Pyridine substitution reaction

Palladium, (diammine)bis(thiocyanato)-isomerism, 1, 185 Palladium, dichlorobis(amine)-substitution reactions stereochemistry, 1, 318 Palladium, dichlorobis(pyridine)-substitution reactions, 1, 314 Palladium, dinitritobis(triisopropylphosphine)-substitution reactions, I, 314 Palladium, ethylene-synthesis... 

Rund et al. have suggested that the pyridine substitution reaction RhClj- +4 py = rrans-Rh py4 CI2 +3 CF... 

The more basic and less hindered pyridines undergo nucleophilic attack at an ethylene coordinated to platinum(II). Pyridine substitution reactions at platinum also occur, and in the presence of excess ethylene, alkene replacement is observed.72 ... 

Electrophilic substitution reactions of unsubstituted quinoxaline or phenazine are unusual however, in view of the increased resonance possibilities in the transition states leading to the products one would predict that electrophilic substitution should be more facile than with pyrazine itself (c/. the relationship between pyridine and quinoline). In the case of quinoxaline, electron localization calculations (57JCS2521) indicate the highest electron density at positions 5 and 8 and substitution would be expected to occur at these positions. Nitration is only effected under forcing conditions, e.g. with concentrated nitric acid and oleum at 90 °C for 24 hours a 1.5% yield of 5-nitroquinoxaline (19) is obtained. The major product is 5,6-dinitroquinoxaline (20), formed in 24% yield. 

Pyrazine and quinoxaline fV-oxides generally undergo similar reactions to their monoazine counterparts. In the case of pyridine fV-oxide the ring is activated both towards electrophilic and nucleophilic substitution reactions however, pyrazine fV-oxides are generally less susceptible to electrophilic attack and little work has been reported in this area. Nucleophilic activation generally appears to be more useful and a variety of nucleophilic substitution reactions have been exploited in the pyrazine, quinoxaline and phenazine series. 

Sulfonate esters are especially useful substrates in nucleophilic substitution reactions used in synthesis. They have a high level of reactivity, and, unlike alkyl halides, they can be prepared from alcohols by reactions that do not directly involve bonds to the carbon atom imdeigoing substitution. The latter aspect is particularly important in cases in which the stereochemical and structural integrity of the reactant must be maintained. Sulfonate esters are usually prepared by reaction of an alcohol with a sulfonyl halide in the presence of pyridine ... 

There is another important factor in the low reactivity of pyridine derivatives toward electrophilic substitution. The —N=CH— unit is basic because the electron pair on nitrogen is not part of the aromatic n system. The nitrogen is protonated or complexed with a Lewis acid under many of the conditions typical of electrophilic substitution reactions. The formal positive charge present at nitrogen in such species further reduces the reactivity toward electrophiles. 

The pyridine family of heteroaromatie nitrogen compounds is reactive toward nueleophilie substitution at the C-2 and C-4 positions. The nitrogen atom serves to aetivate the ring toward nueleophilie attack by stabilizing the addition intermediate. This kind of substitution reaction is especially important in the ehemistiy of pyrimidines. 

The reactions of pyridinium N-alkoxides (158-161) orpyridinium N-amides (162) with cyanide demonstrate a useful substitution reaction for pyridines. 

In 1904, Zincke reported that treatment of Al-(2,4-dinitrophenyl)pyridinium chloride (1) with aniline provided a deep red salt that subsequently transformed into A-phenyl pyridinium chloride 5 (Scheme 8.4.2). Because the starting salt 1 was readily available from the nucleophilic aromatic substitution reaction of pyridine with 2,4-dinitrochlorobenzene, the Zincke reaction provided access to a pyridinium salt (5) that would otherwise require the unlikely substitution reaction between pyridine and... 

In their acidity, basicity, and the directive influence exerted on electrophilic substitution reactions in benzenoid nuclei, acylamino groups show properties which are intermediate between those of free amino and hydroxyl groups, and, therefore, it is at first surprising to find that the tautomeric behavior of acylaminopyridines closely resembles that of the aminopyridines instead of being intermediate between that of the amino- and hydroxy-pyridines. The basicities of the acylaminopyridines are, indeed, closer to those of the methoxy-pyridines than to those of the aminopyridines, the position of the tautomeric equilibrium being determined by the fact that the acyl-iminopyridones are strong bases like the iminopyridones and unlike the pyridones themselves. Thus, relative to the conversion of an... 

Py refers to the series of substituted pyridines undergoing reaction, i.e., Py = RC5H4N where R is a substituent. 

Compound 40 has not yet been synthesized. However, there is a large body of synthetic data for nucleophilic substitution reactions with derivatives of 41 [synthesized from aliphatic and aromatic aldehydes, pyridine, and trimethylsilyl triflate (92S577)]. All of these experimental results reveal that the exclusive preference of pathway b is the most important feature of 41 (and also presumably of 40). 

The presently known electrophilic substitution reactions all occur at the 4-position of the isoxazole nucleus, corresponding to the j3-position in pyridine. Thus the influence of the nitrogen atom is predominant. The introduction of alkyl and, particularly, aryl substituents into the isoxazole nucleus markedly increases its reactivity (on the other hand, during nitration and sulfonation the isoxazole nucleus also activates the phenyl nucleus). 

Alcohols react with p-toluenesulfonyl chloride (tosyJ chloride, p-TosCl) in pyridine solution to yield alkyl tosylates, ROTos (Section 11.1). Only the 0-H bond of the alcohol is broken in this reaction the C—O bond remains intact, so no change of configuration occurs if the oxygen is attached to a chirality center. The resultant alkyl tosylates behave much like alkyl halides, undergoing both SN1 and Sjsj2 substitution reactions. 

Unlike benzene, pyridine undergoes electrophilic aromatic substitution reactions with great difficulty. Halogenation can be carried out under drastic conditions, but nitration occurs in very low yield, and Friedel-Crafts reactions are not successful. Reactions usually give the 3-substituted product. 

Problem 24.22 Electrophilic aromatic substitution reactions of pyridine normally occur at C3. Draw... 

Only relatively few nucleophilic substitution reactions at sulfur proceed with retention. Oae found that (R)-(+)-methyl p-tolyl sulfoxide exchanged 180 with dimethyl sulfoxide at 150 °C much faster than it racemized thus, the exchange took place with retention. A cyclic intermediate, 136, was proposed to account for this behavior12,147. The same sulfoxide was found to react with N, JV -ditosylsulfurdiimide, 137, with either retention or inversion depending on the reaction conditions. Christensen148 observed retention in benzene whereas Cram and coworkers149 found that inversion took place in pyridine. A four-membered ring intermediate, 138, was postulated to account for the retention, whereas a... 

The Ullman reaction has long been known as a method for the synthesis of aromatic ethers by the reaction of a phenol with an aromatic halide in the presence of a copper compound as a catalyst. It is a variation on the nucleophilic substitution reaction since a phenolic salt reacts with the halide. Nonactivated aromatic halides can be used in the synthesis of poly(arylene edier)s, dius providing a way of obtaining structures not available by the conventional nucleophilic route. The ease of halogen displacement was found to be the reverse of that observed for activated nucleophilic substitution reaction, that is, I > Br > Cl F. The polymerizations are conducted in benzophenone with a cuprous chloride-pyridine complex as a catalyst. Bromine compounds are the favored reactants.53,124 127 Poly(arylene ether)s have been prepared by Ullman coupling of bisphenols and... 

It may be mentioned that this interpretation is in agreement with the deactivating and /3 directing influence of nitrogen in pyridine and its analogs14 with respect to substitution reactions. 

In this review, CPOs constructed by covalent bonds are mainly focused on however, stable coordination bonds comparable to the stability of the covalent bonds have potential for future enhanced molecular design of novel CPOs. One representative is the bond between pyridine-type nitrogen and metal, which is widely used in supramolecular chemistry, that is, the cyclic supramolecular formation reaction between pyridine-substituted porphyrin and metal salts (Fig. 6d) [27,28]. Palladium salts are frequently used as the metal salts. From the viewpoint of the hard and soft acid and base theory (HSAB), this N-Pd coordination bond is a well-balanced combination, because the bonds between nitrogen and other group X metals, N-Ni and Ni-Pt coordination bonds, are too weak and too strong to obtain the desired CPOs, respectively. For the former, the supramolecular architectures tend to dissociate into pieces in the solution state, and for the latter. 

Hydrolysis of diphenyl phosphorochloridate (DPPC) in 2.0 M aqueous sodium carbonate is also believed to be a two-phase process. DPPC is quite insoluble in water and forms an insoluble second phase at the concentration employed (i.e. 0.10 M). It seems highly significant that the hydrophobic silicon-substituted pyridine 1-oxides (4,6,7) are much more effective catalysts than hydrophilic 8 and 9. In fact, 4 is clearly the most effective catalyst we have examined for this reaction (ti/2 < 10 min). Since derivatives of phosphoric acids are known to undergo substitution reactions via nucleophilic addition-elimination sequences 1201 (Equation 5), we believe that the initial step in hydrolysis of DPPC occurs in the organic phase. Moreover, the... 

---