Aminopyridiniums

The reaction of 1-aminopyridinium iodide (429) with dimethyl chlorofumarate in ethanol/K2C03 to form, ultimately, a pyrazolo[l,5-n]pyridine also occurs via a 1,5-dipolar mechanism. The initially formed 1 1 adduct (430), stabilized by delocalization of the negative charge, underwent disrotatory ring closure as shown to give (431) in which the 3... 

The imine (161), obtained from 1-aminopyridinium iodide and potassium carbonate, combines with dimethyl acetylenedicarboxylate yielding in the first place (162) which then with more ester gives dimethyl fumarate and the pyrazolopyridine (163), isolated in 15% yield. A corresponding reaction with isoquinoline imine gave 75% of the primary adduct [(cf. (162)]. ... 

The neutral complex is more stable than the 2-aminopyridinium formate complex. 

The authors claim that these associations, which are destroyed in fixed compounds, play an important role in the calculation of Ty.The cases of 1,2,4-triazole-5-thiones 74 [97SA(A)699] and of pyridone dimers 15a-15a and 15a-15b were also studied [96MI(13)65]. (3) The recording of IR spectra in solution at different temperatures to determine the effect of the temperature on Kj-, for instance, in pyrazolinones [83JPR(325)238] and in cytosine-guanine base pairs [92MI(9)881]. (4) The determination of the equilibrium 2-aminopyridine/acetic acid 2-aminopyridinium acetate (see Section III.E) in the acid-base complex was carried out by IR (97NKK100). 

Heating the crystalline salt 2-aminopyridinium propiolate (346) at 100 °C in the solid state led to a 10 9 mixture of 2/f-pyrido[l,2-n]pyrimidin-2-one and ( )-3-(2-imino-l,2-dihydro-l-pyridyl)acrylic acid (347). Analysis of differental scanning calorimetry data shows unambiguously that the reaction takes place in the solid state. An endothermic peak at 81.1 °C corresponds to a solid state reaction, and a peak at 122-123 °C is attributed to melting. The product ratio of 2//-pyrido[l, 2-n]pyrimidin-2-one and 347 is 1 2.5 at 60°C, and 1 1.4 at 80°C (94MI12). 

Aminopyridines, aminopyridine oxides, and 3-aminoquinoline are obviously diazotized by analogous mechanisms. Kalatzis (1967 b) studied the diazotization of 4-aminopyridine over a very large range of acid concentrations (0.0025-5.0 m HC104). This compound is comparable to 2-aminothiazole in its acid-base properties the heterocyclic nitrogen is easily protonated at pH 10, whereas the amino group is a very weak base (pKa = -6.5). Therefore, the kinetics indicate that the (mono-protonated) 4-aminopyridinium ion reacts with the nitrosyl ion. The... 

Fourteen milliliters (22 g., 0.10 mole) of 57% hydriodic acid is added to the filtrate, and the resulting solution is stored at — 20° for 1 hour (Note 3). The solid that separates is collected weight 15.5-17.5 g. Recrystallization of this solid from about 100 ml. of absolute ethanol gives 14-16 g. (63-72%) of 1-aminopyridinium iodide as almost-white crystals, m.p. 160-162° (Note 4). 

The temperature is kept at — 20° or lower by a bath of dry ice and methanol. If the temperature rises above —20°, an appreciable quantity of 1-aminopyridinium iodide may redissolve and be lost. 

The formation of 1-aminopyridinium chloride has been accomplished by the acid hydrolysis of N- ( -acetaminobenzene-sulfonimido)pyridine.4 Also, the rearrangement of a substituted diazepine has been observed to give a 1-aminopyridine derivative.5 The present procedure is an adaptation of that described by GosI and Meuwsen.1... 

Monocyclic 2H-[ 1,2,3 Idiazaphospholes (B) are easily accessible from the condensation of the four-membered chain incorporated in hydrazones or azoalkanes with phosphorus trichloride making available a large number of representatives that have been intensively studied [2, 4, 7], In contrast, their 1//-isomers (A) are less known and are obtained only as second minor product during the synthesis of 2//-[l,2,3]diazaphospholes in some cases. A facile synthesis for pyrido-anellated azaphospholes has been developed in our group by making use of 1,2-disubstituted pyridinium salts for condensation with phosphorus trichloride [8, 13-15], Accordingly, cyclocondensation of 2-alkyl-1-aminopyridinium iodides (1) with phosphorus trichloride in the presence of triethylamine affords pyrido-anellated l//-[l,2,3]diazaphospholes, i.e. l,2,3]diazaphospholo 1,5-a] pyridines (2) (Scheme 1) [16],... 

The literature of mechanistic aromatic photochemistry has produced a number of examples of [4 + 4]-photocycloadditions. The photodimerization of anthracene and its derivatives is one of the earliest known photochemical reactions of any type97. More recently, naphthalenes98, 2-pyridones" and 2-aminopyridinium salts100 have all been shown to undergo analogous head-to-tail [4 + 4]-photodimerization. Moreover, crossed [4+4]-photocycloaddition products can be obtained in some cases101. Acyclic 1,3-dienes, cyclohexadienes and furan can form [4 + 4]-cycloadducts 211-214 with a variety of aromatic partners (Scheme 48). 

Table 3 Synthesis through ring closure of /V-aminopyridinium derivatives...

Examples reported in Table 3 merit additional comments the high regioselectivity observed with nonsymmetric aminopyridiniums is clearly an advantage of this synthetic route however, most yields are quite low. 

Recent literature also focused on condensations of iV-aminopyridiniums with aldehydes. In this case, a further rearomatization step is required, in general with air in alkaline conditions. Most pyridines used in these preparations are 2,3- or 2,6-diaminopyridines, leading to isomers 235 <2004BML3307> and 236 (X = COOMe <2003TL1675, 2003JC0233> or Br <2001SL1917>, respectively) (Scheme 59). 

A bicyclic system, 5-azaindole, may be mentioned here because it owes its relatively high basic strength (p/sTg = 8 3) to a resonance stabilization of the cation [71] which is analogous to that of 4-aminopyridinium ion (Adler and Albert, 1960). Nmr spectra of the cations of 5-azaindole and its 1-phenyl derivatives have recently been reported (Dvoryantseva et al., 1973). 

The other ring contraction involves cleavage of the pjo idine ring under very mild conditions. Diazotization of 3-aminopyridinium salts (R = alkyl, allyl, aryl) gives lH-triazole-4-acraldehyde derivatives. A possible mechanism for the reaction is shown in Scheme 27. 

This may be rationalized from a consideration of resonance in the conjngate acids. The conjngate acids from ring protonation benefit from charge delocalization, which is greater in 4-aminopyridininm that in 2-aminopyridinium. This type of delocalization is not possible in 3-aminopyridinium 3-aminopyridine (p Ta 6.0) is the weakest base of the three aminopy-ridines, and has basicity more comparable to that of pyridine (pATa 5.2). 

Alkyl-l-aminopyridinium iodides (88) condense with PCI3 in presence of NEtj to give 1,2,3-diazaphospholo[l,5-a]pyridines (89). 2-Methyl-1-aminopyridinium iodide, on reacting with two equivalents PCI3 under these conditions, forms 1 -dichlorophosphino-1,2,3-diazaphospholo[l, 5-a]py-ridine (89), R = PCI2 (Equation (8)) <95S173>. 

An unusual photochemical reaction of 2-pyridones, 2-aminopyridinium salts and pyran-2-ones is photodimerization to give the so-called butterfly dimers. These transformations are outlined in equations (13) and (14). Photodimerization by [2+2] cyclization is also a common and important reaction with these compounds. It has been the subject of particular study in pyrimidines, especially thymine, as irradiation of nucleic acids at ca. 260 nm effects photodimerization (e.g. equation 15) this in turn changes the regular hydrogen bonding pattern between bases on two chains and hence part of the double helix structure is disrupted. The dimerization is reversed if the DNA binds to an enzyme and this enzyme-DNA complex is irradiated at 300-500 nm. Many other examples of [2+2] photodimerization are known and it has recently been shown that 1,4-dithiin behaves similarly (equation 16) (82TL2651). 

The principal interest in N-aminopyridinium salts and their benzo analogues is related to the fact that they can provide access to the ylide-like pyridinium imines, e.g. (100), and benzo analogues (Scheme 87) (80YZ1). 

The principal disadvantage to the aminopyridinium ion route is the accessibihty of the precursors. None are available commercially, and most require multistep syntheses giving relatively low yields. Another potential pitfall is the formation of the pyridine byproduct (54). Pyridines can function as nucleophiles, attacking the nitrenium ion and creating complex mixmres. Finally, pyiidinium ions are electron deficient and can serve as good ground-state electron acceptors. Many of the stable products generated from nitrenium ion reactions are amines and are relatively easy to oxidize. Thus, a potential problem is secondary reaction, whereby primary photoproducts are oxidized by the precursor. 

The aminopyridinium route has been employed in flash photolysis studies of aryl as well as diarylnitrenium ions. Several examples of nitrenium ion species, along with their absorption maxima and some trapping rate constants are given in Table 13.7. To the extent the data are comparable, there is good agreement with the behavior of nitrenium ions generated by the azide route. For example, the 4-biphenylyl systems from the azide protonation and /-aminopyridinium routes both give absorption maxima at 460 nm and live for several microseconds in water. Likewise, the 4-methoxyphenyl systems show maxima at 300 nm (from azide) and 320 nm (from aminopyridinium ion). The discrepancy in this case can be attributed to the A -methyl substituent, present in the aminopyridinium route, but absent in the azide experiment. 

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