Pyridine nucleophilic addition

Pyridine, nucleophilic addition to 4-chloro-l,3-din1trobenzenc, 62, 134 Pyridinlum, 3-carbamoyl-l-6-D-r1bofuranosyl hydroxide, 5 5 - ester with adenosine 5 -(trihydrogen pyrophosphate). Inner salt, 63, 17 Pyr1do(2,l,6-de)qu1noll2lne, dodecahydro-, c1s,cis- (3ao,6ao,9aa) [57147-56-6] cis.trans- 3aa,6ac,9ae) [57194-67-9], 61, 108 Pyrrole, 3-acyl, 62, 115 Pyrrole, S-d-hydroxyalkyl), 62, 115... 

The conversion of indoles to oxindoles can be achieved in several ways. Reaction of indoles with a halogenaling agent such as NCS, NBS or pyridin-ium bromide perbromide in hydroxylic solvents leads to oxindoles[l]. The reaction proceeds by nucleophilic addition to a 3-haloindolenium intermediate. 

The N-oxides readily undergo nucleophilic addition followed by elimination, which forms the basis of several useful syntheses of 2-substituted pyridines. Chlorination of (13) with POCl to give 2-chloropyridine (17) is a good example (eq. 4) some chlorination may occur also at C-4 (11). 

The Zincke reaction is an overall amine exchange process that converts N- 2,A-dinitrophenyl)pyridinium salts (e.g, 1), known as Zincke salts, to iV-aryl or iV-alkyl pyridiniums 2 upon treatment with the appropriate aniline or alkyl amine. The Zincke salts are produced by reaction of pyridine or its derivatives with 2,4-dinitrochlorobenzene. This venerable reaction, first reported in 1904 and independently explored by Konig, proceeds via nucleophilic addition, ring opening, amine exchange, and electrocyclic reclosure, a sequence that also requires a series of proton transfers. By... 

Zincke s aldehyde (61) and cyanomethyltriphenylphosphonium chloride in acetic anhydride at 100 °C gave the salt (62), isolated as the perchlorate, whereas the same reagents in pyridine gave the phosphorane-phosphonium salt (63), presumably via nucleophilic addition of cyanomethylenephos-phorane to the terminal carbon of (62). 

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... 

Other types of reactions have been studied as, for example, a mixture of nucleophilic addition and substitution reactions.3296-3298 An interesting reaction due to the potential catalytic applications is the reversible addition of H2 to [Pt(AuPPh3)8]2+ to give the 18-electron dihydrido cluster [Pt(H)2(AuPPh3)8]2+.3299,3300 In nonbasic solvents the dihydrido cluster is stable and upon removal of the H2 atmosphere, it rapidly loses H2 to reform [Pt(AuPPh3kl2+. These reactions are completely reversible in pyridine solutions as shown in Equation (50) 3... 

AUenyl pyridinium salts 303 are a class of electron-deficient allenes, of which the center carbon atom can accept nucleophilic addition of diethylamine and pyridine derivatives [147, 148]. 

This preparation illustrates an efficient two-step process for the transformation of a cycloalkenone to the corresponding a-substituted derivative. The first step involves the installation of an a-iodo substituent by a process thought to involve nucleophilic addition of pyridine, iodine capture of the resulting enolate, and pyridine-promoted elimination of pyridine.5 The resulting vinyl iodides are superior to other vinyl halides as participants in a variety of transition-metal catalyzed coupling reactions, illustrated here by the Suzuki coupling with an arylboronic acid. Other coupling partners that... 

The pffa of 3-methylpyridine, whose anion cannot be delocalized onto N, is closer to that of toluene, and deprotonation gives only low yields with most bases. However, with a combination of BuLi and lithiodimethylaminoethanol (LiDMAE) deprotonation is quantitative but yields products 561 arising from apparent lithiation a to N (Scheme 224) Trying to force lateral lithiation of pyridines is generally doomed to failure, as ring lithiation or nucleophilic addition nsnally takes place first . 

The formation of jp -carbanions adjacent to pyridine-like nitrogen in 6-membered heteroaromatic rings is complicated by the fact that with alkyl and aryllithiums, 1,2-nucleophilic addition to the azomethine double bond (Scheme 103) normally occurs in preference to metalation [88H2659, 88MI2 88T1 90H(31)1155 91AHC(52)187]. 

Halopyridines and other re-deficient nitrogen heterocycles are excellent reactants for nucleophilic aromatic substitution.112 Substitution reactions also occur readily for other heterocyclic systems, such as 2-haloquinolines and 1-haloisoquinolines, in which a potential leaving group is adjacent to a pyridine-type nitrogen. 4-Halopyridines and related heterocyclic compounds can also undergo substitution by nucleophilic addition-elimination but are somewhat less reactive. 

The osmylation of C q with 0.75 equiv of OSO4 in pyridine-toluene at 0 °C leads to the two regioisomers 15 (major product) and 16 (minor) (Scheme 8.7) [58]. The same regioselectivity was observed in the hydrogenation (Chapter 5) [59], nucleophilic additions (Chapter 3) [60] as well as in Ir-adduct formations (Chapter 7) [61] of C70 and is in line with the predicted stabilities [59,62] of C70 adducts. The reaction occurs at the most reactive [6,6] double bonds, with the closest geometric similarity to the [6,6] double bonds of C q. These are the double bonds between C-l/C-2 (bond 1, Scheme 8.7) and C-5/C-6 (bond 2, Scheme 8.7) respectively. 

There is a strong similarity between the reactions of pyridines and quino- Scheme 3.5 lines towards nucleophiles. Addition occurs mainly at C-2, giving 1,2-dihydroquinolines, but the locus of the reaction can be diverted to C-4, particularly if there is a good leaving group located at this position. 

Reaction of nucleophiles with the polarized N=C bond of azines proceeds via dearomatization and formation of the corresponding 1,2-adduct. With alkyllithiums, for example, it is possible to isolate the dihydro products by careful neutralization of the reaction mixtures these are, in general, rather unstable, however, and can easily be reoxidized to the fully aromatic compounds (Scheme 4). The dihydro adducts formed in these direct nucleophilic addition reactions can also be utilized for the introduction of substituent groups /3 to the heteroatom. Thus, reaction of (35) with one of a number of electrophiles, followed by oxidation of the intermediate dihydro product, constitutes a simple and, in many cases, effective method for the introduction of substituent groups at both the 2- and 5-positions of the pyridine ring (Scheme 4). Use of LAH in this sequence, of course, results in the formation of 3-substituted pyridines. 

He have found that, In hydrocarbon solvents, the activating effect of the pyridine ring upon the reactivity of the doublebond, allows nucleophilic addition from non-solvated R Mg R derivatives. 

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