The formation of dicyanoterphenyls by the interaction of terephthalonitrile dianion with biphenylcarbonitriles in liquid ammonia

Terephthalonitrile dianion couples with biphenylcarbonitriles providing dicyanosubstituted m - and p -terphenyls. The influence of the cyano group position in biphenylcarbonitrile on the structure of the terphenyl scaffold is discussed.


Introduction
Recently we reported that terephthalonitrile dianion 1 2-generated by the action of alkali metal on terephtalonitrile 1 in liquid ammonia operates as a reagent for para-cyanophenylation of benzoor m-tolunitrile to furnish corresponding 4,4'-dicyanobiphenyls in high yields (up to 90%). 1 To the best of our knowledge, arylation of a neutral compound by an arene anionic reduced form is only little exemplified and involved into the synthetic practice.For few instances, a radical anion (RA) and dianion (DA) of benzophenone react with quinoline, 2a pyridine 2b or 2-methylpyridine 2c N-oxides to form N-oxide diphenyloxymethyl derivatives.1-Naphthyldiphenylmethanol is formed in the reaction of benzophenone RA salts with naphthalene in dioxane.2d,e The crosscoupling also takes place in the interaction of 2,3-biquinolyl DA and aryl or heteroaryl halides. 3ventually, DA lithium salts generated from fused arenes (biphenyl, naphthalene, phenanthrene) arylate terminal alkenes affording partially dearomatized alkylated anions, which are quenched by electrophiles (D2O or ketones) providing as a rule regio-and stereocontrolled products. 4mportantly, in all these cases the use of arene anionic reduced forms as synthons provide unprecedentedly concise routes to the target products.To develop this technique as a general synthetic methodology in application to the anionic reduced forms of aromatic nitriles as versatile cyanoarylating reagents, it is necessary to reveal the scope of aromatic substrates suitable for para-cyanophenylation by DA 1 2-.In this connection, the aim of the present article is to study the interaction of 1 2-with biphenylcarbonitriles differing by the position of cyano group in an aromatic core: biphenyl-2-carbonitrile 2, 4'-methylbiphenyl-2-carbonitrile 3, biphenyl-3carbonitrile 4, biphenyl-4-carbonitrile 5.When the desirable cross-coupling is successful, the structural diversity of selected cyanobiphenyls would allow to readily obtain dicyanoterphenyls with varied aromatic scaffolds.It is noteworthy that terphenyls are of increased research interest because of their valuable photophysical properties and potential biological activity.For example, cyano-p-terphenyls were reported as perspective oligomeric analogues of poly-para-phenylenevinylene (PPV) which is used as the emitter in organic light emitting diode (OLED) fabrication. 5he relevant role of electron-withdrawing cyano group is to lower the energy of p-terphenyl LUMO and, respectively, the energy barrier of electron injection thereby to promote its electroluminescent operation.Moreover, many natural compounds containing substituted p-and m-terphenyl scaffolds derived from fungi and plant kingdoms exhibit pronounced immunosuppressive, antibiotic, neuroprotective and cytotoxic activities. 6
In contrast to above results, nitrile 5 provided no terphenyls, the reaction mixture work-up resulted in starting nitrile 5, 1 and benzonitrile, the latter obviously emerging from protolysis of DA 1 2-. 7,8.00 2.12 5 1.0 a According to the combined 1 H NMR and GC-MC data for solid and organic fractions (see the general procedure).b Besides the product, the starting compounds and benzonitrile are present in a reaction mixture.c Benzonitrile content in the product mixture is 0.49 mmol.
To rationalize the formation of terphenyls 6−9, we involve the notion 1 of the intermediacy of charge-transfer complex (CTC) between DA 1 2-and cyanoarene as a key intermediate followed by an intracomplex electron transfer and the bond formation between the ipso position of DA 1 2- and the para position of arenecarbonitrile to give a dimeric bis-cyclohexadienyl DA as a primary cross-coupling product.Applying this idea to the interaction of DA 1 2-with cyanobiphenyls (Scheme 2), the structures of the obtained terphenyls 6−9 show that the regioselectivity of coupling inside CTC can occur both para and ortho to a cyano group of an arenecarbonitrile component depending on its structure.CTCs formed by nitriles 2 and 3 undergo para-coupling to produce DAs 10 followed by decyanation and oxidation to the complete formation of mterphenyls 6 and 7, respectively.The regioselectivity in these cases is in accordance with the para-orientation revealed earlier for the interaction of DA 1 2-and benzonitrile. 1Unlike this, the structure of p-terphenyl 8 displays the CTC formed by 4 to undergo coupling ortho to a cyano group thus deriving the intermediate DA 11.The minor formation of terphenyl 9 elucidates that the alternative para-coupling also occurs to produce the isomeric DA 12, but to essentially lesser degree.Both these DAs are stabilized by electron-withdrawing effects of cyano and phenyl groups, however the steric hindrance exerted by a phenyl group ortho to the site of coupling obviously causes DA 12 to be less stable compared with the "straight-shaped" DA 11.As indicated above, further conversions of DAs 11 and 12 into products 8 and 9 include rapid cyanide-ion elimination 7,8 resulting in cyclohexadienyl anions 13 and 14.Having no a good leaving group at the saturated carbon, these anions are stable 10 under inert reaction conditions but undergo oxidative aromatisation by exposing to air (Scheme 2).
As for the reason why nitrile 5 gave no terphenyl product with DA 1 2-, meaningful seems an experimental fact as follows.The dark-brown suspension of the DA 1 2-salt became deep greenish-blue immediately with the addition of nitrile 5, and then this color was kept until the reaction mixture was quenched with air and water.This is possible evidence for the formation in this case of CTC 15 which is comparably stable under anaerobic and aprotic conditions.Perhaps, the transition state (TS) of its para-coupling, modeled by structure 16, is to a large extent sterically hindered by the ipso-phenyl group.This is consonant with our previous report on a similar failure of the cross-coupling between DA 1 2-and para-octylbenzonitrile. 1 The reason why an ortho-coupling product also did not form is not yet clear.Supposedly, this can be caused by the lack of a substituent, capable of resonance stabilization of a negative charge, in one of the anionic cyclohexadienyl moieties of the TS modeled by structure 17.Anyway, it is evident that the interaction of DA 1 2-with nitrile 5 merits the special experimental and quantum-chemical investigation.

Crystallographic analysis
XRD data (Table 2) for 6−8 were obtained on a Bruker Kappa Apex II CCD diffractometer.Absorption correction was applied using the SADABS program.The structure was solved using direct methods implemented in the SHELXS-97 program 11 and refined by the full-matrix leastsquares method in an anisotropic approximation using the SHELXL-97 program. 11The obtained crystal structures were analyzed for short contacts between non-bonded atoms using the PLATON program. 12CCDC-779107 (8), -779108 (7), -779109 (6) contain the supplementary crystallographic data for this paper.These data can be obtained free of charge from The Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/data_request/cif.

Solid-state molecular structures
Crystallographic data on the 3 new compounds 6−8 can be found in Table 2. Figure 1 depicts the solid-state molecular structures.Bond lengths of terphenyl fragment are very close to the corresponding ones found in Cambridge structural database. 13The dihedral angle between benzene planes for compounds 6−8 lie in 31.96(7)

Conclusions
The results obtained extend the scope of synthetic utilization of DA 1 2-as a para-cyanophenylation synthon over its reactions with cyanobiphenyls.Also we revealed the influence of the cyano group position in starting cyanobiphenyl on the structure of formed cyanoterphenyl.On this basis the aimed synthesis of p-and m-dicyanoterphenyls has been realized.In comparison with the methodology based on the Suzuki reaction, 5,6,14 the advantages of our approach consist in more accessible starting compounds and more convenient reaction protocols.

Experimental Section
General. 1  Liquid ammonia was purified just before use by dissolving in it metallic sodium, followed by distillation into a reaction vessel, cooled to -80  -70 ºC.Commercial terephthalonitrile was purified by sublimation and dried over P2O5 in vacuum.Biphenyl-2-carbonitrile 2, biphenyl-3carbonitrile 4 and biphenyl-4-carbonitrile 5 were synthesized from corresponding acids by sequential conversion into carbonyl chlorides under the action of SOCl2, then to amides under the action of aqueous NH3, finally to carbonitriles under the action of SOCl2 and purified by distillation or crystallization, their spectral characteristics, boiling and melting points agree with data provided in literature [15][16][17] for 2, 4 and 5 correspondingly.4'-Methylbiphenyl-2-carbonitrile 3 was purchased (ABCR) and used without further purification.Melting points of isolated terphenyls 6−8 are uncorrected.
13and13C NMR spectra of 1 and 6−9 were acquired on a Bruker Avance-III 600 instrument at 600.30 MHz ( 1 H) and 150.96 MH ( 13 C) in acetone-d6, chemical shifts (δ) are in ppm relative to TMS using the solvent signals as the internal standard (H = 2.05 ppm, C = 29.8ppm).Signal assignment and structure justification were carried out on the 2D COSY, HSQC and HMBC data. I spectra were recorded on a Vector-22 instrument for samples pelleted with KBr (0.25%).The GC-MS analysis was performed on a Hewlett-Packard G1081A instrument consisting of an HP-5890 Series II gas chromatograph and an HP-5971 mass-selective detector (IE, 70 eV) with an HP5 capillary column: (30000  0.25) mm x 0.25 µm. Th He flow (1 ml/min) was used as carrier gas.The following temperature regime program was applied: 2 min at 50 C, 50 C to 280 C at a rate of 10 deg/min, 5 min at 280 C.Evaporator temperature was 280 C.Ion source temperature was 173 C.The scanning velocity was 1.2 scan/s in the mass interval 30 -650 amu.The precise molecular ion weights were determined on a DFS instrument.Elemental analysis was carried out in a Carlo Erba automatic C, H, N-analyzer model 1106.