135

Chapter 5

Synthesis of highly functionalized benzo[h]quinoline and

tetracyclic dilactam fluorophores

5.1 INTODUCTION

In this chapter, we report the synthesis of tricyclic quinoline (tetrahydrobenzo [h]

quinoline) (16) and tetracyclic quinoline (3-(epiminomethano) benzo[h]quinoline-2,

12(3H)-dione) (17) fluorophores in an efficient and simple method starting from

simple precursor α-tetralone, aryl aldehyde and cyanoacetamide. When the

equivalence of the addition of cyanoacetamide to the reaction changed, the product

formation also differed (i.e.) when one equivalence of cyanoacetamide was used in

this reaction, we got tricyclic monoamide fluorophore (16) but when the reaction was

carried out with two equivalence of cyanoacetamide, we got tetracyclic diamide

fluorophore (17). This domino reaction is more interesting and fascinating and

provides a quick access to the synthesis of highly functionalized tetracyclic quinoline

derivatives which give access to tetracyclic dilactams possessing two quaternary

amino functionality among four stereogenic centers. Such observation is truly

interesting and very rare in organic chemistry. We are the first to report such skeletal

arrangement of dilactam in fused tetracyclic ring system using four components via a

domino reaction. Initially, we optimized the reaction condition and found the optimal

condition for this reaction. Then the reaction was carried out with diverse range of

aryl aldehyde, and their reaction mechanism was studied. Several reactions were

carried out to investigate the exact mechanism involved in this reaction and the most

feasible mechanism for the formation of tetracyclic dilactam was proposed.

Figure 5.1 Tricyclo monolactam and multifunctionalized tetracyclic dilactam – A

new class of quinoline fluorophore

136

5.2 LITERATURE DISCUSSION

Numerous synthetic methods have been reported for the synthesis of benzo [h]

quinoline derivatives and several quinoline derivatives were reported to show

fluorescence properties. Several research groups have established the unique

behaviour of fluorescence property of numerous quinoline derivatives. Following are

the literature found for the synthesis of various fused cyclic lactam derivatives

(quinoline).

5.2.1 SYNTHESIS OF TRICYCLO MONOLACTAM

In 1975, Zahran et. al., reported the synthesis of few benzoquinolines and

benzacridines from 2-Arylidene-3,4-dihydro-l(2H)-naphthalenones and ethyl

cyanoacetate in presence of ammonium acetate (Zahran et al., 1975). Initially they

synthesised 2-benzylidene-3,4-dihydronaphthalen-1(2H)-one starting from α-tetralone

and benzaldehyde, with the obtained aldol product they treated this product with

various reagents like cyanoacetamide, cyanoacetamide with cyclohexanone/ α-

tetralone, ammonium acetate. From these various reactions, they obtained several

benzoquinoline and benzacridine derivatives. 2-oxo-4-phenyl-1, 2, 5, 6-

tetrahydrobenzo [h] quinoline-3-carbonitrile was obtained from the reaction between

2 -benzylidene-3, 4-dihydronaphthalen-1(2H)-one and cyanoacetamide as shown in

Scheme 5.1.

Scheme 5.1 Synthesis of tetrahydrobenzo [h] quinolines

Otto et. al., in 1979, described the synthesis of tetrahydrobenzo [h] quinoline

derivatives starting from 2-arylidene-tetralone and cyanoacetamide under mild

condition (Otto et al., 1979). They synthesised the same derivatives in other way by

reacting 2-arylidene-tetralone with cyanoacetates under the same conditions. The

benzo [h] quinoline-2-ones were formed by cyclisation of 2-arylidene-tetralone with

the carboxamide group of cyanoacetamide; and they did not isolate the intermediate.

137

Scheme 5.2 Synthesis of benzo [h] quinolines in different ways.

Rong et. al., in 2009 reported an efficient method for the synthesis of 4-aryl-3-cyano-

1, 2, 5, 6- tetrahydrobenzo[h]quinolin-2-one derivatives under solvent free conditions

(Rong et al., 2009). This group carried out the reaction in one-pot in the presence of

sodium hydroxide as catalyst. Initially they optimized this reaction with various

catalysts and also with various polar solvents. They found an appropriate method for

these reactions to synthesise 4-aryl-3-cyano-1, 2, 5, 6- tetrahydrobenzo[h]quinolin-2-

one. The same reaction conditions were further extended to synthesise 4-aryl-3-

cyano-2,5-dihydro-1H-indeno[ 1,2-b]pyridin-2-one starting from indan-1-one, aryl

aldehyde and cyanoacetamide.

Scheme 5.3 The reaction of α-tetralone, aryl aldehydes, and 2-cyanoacetamide.

5.2.3 SYNTHESIS OF FUSED CYCLIC DILACTAM

In 1964, Paquette et. al., described the use of 1,3-Dihydro-2H-azepin-2-one on

various Diels-Alder Studies and synthesised fused cyclic lactams (Paquette et al.,

1964). 1, 3, 5, 7-tetramethyl and l-ethyl-3, 5, 7-trimethyl-1,3-dihydro-2H-azepin-2-

ones reacted rapidly with tetracyanoethylene thereby the solution immediately turned

into violet-brown colour. This got restored to colourless solution when the reaction

mixture was kept at room temperature for about 30 min. The mixture was allowed to

stand overnight to give rise to dimethyl 2-ethyl-1,4,4,6-tetramethyl-3-oxo-2-

138

azabicyclo [3.2.2] non-6-ene-8,9-dicarboxylate and dimethyl 1,2,4,4,6-pentamethyl-3-

oxo-2-azabicyclo[3.2.2]non-6-ene-8,9-dicarboxylate.

Scheme 5.4 Synthesis of fused cyclic lactams via Diels-Alder reaction.

Sato et. al., in 1989, presented the photoaddition of conjugated dienes to 2-Pyridones

and 2-Quinolones (Sato et al., 1989). Irradiation of 2-Pyridones with cyclopentadiene

(10 equivalence) through a Pyrex filter with a 500-W high-pressure mercury lamp

gave intermolecular product 7-azatricyclo [4.2.2.12, 5

] undeca-3, 9-dien-8-one (dimer)

as shown in Scheme 5.5. Similarly they carried out [4+4] cycloaddition on 2-

Pyridones with 1, 3-butadiene followed by Diels-Alder reaction between the adduct

thus formed with 1, 3-butadiene to give 1, 4, 4a, 5, 6, 9, 10, 10a-octahydro-6, 9-

(epiminomethano) benzo [8] annulen-11-one as shown in Scheme 5.6.

ν

Scheme 5.5 Photoaddition of 2-Pyridones with cyclopentadiene.

ν ν

Scheme 5.6 Photoaddition of 2-Pyridones with 1, 3-butadiene.

139

Kalme et. al., in 1989 accounted the synthesis of 2, 7-diazabicyclo [2.2.2] octane-3, 8-

diones from 3, 4-dihydropyridin-2(IH)-ones under alkaline medium (Kalme et al.,

1989). They found that the synthesis of diazabicyclo [2.2.2] octane-3, 8-diones was

obtained by intramolecular cyclisation of 6-hydroxy-2-oxo-4, 6-diphenylpiperidine-3-

carboxamide and 3-carbamoyl-4, 6-diphenyl -3,4-dihydropyridin-2(IH)-one in an

alkaline medium as shown in Scheme 5.7. Similarly, they tried to synthesise

diazabicyclo [2.2.2] octane derivatives possessing thiones by replacing carbonyl

group with thio carbonyl group and successfully synthesised diazabicyclo [2.2.2]

octane-3, 8-dithiones.

Scheme 5.7 Synthesis of bicyclic dilactams from tetrahydropyridine.

Guigen Li et. al., in 2009 accounted the synthesis of multifunctionalized quinazoline

derivatives starting from cyclic ketone, cyanoacetamide and aryl aldehydes (Guigen et

al., 2009) as shown in Scheme 5.8. Initially they optimized the reaction condition

with various solvents and bases, and found an optimal condition. They proposed the

most feasible mechanism for this reaction which underwent the tandem formations of

two different Knoevenagel intermediates by [4+2] cycloaddition. This was followed

by intramolecular Michael addition and nucleophilic reaction. They tried the same

reaction with aliphatic aldehyde to synthesise the corresponding quinazoline

derivatives, but this reaction proceeded in another way to form tricyclo [6.2.2.01, 6

]

dodecane. The same group, in 2010, reported the synthesis of highly functionalized

tricyclo [6.2.2.01, 6

] dodecane derivatives via four components domino reaction

providing an access tricyclic monolactam (Guigen et al., 2010) as shown in Scheme

140

5.9. They were the first to report the skeleton possessing one quaternary carbon-amino

attachment among four stereogenic centers.

Scheme 5.8 Synthesis of multifunctionalized Quinazoline derivatives.

Scheme 5.9 Synthesis of highly functionalized tricyclo [6.2.2.01, 6

] dodecanes.

5.2.3 FLUORESCENCE STUDIES

Tang et. al., in 2001 reported the aggregation induced emission of 1-methyl-1, 2, 3, 4,

5-pentaphenylsilole which greatly increased the efficiency of silole emission (Tang et

al., 2001). Initially they diluted the 1-methyl-1, 2, 3, 4, 5-pentaphenylsilole with

ethanol solution; excited the sample at 381 nm and found no photoluminescence

signals. At the same concentration they prepared the sample with large amount of

water; excited the sample at 381 nm and found that intense photoluminescence signals

were observed. However, water is non-solvent for pentaphenylsilole. Use of water

system aggregated in the solvent mixture and it was found that the solution was

macroscopically homogenous with no precipitate. This suggests that the silole

aggregates are of nanodimension.

Figure 5.2 Molecular structure and conformational rotamers of silole.

In 2012, Jianbing et. al., reported the aggregation-induced emission enhancement to

dual-channel fluorescence response for conjugated copolymers consisting of

tetraphenylethylene (Jianbing et al., 2012). This group designed a series of new

conjugated polymers which consisted of tetraphenylethylene and fluorene units and

141

were synthesized by Suzuki cross coupling polymerization as shown in Scheme 5.10.

When they tried to aggregate tetraphenylethylene in solution, the polymers exhibited

aggregation-induced emission enhancement and dual-channel fluorescence response

as shown in Fig 5.3.

Scheme 5.10 Synthetic routes of tetraphenylethylene and fluorene.

Figure 5.3 Photographs of the polymer fluorescence under UV illumination at

365 nm [RU] = 10 μM in 99:1 water/THF mixture.

In 2013, Ryousuke et. al., described the synthesis of a series of boron ketoiminate

derivatives from 1,3-enaminoketone derivatives and boron trifluoride-diethyl etherate

(Ryousuke et al., 1989). From the result obtained, they suggested that the AIE effect

was derived from rotational or vibrational molecular motions of boron-chelating rings

with a boron-nitrogen bond. This group was the first to state that boron complexes

possessing four-coordination would inherently provide strong effect on the generation

of AIE properties.

Figure 5.4 Photograph of boron complex of 3-amino-1,3-bis(4-methoxyphenyl)

prop-2-en-1-one with solvent compositions of the THF/H2O mixture.

142

5.3 RESULTS AND DISCUSSION

For the first time, we report the tetracyclic quinoline (3-(epiminomethano)

benzo[h]quinoline-2, 12(3H)-dione (17) fluorophores skeletal motif which was

synthesised from an efficient method using NaOH as catalyst from simple starting

materials α-tetralone, aryl aldehyde and cyanoacetamide. We tried to synthesize

quinolines starting from α-tetralone, aryl aldehyde and cyanoacetamide using the

same condition which is used in chapter 4. Interestingly, the obtained 2-oxo-4-

phenyl-1, 2, 5, 6-tetrahydrobenzo[h]quinoline-3-carbonitrile possesses fluorescence

properties. To clarify further, we recorded single crystal XRD to evaluate the

interaction of the molecule in crystal lattice, and it clearly showed that the synthesized

molecule exhibited aggregation induced emission which provoked the fluorescence

emission (i.e.) quinoline dimers linked through dimeric N–H•••O hydrogen bonds as

shown in Spectra 5.5. From the obtained quinoline fluorophore derivatives, we

extended the same reaction condition by adding one more equivalence of

cyanoacetamide to synthesize quinazolines as Guigen Li et. al. reported (Guigen et al.,

2009). Guigen Li et. al. reported the synthesis of multifunctionalized quinazolines

starting from cycloketones, aryl aldehyde and cyanoacetamide (Guigen et al., 2010).

But, unexpectedly, we obtained tetracyclic dilactam of highly functionalized

benzo[h]quinoline fluorophores. This synthesized tetracyclic dilactam also showed

fluorescence property due to the formation of aggregation in the crystal packing

(Ryousuke et al., 2013). One more interesting phenomenon for the formation of

aggregation in these tetracyclic dilactam was water hydrogen bonding between the

molecules. When the equivalence of cyanoacetamide used in the reaction was reduced

to 1 eq. instead of 2 eq., the reaction proceeded in different way to give 2-oxo-4-

phenyl-1, 2, 5, 6-tetrahydrobenzo[h]quinoline-3-carbonitrile. General representation

for the synthesis of tricyclo monolactam and tetracyclic dilactam is shown in Scheme

5.11.

Scheme 5.11 Synthesis of tricyclo monolactam and tetracyclic dilactam

143

5.3.1 OPTIMISATION OF REACTION CONDITION

Initially, we evaluated the efficiency of the catalyst for this reaction by investigating

the optimal condition under various circumstances. We screened several metal

hydroxides and found an optimal condition for this reaction. From Table 1 (entry 1-9),

it is very clear that the reaction did not proceed in the absence of catalyst and that the

reaction proceeded only in the presence of any metal hydroxide to yield highly

functionalized benzo[h]quinoline.

Table 5.1: Screening of catalyst and solvent effect on four component domino

reaction

Entry Catalyst (mol %) Solvent (ml) Yield (%)

a

1 None Methanol -

2 LiOH (1) Methanol 24

3 LiOH (0.5) Methanol 11

4 KOH (1) Methanol 28

5 KOH (0.5) Methanol 16

6 NaOH (2) Methanol 82

7 NaOH (1) Methanol 82

8 NaOH (0.5) Methanol 82

9 NaOH (0.25) Methanol 71

10 NaOH (0.5) None -

11 NaOH (0.5) CH3CN -

12 NaOH (0.5) DCM -

13 NaOH (0.5) Ethanol 73

14 NaOH (0.5) IPA 64

15 NaOH (0.5) Benzene -

16 NaOH (0.5) Hexane -

aIsolated yield

144

Table 5.2: Domino reaction for the synthesis of multifunctionalized benzo[h]

quinoline-2,12(3H)-dione

Entry ArCHO Product Yield (%)b

1 2a

16a

81

2 2b

16b

76

3 2t

16c

72

4 2c

16d

78

5 2g

16e

84

6 2u

16f

85

7 2s

16g

82

8 2e

16h

58

145

9 2a

17a

58

10

2v

17b

62

11 2m

17c

69

12 2e

17d

45

13 2g

17e

89

14 2u

17f

65

146

15 2s

17g

80

16 2b

17h

83

17 2c

17i

80

18 2f

17j

75

19 2r

17k

89

20 2j

17l

95

aReaction conditions: α-tetralone (10 mmol); Benzaldehyde (10 mmol) and

cyanoacetamide (10/20 mmol) at room temperature (30oC).

bIsolated yield

147

When sodium hydroxide was used as catalyst in this reaction, it was significant to

note that we got remarkable yield. So, in order to investigate further on the molar

percentage of the catalyst required to give excellent yield, the reaction was carried out

with 0.1 mol%, which was increased up to 1 mol% of catalyst. A high yield was

observed on using 0.5 mol% of NaOH as catalyst, whereas the use of increased

quantities of catalyst did not further improve the yield significantly. We carried out all

the reactions with 0.5 mol%. The solvent used in the reaction was the next factor

considered for obtaining better yield. So, we carried out these experiments in various

solvents like polar protic, aprotic and nonpolar solvents under same condition (Table

1, entry 8, 10–16). We got better yields with polar protic solvents such as ethanol,

methanol and isopropyl alcohol (IPA) but we did not get the desired product in the

absence of solvent and with polar aprotic solvents like acetonitrile, dichloromethane

(DCM) and nonpolar solvents like hexane, benzene. Thus, the optimal condition for

these reaction transformations was 0.5 mol% of NaOH with methanol as solvent

medium. With the obtained optimal conditions, we carried out these four components

domino reaction with a diverse range of aryl aldehydes under the same conditions to

investigate the generality of the reaction in other system. The results obtained are

summarized in Table 5.2. The synthesised multifunctionalized benzo[h]quinolines

possess two quaternary amine functionalities among four stereogenic centers; such

observation is certainly rare, fascinating and quite interesting in organic chemistry.

We also examined the scope and the limitation of these four component domino

reactions. When the reaction was carried out with other cyclic ketone as substrate

instead of α-tetralone, the reaction proceeded in another path. This is being studied by

other researchers in our laboratories. We also tried these reactions with aliphatic

aldehydes instead of aryl aldehydes under the same condition but failed to get the

desired product.

5.3.2 MECHANISTIC INSIGHT

5.3.3.1 TRICYCLIC MONOLACTAM

There are two possible ways for the formation of tricyclic monolactam (16). One

possible way is the formation of aldol product between α-tetralone and benzaldehyde,

which in turn undergoes cyclisation with cyanoacetamide to yield the expected

product as shown in Scheme 5.12. Another possible way is the formation of

148

Knoevenagel product (14a) followed by the cyclisation of 14a with α-tetralone to

yield the desired product as shown in Scheme 5.13.

Scheme 5.12 One possible way for the formation of compound 16.

Thus, to investigate the exact mechanism, we carried out two reactions by changing

the sequence of addition of precursor to the reaction under the same conditions. In one

reaction we took α-tetralone and benzaldehyde initially followed by the addition of

cyanoacetamide to this reaction mixture but the reaction did not proceed to yield the

expected product. In another reaction we took cyanoacetamide and benzaldehyde

initially followed by the addition of α-tetralone to this reaction mixture and monitored

the reaction. In this sequential addition, we got the product 16a.

Scheme 5.13 Another possible ways for the formation of compound 16.

Scheme 5.14 A proposed mechanism for the formation of quinolines (16).

Here, the synthesised Knoevenagel product (14a) under this condition showed

fluorescence property. So, to further confirm the reaction pathway, we synthesised

non- fluorescence Knoevenagel product from cyanoacetamide and benzaldehyde

using polar aprotic solvent. With the obtained non-fluorescence Knoevenagel product,

we carried out the same reaction with 15 but we failed to get the desired product. So,

the synthesized tricyclic monolactam got fluorescence property only via

phenylacrylamide fluorophore. Thus, from these two reactions, we found that the

149

mechanism for the formation of quinolines proceeded only via phenylacrylamide

fluorophore followed by cyclisation of 15 as shown in Scheme 5.14.

5.3.3.1 TETRACYCLIC DILACTAM

In this reaction also two ways are possible for the formation of tetracyclic dilactam

(16). One possible mechanism is that aldol product would be formed in the first step;

malonamide would be formed by condensation of cyanoacetamide in the second step

followed by the cyclisation of these two intermediates in the third step, which would

give the desired product as shown in Scheme 5.15.

Scheme 5.15 One possible way for the formation of 17a via int5a and int5c.

Another possible mechanism is that two different Knoevenagel condensations with

cyanoacetamide using α-tetralone and benzaldehyde give two intermediates, which in

turn rearranges C-C bond followed by [4+2] cycloaddition and intramolecular

Michael-type addition. Thus, to examine the exact mechanism, we synthesised all the

intermediates formed in these two possible ways under the same conditions. With

these intermediates, we carried out two reactions by mixing the appropriate

intermediate to obtain the desired product as shown in Scheme 5.16.

Scheme 5.16. Another possible way for the formation of 17a via int5d and 14a.

150

One reaction was between int5b and int5c under the same condition, but we failed to

get the product in this way as shown in Scheme 5.15. Another reaction was between

int5d and 14a under the same condition and it was found that the reaction proceeded

smoothly in this way as shown in Scheme 5.16. To further look through the

fluorescence behaviour in these derivatives, we tried the same reaction with non-

fluorescence Knoevenagel product under the same condition, but we couldn’t get the

product. Thus, from these reactions it is clear that the fluorescence properties of

phenylacrylamide were carried over through these reactions to the synthesised

tetracyclic dilactam fluorophore. It also clearly shows that the reaction proceeded only

via phenylacrylamide fluorophore followed by [4+2] cycloaddition and intramolecular

Michael-type addition as shown in Scheme 5.17.

Scheme 5.17. A proposed mechanism for the formation of tetracyclic dilactams.

5.3.3 PHOTOPHYSICAL STUDIES

5.3.3.1 TRICYCLIC MONOLACTAM

UV-visible absorption and fluorescence spectral studies for these synthesised

compounds 16a – 16h were carried out to understand the electronic properties to

explore the influence of electron withdrawing or electron donating nature of the

substituent.

151

The absorption spectra of 16 measured in acetonitrile solvent showed peaks at 227-

229 nm. It showed slightly bathochromic-shifted absorption spectrum with respect to

parent compound (16a), and it even showed slightly bathochromic-shifted emission

with respect to 16a as shown in Spectra 5.1 and Fig.5.5.

280 290 300 310 320 330

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Flu

ore

sc

en

ce

In

ten

sit

y (

a.u

)

Wavelength (nm)

16a

16b

16c

16d

16e

16f

16g

16h

Figure 5.5: Emission spectra for the synthesised compound 16a-16h

5.3.3.2 TETRACYCLIC DILACTAM

UV-visible absorption and fluorescence spectral studies for these compounds were

carried out to understand the electronic properties, and also to explore the influence of

electron donating or electron withdrawing nature of the substituent on electronic

properties. The absorption spectra of 17a measured in tetrahydrofuran (THF) solvent

showed peaks at 255, 336, 348, 396, and 412 nm, which was a concentration

dependent behaviour. Interestingly, though the chromophoric unit in this case was

restricted to the benzene moiety, 17l significantly showed the red-shifted absorption

spectrum with respect to benzene where the absorption features were generally

observed below 300 nm.

Table 5.3: Photophysical data of synthesized compound 17a to 17l

S.No Code Abs.max (nm) Flu.max (nm)a Stokes shift (cm

-1 )

1. 17a 393 456 3515

152

2. 17b 383 446 3688

3. 17c 391 458 3741

4. 17k 394 460 3642

5. 17d 393 456 3515

6. 17e 395 458 3482

7. 17f 395 458 3482

8. 17g 394 458 3547

9. 17h 392 455 3532

10. 17i 393 456 3515

11. 17j 394 458 3547

12. 17l 393 456 3515 aMolecules are excited at respective absorption maximum.

At lower concentration levels i.e. 10-4

M, only monomer absorption was noticed,

when the concentration was increased further, i.e. greater than critical aggregation

concentration (CAC) the benzo[h]quinoline-2, 12(3H)-dione started aggregation and

showed new absorption bands at lower wavelength regions. The intermolecular

hydrogen bonding interaction through cyclic amide bonds induced the aggregation

process. It has been known, particularly, for benzene based systems that the dimer or

higher aggregates absorbed at longer wavelengths than that of monomers.

Nevertheless, trans-annular interactions between the benzene ring in cyclophane

analogous systems led to longer wavelength absorption peak which was observed

below 300 nm. However, 17a shows the longest absorption spectrum close to 400 nm.

To the best of our knowledge, this is the first observation with benzene aggregates

showing lowest energy absorption in the visible region. The fluorescence spectra of

17a in THF solvent showed maximum emission wavelength at 426 and 448 nm with

mirror image relationship with the lowest energy absorption spectrum. The compound

17l, naphtho[h]quinoline-2, 12(3H)-dione also showed concentration dependent

absorption.

153

300 400 500 6000.0

0.2

0.4

0.6

0.8

1.0

1.2

Ab

so

rba

nc

e(a

.u)

Wavelength(nm)

17a-1.603X10-3 M

17e-1.6875X10-3 M

17c-1X10-5 M

17k-1.3267X10-3 M

17d-1X10-5 M

17b-1.0388X10-5 M

17f-1.529X10-3 M

17g-1X10-5 M

17h-1.09X10-3 M

17i-1X10-5 M

17j-1.164X10-3 M

17l-1.6313X10-3 M

Figure 5.6: Absorbance spectra for the synthesised compound 17a-17l

450 500 550 600 6500.0

0.2

0.4

0.6

0.8

1.0

Flu

ore

sc

en

ce

In

ten

sit

y(a

.u)

Wavelength(nm)

17a-1.603X10-3 M

17e-1.6875X10-3 M

17c-1X10-5 M

17k-1.3267X10-3 M

17d-1X10-5 M

17b-1.0388X10-5 M

17f-1.529X10-3 M

17g-1X10-5 M

17h-1.09X10-3 M

17i-1X10-5 M

17j-1.164X10-3 M

17l-1.6313X10-3 M

Figure 5.7: Emission spectra for the synthesised compound 17a-17l

At higher concentration the ground state dimer absorption was predominant at 265,

336, 346, 378, 394 and 414 nm and at lower concentrations monomer spectra were

noticed. The observed spectra matched with the reported value for the dimer

absorption where naphthalene moieties were tethered covalently to the dendrimer

moiety. Indeed, intense fluorescences at 438 and 459 nm were observed for

naphthalene dimers in THF solutions and that of monomer was observed at 328, 340

nm along with the shoulder at 354 nm. The red-shifted absorption and fluorescence

spectra at higher concentration was solely due to the self-assembly formation which

was aided by the hydrogen bonding interaction.

154

300 400 500 6000.0

0.2

0.4

0.6

0.8

1.0

Ab

so

rba

nc

e(a

.u)

Wavelength(nm)

100% THF

80% THF & 20% WATER

60% THF & 40% WATER

40% THF & 60% WATER

30% THF & 70% WATER

20% THF & 80% WATER

10% THF & 90% WATER

Figure 5.8 Absorbance Spectrum of Compound 17l in various percentages of

water and THF at 1.356 X 10-2

M

300 400 5000.0

0.2

0.4

0.6

0.8

1.0

Flu

ore

sc

en

ce

In

ten

sit

y(a

.u)

Wavelength(nm)

100% THF

80% THF & 20% WATER

60% THF & 40% WATER

40% THF & 60% WATER

30% THF & 70% WATER

20% THF & 80% WATER

10% THF & 90% WATER

Figure 5.9 Fluorescence Spectrum of Compound 17l exi-270nm in various

percentages of water and THF at 1.356 X 10-2

M

’

Figure 5.10 Fluorescent photographs of compound 17l in THF/water mixtures

with different water fractions taken under UV illumination

155

In order to enable the self-assembly even at lower concentrations, we used the

reprecipitation method where the concentrated 17l was injected rapidly into the water,

water-THF solvent mixtures in different ratios (V/V). The concentration of 17l was

maintained at 2.712×10-4

M, where only the monomer absorption was observed.

Addition of 17l to the water-THF mixture caused slight changes in the spectral

maxima; however, a significant reduction in absorbance characteristic to the solvent

ratio has been noticed. Thus, we can say that the formed self-assembly is quite stable

as understood from the lack of time-dependent absorption spectral changes. It should

be noted that solvent aided self-assembled structure formed in water-THF solvent

mixture at lower concentrations does not form the naphthalene dimers. Nonetheless,

the fluorescence from the monomeric units becomes intense when the water-THF

ratio is 20-80, 40-60, 60-40%. (SI, Figure,). The dimer also exists in the solid state as

can be understood from the UV-visible diffuse reflectance spectra of the solid

samples.

156

5.4 SPECTRAL DISCUSSION

Characterization of compound 16h and 17b was discussed as a representative

compound of this chapter 16a – 16h and 17a – 17l respectively.

Figure 5.11: Structure of 4-(4-methoxyphenyl)-2-oxo-1, 2, 5, 6-tetrahydrobenzo [h]

quinoline-3-carbonitrile (16h) and 4-(2-(trifluoromethyl) phenyl)-4, 4a, 5, 6-tetrahydro-

1H-10b, 3-(epiminomethano) benzo[h]quinoline-2, 12(3H)-dione (17b)

4-(4-methoxyphenyl)-2-oxo-1, 2, 5, 6-tetrahydrobenzo [h] quinoline-3-carbonitrile

(16h): Green crystal was obtained by slow evaporation from ethanol and THF (1:1)

mixture. Yield and melting point are 58 and > 300 ⁰C respectively. FT-IR spectra of

compound 16h, showed the absorption band at 3352 cm-1

representing the secondary

amide N-H stretching. A band at 3035 cm-1

indicates the aromatic C-H stretching. The

absorption band at 2810 cm-1

represents the aliphatic C-H stretching. A band at 2358

cm-1

confirms the presences of CN stretching and a band at 1678 cm-1

confirms the

presence of C=O stretching (Spectra 5.2). 1H and

13C-NMR spectra have been

recorded in 400 MHz Bruker using CDCl3 as solvent. 1H-NMR spectra of compound

16h shows doublet of doublet peak at 1.77-1.85 ppm, corresponding to one aliphatic

CH2 proton and peak at 2.08-2.17 ppm shows doublet of doublet, corresponding to

one aliphatic CH2 proton. Two doublet of doublet peaks showed at 2.82-3.00 ppm

corresponding to two proton of aliphatic CH2. A singlet peak at 3.78 ppm showed the

presence of methoxy (OCH3) proton. The other aromatic CH proton appeared at 6.85-

7.52 ppm and singlet peaks at 7.00 ppm corresponding to one amide NH proton

(Spectra 5.3). 13

C-NMR spectra of compound 16h showed peaks at 23.13, 29.81,

53.04, 56.02, 64.16 ppm corresponding to aliphatic CH2 carbon. The peak at 110.83-

156.37 ppm corresponded to aromatic carbon and peak at 169.91 ppm indicated amide

157

carbonyl carbon (Spectra 5.4). Additional information of 16h structure was obtained

from single crystal X-ray diffraction analysis (Spectra 5.5).

4-(2-(trifluoromethyl) phenyl)-4, 4a, 5, 6-tetrahydro-1H-10b, 3-(epiminomethano)

benzo[h]quinoline-2, 12(3H)-dione (17b): Light green crystal was obtained by slow

evaporation from ethanol and THF (1:1) mixture. Yield and melting points were 62

and > 300 ⁰C respectively. FT-IR spectra of compound 17b, showed the absorption

band at 3510 cm-1

representing the secondary amide N-H stretching. A band at 3195

cm-1

indicated the aromatic C-H stretching. The absorption band at 2939 cm-1

represented the aliphatic C-H stretching. A band at 1708 cm-1

confirmed the presence

of C=O stretching (Spectra 5.6). 1H-NMR spectra of compound 17b showed doublet

of doublet peak at 1.46-1.49 ppm, corresponding to one aliphatic CH2 proton and peak

at 1.55-1.58 ppm showed doublet of doublet, corresponding to one aliphatic CH2

proton. Triplet Peak at 2.41-2.43 ppm showed one aliphatic CH proton. Peak at 2.75-

2.78 ppm showed multiplet, corresponding to one aliphatic CH proton (1H) and one

aliphatic CH2 proton (2H). Peak at 3.38-3.41 showed doublet, corresponding to one

aliphatic CH proton (1H). The other aromatic CH proton appeared at 6.60-7. 52 ppm

and singlet peak at 7.63 ppm corresponding to two amide NH proton (Spectra 5.7).

13C-NMR spectra of compound 17b showed peak at 30.42, 46.44, 57.33, 60.21 ppm

corresponding to aliphatic CH2 and CH carbon. Peak at 114.87-138.72 ppm

corresponded to aromatic carbon; peak at 162.22 and 163.16 ppm indicate two amide

carbonyl carbons (Spectra 5.8). Additional information of 17b structure was obtained

from single crystal X-ray diffraction analysis (Spectra 5.9). The structures of all the

synthesised compounds (16a – 16h) were confirmed using FT-IR, 1H,

13C-NMR,

HRMS analysis (Table 5.4) and few of the crystalline product were confirmed using

single crystal XRD analysis.

15

8

20

02

50

30

03

50

-0.1

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Absorbance (a.u)

Wa

ve

len

gth

(nm

)

16

a

16

b

16

c

16

d

16

e

16

f

16

g

16

h

Sp

ectra 5

.1: A

bso

rban

ce spectra

for th

e syn

thesised

com

pou

nd

16a

-16h

15

9

Sp

ectra 5

.2: F

T-IR

of 4

-(4-m

ethoxyp

hen

yl)-2

-oxo-1

, 2, 5

, 6-tetra

hyd

rob

enzo

[h] q

uin

olin

e-3

-carb

on

itrile (16

h)

16

0

Sp

ectra 5

.3: 1H

– N

MR

of 4

-(4-m

ethoxyp

hen

yl)-2

-oxo-1

, 2, 5

, 6-tetra

hyd

rob

enzo

[h] q

uin

olin

e-3

-carb

on

itrile (16

h)

16

1

Sp

ectra 5

.4: 1

3C –

NM

R o

f 4-(4

-meth

oxyp

hen

yl)-2

-oxo-1

, 2, 5

, 6-tetra

hyd

rob

enzo

[h] q

uin

olin

e-3

-carb

on

itrile (16

h)

16

2

Sp

ectra 5

.5: O

RT

EP

dia

gra

m o

f 4-(4

-meth

oxy

ph

enyl)-2

-oxo-1

, 2, 5

, 6-tetra

hyd

rob

enzo

[h] q

uin

olin

e-3

-carb

on

itrile (16h

)

16

3

Sp

ectra 5

.6: F

T-IR

of 4

-(2-(triflu

oro

meth

yl) p

hen

yl)-4

, 4a, 5

, 6-tetra

hy

dro

-1H

-10b

, 3-(ep

imin

om

ethan

o) b

enzo

[h]q

uin

olin

e-2

,

12(3

H)-d

ion

e (17b

)

16

4

Sp

ectra 5

.7: 1H

– N

MR

of 4

-(2-(triflu

oro

meth

yl) p

hen

yl)-4

, 4a, 5

, 6-tetr

ah

yd

ro-1

H-1

0b

, 3-(ep

imin

om

eth

an

o) b

enzo

[h]q

uin

olin

e-2

,

12(3

H)-d

ion

e (17b

)

16

5

Sp

ectra 5

.8: 1

3C –

NM

R o

f 4-(2

-(trifluoro

meth

yl) p

hen

yl)-4

, 4a, 5

, 6-tetra

hyd

ro-1

H-1

0b

, 3-(ep

imin

om

eth

an

o) b

enzo

[h]q

uin

olin

e-

2, 1

2(3

H)-d

ion

e (17b

)

16

6

Sp

ectra 5

.9: O

RT

EP

dia

gra

m o

f 4-(2

-(trifluoro

meth

yl) p

hen

yl)-4

, 4a, 5

, 6-tetra

hyd

ro-1

H-1

0b

, 3-(ep

imin

om

ethan

o)

ben

zo[h

]qu

inolin

e-2, 1

2(3

H)-d

ion

e (17b

)

16

7

Tab

le 5.4

Sp

ectral D

ata

of co

mp

ou

nd

16a

-16h

an

d 1

7a

-17l

Pro

du

ct

cod

e

FT

-IR

(cm-1)

Rf -

TL

C

(EA

:

hex

ane)

1H-N

MR

(δ) in

pp

m

13C

-NM

R (δ

) in p

pm

HR

MS

MP

(⁰C)

Ca

lcula

ted

Fo

un

d

16

a

33

52

,

30

35

,

28

10

,

23

58

,

16

78

0.8

4

(55

%)

1.9

8-2

.05

(dd

, CH

2 , 2H

), 2.8

2-3

.00

(dd

, CH

2 , 2H

),

7.1

6-7

.61

(ArH

, 9H

), 7.8

3 (s, C

ON

H2 , 2

H)

24

.73,

25.6

4,

54

.83

, 5

5.6

4,

115

.73,

12

0.9

1, 1

26

.84

, 128

.52, 1

29.6

1, 1

30

.85,

13

3.5

1, 1

34

.85

, 14

3.4

1, 1

52.1

4, 1

70

.02

C2

0 H1

4 N2 O

([M]

+)

29

8.1

10

6

29

8.1

10

8

>3

00

16

b

33

73

,

30

93

,

28

73

,

23

64

,

16

92

0.4

5

(55

%)

1.8

3-1

.89

(dd

, CH

2 , 2H

), 2.3

8 (s, C

H3 , 3

H), 2

.95

-

3.0

1 (d

d, C

H2 , 2

H), 6

.97

-7.6

1 (A

rH, 8

H), 7

.86 (s,

CO

NH

2 , 2H

)

19

.41,

25

.82

, 2

8.7

3,

55

.84

, 5

6.7

2,

11

2.7

4, 1

22

.49

, 126

.40, 1

28.8

4, 1

29

.51,

13

1.6

2, 1

33

.81

, 134

.75, 1

41.4

2, 1

45

.14,

16

8.8

4

C2

1 H1

6 N2 O

([M]

+)

31

2.1

26

3

31

2.1

26

3

>3

00

16

c

33

84

,

30

31

,

28

01

,

23

74

,

16

91

0.7

4

(55

%)

1.7

9-1

.85

(dd

, CH

2 , 2H

), 2.2

5 (s, C

H3 , 3

H), 2

.99

-

3.0

6 (d

d, C

H2 , 2

H), 6

.85

-7.5

2 (A

rH, 8

H), 7

.82 (s,

CO

NH

2 , 2H

)

20

.12,

24

.73

, 2

6.9

1,

52

.63

, 5

4.3

4,

11

6.3

4, 1

19

.59

, 122

.54, 1

27.5

4, 1

29

.35,

13

0.6

8, 1

32

.69

, 134

.74, 1

42.7

4, 1

52

.64,

16

7.7

2

C2

1 H1

6 N2 O

([M]

+)

31

2.1

26

3

31

2.1

26

2

>3

00

16

d

34

72

,

31

74

,

28

94

,

23

62

,

16

83

0.7

2

(55

%)

1.9

7-2

.04

(dd

, CH

2 , 2H

), 2.4

7 (s, C

H3 , 3

H), 2

.89

-

2.9

5 (d

d, C

H2 , 2

H), 6

.78

-7.4

9 (A

rH, 8

H), 7

.64 (s,

CO

NH

2 , 2H

)

19

.73,

25

.74

, 2

6.8

2,

51

.43

, 5

2.6

4,

11

8.6

4, 1

22

.86

, 126

.64, 1

28.5

2, 1

29

.18,

13

0.7

6, 1

34

.65

, 136

.15, 1

43.3

8, 1

51

.27,

17

1.5

5

C2

1 H1

6 N2 O

([M]

+)

31

2.1

26

3

31

2.1

26

0

>3

00

16

8

16

e

33

17

,

30

73

,

28

94

,

23

28

,

16

46

0.8

4

(55

%)

2.0

3-2

.09

(dd

, CH

2 , 2H

), 2.9

3-3

.05

(dd

, CH

2 , 2H

),

6.9

4-7

.59

(ArH

, 8H

), 7.7

8 (s, C

ON

H2 , 2

H)

27

.65,

28.7

4,

52

.17

, 5

3.0

4,

121

.64,

12

3.6

4, 1

26

.63

, 127

.76, 1

28.3

8, 1

30

.15,

13

1.6

4, 1

32

.41

, 14

0.8

4, 1

47.7

1, 1

68

.83

C2

0 H1

3 FN

2 O

([M] +)

31

6.1

01

2

31

6.1

01

4

>3

00

16

f

32

91

,

30

03

,

28

63

,

23

84

,

16

91

0.6

1

(55

%)

1.8

8-1

.97

(dd

, CH

2 , 2H

), 2.7

6-2

.84

(dd

, CH

2 , 2H

),

6.9

1-7

.50

(ArH

, 8H

), 7.6

3 (s, C

ON

H2 , 2

H)

24

.16,

24.9

3,

55

.74

, 5

3.7

2,

119

.84,

12

0.1

9, 1

25

.39

, 127

.92, 1

29.6

4, 1

30

.83,

13

1.8

5, 1

34

.74

, 14

4.8

1, 1

52.3

7, 1

71

.18

C2

0 H1

3 FN

2 O

([M] +)

31

6.1

01

2

31

6.1

01

1

>3

00

16

g

33

83

,

30

99

,

28

64

,

23

16

,

16

90

0.5

8

(55

%)

1.9

9-2

.07

(dd

, CH

2 , 2H

), 2.9

8-3

.09

(dd

, CH

2 , 2H

),

6.8

1-7

.54

(ArH

, 8H

), 7.8

9 (s, C

ON

H2 , 2

H)

27

.54,

29.3

4,

55

.23

, 5

6.3

4,

112

.53,

11

9.1

2, 1

20

.34

, 124

.59, 1

28.8

4, 1

30

.83,

13

1.9

4, 1

32

.41

, 14

1.8

4, 1

54.8

2, 1

70

.27

C2

0 H1

3 FN

2 O

([M] +)

31

6.1

01

2

31

6.1

01

2

>3

00

16

h

33

95

,

30

71

,

28

75

,

23

42

,

16

12

0.4

0

(55

%)

1.7

7-1

.85

(d, C

H2 , 1

H), 2

.08

-2.1

7 (d

d, C

H2 , 1

H),

2.8

2-3

.00

(d

d,

CH

2 , 2

H),

3.7

8

(s, O

CH

3 , 3

H),

6.8

5-7

.52

(ArH

, 8H

), 7.0

0 (s, C

ON

H2 , 2

H)

23

.13,

29

.81

, 5

3.0

4,

56

.02

, 6

4.1

6,

11

0.8

3, 1

21

.28

, 127

.32, 1

28.2

6, 1

29

.59,

13

0.9

0, 1

33

.90

, 134

.26, 1

45.3

5, 1

56

.37,

16

9.9

1

C2

1 H1

6 N2 O

2

([M] +)

32

8.1

21

2

32

8.1

21

1

>3

00

17

a

35

10

,

31

95

,

29

39

,

17

08

0.8

2

(60

%)

1.7

4-1

.87

(td, C

H2 , 2

H), 2

.44

-2.4

8 (t, C

H, 1

H),

2.9

7-2

.99

(m, C

H, 1

H), 3

.08

-3.1

3 (m

, CH

2 , 2H

),

3.9

7-3

.98

(d, C

H, 1

H), 6

.90

-7. 2

9 (A

rH, 9

H), 8

.72

(s, CO

NH

2 , 2H

)

29

.04,

34

.37

, 4

5.5

2,

50

.12

, 6

0.0

8,

11

8.2

4, 1

28

.35

, 128

.72, 1

29.6

2, 1

30

.89,

13

1.7

6, 1

35

.86

, 16

0.0

5, 1

66.0

6

C2

0 H1

8 N2 O

2

([M] +)

31

8.1

36

8

31

8.1

36

8

>3

00

17

b

35

01

, 0

.79

1

.46

-1.4

9 (d

, CH

2 , 1H

), 1.5

5-1

.58

(dd

, CH

2 , 1H

), 3

0.4

2,

46.4

4,

57

.33

, 6

0.2

1,

114

.87,

C2

1 H1

7 F3 N

2 O2

38

6.1

24

3

>3

00

16

9

31

83

,

29

16

,

16

92

(60

%)

2.4

1-2

.43

(t, CH

, 1H

), 2.7

5-2

.78

(m, C

H &

CH

2 ,

3H

), 3.3

8-3

.41

(d, C

H, 1

H), 6

.60

-7. 5

2 (A

rH, 8

H),

7.6

3 (s, C

ON

H2 , 2

H)

11

5.3

7, 1

22

.09

, 124

.79, 1

25.4

2, 1

28

.36,

12

9.1

3, 1

30

.42

, 137

.91

, 13

8.7

2, 1

62

.22,

16

3.1

6

([M] +)

38

6.1

24

2

17

c

35

51

,

31

84

,

29

74

,

17

21

0.6

8

(60

%)

1.7

3-1

.85

(td, C

H2 , 2

H), 2

.58

-2.6

2 (t, C

H, 1

H),

3.0

0-3

.02

(m, C

H2 , 2

H), 3

.36

-3.3

8 (t, C

H, 1

H),

3.9

3-3

.94

(d, C

H, 1

H), 6

.87

-7. 5

6 (A

rH, 8

H), 9

.62

(s, CO

NH

2 , 2H

)

22

.39,

29

.07

, 5

2.3

0,

55

.28

, 6

6.8

3,

11

0.0

9, 1

20

.54

, 126

.58, 1

28.0

4, 1

30

.16,

13

3.5

2, 1

44

.61

, 15

5.6

3, 1

75.9

3

C2

0 H1

7 BrN

2 O2

([M] +)

39

6.0

47

3

39

6.0

47

1

>3

00

17

d

35

84

,

31

41

,

29

82

,

17

12

0.7

1

(60

%)

1.7

1-1

.82

(td, C

H2 , 2

H), 2

.23

-2.2

6 (t, C

H, 1

H),

2.9

8-3

.00

(m, C

H, 1

H), 3

.15

-3.2

0 (t, C

H2 , 2

H),

3.8

1 (s, O

CH

3 , 3H

), 3.8

8-3

.89

(d, C

H, 1

H), 6

.91

-

7. 4

0 (A

rH, 8

H), 8

.53

(s, CO

NH

2 , 2H

)

23

.06,

27

.25

, 5

5.6

4,

56

.33

, 6

9.9

4,

11

1.7

3, 1

16

.15

, 120

.76, 1

25.2

1, 1

27

.08,

12

9.3

4, 1

31

.16

, 13

9.2

9, 1

55.5

4, 1

72

.24

C2

1 H2

0 N2 O

3

([M] +)

34

8.1

47

4

34

8.1

47

3

>3

00

17

e

35

00

,

31

02

,

29

72

,

17

18

0.7

6

(60

%)

1.7

3-1

.89

(td, C

H2 , 2

H), 2

.28

-2.3

0 (t, C

H, 1

H),

2.5

1-2

.54

(m, C

H2 , 2

H), 3

.09

-3.1

1 (t, C

H, 1

H),

3.9

5-3

.96

(d

, C

H,

1H

), 6

.91

-7.

60

(A

rH,

8H

),

10

.25

(s, CO

NH

2 , 2H

)

18

.98,

32.7

4,

58

.63

, 6

0.0

3,

117

.66,

12

5.8

5, 1

27

.10

, 129

.25, 1

30.2

1, 1

34

.24,

14

0.0

0, 1

61

.27

, 16

6.4

8

C2

0 H1

7 FN

2 O2

([M] +)

33

6.1

27

4

33

6.1

27

4

>3

00

17

f

34

72

,

31

36

,

29

84

,

16

92

0.7

8

(60

%)

1.7

2-1

.85

(td, C

H2 , 2

H), 2

.45

-2.4

9 (t, C

H, 1

H),

2.9

7-2

.99

(m, C

H, 1

H), 3

.11

-3.1

5 (t, C

H2 , 2

H),

3.9

8-3

.99

(d, C

H, 1

H), 6

.91

-7. 2

2 (A

rH, 8

H), 9

.23

(s, CO

NH

2 , 2H

)

13

.90,

20

.61

, 3

0.5

0,

57

.72

, 5

9.9

4,

11

4.5

5, 1

16

.03

, 123

.03, 1

29.9

7, 1

30

.33,

13

6.5

7, 1

60

.56

, 16

3.2

2, 1

63.4

8

C2

0 H1

7 FN

2 O2

([M] +)

33

6.1

27

4

33

6.1

27

3

>3

00

17

g

35

18

,

31

81

,

29

25

,

16

71

0.8

1

(60

%)

1.7

4-1

.86

(td, C

H2 , 2

H), 2

.47

-2.5

1 (t, C

H, 1

H),

2.8

8-2

.89

(m, C

H, 1

H), 2

.95

-2.9

7 (t, C

H2 , 2

H),

3.9

8-4

.00

(d, C

H, 1

H), 6

.91

-7. 1

8 (A

rH, 8

H), 8

.83

(s, CO

NH

2 , 2H

)

22

.33,

26

.95

, 4

9.7

1,

54

.72

, 6

2.5

3,

11

3.3

2, 1

22

.21

, 123

.30, 1

25.8

5, 1

28

.98,

13

7.1

7, 1

60

.42

, 16

5.7

0

C2

0 H1

7 FN

2 O2

([M] +)

33

6.1

27

4

33

6.1

27

6

>3

00

17

h

34

86

,

31

72

,

0.7

2

(60

%)

1.6

9-1

.83

(td, C

H2 , 2

H), 2

.29 (s, C

H3 , 3

H), 2

.58

-

2.6

0 (t, C

H, 1

H), 2

.91

-2.9

5 (m

, CH

, 1H

), 3.3

0-

23

.26,

27

.78

, 5

4.6

8,

63

.58

, 6

7.9

3,

11

3.2

3, 1

23

.97

, 126

.64, 1

29.8

3, 1

38

.13,

C2

1 H2

0 N2 O

2

([M] +)

33

2.1

52

4

>3

00

17

0

29

79

,

17

09

3.3

2 (m

, CH

2 , 2H

), 3.9

6-3

.97

(d, C

H, 1

H), 6

.88

-7.

30

(ArH

, 8H

), 8.8

2 (s, C

ON

H2 , 2

H)

15

8.5

4, 1

68

.96

3

32

.15

25

17

i

35

51

,

31

62

,

29

84

,

17

08

0.7

5

(60

%)

1.7

1-1

.85

(td, C

H2 , 2

H), 2

.19 (s, C

H3 , 3

H), 2

.34

-

2.3

6 (d

, CH

, 1H

), 2.6

9-2

.71

(t, CH

2 , 2H

), 2.8

9-

2.9

1 (t, C

H, 1

H), 3

.94

-3.9

5 (d

, CH

, 1H

), 6.9

1-7

.

13

(ArH

, 8H

), 8.6

5 (s, C

ON

H2 , 2

H)

20

.96,

35

.52

, 3

8.9

4,

55

.21

, 6

3.2

9,

11

7.8

4, 1

23

.31

, 126

.80, 1

29.3

6, 1

36

.27,

13

7.4

3, 1

63

.57

, 16

6.4

0

C2

1 H2

0 N2 O

2

([M] +)

33

2.1

52

5

33

2.1

52

6

>3

00

17

j

34

77

,

32

01

,

28

91

,

16

82

0.7

6

(60

%)

1.7

6-1

.86

(td, C

H2 , 2

H), 2

.39

-2.4

1 (d

, CH

, 1H

),

2.6

4-2

.68

(m, C

H2 , 2

H), 3

.47-3

.49

(m, C

H, 1

H),

3.9

5-3

.96

(d, C

H, 1

H), 6

.91

-7. 6

6 (A

rH, 8

H), 8

.60

(s, CO

NH

2 , 2H

)

26

.63, 2

9.4

1, 4

1.8

3, 5

0.0

9, 5

8.7

9, 6

9.5

6,

12

6.8

5, 1

28

.09

, 129

.35, 1

30.0

6, 1

33

.76

,

13

7.4

7, 1

72

.12

2

C2

1 H2

0 N2 O

2

([M] +)

33

2.1

52

5

33

2.1

52

5

>3

00

17

k

35

73

,

31

72

,

29

74

,

17

01

0.8

3

(60

%)

1.6

4-1

.78

(td, C

H2 , 2

H), 2

.59

-2.6

1 (d

, CH

, 1H

),

2.8

7-2

.89

(CH

, 1H

), 2.9

9-3

.02

(t, CH

2 , 2H

), 3.8

7-

3.8

8 (d

, CH

, 1H

), 6.9

1-7

. 36

(ArH

, 8H

), 11

.89 (s,

CO

NH

2 , 2H

)

30

.68,

36

.68

, 4

6.2

7,

47

.65

, 5

7.8

9,

11

6.6

1, 1

27

.65

, 129

.12, 1

30.8

9, 1

33

.62,

13

4.4

3, 1

63

.96

, 17

2.0

54

C2

0 H1

7 ClN

2 O2

([M] +)

35

2.0

97

9

35

2.0

97

7

>3

00

17l

35

92

,

31

43

,

29

48

,

17

04

0.8

5

(60

%)

2.0

3-2

.16

(td, C

H2 , 2

H), 2

.93

-2.9

5 (d

, CH

, 1H

),

3.1

3-3

.18

(m, C

H2 , 2

H), 3

.68

-3.7

0 (d

, CH

, 1H

),

4.0

9-4

.10

(d, C

H, 1

H), 6

.91

-8. 0

9 (A

rH, 8

H), 8

.76

(s, CO

NH

2 , 2H

)

22

.19,

32

.13

, 5

0.1

8,

59

.94

, 6

8.6

3,

11

8.3

0, 1

23

.52

, 125

.44, 1

26.3

9, 1

27

.47,

12

8.6

7, 1

31

.15

, 132

.70, 1

33.3

9, 1

59

.28,

16

6.2

9

C2

4 H2

0 N2 O

2

([M] +)

36

8.1

52

5

36

8.1

52

5

>3

00

171

5.5 CRYSTALLOGRAPHY DISCUSSION

The diffraction quality crystals for 17b were grown and examined using X-ray

diffraction method. The molecular structure is illustrated in Fig. 5.12. The asymmetric

unit comprised of 2 conformers (A and B) of 17b hydrated with three water

molecules. In the tetracyclic ring, the diazabicyclo-octane-dione (DBOD) and

tetrahydronaphthalene (THP) were fused together. In the reported centrosymmetric

structure, the stereogenic centers of DBOD rings (C10 & C11) in 17b (A) and 17b (B)

assumed R, R configurations. The cyclohexene ring of THP adopts a twisted-chair

configuration and trifluoromethylbenzene substitutent of DBOD ring is in equatorial

position.

Figure 5.12 Molecular structures of 17b, together with the atomic-labeling

scheme. Displacement ellipsoids are drawn at 30% probability levels and

hydrogens are shown as small spheres of arbitrary radii.

In the crystal packing, 17b molecules associate along a-axis to form a channel

occupied by water that form a multiple bridge interactions with one of the amide

groups in DBOD bicyclic ring system. These channels at the unit cell corners (see Fig

5.13 in projected unit cell along a-axis) interacted via closed dimeric N1A-

H1A…O1A interactions between amide groups of DBOD ring and augmented by

Intermolecular C-H…F interactions (Table 5.5).

172

Figure 5.13 Crystal packing projected along a-axis displaying nanotube structure

of 17b occupied with water

Table 5.5 Inter and intra-molecular interactions observed in 17b Donor

(D)

H Acceptor

(A)

D-H H…A D…A Angle(D-

H…A)

(Å) (Å) (Å) (°)

N-H…O N1A H1A O1Ai 0.86 2.05 2.886(2) 164

N1B H1B O3Wii 0.86 2.12 2.964(2) 166

N2A H2A O1Biii 0.86 2.03 2.852(2) 161

N2B H2B O2Wiv 0.86 2.05 2.874(3) 159

Ow-H…X O1W H1W1 O2A 0.89(5) 2.10(5) 2.968(3) 167(4)

O1W H1W2 O3Wv 0.94(4) 2.00(4) 2.922(3) 166(3)

O2W H2W1 O1Wvi 0.96(4) 1.91(4) 2.852(3) 167(3)

O2W H2W2 O1Bvii 0.73(6) 2.22(6) 2.927(3) 165(5)

O3W H3W1 O2Aviii 0.78(4) 2.18(4) 2.940(2) 166(3)

O3W H3W2 O2B 0.92(4) 1.89(4) 2.807(2) 175(4)

C-H…O C5A H5A O1Aix 0.93 2.52 3.160(2) 126

C-H….F C4A H4A F1Biii 0.93 2.52 3.354(3) 150

C8A H8A1 F2B 0.97 2.54 3.378(3) 145

C11A H11A F1A 0.98 2.30 3.037(2) 131

C11A H11A F2A 0.98 2.46 3.037(2) 117

C11B H11B F1B 0.98 2.34 2.948(2) 119

C11B H11B F2B 0.98 2.37 3.083(2) 129

C17A H17A F3A 0.93 2.33 2.680(3) 102

C17B H17B F3B 0.93 2.33 2.678(3) 102

Symmetry codes: (i) -x,-y,1-z, (ii) 1-x,2-y,-z, (iii)x,-1+y,z, (iv) x,y,-1+z, (v)1-x,1-y,-z,

(vi) 1-x,1-y,1-z, (vii) 1-x,2-y,1-z, (viii)1+x,1+y,z, (ix) 1+x,y,z.

173

5.6 CONCLUSION

We report a synthetic method for the synthesis tetrahydrobenzo [h] quinoline-

3-carbonitrile fluorophore and a novel four-component domino reaction for the

synthesis of highly functionalized benzo[h]quinoline-2, 12(3H)-dione

(tetracyclic dilactams) which gives access to tetracyclic dilactam.

The reaction was easy to perform by simply mixing four common reactants in

the presence of sodium hydroxide as catalyst at room temperature. The

reaction was fast and got completed within 30 minutes. Importantly, it did not

require high energy, and water was the only major by-product, making the

reaction greener and cost effective.

Four stereogenic centers with two quaternary carbon-amino functions were

controlled very well and the stereochemistry was unequivocally determined by

X-ray structural analysis. The resulting product was of significance in organic

and medicinal chemistry research.

At higher concentrations, all the compounds exist as dimers which are aided

by the hydrogen bonding interactions between the amide groups. The dimers

show much red-shifted absorption spectrum than the monomer.

To the best of our knowledge, this report is the first to specify an interesting

finding of tetracyclic dilactam fluorophore which has an inherently strong

effect on the generation of aggregation-induced emission properties.

Indeed, all the compounds show intense blue fluorescence with a maximum at

460 nm. These molecules can be used as blue emitters also the presence of

amide group might help to use these molecules as fluorescent markers for

probing biological functions.

174

5.7 EXPERIMENTAL DISCUSSION

Chemicals were purchased from Aldrich and they were used without further

purification. TLC -Thin layer chromatography (Merck, Silica gel 60 F254) was

performed on alumina plates (pre-coated silica gel). FT-IR spectra were recorded in

the range of 4000-400cm-1

on JASCO-4100 spectrometer instrument using KBr

pellets. 1H NMR and

13C NMR spectra recorded using a Bruker AMX 400 FT. HRMS

analysis was obtained from JEOL GC Mate. The X-ray crystallographic diffractions

were determined using a Smart – CCD (Bruker, 2004). The UV-visible absorption

spectra were measured using Shimadzu UV-1800 double beam spectrophotometer.

Fluorescence spectra were measured using Varian-Cary Eclipse fluorescence

spectrophotometer.

5.7.1 GENERAL PROCEDURE FOR THE SYNTHESIS OF TRICYCLIC

QUINOLINE (16a – 16h)

A dry 100ml Erlenmeyer flask was charged with α-tetralone (10 mmol); aromatic

aldehydes (10 mmol); cyanoacetamide (10 mmol); sodium hydroxide (0.5 mol %) and

methanol (15 ml). The reaction mixture was stirred at room temperature for 30-60

min. The reaction was monitored by TLC and after the completion of reaction, the

mixture was neutralised using 0.1 N HCl and extracted into DCM (3 X 20 ml). The

crude reaction mixture was purified by column chromatography on silica gel using

ethyl acetate/hexane as the eluents.

5.7.2 GENERAL PROCEDURE FOR THE SYNTHESIS OF TETRACYCLIC

QUINOLINE (17a – 17l)

A dry 100ml Erlenmeyer flask was charged with α-tetralone (10 mmol); aromatic

aldehydes (10 mmol); cyanoacetamide (20 mmol); sodium hydroxide (0.5 mol %) and

methanol (15 ml). The reaction mixture was stirred at room temperature for 30-60

min. The reaction was monitored by TLC and after the completion of reaction, the

mixture was neutralised using 0.1 N HCl and extracted with DCM (3 X 20 ml). The

crude reaction mixture was purified by column chromatography on silica gel using

ethyl acetate/hexane as the eluents.

175

5.7.3 X-RAY CRYSTALLOGRAPHY

Single crystals of data collection quality for 17b were grown from a mixture of

ethanol and THF (1:1) Data were collected on an Oxford Diffraction Xcalibur Eos

Gemini diffractometer (Oxford Diffraction, 2010). The structure was solved by

applying the direct phase-determination technique using SHELXS-97, and refined by

full-matrix least square on F2 using SHLEXL-97 (Sheldrick, 2008). Structural

calculations were performed with WinGX suit of programs (version 1.85.05)

(Farrugia, 1999). Hydrogens were stereochemically fixed and refined with the riding

options. Amide NH and water hydrogens were isotropically refined. The N-H and O-

H distance in the final cycle of refinement was 0.91(3)-0.92(3) Å & 0.81(3)-0.82(3)

Å, respectively. Distances with rest of the hydrogen atoms are: aromatic/sp2 C—H =

0.93 Å, methine C—H = 0.98 Å, and Uiso = 1.2 Ueq(parent). Essential crystal data

are listed in Table 5.6. Crystallographic data for the structures in this paper have been

deposited with the Cambridge Crystallographic Data Centre having accession

numbers, CCDC 956630. Copies of the data can be obtained, free of charge, on

application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44 (0)1223

336033 or email: deposit@ccdc.cam.ac.uk).

Table 5.6 Crystal data of compound 17b

17b

Crystal Data

Empirical formula 2(C21 H17 F3 N2 O2), 3(H2 O)

Molecular weight 826.78

Morphology Colorless, block

Crystallizing solvent CH3CN : THF (1:1)

Crystal size (mm) 0.20x0.15x0.10

Cell Parameters

a(Å) 10.0111(6)

b(Å) 11.8131(7)

c(Å) 16.4284(9)

(º) 84.685(2)

β(º) 84.790(3)

(º) 83.889(3)

V (Å3) 1923.39(19)

Cell measuring reflection 9329

θ-range (º) 2.38-27.93

176

Crystal system Triclinic

Space group P1bar

Z/Z’ 4/2

Dx(cal.) (g/cm3) 1.428

μ (mm-1

) 0.117

Absorption correction multi-scan

F(000) 860

Data Collection

Radiation MoKα

Temperature (0K) 295(2)

θ-range (º) 1.74 – 28.71

Index ranges -12