Reactions with Pyridine

With the discovery of benzyne formation by pyrolysis of phthalic anhydride, a new field was opened for the investigation of aryne reactions at high temperatures. A first concern was to determine the generality of aryne formation from aromatic acid anhydrides. Such syntheses could be of considerable significance because of the enormous quantities of aromatic mono- and polyanhydrides available from petroleum aromatics by oxidation. 

Accordingly, nine aromatic and two heterocyclic anhydrides were pyrolyzed in admixture with pyridine under standardized conditions, and the relative amounts of aryne or heteroaryne produced were determined by analysis of the reaction products (Fields and Meyerson, 

1966e). Although benzene as reactant gave far fewer products and isomers, it has the disadvantage of pyrolyzing to bi- and terphenyl, and there appeared no easy way to distinguish the products formed by benzene pyrolysis from those formed by aryne insertion. 

The products were identified in all cases by mass spectrometry, and in some by gas chromatography or by directly coupled gas chromatography-mass spectrometry. 

In a typical experiment, a solution of 1-48 g (0-01 mole) of phthalic anhydride in 8-05 ml (0-1 mole) of pyridine was pyrolyzed at 690° in dry, high-purity nitrogen flowing at the rate of 2-7 1/hr. Contact time was 20-2 sec. The products were distilled to recover 6-34 ml of pyridine. The distillation residue weighed 2-12 g, of which 0-06 g was removed for analysis by mass spectrometry. The remainder was dissolved in ether and separated into nitrogen bases (1-44 g) and hydrocarbons (0-62 g) by extraction with dilute hydrochloric acid. Analysis by gas chromatography, by comparison of retention times with authentic samples, gave the results shown in Table 9. 

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Because of the increased importance of inductive electron withdrawal, nucleophilic attack on uncharged azole rings generally occurs under milder conditions than those required for analogous reactions with pyridines or pyridones. Azolium rings are very easily attacked by nucleophilic reagents reactions similar to those of pyridinium and pyrylium compounds are known azolium rings open particularly readily. 

These Br nsted-type plots often seem to be scatter diagrams until the points are collated into groups related by specific structural features. Thus, p-nitrophenyl acetate gives four separate, but parallel, lines for reactions with pyridines, anilines, imidazoles, and oxygen nucleophiles.Figure 7-4 shows such a plot for the reaction of trans-cmmm c anhydride with primary and secondary aliphatic amines to give substituted cinnamamides.All of the primary amines without substituents on the a carbon (R-CHi-NHi) fall on a line of slope 0.62 cyclopentylamine also lies on this line. If this line is characteristic of normal behavior, most of the deviations become qualitatively explicable. The line drawn through the secondary amines (slope 1.98) connects amines with the structure R-CHi-NH-CHi-R. The different steric requirements in the acylation reaction and in the model process... 

The crude 2,2 -bipyridine obtained from the reaction of pyridine and degassed Raney nickel was found to contain 1.5% of 2 6, 2"-terpyridine, but no 2,2 2, 2" 6 ",2 "-quaterpyridine could be detected. Moreover, experiments with 2,2 -bipyridine and Raney nickel have failed to yield quaterpyridine, and the amount of terpyridine formed in experiments with mixtures of pyridine and 2,2 -bipyridine was found to be no higher than in the reaction with pyridine itself. " ... 

The reactivity of a remarkable electronically unsaturated tantalum methyli-dene complex, [p-MeCgH4C(NSiMe3)2]2Ta( = CH2)CH3, has been investigated. Electrophilic addition and olefination reactions of the Ta = CH2 functionality were reported. The alkylidene complex participates in group-transfer reactions not observed in sterically similar but electronically saturated analogs. Reactions with substrates containing unsaturated C-X (X = C, N, O) bonds yield [Ta] = X compounds and vinylated organic products. Scheme 117 shows the reaction with pyridine N-oxide, which leads to formation of a tantalum 0x0 complex. ... 

However, Baker and Nathan ° observed that the rates of reaction with pyridine of p-substituted benzyl bromides (see Reaction 10-44) were about opposite that expected from electron release by the field effect. That is, the methyl-substituted compound reacted fastest and the tert-butyl-substituted compounded reacted slowest. 

Mono- and dilithio derivatives of p-tosylmethyl isocyanide 297a were shown to display interesting reactions. Reaction of the monoanion with unsaturated esters was shown to give pyrrole derivatives . Dianion 297b was found to add to the carbon-nitrogen double bonds of isoquinoline, quinoline and quinoxaline affording compounds 298, 299 and 300, respectively. In the reactions with pyridine iV-oxide and pyridazine iV-oxide, unstable open-chain products 301 and 302 were obtained . 

Scheme 1.36 Test reaction with pyridine thioether and dithioether ligands.

Host-guest complexes such as (67) have been prepared from molecular squares involving Lewis base receptor sites, such as cyclobis[(cw-(dppp)Pt(4-ethynylpyridyl)2)(cM-LM)]Ag2 6+(OTf)6, where M = Pdn or Ptn and L = dppp or 2PEt3, by reaction with pyridine, pyrazine, phenazine, or 4,4 -dipyridyl ketone.519... 

Reaction of compound 37 with bromine in chloroform results in mono-bromination a to the sulfur. Treatment of this brominated derivative with NaBH3CN in AcOH gives a mixture of products resulting from reduction of the C=N double bond and of elimination of HBr. Reaction of 44 with sodium ethoxide results in the ethoxy-substituted derivative 45, whereas reaction with pyridine gives the dehydrobrominated derivative 46. Reaction of either 44 or 46 with sodium cyanide in dimethyl sulfoxide (DMSO) gives the cyano-derivative 47 <1983HCA971> (Scheme 13). 

Cyclic ylide complexes are readily oxidized not only by aggressive reagents like elemental halogens but also by milder oxidants like disulfides, or even mercaptanes in the presence of molecular oxygen, as shown for a reaction with pyridine-2-thiol in air (Equation (34)).182 A similar reaction is known to take place with thiuramdi-dulfides.2,180... 

In a certain solvent (A), the O-H stretching band of methanol is observed at 3642cm-1. In that solvent, the heat of reaction of methanol with pyridine is -36.4 kl mol-1. In another solvent (B), the O-H stretching band is observed at 3620 cm-1 and the heat of reaction with pyridine is —31.8kJ mol-1. 

The ligand diethylenetriamine, H2NCH2CH2NHCH2CH2NH2, forms stable complexes with Pt2+. When the complexes [Pt(dien)X]+ undergo reaction with pyridine, the rate constants for X = Cl-, I-, and N02- are 3.5 X 10-5, 1.0 X 10-s,and5.0 X 10-8 sec-1, respectively. What is the mechanism forthe substitution reactions Provide an explanation for the difference in rates of the reactions. What would be a reasonable estimate for the rate constant when X = Br- Explain your answer. 

In our hands, this gave as principal product on reaction with pyridine the complex [PtCl2(py) CHD=C(Me)CDMe2 ] and not the product shown in equation (3). This reaction is complicated by a side reaction apparently involving 8-elimination from one of the methyl substituents, but an analysis similar to that described above by H, 13C 1H and 2H 1H NMR spectroscopy showed that the major product was formed by the a-elimination pathway (15). 

The yields of the first and the second stages were 53% and 48%, respectively. The yields of the para-analog of 414 were similar (55% and 35%, respectively). A one-pot reaction with pyridine-2,6-biscarbohydroximinoyl dichloride gives a pyridine analog of 414 as a minor product (8%). The main product 416 (25% yield) arises from an intramolecular nitrile oxide dimerization. The macrocyclic cycloadducts have been characterized spectroscopically and by X-ray crystallography (452). 

As early as 1967, after their success in isolating atropisomers of haloacetamide derivatives (12), Chupp and Olin (49) examined the separate reactivities of these atropisomers in Menschutkin reactions with pyridine (Scheme 7). They found... 

Both reactions depicted in Eqs. 27.2 and 27.3 involve follow-up chemical reactions. Popov and Geske [7] claimed that the recombination of L, in solution, is slow compared to its reaction with pyridine ... 

Nucleophilic substitution occurs at C-2, and to a lesser extent C-4, as might be predicted from similar reactions with pyridine. Chichibabin amination occurs rather more readily than with pyridine, giving 2-aminoquinoline. A typical hydride abstraction process occurs when qninoline is heated with sodinm... 

Scheme 8.21 RCM reactions with pyridine indenylidene catalyst XXVI.

Reaction with pyridine leads to the formation of a UV-active pyridinium ylide. Rate constants for the alkylcarbene reaction(s) can be extracted from the intercept of the linear correlation of feobs for ylide formation versus the pyridine concentration. Consider first the 1,2-H shift that converts chloromethylcarbene (48) into vinyl chloride (Scheme 7.17). The LFP experiments show that the H shift occurs with k= 1.2 — 3.0 X 10 s in isooctane, cyclohexane, or dichloroethane at 21-25 The rearrangement is fast, but not ultrafast carbene (48) has a lifetime... 

The rate constants of reactions in CH2CI2 deduced using the data of Poe et and the absolute rate constant of reaction with pyridine. ... 

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