Characterization Studies of 1-( 4-Cyano-2-oxo-1 , 2-dihydro-1-pyridyl )-3-( 4-cyano-1 , 2-dihydro-1-pyridyl ) propane Formed from the Reaction of Hydroxide Ion with 1 , 3-Bis-( 4-cyano pyridinium ) propane

The 1,3-bis(4-cyanopyridinium)propane bromide, 1, was synthesized taking 32.27 g (310 mmol) of 4-cyanopyridine and 16.15 g (80 mmol) of 1,3-dibromo propane in acetonitrile (50 mL). The mixture was heated under reflux and stirred for 48 h in the dark. The precipitated product was filtered and recrystallized in ethanol/water (×3) yielding yellow needles. Compounds 2 and 3 were prepared in a similar way. Compound 1 Yield 16.7 g (51%). Absorption at 278.0 nm (e = 8.90×10 L mol cm). mp 276-278 C (dec) (276-277 C). Anal. Calc. for C15H14N4Br2: C, 43.93; H, 3.44; N, 13.66; Br, 38.97. Found: C, 43.54; H, 3.50; N, 13.53; Br, 37.8. IR (KBr) νmax/cm: 2241 (CN). MS (m/z) 118 (C7H6N2), 104 (118 CH2, base peak), 77 (104 HCN). H NMR (60 MHz, D2O) d (ppm), 9.3 (4H,d), 8.6 (4H,d), 5.0 (4H,t), 2.8 (2H,s).


Introduction
N-alkylpyridinium ions undergo a variety of chemical reactions, such as nucleophilic substitutions and photochemical and electrochemical redox processes. 1,2he structure and facile synthesis of substituted N-alkylpyridinium ions make these compounds of particular interest as models for the study of a range of different problems, including micellar effects on chemical reactivity and biological redox mechanisms. 3,45][6][7] RCP compounds usually undergo attack by OH -ion at two different sites, carbon 4 of the pyridinium ring (ipso attack) and the -CN group, yielding the respective pyridone (P) and carboxamidopyridinium (A), as illustrated in Scheme 1. 1 The reaction rate constants and the product ratios (P/A) of RCP derivatives are pH-and dielectric constant-dependent and these features can be used as tools to investigate several reactional details. [4][5][6] For example, the reaction of micelle-incorporated RCP with OH -ion yields only P. 4 The determination of the effect of micelles on the reaction Scheme 1. Reaction pathways of RCP compounds with OH -ion.
Vol. 22, No. 9, 2011 rate and product composition was therefore used to study the interfacial region in ionic and zwitterionic micelles. 6he RCP analog N-hexadecyl-4-cyanopyridinium (HCP) shows a reactivity pattern that is completely different from that of N-methyl-4-cyanopyridinium (MCP); HCP presents surfactant characteristics, while MCP behaves as a simple pyridinium salt. 5The HCP molecule has been demonstrated to self-associate even below its critical micelle concentration (CMC).This premicellar aggregation was demonstrated on the basis of concentration-dependent rate constant and product composition differences in alkaline hydrolysis reaction as a function of the HCP concentration. 5he increased reactivity of the premicellar aggregates (as dimers) formed by HCP led us to synthesize a series of bis(substituted-pyridinium) salts with the two pyridinium rings covalently linked by methylene spacers in order to investigate their kinetic behavior and product composition against distinct nucleophiles. 8,9For example, the reaction of 1,ω-bis(2-bromopyridinium)alkanes with hydroxide 8 and azide 9 was investigated in order to analyze the charge-conformational effects on their reactivity.
Even under moderate OH -concentration, salt 1 yields a novel additional product besides the expected P and A. The aim of the present work is to characterize this new compound.

Results and Discussion
UV spectra of RCP and the products of its alkaline hydrolysis show characteristic electronic transitions with absorption maxima centered at 278 nm and at 262 nm, respectively. 1Spectral changes observed upon the addition of compounds 2 and 3 (Scheme 2) to an alkaline aqueous solution (pH 9.0 to 13.8) were very similar to those obtained with RCP, 7 indicating that the reaction products are constituted by pyridone and carboxamidopyridinium moieties (Scheme 1), both absorbing at the 262 nm region.
The UV spectra of the alkaline hydrolysis products of 1,3-bis-(4-cyano pyridinium)propane dibromide (1)  at pH values below 11.5 were similar to those obtained from 2 and 3.However, at pH values higher than 11.5, the spectrum of products from 1 exhibits an additional band at 336 nm beside the usual band at 262 nm (related to the P and A units) (Figure 1).
Figure 1 shows that as the OH -concentration increases, the band at 336 nm also increases.Therefore, a highly alkaline concentration favors the formation of the additional product from compound 1.
A scaled-up reaction of 1 with aqueous NaOH at room temperature led immediately to a brown-yellowish solution and a brown precipitate.The solid product, which was responsible for the absorption band at 336 nm, was filtered off.This product, both in solid state and in solution, promptly changed to a dark color, exhibiting high susceptibility to oxidation.
Initial attempts to isolate the solid product in pure state by column chromatography and rotating disk TLC (chromatroton) failed due to the fast decomposition of the material at room temperature.Instead of filtration, an alternative two-phase transfer isolation technique at low temperature was performed (see Experimental section).
For NMR analysis, a D 2 O solution of 1 was reacted with a heterogeneous mixture of NaOD/D 2 O/CDCl 3 at low temperature.In this strategy, the additional product was transferred to the organic phase and properly analyzed as soon as it was formed.
1 H and 13 C NMR, MS, FT-IR, and elemental analyses indicate that the product has the structure shown in Scheme 3.
The mass spectrum shows a molecular ion peak at 266, which is in agreement with the elemental analysis (C 15 H 14 N 4 O) and in full accordance with the proposed structure 4. The NMR data are summarized in Table 1.As can be seen, the 13 C NMR spectrum (Table 1) shows 15 signals that point to an asymmetrical structure, with two different pyridine-like rings.The DEPT 90 and 135 analyses confirmed the presence of 4 signals relative to methylenic carbons (CH 2 ), six signals of methynic carbons (CH), and five non hydrogen-bonded carbons (C).
Regarding the 4-cyano-2-pyridone moiety, the signal at 160.6 ppm is related to the carbonyl group (C2), the signal at 118.2 ppm is associated with the carbon of the cyano group (C7), and the signal at 123.9 ppm corresponds to the carbon connected to the cyano group (C4).These results were confirmed by FT-IR analysis which spectrum exhibited the 1665 cm -1 peak that corresponds to the carbonyl and the axial deformation band of the (two) CN groups at 2216 and 2234 cm -1 .
The 1 H NMR data are also consistent with the proposed structure.The 1 H NMR and 1 H-1 H COSY spectra show two doublets of doublets from ortho-coupled hydrogens at 6.37 ppm and 7.44 ppm, and another mutually coupled doublet of doublets at 6.94 ppm, attributed to the hydrogen connected to C3. 1 H and 13 C analyses are in agreement with those obtained from a similar known compound in the literature (4-cyano-2-pyridone). 10 The methylenic carbons at 48.4 ppm (C8) and 52.0 ppm (C8') are related to carbons of the chain bridge.The 1 H NMR spectrum has two triplets centered at 4.00 ppm and 3.00 ppm, which, according to HMQC analysis, are attached to carbons C8 and C8', respectively.Finally, C9 is observed in the 13 C NMR spectrum at 25.7 ppm.The corresponding hydrogen atoms appear in the 1 H spectrum as a quintet centered at 1.99 ppm.All signal attributions were confirmed by HMQC and 1 H-1 H COSY analyses.
For the other moiety, proposed to be a 4-cyano-1,2-dihydropyridine-type derivative, the identification was evidenced by the methylenic carbon signal observed at 46.8 ppm in the 13 C NMR spectrum (C2').The 1 H NMR signal at 4.01 ppm (integration for two hydrogens) is associated with the corresponding methylenic hydrogens, as indicated by the HMQC and COSY spectra.The 13 C NMR signal at 115.9 ppm is associated with the carbon of the cyano group (C7'), while the signal at 112.3 ppm corresponds to C4' (the carbon bearing the cyano group).
The 1 H NMR spectrum shows a triplet of doublets of doublets at 5.74 ppm, two doublets of doublets at 4.71 ppm and 6.10 ppm, and a doublet at 4.01 ppm (integrating for two hydrogens).The 1 H NMR analyses are consistent with a similar compound described in the literature (N-methyl-1,2-dihydropyridine). 11n addition to the absorption band at 336 nm, compound 4 emits fluorescence.We experimentally observed that the 4-pyridone moiety does not show fluorescence, while 2-pyridone does, reinforcing the presence of a 2-pyridone group in the structure of 4.
The instability of compound 4 may be attributed to the 1,2-dihydropyridine portion of the molecule, which is easily oxidized. 12,13The kinetic study of 4 in water at pH 12 monitored by UV-Vis showed a slow reaction in which the band at 336 nm is shifted to 315 nm with the simultaneous formation of a new band at 262 nm.These products were not identified due to their low concentrations.No ring-opening products, such as glutaconaldehyde derivatives, 13,14 were observed.However, at room temperature, the compound acquired a dark color, even in the solid state, which probably indicates an oxidative process.This behavior is in fact expected, considering that some N-methylhydropyridines, enamine derivatives, are unstable.Some enamines are susceptible to acid-catalyzed dimerization however in the absence of potassium hydroxide pellets, N-methyl-1,2-dihydropyridine is stable to dimerization for days while N-methyl-1,4-dihydropyridine is stable for weeks under similar conditions. 15Decomposition can be minimized under argon at -30 °C. 16inally, it is possible to speculate the mechanism that leads to 4. Our kinetic experiments monitored by  absorption and fluorescence spectrophotometries showed that the appearance of the 336 nm absorption band is not accompanied by immediate fluorescence emission.
The 336 nm UV-Vis band appeared in a time scale of seconds, while the fluorescence emission was observed in a time scale from minutes to hours.However, product 4 is fluorescent.Therefore, these results indicate that a non-fluorescent intermediate is produced and consumed before 4. The reaction route of 1 with OH -usually leads to (i) pyridone, as result of the ipso attack of OH -at the ring, forming the respective pseudo base at position 4-, and (ii) carboxamidopyridinium, resulting from the nucleophilic attack of OH -in the cyano group.Therefore the intermediate should be formed by an alternative reaction route: the nucleophilic attack of OH -at C2 is possible due to the well-known reactivity of this position. 17The formed pseudo base at C2 undergoes ionization at pH values higher than 11. 5,12,13,18which due to the relative proximity to the unreacted vicinal pyridinium ring may lead to a cyclic ethertype intermediate.This ether could rearrange through an intramolecular hydride shift, resulting in the product 4, as depicted in Scheme 4. The reaction intermediates before compound 4 formation can be non-fluorescent species.Geometry minimization simulation using Gaussian 3.0 software with semi-empirical PM3 method, showed that the oxygen of the alkoxyde may approximate to the (unreacted) pyridinium ring.In addition, an unstable compound at room temperature with two pyridine rings connected by oxygen was found in the alkaline hydrolysis of 1-benzyl-3-acetylpyridinium chloride. 13,14,19This noncyclic ether is similar to compound 4.These facts suggest the conversion of the intermediate cyclic ether into 4 through an internal rearrangement. 11,15,16n the context of the present work, it is worth mentioning the results published by Gündel 20 involving a system closely related to ours.The author worked with bridged pyridinium salts bearing -CN substituents at the 3-position (compound 5) which was observed to rearrange by intermolecular mechanism to product 6 under basic conditions, although in very low yield (Scheme 5).
However, in contrast to 1, an intramolecular process in this compound is unlikely due to the relative position of the -CN groups, as postulated by the author.Considering that even the compound bearing a six-atom bridge showed rearrangement, it is more plausible that an intermolecular process took place instead.This would be in agreement with all the experiments performed by our group (including those involving different concentrations of the reactant species), with derivatives 2 (six-atom bridge) and 3 (eight-atom bridge), which resulted only in non rearranged products.

Conclusions
A new compound from the alkaline hydrolysis of pyridinium salt 1 was obtained and unambiguously identified as 1-(4-cyano-2-oxo-1,2-dihydro-1-pyridyl)-3-(4-cyano-1,2-dihydro-1-pyridyl)propane (4).The generation of this product can be explained by a proximity effect of the nucleophile inserted between the two pyridinium moieties, which are not observed for the hydrolysis of derivatives 2 and 3. We previously showed the accommodation of the nucleophiles into bis(substituted-pyridinium) ions with short methylene spacers. 8,9However, the generation of 4 is related to a peculiar reactivity of the bis-(4-cyanopyridinium) compound linked by a three-methylene bridge.The formation of the cyclic ether
MHz for13 C; b 300.059MHz for 1 H; c J in Hz.