Synthesis and solid-state fluorescence of aryl substituted 2-halogenocinchomeronic dinitriles

Abstract

Based on the reaction of available adducts of tetracyanoethylene (TCNE) and aromatic ketones (4-aryl-4-oxoalkane-1,1,2,2-tetracarbonitriles) with hydrogen chloride, several aryl substituted 2-halogencinchomeronic dinitriles were synthesized. We found that aryl substituted derivatives, in contrast to alkyl substituted ones, possess an intensive solid state fluorescence. The relationship between the chemical structures and photophysical properties of these compounds was investigated.

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Introduction

Solid-state fluorescent compounds have a significant theoretical and practical importance.¹ For instance, fluorescent pyridine derivatives are essential for light-emitting diodes (OLED) and various electroluminescent devices.^2a,b In particular, pyridine-3-carbonitriles are known as promising dyes for textile^2c,d and security papers.^2e,f

The luminescent properties of heterocycles of the pyridine series are well studied for hydroxypyridines (especially for tautomeric pyridine-2-ones)^3a–e and aminopyridines.^3f There was also noted a positive effect of a carbonitrile substituent in a pyridine moiety on the intensity and quantum yield of their emission.^3d Previously we reported about the synthesis of cyano substituted pyridine-2-ones with intensive fluorescence in various solvents.⁴ Continuing with our interest in this area we have found that some 2-halogeno substituted pyridine-3,4-dicarbonitriles (2-halogenocinchomeronic dinitriles) also possess fluorescent properties. However, there is only one report on the solid state fluorescence of 2-halogenopyridine-3-carbonitriles in the visible region,^5a and several examples of similar compounds with an emission band in the UV region.^5b,c

Results and discussions

Previously we reported about the synthesis of various 2-halogenopyridine-3,4-dicarbonitriles,⁶ however, we found that alkyl substituted derivatives were not fluorescent both in the UV and visible regions. This is not surprising, because it is generally known that an extensive conjugated network has a great influence on the absorption and fluorescent properties of the molecule. A new aromatic ring on the end of the conjugated chain leads to significant bathochromic and bathofluoric shifts. Also, the extension of the conjugated chain often increases the intensity of the emission. In fact, we have observed that aryl substituted 2-chloropyridine-3,4-dicarbonitriles become fluorescent in the solid-state in contrast to the alkyl-substituted derivatives. To continue our investigations in this field, we synthesized several aryl-substituted 2-halogenopyridines 2a–n, and decided to study the influence of the nature and position of the substituents on the optical properties of the molecule.

Synthesis of aryl substituted 2-halogenocinchomeronic dinitriles

Aryl-substituted cinchomeronic dinitriles 2 were obtained as a result of the interaction between the available and reactive adducts of TCNE and ketones (4-oxoalkane-1,1,2,2-tetracarbonitriles)⁷ 1 with hydrogen chloride in 69–98% yields (Table 1). The structure of the synthesized compounds 2 was confirmed by spectroscopic and elemental analysis data.

Table 1 Synthesis of compounds 2

2	R^1	R^2	Yield^a%	2	R^1	R^2	Yield^a%
a Yield has been reported for isolated crude product.
2a	Ph	H	89	2h	Ph	Me	98
2b	4-NO2–C6H4	H	74	2i	4-Me–C6H4	Me	81
2c	4-Me–C6H4	H	82	2j	4-MeO–C6H4	Me	94
2d	4-MeO–C6H4	H	69	2k	Ph	Et	82
2e	2,5-Di-MeO–C6H3	H	79	2l	Me	4-MeO–C6H4	97
2f	3,4-Di-MeO–C6H3	H	82	2m	Ph	Ph	92
2g		H	92	2n			88

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The reaction proceeded easily in anhydrous propan-2-ol, which had been preliminary saturated by a five-fold excess of dry hydrogen chloride. However, this procedure had a series of drawbacks, including the necessity of complex equipment, constant monitoring of the amount of hydrogen chloride in the reaction mixture, and the formation of 2-chloropropane as a reaction byproduct. Therefore, we developed a simpler and more convenient procedure for the production of hydrogen chloride in situ, through the preliminary mixing of acetyl chloride and propan-2-ol. The main advantage of this approach is for the facile control of the amount of hydrogen chloride and an absence of unwanted side reactions.

Formation of pyridines 2, apparently starts from the hydrogen chloride addition to one of the terminal cyano groups (Scheme 1). Such a selectivity could be caused by a potential ketenimine tautomerism between forms 1 and A, while the latter is more vulnerable in addition reactions. The resulting enaminonitrile B, apparently cyclizes to a carbonyl group which is activated by acidic media, and leads to the formation of the pyridine ring C. The further dehydration and dehydrocyanation processes completes the assembly of compounds 2.

Scheme 1 The proposed reaction pathway for the synthesis of 2-chloropyridine-3,4-dicarbonitriles 2.

It was also found that for the successful implementation of the reaction, at least a five-fold excess of HCl is necessary. Otherwise, the reaction was found to take a long time (2–3 days) and various byproducts were obtained. We could isolate a product in the reaction arising due to the interaction between tetracyanoethyl substituted acetophenone 1a and an equimolar amount of dry hydrogen chloride. Basing on ¹H NMR data, we proposed the formation of a carboxamide derivative 3 (Scheme 2) as a result of the reaction.

Scheme 2 The plausible mechanism for the formation of 2-chloro-3-cyanopyridine-4-carboxamide 3.

Formation of 3 is caused by the insufficient acidity for dehydration of intermediate hydroxypyridine C. Therefore, an alternative transformation of intermediate C had occurred. Namely, the intramolecular interaction of hydroxy and cyano groups (variation of the Pinner reaction) led to the formation of the cyclic iminoester–iminolactone D. The latter was decyclized and the pyridine ring was completely aromatized through dehydrocyanation. It should be noted that during the formation of compound 3, the so-called CACHE process occurred,^4,7e (i.e. the carbonyl group became a source of a hydroxyl and promoted the quasi-hydrolysis of the cyano group via iminolactone formation).

It was also found that the presence of water in the reaction mixture significantly decreased the yield of aryl-substituted 2-chloropyridines. It was especially true for the derivatives with electron-rich aryl substituents. Thus, we previously reported on the reaction of 4-oxoalkane-1,1,2,2-tetracarbonitriles 1d, f, j with concentrated hydrochloric acid (36% aqueous solution) in propan-2-ol with the formation of diimides 4 as the major products.^6d,8 Moreover, we observed that the presence of water also led to pyrid-2-ones 5 (Scheme 3) as minor products,⁴ due to the competing addition of water to ketenimine A (Scheme 1).

Scheme 3 Known side reactions for substituted 4-oxoalkane-1,1,2,2-tetracabonitriles 1 in aqueous acidic media.

The use of propan-2-ol as a solvent was found to be most convenient. The resulting pyridines 2 were insoluble in this solvent, and were found to precipitate out while cooling and do not require any further purification.

Thus, the convenient approach to the aryl-substituted 2-chloropyridine-3,4-dicarbonitriles 2 was developed which is based on the use of an acetyl chloride/propan-2-ol mixture as a source of dry hydrogen chloride. For the first time, the possible side reaction was studied and it was found that a five-fold excess of hydrogen chloride and absence of water are necessary for the successful preparation of compounds 2 with excellent yields.

Solid-state fluorescence of synthesized compounds

We have already mentioned that pyridine derivatives are often essential for practically useful light-sensitive materials. However, 2-halogen substituted pyridine-3,4-dicarbonitriles have not been investigated in this field. As a result, we studied their photophysical properties.

We found that 2-halogenocinchomeronic dinitriles 2 without aryl substituents were not luminescent both in solution and the solid-state, while 5- or/and 6-aryl substituted compounds 2 possessed a solid-state emission with various intensities.

The excitation spectra of the synthesized compounds, which were preliminary crushed in a mortar and pestle, were recorded at room temperature in a powder and characterized with broad wavy bands (300–500 nm). Due to this, the determination of the exact excitation maximum was complicated in most cases. It was also found that the fluorescence maxima, which lie in a blue-green region of the spectrum (410–535 nm), are strongly dependent on the nature and position of the substituent in the aryl ring, and also on the substituent in the fifth position of the pyridine heterocycle. Strong electron-donating substituents (such as –OMe, –Me) in the aryl moiety caused a bathochromic shift, but significantly decreased the intensity of the emission of derivatives 2c, d, e, f (Fig. 1), while the electron-withdrawing group (–NO₂) in compound 2b completely quenched the fluorescence. We also compared the fluorescence properties of derivatives 2a, h, k, m, n with different substituents in the fifth position of pyridine heterocycle. We noted that the replacement of the methyl fragment (2h) with a bulkier ethyl moiety (2k) led to a hypsofluoric shift, apparently due to steric hindrances and a partially broken planarity and conjugation network of the molecule (Fig. 2).

Fig. 1 Solid-state emission spectra and images under UV radiation (365 nm) of 2-chloro-6-arylpyridine-3,4-dicarbonitriles 2a, c, d, e, f.

Fig. 2 Solid-state emission spectra and images under UV radiation (365 nm) of synthesized pyridines with different substituents in fifth position 2a, h, k, m, n.

At the same time, derivatives 2m and 2n with a “locked” aryl ring showed a 50 nm bathofluoric shift and no significant decrease in the intensity of the emission.

It is known that molecules with a narrow bandgap (less than 4.0 eV) and high fluorescence intensity are important for modern light-sensitive materials.⁹ The HOMO and LUMO values for the synthesized pyridine derivatives 2 were calculated by the DFT-B3LYP functional with the 6-31G+(d,p) basis set (Table 2). Fig. 3 shows the frontier orbitals for compound 2a.

Table 2 The molecular electronic properties and solid-state photophysical data for pyridines 2

2	λex, nm	λem, nm	R.I.^a	HOMO, eV	LUMO, eV	GAP, eV
a Relative intensity of emission, intensity of 2a was adopted as 1.00.b Excitation at 330 nm.
2a	375	463	1.00	−7.45	−3.32	4.13
	440
2b	—	—	—	−8.11	−3.98	4.13
2c	345	490	0.06	−7.21	−3.19	4.02
	429
2d	342	498	0.35	−6.79	−3.09	3.70
	399
2e	344	533	0.03	−6.22	−3.06	3.16
	428
	485
2f	350	530	0.07	−6.37	−3.06	3.31
	420
2g	341	470	0.11	−7.18	−3.30	3.88
	430
2h	413	469	0.47	−7.46	−3.13	4.33
2i	350	470	0.43	−7.21	−3.06	4.15
	386
	425
2j	342	476	1.78	−6.76	−3.00	3.76
	426	500	1.98
2k	342	411	0.92^b	−7.51	−3.08	4.43
	384
2l	345	440	0.33	−6.79	−2.93	3.86
	405
2m	429	501	0.99	−7.19	−3.11	4.08
	453
2n	350	505	0.69	−7.23	−3.15	4.08
	395
	450

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Fig. 3 (a) HOMO and (b) LUMO for 2a, computed with TD-DFT(B3LYP)/6-31+G(d,p). The pink (purple) lobes indicate a positive (negative) isocontour value.

We observed low gap values for compounds 2d, e, f, j, l while compounds 2h, k showed high gap values (Table 2). The observed low gap values may be due to strong electron donating groups such as –OMe and high gap values for 2h, k are due to a partially broken conjugation network in the molecules. Based on the DFT calculations of the values of the frontier orbitals and the experimental fluorescence investigations, further research on certain compounds of 2 shows great promise for the development of light-sensitive materials.

Our studies showed that pyridine derivative 2j possesses an abnormally high relative intensity of fluorescence and a relatively narrow bandgap. Moreover, the solid-state emission spectrum of compound 2j is characterized by an additional peak (Fig. 4).

Fig. 4 Emission spectrum and the image under UV radiation (365 nm) of pyridine 2j.

An X-ray diffraction study¹⁰ showed that crystals of 2j contain two independent rotational isomers 2jA and 2jB with different torsion angles N1–C6–C10–C15 at 31.5° and 25.6°, respectively (Fig. 5). Crystals of 2j that were suitable for an X-ray diffraction study were obtained by slow evaporation of a solution of this compound in acetonitrile. Adjacent molecules 2jA and 2jB are stacked by means of π–π interactions to form segregated A and B columns. The π–π interactions between adjacent molecules in columns A differ from those in columns B. The shortest distances between atoms of adjacent molecules in columns of 2jA are C5A⋯C11Aⁱand C5A⋯C14Aⁱⁱ at 3.42–3.48 Å (see Fig. 6, i = 1.5 − x, 0.5 + y, 0.5 − z; ii = 1.5 − x, −0.5 + y, 0.5 − z). For B columns, the shortest distances are C2B⋯C11Bⁱ and C4B⋯C15Bⁱⁱ at 3.52–3.59 Å (see Fig. 7, i = 0.5 − x, 0.5 + y, 0.5 − z; ii = 0.5 − x, −0.5 + y, 0.5 − z).

Fig. 5 Adjacent molecules 2jA and 2jB in the crystal of 2j.

Fig. 6 Segregated A columns of molecules 2jA in the crystal.

Fig. 7 Segregated B columns of molecules 2jB in the crystal.

Therefore, the energy states of 2jA and 2jB molecules in A and B columns are different, which is reflected by the difference in the spectral characteristics.

As mentioned above, the presence of a nitro group in the aryl moiety completely quenches the fluorescence. To support this, we directly synthesized aryl-substituted 2-chloropyridine derivatives containing a nitro group 2o and 2p. They were prepared by the reaction of concentrated nitric acid with the appropriate pyridines 2d and 2h (Scheme 4). As expected, the obtained derivatives 2o, p were not fluorescent.

Scheme 4 Synthesis of nitro substituted derivatives 2o, p.

All of previously described compounds 2 possess the chlorine atom in the second position of the pyridine heterocycle. To investigate the influence of the halogen atom on the emission, we synthesized the corresponding 2-bromo (2q) and 2-iodopyridine (2r) derivatives (Scheme 5) in 72% and 64% yields, respectively, from 3-methyl-4-oxo-4-phenylbutane-1,1,2,2-tetracarbonitrile 1h. It was found that a replacement of the chlorine by an iodine atom led to the heavy-atom quenching of fluorescence, while inserting of bromine atom does not significantly affect the emission.

Scheme 5 Synthesis of 2-bromo and 2-iodo substituted derivatives 2q, r.

Conclusions

In conclusion, we developed a convenient approach to a wide group of pyridine derivatives, possessing solid-state fluorescence. We found that aryl substituted 2-halogenocinchomeronic dinitriles 2 are fluorescent in a powder in contrast to alkyl substituted derivatives. Moreover, we observed that electron-donating groups in the aryl moiety and substituent in the fifth position of the pyridine heterocycle have a significant influence on the fluorescence emission. In addition, the electron-withdrawing groups in the aryl moiety, as well as the replacement of a chlorine atom by an iodine atom, are able to completely quench the fluorescence. By varying these structural fragments, we were able to directionally change the efficiency of the solid-state emission and the position of the maximum. The synthesized 2-halogenocinchomeronic dinitriles are promising fluorescent building-blocks due to the presence of easily modifiable groups in the structure. These compounds may be attached to various biomolecules or nanomaterials via substitution and addition reactions due to replaceable halogen atoms and reactive cyano groups.¹¹

Acknowledgements

This work was supported by the Russian Foundation for Basic Research, Grant No. 15-33-21087. The XRD study was carried out using the equipment purchased from the funds of the Program of Development of Moscow University and within the framework of the agreement on the collaboration between the Chemical Department of Lomonsov Moscow State University and the Chemical and Pharmaceutical Department of the I. N. Ulyanov Chuvash State University.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. CCDC 1488168. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra16787j

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