Accepted Manuscript Pyrazolo[4,3-a]quinindoline as a new highly fluorescent heterocyclic system: Design, synthesis, spectroscopic characterization and DFT calculations Elaheh Alikhani, Mehdi Pordel, Leila Rezaei Daghigh PII: DOI: Reference:

S1386-1425(14)01537-6 http://dx.doi.org/10.1016/j.saa.2014.10.040 SAA 12855

To appear in:

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Received Date: Revised Date: Accepted Date:

10 March 2014 13 October 2014 14 October 2014

Please cite this article as: E. Alikhani, M. Pordel, L.R. Daghigh, Pyrazolo[4,3-a]quinindoline as a new highly fluorescent heterocyclic system: Design, synthesis, spectroscopic characterization and DFT calculations, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (2014), doi: http://dx.doi.org/10.1016/j.saa. 2014.10.040

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Pyrazolo[4,3-a]quinindoline as a new highly fluorescent heterocyclic system: Design, synthesis, spectroscopic characterization and DFT calculations Elaheh Alikhani, Mehdi Pordel* and Leila Rezaei Daghigh Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran *Corresponding author. Tel.: +98 0511 8414182; fax:+ 98 0511 8424020. E-mail: [email protected]

Abstract- After obtaining the desired precursors in several reactions, new N-alkyl-substituted heterocyclic system pyrazolo[4,3-a]quinindolines (pyrazolo[4,3-f]-indolo[2,3-b]quinolines) were synthesized by one-pot reaction of 1-alkyl-5-nitro-1H-indazole with 2-(1-alkyl-1H-3indolyl)acetonitrile in MeOH/KOH solution via the nucleophilic substitution of hydrogen in excellent yields. Spectral (UV-Vis, FT-IR, NMR and fluorescence) and analytical data allowed the structures of the synthesized compounds to be established. The values of absorption and fluorescence maxima, extinction coefficients and fluorescence quantum yield of these new heterocyclic fluorophores were obtained and they show highlighting interesting photophysical properties. Density functional theory (DFT) calculations of one structure by using the B3LYP hybrid functional and the 6-311+G(d,p) basis set were performed to provide the optimized geometry, relevant frontier orbitals and the prediction of 1H NMR chemical shifts. Calculated electronic absorption spectrum of one structure was also obtained by time-dependent density functional theory (TD-DFT) method. Solvatochromic properties of these dyes have been discussed and the results showed that the absorption and emission bands in polar solvents undergo a modest red shift. Keywords: Pyrazolo[4,3-a]quinindoline; NMR spectroscopy; Fluorescence; Intramolecular charge transfer; Density functional theory calculations; Emission and absorption spectra.

1

1. Introduction Compounds classified as heterocyclic probably constitute the largest and most varied family of organic compounds. Among these valuable compounds, nitrogen heterocycles are of special interest because they constitute an important class of natural and non-natural products, many of which exhibit useful biological activities and unique electrical and optical properties [1–4]. Pyrazoles have attracted much attention in the last 30 years as their synthesis has become more accessible and their diverse properties appreciated [5]. Alongside the traditional pyrazole dyes [6], couplers for photographic materials [7], herbicides [8], and luminescent and fluorescent substances [9], pyrazoles with antiarrhythmic [10] and cholesterol synthesis-inhibiting activities [11] have appeared. Other pyrazoles include effective antirheumatoidal (SC-58635 Celecoxib) [12] and antiviral agents (Pyrazomycin) [13], hormone oxytocin agonists (WAY-VNA-932) [14] and selective Human C1s inhibitors [15]. Recently, pyrazoles became of interest as intermediates for fused pyrazoles [16], and also as chiral catalysts [17], ligands [18] or as moieties to enhance region- and stereo-selectivity [19]. On the other hand, indoloquinoline alkaloids have recently received considerable attention due to their promising DNA intercalating [20] and antimalarial properties [21-23]. Particularly, indolo[2,3-b]quinolines (which is also nominated quinindoline), are a group of synthetically obtained analogues of the natural alkaloid and neocryptolepine. They share many biological properties with this compound, including the ability to interact with DNA as intercalators and to inhibit topoisomerase II reactivity. The quinindoline derivatives also revealed antimicrobial, antimuscarinic, antiviral, and cytotoxic potential [24-27]. A combination of the pyrazole moiety with the quinindoline nucleus may enhance optical and biological properties. Taking this body of research into consideration and in continuation of our studies on the synthesis of nitrogen heterocyclic compounds, specially new dyes and fluorescent heterocyclic compounds [28-35], in current work, we decided to design and synthesis of a new heterocyclic system pyrazolo[4,3-a]quinindoline via the nucleophilic substitution of hydrogen [36] of 1-alkyl5-nitro-1H- indazole with 2-(1-alkyl-1H-3-indolyl)acetonitrile in basic media. Spectroscopic characterization, fluorescence properties, DFT and TD-DFT calculations of these dyes were also studied. 2

2. Experimental 2.1. Materials Methanol, N,N-dimethylformamide (DMF), toluene, ethyl acetate, 1,4-dioxane, n-hexane, methyl iodide, ethyl bromide, dimethylamine, formaldehyde, potassium cyanide, 5-nitro-1Hindazole and indole were purchased from Merck. Potassium hydroxide was purchased from Sigma–Aldrich. All solvents were dried according to standard procedures. Dielectric constant values of the used solvents can be found in Table 3. Compounds 1a,b [37] and 2a,b [38,39] were synthesized as in literature. 2.2. Equipment Melting points were measured on an Electrothermaltype-9100 melting-point apparatus. The IR (as KBr discs) spectra were obtained on a Tensor 27 spectrometer and only noteworthy absorptions are listed. The

13

C NMR (100 MHz) and the 1H NMR (400 MHz) spectra were

recorded at on a Bruker Avance DRX-400 FT spectrometer in CDCl3. Chemical shifts are reported in ppm downfield from TMS as internal standard; coupling constant J is given in Hz. The mass spectra were recorded on a Varian Mat, CH-7 at 70 eV. Elemental analysis was performed on a Thermo Finnigan Flash EA microanalyzer. All measurements were carried out at room temperature. The fluorescence properties (wavelengths of maximum absorbance, wavelengths of fluorescence excitation, wavelengths of fluorescence emission, values of extinction coefficient and fluorescence quantum yield data) of the compounds 3a-d were characterized by using an UV-Vis spectrophotometer (Varian 50-bio UV-Visible) and a fluorescence spectrophotometer (Varian Cary Eclipse). The fluorescence absorption and emission spectra of 3a-d were recorded at concentrations of 10-5 and 3 × 10-6 mol L-1 respectively in ethyl acetate. Values of extinction coefficient (ε) were calculated as the slope of the plot of absorbance vs concentration. The fluorescence excitation (λex) wavelength at 400 nm (λex /nm) was used for all compounds 3a-d. The fluorescence quantum yields (ΦF) of compounds 3a-d were determined via comparison methods, using fluorescein as a standard sample in 0.1 M NaOH and MeOH solution [40]. The used value of the fluorescein emission quantum yield is 0.79. All measurements were carried out at room temperature. 2.3. Computational methods 3

DFT calculations have been performed with the Gaussian 98 software package [41] by using the B3LYP hybrid functional [42] and the 6-311+G(d,p) basis set. Firstly, geometry of the compound 3a was fully optimized in the chloroform solution. The optimized geometry was confirmed to have no imaginary frequency. Then, its optimized geometry was used for frequency calculations. Here, one of self-consistent reaction field methods, the sophisticated Polarized Continuum Model (PCM) [43] has been used for investigation of the solvent effects. The PCM calculations have been performed in the chloroform solution and the zero-point corrections were considered to obtain energies. The 1H NMR chemical shifts of the 3a were predicted with respect to tetramethylsilane (TMS). Here, the GIAO (gauge-including atomic orbitals) method was used for prediction of DFT nuclear shielding [44]. Based on the optimized geometry and using time-dependent density functional theory (TD-DFT) [45] methods, the electronic spectrum of the compound 3a was predicted. 2.4. General procedure for the synthesis of 3a-d from 1a,b and 2a,b. Compounds 1a,b (10 mmol) and 2a,b (12 mmol) were added with stirring to a of KOH (13 g, 238 mmol) in methanol (50 mL). The mixture was stirred at rt for 24 h. After concentration of the solution at reduced pressure, the precipitate was collected by filtration, washed with water, following with acetone, and then air dried to give practically pure 3a-d. 3,7-Dimethyl-3,7-dihydropyrazolo[4,3-a]quinindoline-12-carbonitrile (3a). Compound 3a was obtained as shiny yellow needles (EtOH), yield (73%), mp 327-329 °C; 1H NMR (CDCl3) δ 4.01 (s, 3H), 4.23 (s, 3H), 7.45 (t, J= 7.2 Hz, 1H), 7.51 (d, J= 8.8 Hz, 1H), 7.69 (t, J= 7.2 Hz, 1H), 7.75 (d, J= 9.2 Hz, 1H), 8.07 (d, J= 9.2 Hz, 1H), 8.70 (d, J= 7.6 Hz, 1H), 9.08 (s, 1H) ppm;

13

C NMR (CDCl3): δ 36.56, 43.23, 104.62, 109.80, 113.29, 116.59, 117.16, 117.22,

118.63, 118.88, 120.75, 123.89, 128.51, 129.76, 132.50, 136.94, 142.21, 143.21, 149.21 ppm; IR (KBr disk): ν 2223 cm-1 (CN). MS (m/z) 311 (M+). Anal. Calcd for C19H13N5 (311.3): C, 73.30; H, 4.21; N, 22.49. Found: C, 73.07; H, 4.17; N, 22.15. 7-Ethyl-3-methyl-3,7-dihydropyrazolo[4,3-a]quinindoline-12-carbonitrile (3b). 4

Compound 3b was obtained as shiny yellow needles (EtOH), yield (75%), mp 279-281 °C; 1H NMR (CDCl3) δ 1.52 (t, J= 7.2 Hz, 3H), 4.25 (s, 3H), 4.31 (q, J= 7.2 Hz, 2H), 7.44 (t, J= 7.2 Hz, 1H), 7.50 (d, J= 8.8 Hz, 1H), 7.69 (t, J= 7.2 Hz, 1H), 7.75 (d, J= 9.2 Hz, 1H), 8.06 (d, J= 9.2 Hz, 1H), 8.71 (d, J= 7.6 Hz, 1H), 9.11 (s, 1H) ppm;

13

C NMR (CDCl3): δ 13.78, 35.26, 43.78,

104.25, 109.71, 113.15, 116.17, 116.97, 117.25, 118.87, 119.07, 120.34, 123.12, 128.67, 129.34, 132.25, 136.09, 142.08, 143.78, 149.82 ppm; IR (KBr disk): ν 2225 cm-1 (CN). MS (m/z) 325 (M+). Anal. Calcd for C20H15N5 (325.4): C, 73.83; H, 4.65; N, 21.52. Found: C, 73.61; H, 4.61; N, 21.41. 3-Ethyl-7-methyl -3,7-dihydropyrazolo[4,3-a]quinindoline-12-carbonitrile (3c). Compound 3c was obtained as shiny yellow needles (EtOH), yield (70%), mp 308-309 °C; 1H NMR (CDCl3) δ 1.65 (t, J= 7.2 Hz, 3H), 4.03 (s, 3H), 4.62 (q, J= 7.2 Hz, 2H), 7.44 (t, J= 7.2 Hz, 1H), 7.49 (d, J= 8.8 Hz, 1H), 7.69 (t, J= 7.2 Hz, 1H), 7.75 (d, J= 9.2 Hz, 1H), 8.05 (d, J= 9.2 Hz, 1H), 8.72 (d, J= 7.6 Hz, 1H), 9.13 (s, 1H) ppm;

13

C NMR (CDCl3): δ 15.39, 35.13, 46.34,

104.23, 109.67, 113.09, 116.15, 116.90, 117.35, 118.95, 119.33, 120.31, 123.08, 128.66, 129.32, 132.20, 136.04, 142.01, 143.65, 149.66 ppm; IR (KBr disk): ν 2225 cm-1 (CN). MS (m/z) 325 (M+). Anal. Calcd for C20H15N5 (325.4): C, 73.83; H, 4.65; N, 21.52. Found: C, 73.48; H, 4.59; N, 21.39. 3,7-Diethyl -3,7-dihydropyrazolo[4,3-a]quinindoline-12-carbonitrile (3d). Compound 3d was obtained as shiny yellow needles (EtOH), yield (80%), mp 303-305 °C; 1H NMR (CDCl3) δ 1.53 (t, J= 7.2 Hz, 3H), 1.64 (t, J= 7.2 Hz, 3H), 4.57-4.66 (m, 4H), 7.42 (t, J= 7.2 Hz, 1H), 7.53 (d, J= 8.4 Hz, 1H), 7.70 (t, J= 7.2 Hz, 1H), 7.79 (d, J= 9.2 Hz, 1H), 8.07 (d, J= 9.2 Hz, 1H), 8.72 (d, J= 8.0 Hz, 1H), 9.14 (s, 1H) ppm;

13

C NMR (CDCl3): δ 13.81, 15.40,

36.30, 44.34, 104.41, 109.23, 113.70, 116.81, 117.35, 117.92, 118.10, 118.28, 120.57, 123.40, 128.33, 129.70, 132.91, 136.21, 142.00, 143.64, 149.10 ppm; IR (KBr disk): ν 2225 cm-1 (CN). MS (m/z) 339 (M+). Anal. Calcd for C21H17N5 (339.4): C, 74.32; H, 5.05; N, 20.63. Found: C, 74.09; H, 4.99; N, 20.35.

5

3. Results and Discussion 3.1. Synthesis and Structure of new compounds 3a-d The commercially available 5-nitro-1H-indazole was alkylated with MeI and EtBr in KOH and DMF to afford 1-alkyl-5-nitro-1H-indazole 1a,b in very good yields [37]. Other precursors 2-(1alkyl-1H-3-indolyl)acetonitriles 2a,b were prepared in four steps explained in the following manners. Reaction of indoles which are alkylated [38] with Mannich reagent led to formation of N,N-dimethyl(1-alkyyl-1H-indol-3-yl)methanamines. These compounds were converted to the corresponding salts by the reaction with MeI in excellent yields. Compounds 2a,b were finally obtained from the reaction of trimethyl[(1-methyl-1H-3-indolyl) methyl]ammonium salts with KCN in good yields [39]. The

one-pot

reaction

of

2a,b

indolyl)acetonitriles

1a,b

1-alkyl-5-nitro-1H-indazoles

led

to

the

formation

of

the

with new

2-(1-alkyl-1H-3-

3-alkyl-7-alkyl-3,7-

dihydropyrazolo[4,3-a]quinindoline-12-carbonitriles 3a-d in basic MeOH solution via the nucleophilic substitution of hydrogen [36, 46] which proceeded at room temperature with subsequent cyclisation and in excellent yields. Preparation of the pyrazolo[4,3-a]quinindoline derivatives 3a-d is outlined in Scheme 1. The work-up procedure was very simple which was performed by filtration of the precipitated product after the mixture was concentrated at reduced pressure. Washing the precipitated product with suitable solvents (water and then acetone) gives practically pure compounds 3a-d. O2N

O 2N

R-X

N

N

KOH, DMF, rt

N

N R

H 5-nitro-1H-indazole

1a,b CH2N(Me)2

CH2O, NH(Me)2

R'-X N H

KOH, DMF, rt

N

N

rt, 1 h

CH2CN

R 1a,b

N

N

N

R'

2a,b

3a-d

Scheme 1. Synthesis of new compounds 3a-d. 6

2a,b

N R

rt, 24 h

R'

N R'

trimethyl[(1-alkyl-1H-3-indolyl) methyl]ammonium N CN

KOH, MeOH

N

reflux, 4h

R'

N,N-dimethyl(1-alkyl-1Hindol-3-yl)methanamine

O 2N N

N

R'

1-alkyl-1H-indole

CH2CN

KCN, H2O

MeI, EtOH

HOAC

R'

indole

CH2N(Me)3

3a: R= Me, R'= Me (73%) 3b: R= Me, R'= Et (75%) 3c: R= Et, R'= Me (70%) 3d: R= Et, R'= Et (80%)

In the following mechanism [29-35] the ring closure proceeding occurs via an electrocyclic pathway, wherein intermediate B is converted to C followed by losing one H2O molecule, compounds 3a-d are obtained (Scheme 2).

2a,b N

R'

CN R'

O O

- H 2O

N

H

N N O

C

R' 6π

N H HO

C

- H 2O N R

R B

3a-d

N

N

A

N

N

N

R

R

N

N

N

N

1a,b

HO

N

N

N

R'

CN

C

Scheme 2. Proposed reaction mechanism for the formation of compounds 3a-d. The structure of target products 3a-d was confirmed by NMR techniques, FT-IR spectroscopy, mass spectral and microanalytical data. The spectral details of all these are given in experimental section. For example, in the expanded aromatic region of the 1H NMR spectrum of compound 3d, there are two triplet signals at δ = 7.42 and 7.70 ppm and two doublet signals (δ = 7.53 and 8.72 ppm) can be attributed to A ring, two doublet peaks at δ = 7.79 and 8.06 ppm assignable to two protons of D aromatic ring and a singlet peak at δ = 9.14 ppm correspond to E ring (Scheme 3). Also, there are 21 carbon atoms in the

13

C NMR spectrum of compound 3d. Moreover, the

FT-IR spectrum of 3d in KBr showed an absorption band at 2225 cm–1 corresponding to the cyano group. All this evidence plus molecular ion peak at m/z 339 (M+) and microanalytical data strongly support the pentacyclic structure of compound 3d.

7

Scheme 3. Expanded aromatic region of the 1H NMR spectrum of compound 3d. 3.2. Fluorescence spectra and quantum yields Figures 1 and 2 show the visible absorption and emission spectra of compounds 3a-d whereas numerical spectral data are presented in Table 1. The absorbance and fluorescence spectral properties (Table 1) of compounds 3a-d are similar to each other and extinction coefficient (ε) in compound 3a (R=Me, R'=Me) and fluorescence intensity in compound 3d (R=Et, R'=Et) were the biggest values. Table 1. Photophysical data for absorption and fluorescence of 3a-d in EtOAC. Dye

3a

3b

3c

3d

λabs (nm)a

383

383

383

383

ε × 10 -4 [(mol L-1)-1 cm-1]b 9.2

7.9

8.0

7.5

λex (nm)c

400

400

400

400

478

476

473

476

λem (nm) ΦFe

d

0.51 0.45 0.56 0.60

a

Wavelengths of maximum absorbance Extinction coefficient c Wavelengths of fluorescence excitation d Wavelengths of fluorescence emission e Fluorescence quantum yield b

8

1 0.9 0.8

Absorbance

0.7 0.6 3d 0.5 3c 0.4

3b

0.3

3a

0.2 0.1 0 300

320

340

360

380

400

420

440

460

480

500

Wavelength (nm)

Figure 1. Visible absorption spectra of compounds 3a-d in EtOAC (10-5 mol L-1)

900 800

Intensity (a.u.)

700 600 3d 500 3c 400

3b

300

3a

200 100 0 420

440

460

480

500

520

540

560

580

600

Wavelength (nm)

Figure 2. Emission spectra of compounds 3a-d in EtOAC (3 × 10-6 mol L-1). An efficient intramolecular charge transfer (ICT) states from the donor site (endocyclic N) to the acceptor moiety (CN group) [19-24] can be considered as the main reason for the fluorescence intensity in these compounds. A typical photoinduced charge transfer system consists of a donor 9

(D) and acceptor (A) couple, which can be separate chromophores within a large molecule, leading to intramolecular charge transfer (ICT). In Scheme 4 neutral and some charge-separated mesomeric structures of 3a-d are presented. N

C

C

N

N

N

N

N

R N

N

N N

R N

N

R

N

R'

R'

R'

R'

C

N

C

N N

R

N

N

N

N

Scheme 4. Neutral and some charge-separated mesomeric structures of 3a-d The fluorescence quantum yields (ΦF) of the new compounds 3a-d are comparable with some fluorescent heterocyclic compounds which we have previously reported. A comparison of ΦF between 3d and some of them has been shown in Table 2.

Table

2.

Comparing

the

fluorescence

quantum

yield

of

3d

and

some

recently synthesized fluorescent heterocyclic compounds Comp. CN

Comp.

ΦF N N

CN

Et N

0.60 N

N

Et

ΦF

0.66 [33]

N

N

N

3d

Bu

CN

CN

N N

N Bu

0.90 [29] N

CN

Cl

Cl CN

0.59 [31]

N

0.92 [30]

N

N N Et

H3CO

N

N N CH 3

S

0.65 [34]

N

Solvatochromic properties of compound 3d were also studied in some solvents such as tetrahydrofuran (THF), acetonitrile (MeCN), methanol, etc. (Figures 3 and 4). As it is depicted in these figures, the absorption and emission spectra of 3d in polar solvents undergo a relatively modest red shift. Increasing solvent polarity stabilizes the ICT excited-state molecule relative to the ground-state molecule with the observed red shift of the absorption and emission maximums 10

as the experimentally observed result. Also, the increase of polarity does not induce only a red shift of emission maxima but also a progressive loss of the vibrational structure. Table 3 shows the spectroscopic data for 3d in dependence of the solvent. For example, λem shift from 450 to 510 nm is observed as the solvent is changed from n-hexane to methanol.

1 0.9

Absorbance

0.8 0.7

n-hexane

0.6

toluene

0.5

1,4-dioxane

0.4

THF

0.3 DMF

0.2

MeCN

0.1

MeOH

0 300

350

400

450

500

550

Wavelength (nm) Figure 3. Visible absorption spectra of compound 3d in different solvents (10-5 mol L-1) 900 800

Intensity (a.u.)

700 600

n-hexane

500

toluene 1,4-dioxane

400

THF

300

DMF

200

MeCN 100 MeOH 0 400

450

500

550

600

Wavelength (nm) Figure 4. Emission spectra of compound 3d in some solvents (2 × 10-6 mol L-1)

11

Table 3. Spectroscopic data for 3d at 298K in dependence of the solvent. Solvent

Dielectric constant a λabs (nm) λem (nm)

ΦF

ε × 10 -4 [(mol L-1)-1 cm-1]

n-hexane

1.9

375

450

0.24

6.2

toluene

2.4

381

465

0.35

7.3

EtOAC

6.0

383

476

0.46

7.5

1,4-dioxane

2.2

383

475

0.44

7.4

THF

7.6

385

478

0.45

7.5

DMF

36.7

386

490

0.50

8.5

MeCN

37.5

387

495

0.52

8.7

MeOH

32.7

389

510

0.55

9.7

a

The values in the table above were obtained from the CRC (87th edition), or Vogel's Practical

Organic Chemistry (5th ed.). 3.3. Theoretical calculations We ran DFT calculations at the level of B3LYP/6-311+G(d,p) in order to obtain the optimized geometry, calculated chemical shifts (δ), HOMO and LUMO frontier orbitals of compound 3a. The optimized geometry of the compound 3a is shown in Figure 5. As seen in Table 4, the C=C bond lengths (1.38-1.45 Å) of the aromatic rings are in the expected range [47] and all of these rings and cyano group are essentially planar.

Figure 5. Optimized geometry of the compound 3a 12

Table 4. Selected structural parameters of the 3a. Bond

Bond length (Å)

Angle

Value (°) Dihedral angle Value (°)

B(1,2)

1.405

A(2,1,6)

120.8152

D(6,1,2,26)

-180

B(1,6)

1.3918

A(2,1,25)

119.5371

D(1,2,3,4)

0

B(1,25)

1.0852

A(3,4,7)

128.702

D(2,3,4,7)

180

B(5,6)

1.4013

A(5,4,7)

109.7281

D(5,4,7,8)

-0.0026

B(5,9)

1.4436

A(4,5,9)

106.0598

D(4,5,9,8)

-0.0039

B(7,8)

1.3842

A(4,7,8)

108.5463

D(4,5,9,13)

180

B(7,16)

1.4485

A(8,7,16)

125.0209

D(4,7,8,9)

0

B(8,9)

1.4343

A(7,8,10)

124.6296

D(4,7,16,29)

180

B(8,10)

1.3128

A(9,8,10)

126.4757

D(7,8,9,13)

-180

B(11,17)

1.4352

A(5,9,13)

136.2498

D(9,8,10,11)

-0.0096

B(12,13)

1.4261

A(8,10,11)

116.4844

D(8,9,13,14)

-180

B(13,14)

1.4302

A(12,11,17) 120.3326

D(8,10,11,12)

0

B(19,20)

1.4104

A(9,13,14)

B(19,21)

1.3631

A(18,19,21) 130.0783 D(17,11,12,20)

0.0034

B(20,23)

1.4258

A(20,19,21) 106.7497 D(11,12,20,23)

180

B(21,22)

1.3582

A(19,20,23) 103.8885 D(11,17,18,19)

-0.0141

B(21,24)

1.4487

A(19,21,22) 111.7361 D(21,19,20,23)

-0.0693

B(14,15)

1.1643

A(22,21,24) 120.0187 D(20,19,21,22)

0.114

119.2624 D(10,11,12,20)

180

The DFT calculated chemical shifts (δ) of the compound 3a (Table 5) are well in agreement with the experimental values, confirming validity of the optimized geometry as a proper structure for the 3a.

13

Table 5. DFT calculated and experimental 1H NMR chemical shifts of the 3a.

Atomic number

Chemical shift Cal.

Exp.

H34

9.39

9.08

H28

9.16

H32

Atomic number

Chemical shift Cal.

Exp.

H27

7.49

7.51

8.70

H29

5.19

4.23

8.08

8.07

H37

4.46

4.01

H33

7.80

7.75

H35

3.99

4.01

H26

7.77

7.69

H36

3.97

4.01

H25

7.54

7.45

H30, H31

3.39

4.23

The energy difference between the HOMO and LUMO frontier orbitals is one of the important characteristics of molecules, which has a determining role in such cases as electric properties, electronic spectra and photochemical reactions. The HOMO and LUMO maps of the 3a are shown in Figure 6. It shows that the frontier molecular orbitals of 3a are mainly composed of p atomic orbital, so electronic transition corresponds to above electronic spectra are due to π-π* electronic transitions. As it can be seen; the HOMO and LUMO are totally delocalized because of the unsaturated nature of the system. Energy separation between the HOMO and LUMO (∆ε = εLUMO – εHOMO) is 3.45 eV (359.37 nm). Also, the TD-DFT electronic spectrum calculations on the compound 3a show a relatively sharp peak at 385 nm which correspond to the experimental data (λabs=383 nm) with oscillator strengths of 0.4607. This band can be linked to π- π* transitions from the donor endocyclic nitrogen to the acceptor CN group. The calculated electronic absorption spectrum of compound 3a is shown in the Supporting Information.

14

HOMO

LUMO

Figure 6. The HOMO and LUMO frontier orbitals of the compound 3a.

4. Conclusions In continuation of our investigations on the synthesis of new fluorescent compounds, we have now obtained and characterized new fluorescent substituted heterocyclic system pyrazolo[4,3a]quinindolines by one-pot reaction of 1-alkyl-5-nitro-1H-indazole with 2-(1-alkyl-1H-3indolyl)acetonitrile in basic media. Their photophysical properties clearly show that these compounds have strong fluorescence properties. DFT calculations (B3LYP/6-311+G(d,p)) in order to gain a deeper insight into the charge transfer properties and reveal the stability and 15

aromatic character of one structure were also performed. It was found that 3a has planar geometry and the difference between HOMO-LUMO energy levels (∆ε = εLUMO – εHOMO) is 3.45 eV. Research into possible applications of these dyes is in progress and will soon be reported elsewhere. References 1. Z.J. Hu, J.X. Yang, Y.P. Tian, H.P. Zhou, X.T. Tao, G.B. Xu, et al., J. Mol. Struct. 839, 50 (2007) 2. Y.F. Sun, H.C. Song, W.M. Li, Z.L. Xu, Chin, J. Org. Chem. 23, 1286 (2003) 3. Y.Z. Cui, Q. Fang, Z.L. Huang, G. Xue, W.T. Yu, H. Lei, Opt. Mater. 27, 1571 (2005) 4. F. Bellina, S. Cauteruccio, R. Rossi, Tetrahedron 63, 4571 (2007) 5. O. Migliara, S. Plescia, P. Diana, V. Di Stefano, L. Camarda, R. Dall’Olio, Arkivoc 5, 44 (2004) 6. I. Loewe, W.R. Balzer, S. Gerstung,. Ger Offen, 19,619,112, Chem. Abstr. 128, 16281 (1997) 7. C. Csunderlik, V. Bercean, F. Peter, V. Badea, Arkivoc 2, 133 (2002) 8. T.L. Siddall, D.G. Ouse, Z.L. Benko, G.M. Garvin, J.L. Jackson, J.M. McQuiston, M.J. Ricks, T.D. Thibault, J.A. Turner, J.C. van Heertum, M.R. Weimer, Pest Manag. Sci. 58, 1175 (2002) 9. J. Funaki, K. Imai, K. Araki, A. Danel, P. Tomasik, Pol. J. Chem. 78, 843 (2004) 10. D.M. Bailey, R.G. Powles, U.S. Pat. 4916150, 1990 Chem. Abstr. 113, 59173 (1990) 11. D.S. Karanewsky, M.C. Badia, S.A. Biller, E.M. Gordon, M.J. Sofia, Ger. Offen. 3817298, 1988 Chem. Abstr. 111, 23720 (1989) 12. T.D. Penning, J.J. Talley, S.R. Bertenshaw, J.S. Carter, P.W. Collins, S. Docter, M.J. Graneto, L.F. Lee, J.W. Malecha, J.M. Miyashiro, R.S. Rogers, D.J. Rogier, S.S. Yu, G.D. Anderson, E.G. Burton, J.N. Cogburn, S.A. Gregory, C.M. Koboldt, W.E. Perkins, K. Seibert, A.W. Veenhuizen, Y.Y. Zhang, P.C. Isakson, J. Med. Chem. 40, 1347 (1997) 13. M. Begtrup, H.P. Nytoft, J. Chem. Soc. Perkin Trans. 1, 81 (1985)

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Graphical Abstract CN

CH2CN O2N

R

N R

KOH, MeOH

N N

rt, 24 h

N

N R'

R'

19

N

N

Highlights

•

Pyrazolo[4,3-a]quinindolines are synthesized as new fluorescent heterocyclic systems.

•

The spectral and photophysical properties of these compounds are investigated.

•

Solvent effects on absorption and emission spectra of the fluorophore are studied.

•

DFT and TD-DFT calculations of one structure are performed at the B3LYP/6311+G(d,p) level.

20