2.6- unsubstituted pyridines

Skraup synthesis org chem A method for the preparation of commercial synthetic quinoline by heating aniline and glycerol in the presence of sulfuric acid and an oxidizing agent to form pyridine unsubstituted quinolines. skraup sin-tha-sas slaked lime See calcium hydroxide. slakt iTm )... 

Various reactivities have been observed for cycloheptatrienylidene palladium complexes in the presence of nitrogen heterocyclic aromatics. Unhindered bases such as pyridines unsubstituted on positions 2 and 6 added to the unsaturations of the carbene backbone leading to a dinuclear allyl palladium complex, whereas 2,6-lutidine reacted with the metal centre to yield a mononuclear carbene complex. Reactions with methylim-idazole were found to give the mononuclear complex when up to two equivalents of imidazole were reacted, but addition on the carbene backbone was observed with 2.5 equivalents. 

With the catalysis of strong Lewis acids, such as tin(IV) chloride, dipyrromethenes may aiso be alkylated. A very successful porphyrin synthesis involves 5-bromo-S -bromomethyl and 5 -unsubstituted 5-methyl-dipyrromethenes. In the first alkylation step a tetrapyrrolic intermediate is formed which cyclizes to produce the porphyrin in DMSO in the presence of pyridine. This reaction sequence is useful for the synthesis of completely unsymmetrical porphyrins (K.M. Smith, 1975). 

Isopropylidene and benzylidene hydrazones of selenazole unsubstituted in the 5-position react with p-nitrosodimethylanilines or p-nitrosodiethyl-anilines when heated in organic solvents in the presence of acetic acid or pyridine (49). Highly colored crystalline 2-hydrazono-5-(p-dialkylamino-phenylimino)selenazoles are recovered from the reaction medium (Table X-10). 

Halophenols without 2,6-disubstitution do not polymerize under oxidative displacement conditions. Oxidative side reactions at the ortho position may consume the initiator or intermpt the propagation step of the chain process. To prepare poly(phenylene oxide)s from unsubstituted 4-halophenols, it is necessary to employ the more drastic conditions of the Ullmaim ether synthesis. A cuprous chloride—pyridine complex in 1,4-dimethoxybenzene at 200°C converts the sodium salt of 4-bromophenol to poly(phenylene oxide) (1) ... 

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. 

The pyrazole molecule resembles both pyridine (the N(2)—C(3) part) and pyrrole (the N(l)—C(5)—C(4) part) and its reactivity reflects also this duality of behaviour. The pyridinic N-2 atom is susceptible to electrophilic attack (Section 4.04.2.1.3) and the pyrrolic N-1 atom is unreactive, but the N-1 proton can be removed by nucleophiles. However, N-2 is less nucleophilic than the pyridine nitrogen atom and N(1)H more acidic than the corresponding pyrrolic NH group. Electrophilic attack on C-4 is generally preferred, contrary to pyrrole which reacts often on C-2 (a attack). When position 3 is unsubstituted, powerful nucleophiles can abstract the proton with a concomitant ring opening of the anion. 

Electrophilic mercuration of isoxazoles parallels that of pyridine and other azole derivatives. The reaction of 3,5-disubstituted isoxazoles with raercury(II) acetate results in a very high yield of 4-acetoxymercury derivatives which can be converted into 4-broraoisoxazoles. Thus, the reaction of 5-phenylisoxazole (64) with mercury(II) acetate gave mercuriacetate (88) (in 90% yield), which after treatment with potassium bromide and bromine gave 4-bromo-5-phenylisoxazole (89) in 65% yield. The unsubstituted isoxazole, however, is oxidized under the same reaction conditions, giving mercury(I) salts. 

Because of the cost of pyridine the phosgenation process may be carried out with a mixture of pyridine and a non-hydrohalide-accepting solvent for the polymer and the growing complexes. Suitable solvents include methylene dichloride, tetrachlorethane and chloroform. Although unsubstituted aromatic hydrocarbons may dissolve the solvent they are not effective solvents for the acid chloride-pyridine complexes. 

Thiation was most frequently carried out in pyridine - for unsubstituted compounds which are considerably polar, this is a prerequisite. The less polar iV-alkylated derivatives can be thiated in toluene or xylene for thiation of 6-azathymine, tetralin was also used. ... 

The first reaction series to be considered are the basicities of the various quinolines. Baciocchi and Illuminati have demonstrated that the pK values of quinolines substituted in the B-ring follow the Hammett equation well if ApK, i.e., the difference between the pK values of substituted and unsubstituted compounds, is plotted against a, the quinoline points fall on the same line as the pyridine points, as shown in Fig. 5, so that the p-values for the two series are identical. 

The hydroxy group undergoes 0-acylation and deacylation (79JHC689). These reactions of functionalized hydroxyfurazans are valuable methods for modification of these compounds. Thus, hydroxybifurazan 248 was aroylated with benzoyl chloride in the presence of pyridine with concomitant cleavage of the unsubstituted furazan ring to give nitrile 262 (Scheme 170) (75LA1029). 

Reaction of the potassium salt of salicylaldehyde with chlo-roacetone affords first the corresponding phenolic ether aldol cyclization of the aldehyde with the ketonic side chain affords the benzofuran (1). Reduction of the carbonyl group by means of the Wolf-Kischner reaction affords 2-ethyl-benzofuran. Friedel-Crafts acylation with anisoyl chloride proceeds on the remaining unsubstituted position on the furan ring (2). The methyl ether is then cleaved by means of pyridine hydrochloride (3). lodina-tion of the phenol is accomplished by means of an alkaline solution of iodine and potassium iodide. There is thus obtained benziodarone (4)... 

Taking into account the close relationship to pyridines one would expect 2-pyridones to express similar type of reactivities, but in fact they are quite different. 2-Pyridones are much less basic than pyridines (pKa 0.8 and 5.2, respectively) and have more in common with electron-rich aromatics. They undergo halogenations (a. Scheme 10) [67] and other electrophilic reactions like Vilsmeier formylation (b. Scheme 10) [68,69] and Mannich reactions quite easily [70,71], with the 3 and 5 positions being favored. N-unsubstituted 2-pyridones are acidic and can be deprotonated (pJCa 11) and alkylated at nitrogen as well as oxygen, depending on the electrophile and the reaction conditions [24-26], and they have also been shown to react in Mitsonobu reactions (c. Scheme 10) [27]. 

When L = 4-CNC5H4N (PK3 = 1.86), 2-CIC5H4N (pK = 2.81), or 4-PhCOC5H4N (pKj = 3.35) [Hg2L2] [C10412 can be isolated as solids. However, under the same conditions the more basic unsubstituted pyridine (pK, = 5.21) leads to disproportionation, and no complex can be isolated. Complexes of Hg(I) of these more basic substituted pyridines can be prepared under a N2 atmosphere in MeOH at -70°C. Table 1 shows some Hg(I) complexes prepared with N-donor ligands. The majority contain an Hg2 ion with each atom coordinated to one or two N atoms as in I or II. 

Ethyl substitution at the imidazole 5-position (469) was found to increase potency over the unsubstituted analogue (468), while methyl substitution (470) had a slightly deleterious effect on binding (Table 6.41). Chloro (491), bromo (492), cyano (493) and fluoromethyl (494) substitution at this position were all well tolerated (Table 6.43). Introduction of a chloro-substituted pyridine (475) in place of the more usual / -chlorophenyl group (470) resulted in a slight loss of affinity for the CBi receptor, as did replacement of the p-chloro group of (470) with bromo (471), fluoro (472) and in particular, met-hoxy (473). Trifluoromethyl substitution (474) however, was well tolerated. 

Polymers with triflate groups react with alcohols to form alkoxysubstituted polysilanes. This reaction occurs readily in the presence of bases. The best results were obtained using triethylamine and hindered pyridine. In Fig. 3c the NMR spectrum of the reaction mixture containing the excess of triethylamine is shown, the methyl groups from the polymer chains absorb in the range typical for alkoxysilanes. Reaction in the presence of unsubstituted pyridine leads to the formation of insoluble polymer probably by attack at the p-C atom in the silylated pyridine. 

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