=7.5 Hz), 8.69 (s, 1H). 13C NMR (75 MHz, CDCl3) C: 49.9, 112.4, 113.8,

125.4, 125.5, 126.5, 126.7, 127.0, 127.3, 129.5, 130.0, 132.0, 132.2, 132.3, 132.6, 132.9,

134.0, 135.5, 141.1, 141.9, 144.4, 151.0, 175.6, 180.4, 182.4, 183.7. Anal. Calcd. for

C29H17ClN4O4: C, 66.86; H, 3.29; N, 10.76%. Found C, 66.78; H, 3.40; N, 10.70%.

5.6.2.31. 2-(((1-(2-Imino-2H-chromen-3-yl)-1H-1,2,3-triazol-4-yl)methyl)(p-tolyl)amino)-

naphthalene-1,4-dione (49a)


(s, 2H), 6.10 (s, 1H), 7.13 (d, 2H, J=7.5 Hz), 7.21 (d, 2H, J=7.5 Hz), 7.37-7.44 (m, 2H),

7.61-7.68 (m, 4H), 7.96 (d, 1H, J=7.5 Hz), 8.01 (d, 1H, J=7.2 Hz), 8.56 (s, 1H), 8.60 (s, 1H).

13C NMR (75 MHz, CDCl3) C: 21.0, 50.0, 112.8, 116.7, 118.1, 123.0, 123.8, 125.4, 125.5,

126.1, 126.7, 128.9, 130.6, 132.4, 132.5, 132.7, 133.1, 133.8, 136.9, 143.1, 144.2, 151.6,

152.7, 155.6, 183.0, 183.5. Anal. Calcd. for C29H21N5O3: C, 71.45; H, 4.34; N, 14.37%.

Found C, 71.56; H, 4.48; N, 14.29%.

5.6.2.32. 2-((4-Fluorophenyl)((1-(2-imino-2H-chromen-3-yl)-1H-1,2,3-triazol-4-yl)-

methyl)amino)naphthalene-1,4-dione (49b)

Yellow solid; Yield: 76%; m.p 231 oC; 1H NMR (300 MHz, CDCl3) H: 5.26 (s, 2H), 6.09

(s, 1H), 7.08-7.14 (m, 2H), 7.23-7.27 (m, 2H), 7.38-7.45 (m, 2H), 7.63-7.72 (m, 4H), 7.96

(d, 1H, J=7.2 Hz), 8.01 (d, 1H, J=7.5 Hz), 8.57 (s, 1H), 8.63 (s, 1H). 13C NMR (75 MHz,

CDCl3) C: 49.9, 113.1, 116.6, 116.9, 118.0, 122.9, 123.7, 125.5, 126.6, 128.2, 128.8, 132.2,

132.3, 132.4, 132.7, 133.1, 133.9, 141.6, 143.8, 151.3, 152.6, 155.6, 161.1, 182.7, 183.5.

Anal. Calcd. for C28H18FN5O3: C, 68.43; H, 3.69; N, 14.25%. Found C, 68.30; H, 3.75;

N, 14.34%.

5.6.2.33. 2-(((1-(2-Imino-2H-chromen-3-yl)-1H-1,2,3-triazol-4-yl)-methyl)(3-methoxy-

phenyl)amino)naphthalene-1,4-dione (49c)


(s, 2H), 6.17 (s, 1H), 6.82-6.85 (m, 3H), 7.31 (t, 1H, J=7.8 Hz), 7.38-7.44 (m, 2H), 7.60-7.71

(m, 4H), 7.96-8.03 (m, 2H), 8.56 (s, 1H), 8.59 (s, 1H). 13C NMR (75 MHz, CDCl3) C: 49.8,

55.4, 112.0, 112.6, 11.35, 116.7, 118.0, 118.3, 122.9, 123.8, 125.5, 125.6, 126.7, 128.9, 130.6,

132.3, 132.4, 132.5, 132.8, 133.2, 133.9, 144.1, 146.7, 151.4, 152.6, 155.7, 160.8, 182.8,


109

183.7. Anal. Calcd. for C29H21N5O4: C, 69.18; H, 4.20; N, 13.91%. Found C, 69.26; H, 4.07;

N, 13.82%.

5.6.2.34.2-((2-Chlorophenyl)((1-(2-imino-2H-chromen-3-yl)-1H-1,2,3-triazol-4-yl)

methyl)amino)-naphthalene-1,4-dione (49d)


(s, 1H), 7.27-7.42 (m, 5H), 7.47-7.50 (m, 1H), 7.57-7.69 (m, 4H), 7.93 (d, 1H, J=7.5 Hz),

8.00 (d, 1H, J=7.2 Hz), 8.55 (s, 1H), 8.69 (s, 1H). 13C NMR (75 MHz, CDCl3) C: 49.1, 111.3,

116.6, 117.9, 122.8, 124.0, 125.4, 125.5, 126.6, 128.2, 128.7, 128.9, 129.2, 130.7, 131.6,

132.0, 132.2, 132.4, 132.7, 133.2, 133.8, 142.3, 143.2, 150.1, 152.5, 155.6, 182.0, 183.6.

ESI-MS: m/z. Calcd.: 507.11; Found: 509.18 (M+2H)+. Anal. Calcd. for C28H18ClN5O3:

C, 66.21; H, 3.57; N, 13.79%. Found C, 66.35; H, 3.67; N, 13.70%.

5.6.2.35. 2-((2,4-Dimethylphenyl)((1-(2-imino-2H-chromen-3-yl)-1H-1,2,3-triazol-4-yl)

methyl)amino)naphthalene-1,4-dione (49e)


(s, 3H), 5.03 (s, 1H), 5.48 (s, 1H), 5.73 (s, 1H), 7.04-7.10 (m, 3H), 7.37-7.45 (m, 2H),

7.60-7.71 (m, 4H), 7.99-8.02 (m, 2H), 8.57 (s, 1H), 8.70 (s, 1H). 13C NMR (75 MHz, CDCl3)

C: 17.5, 20.9, 49.2, 110.4, 116.6, 118.0, 123.0, 124.1, 125.3, 125.4, 126.5, 127.1, 128.3,

128.8, 132.1,132.4, 132.6, 133.0, 133.8, 134.4, 137.9, 140.8, 144.2, 150.9, 152.6, 155.6,

183.2, 183.3. Anal. Calcd. for C30H23N5O3: C, 71.84; H, 4.62; N, 13.96%. Found C, 71.91;

H, 4.50; N, 14.06%.

5.6.2.36. 2-(((1-(2-Imino-2H-chromen-3-yl)-1H-1,2,3-triazol-4-yl)-methyl)(phenyl)-

amino)naphthalene-1,4-dione (49f)


(s, 1H), 7.24-7.32 (m, 3H), 7.37-7.44 (m, 4H), 7.60-7.71 (m, 4H), 7.96 (dd, 1H, J=7.5, 0.9

Hz), 8.01 (dd, 1H, J=7.5, 0.9 Hz), 8.56 (s, 1H), 8.59 (s, 1H). 13C NMR (75 MHz, CDCl3)

C: 49.9, 113.3, 116.7, 118.0, 122.9, 123.7, 125.4, 125.5, 126.2, 126.7, 127.0, 128.9, 129.9,

132.3, 132.4, 132.5, 132.8, 133.2, 133.9, 144.0, 145.6, 151.4, 152.6, 155.6, 182.8, 183.6.

Anal. Calcd. for C28H19N5O3: C, 71.03; H, 4.04; N, 14.79%. Found C, 70.96; H, 4.15;

N, 14.71%.

5.6.2.37. 2-(((1-(6-Bromo-2-imino-2H-chromen-3-yl)-1H-1,2,3-triazol-4-yl)methyl)

(p-tolyl)amino)naphthalene-1,4-dione (49g)


CDCl3) H: 2.36 (s, 3H), 5.27 (s, 2H), 6.08 (s, 1H), 7.12 (d, 2H, J=7.5 Hz), 7.21 (d, 2H, J=7.5


110

Hz), 7.31 (d, 1H, J=8.7 Hz), 7.59-7.79 (m, 4H), 7.95 (d, 1H, J=7.5 Hz), 8.00 (d, 1H, J=7.5

Hz), 8.49 (s, 1H), 8.61 (s, 1H). 13C NMR (75 MHz, CDCl3) C: 21.0, 49.9, 112.7, 118.2,

118.3, 119.6, 123.7, 125.4, 126.3, 126.7, 130.6, 131.0, 131.5, 132.3, 132.4, 133.9, 135.4,

137.0, 142.9, 144.3, 151.3, 151.5, 155.0, 183.0, 183.6. Anal. Calcd. for C29H20BrN5O3:

C, 61.49; H, 3.56; N, 12.36%. Found C, 61.43; H, 3.65; N, 12.23%.

5.6.2.38. 2-(((1-(6-Chloro-2-imino-2H-chromen-3-yl)-1H-1,2,3-triazol-4-yl)methyl)

(4-fluorophenyl)amino)naphthalene-1,4-dione (49h)


(s, 1H), 7.08-7.13 (m, 2H), 7.22-7.27 (m, 2H), 7.39 (d, 1H, J=7.5 Hz), 7.56-7.71 (m, 4H),

7.95 (d, 1H, J=7.2 Hz), 8.00 (d, 1H, J=7.2 Hz), 8.50 (s, 1H), 8.63 (s, 1H). 13C NMR (75 MHz,

CDCl3) C: 49.9, 113.2, 116.7, 118.1, 119.1, 123.8, 125.5, 126.7, 128.0, 128.2, 131.1, 131.6,

132.3, 132.6, 132.7, 134.0, 141.6, 144.0, 150.9, 151.3, 155.1, 155.6, 161.2, 182.8, 183.6.

Anal. Calcd. for C28H17ClFN5O3: C, 63.95; H, 3.26; N, 13.32%. Found C, 64.07; H, 3.18;

N, 13.19%.

5.6.2.39. 2-(((1-(2-Imino-6-methyl-2H-chromen-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-

(phenyl)amino)naphthalene-1,4-dione (49i)


(s, 2H), 6.16 (s, 1H), 7.25-7.32 (m, 4H), 7.39-7.44 (m, 4H), 7.61 (td, 1H, J=7.5, 1.5 Hz), 7.68

(td, 1H, J=7.5, 1.5 Hz), 7.95 (d, 1H, J=7.5 Hz), 8.01 (d, 1H, J=7.5 Hz), 8.50 (s, 1H), 8.58

(s, 1H). 13C NMR (75 MHz, CDCl3) C: 20.8, 49.9, 113.3, 116.4, 117.7, 122.8, 123.7, 125.5,

126.2, 127.7, 126.9, 128.6, 129.9, 132.3, 132.4, 132.5, 133.3, 133.9, 135.5, 143.9, 145.7,

150.8, 151.4, 155.8, 182.8, 183.6. Anal. Calcd. for C29H21N5O3: C, 71.45; H, 4.34; N, 14.37%.

Found C, 71.39; H, 4.21; N, 14.45%.

Chapter 5 Spectra ___________________________________________________________________________

Figure 5.6.1H NMR spectrum of 37a

Figure 5.7. 13C NMR spectrum of 37a

Chapter 5 Spectra ___________________________________________________________________________

Figure 5.8. DEPT-135 spectrum of 37a

Figure 5.9. C,H-COSY spectrum of 37a

Chapter 5 Spectra ___________________________________________________________________________


Figure 5.11. HMBC spectrum of 37a

Chapter 5 Spectra ___________________________________________________________________________


Figure 5.13. H,H-COSY spectrum of 37a

Chapter 5 Spectra ___________________________________________________________________________

4MEBA_130723223703 #20 RT: 0.15 AV: 1 NL: 3.55E3T: ITMS + p ESI Full ms [100.00-700.00]

360 370 380 390 400 410 420 430 440 450 460 470 480 490 500 510 520 530 540

m/z

10

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90

100

Re

lati

ve

Ab

un

da

nc

e

431.25

453.25

469.25476.17 532.25

Figure 5.14. ESI Mass spectrum of 37a

Chapter 5 Spectra ___________________________________________________________________________

Figure 5.15. 1H NMR spectrum of 49a

Figure 5.16. 13C NMR spectrum of 49a

Chapter 5 Spectra ___________________________________________________________________________

Figure 5.17. DEPT-135 spectrum of 49a


Chapter 5 Spectra ___________________________________________________________________________

Figure 5.19. C,H-COSY spectrum of 49a (expanded)


Chapter 5 Spectra ___________________________________________________________________________

Figure 5.21. HMBC spectrum of 49a (expanded)

Figure 5.22. H,H-COSY spectrum of 49a

Chapter 5 Spectra ___________________________________________________________________________

2CLS_130806185552 #56 RT: 0.16 AV: 1 NL: 5.95E3T: ITMS + c ESI Full ms [100.00-1000.00]

450 500 550 600 650 700 750

m/z

10

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45

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55

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80

85

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95

100

Re

lative

Ab

un

da

nce

509.18

531.40

Figure 5.23. ESI Mass spectrum of 49d

synthesis of novel heterocycles of -...

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