Pyridinium salts hydrolysis

Quaternization of harman (235) with ethyl bromoacetate, followed by cyclization of the pyridinium salt 236 with 1,2-cyclohexane-dione in refluxing ethanol yielded an ester which on hydrolysis gave the pseudo-cross-conjugated mesomeric betaine 237. Decarboxylation resulted in the formation of the alkaloid Sempervirine (238). The PCCMB 237 is isoconjugate with the 11/7-benzo[u]fluorene anion—an odd nonalternant hydrocarbon anion—and belongs to class 14 of heterocyclic mesomeric betaines (Scheme 78). 

A variety of polar reagents add to P=C or P=N bond when more electronegative part is bonded to phosphorus. Addition of two water molecules on P=C bond in [l,4,2]diazaphospholo[4,5-a]pyridine (76) and P=N bond in [l,2,3]diazaphos-pholo[ 1,5-aIpyridinc (2) causes ring opening (Scheme 23) [16, 68], In the case of 76 (R=C02Et), further hydrolysis to pyridinium salt 78 was observed [73],... 

The reaction of ADC compounds with carbenes and their precursors has already been discussed in Section IV,A- In general, the heterocyclic products are not the result of 1,2-addition but of 1,4-addition of the carbene to the —N=N—C=0 system.1 Thus the ADC compound reacts as a 4n unit in a cheletropic reaction leading to the formation of 1,3,4-oxadiazolines. Recent applications include the preparation of spiro-1,3,4-oxadiazolines from cyclic diazoketones and DEAZD as shown in Eq. (14),133 and the synthesis of the acyl derivatives 85 from the pyridinium salts 86.134 The acyl derivatives 85 are readily converted into a-hydroxyketones by a sequence of hydrolysis and reduction reactions. 

Another classic reaction of pyridinium salts is reduction of the pyridine ring. Donohoe and co-workers reported the partial reduction of A-alkylpyridinium salts <060BC1071>, which is accompanied by subsequent alkylation and hydrolysis to furnish a range of 2,3-dihydropyrid-4-ones. This sequence has the potential to introduce a variety of functional groups at the C-2 position of 2,3-dihydropyrid-4-ones. Reduction of pyridinium ylides with sodium borohydride has also been reported in fair to good yields <06JHC709>. 

After its isolation, the structure of alkaloid deplancheine (7) was unambiguously proved by several total syntheses. In one of the first approaches (14), 1,4-dihydropyridine derivative 161, obtained by sodium dithionite reduction of A-[2-(indol-3-yl)ethyl]pyridinium salt 160, was cyclized in acidic medium to yield quinolizidine derivative 162. Upon refluxing 162 with hydrochloric acid, hydrolysis and decarboxylation took place. In the final step of the synthesis, the conjugated iminium salt 163 was selectively reduced to racemic deplancheine. 

Several total syntheses of antirhine (11) and 18,19-dihydroantirhine (14) have been developed during the last decade. Wenkert et al. (136) employed a facile route to ( )-18,19-dihydroantirhine, using lactone 196 as a key building block. Base-catalyzed condensation of methyl 4-methylnicotinate (193) with methyl oxalate, followed by hydrolysis, oxidative decarboxylation with alkaline hydrogen peroxide, and final esterification, resulted in methyl 4-(methoxycar-bonylmethyl)nicotinate (194). Condensation of 194 with acetaldehyde and subsequent reduction afforded nicotinic ester derivative 195, which was reduced with lithium aluminum hydride, and the diol product obtained was oxidized with manganese dioxide to yield the desired lactone 196. Alkylation of 196 with tryptophyl bromide (197) resulted in a pyridinium salt whose catalytic reduction... 

The synthesis of the four monocarboxylic acids of dibenzothiophene has been recorded in the previous review. However, several modified preparations have since been described. Ethyl 1-dibenzothiophene-carboxylate has been synthesized from 2-allylbenzo[6]thiophene (Section IV,B, 1) hydrolysis afforded the 1-acid (57% overall). In a similar manner, 3-methyl-1-dibenzothiophenecarboxylic acid was obtained from the appropriately substituted allyl compound. This method is now the preferred way of introducing a carbon-containing substituent into the 1-position of dibenzothiophene. 2-Dibenzothiophenecarboxylic acid has been prepared by oxidation of the corresponding aldehyde or by sodium hypoiodite oxidation of the corresponding acetyl compound. Reaction of 2-acetyldibenzothiophene with anhydrous pyridine and iodine yields the acetyl pyridinium salt (132) (92%), hydrolysis of which yields the 2-acid (85%). The same sequence has been carried out on 2-acetyldibenzothiophene 5,5-dioxide. The most efficient method of preparing the 2-acid is via carbonation of 2-lithio-... 

This protective group is introduced by an acid-catalyzed addition of the alcohol to the vinyl ether moiety in dihydropyran. />-Toluenesulfonic acid or its pyridinium salt is used most frequently as the catalyst,3 although other catalysts are advantageous in special cases. The THP group can be removed by dilute aqueous acid. The chemistry involved in both the introduction and deprotection stages is the reversible acid-catalyzed formation and hydrolysis of an acetal (see Part A, Section 8.1). 

Amination of AT-alkylpyridinium salts with amide ions, which in principle should be easier than the reaction with the parent pyridine, has been little studied. The main reason for this is that solvent selection is difficult. Metal amides are only soluble in liquid ammonia (with which pyridinium salts react easily, vide infra), and pyridinium salts are soluble in solvents that are not suitable for use with metal amides. The A/ -methylacridinium cation undergoes direct imination to give (153) in 35% yield by treatment with potassium amide and iron (III) nitrate in liquid ammonia. Two other products (154) and (155) are also formed, probably by hydrolysis and subsequent disproportionation (Scheme 90). One might question whether sodamide is necessary to the above transformation in light of the fact that quin-olinium, isoquinolinium and certain pyridinium ions give cr-complexes (156), (157) and (158) in liquid ammonia alone at 0 °C (73JOC1949). 

A hydrogen attached to a pyridine or pyridine 1-oxide nucleus cannot be replaced directly by cyanide however, addition of cyanide to various quaternary salts constitutes an important class of reactions of synthetic importance. Before surveying these reactions in detail, the four main classes are outlined. In 1905, Reissert reported the first example, the reaction of quinoline with benzoyl chloride in aqueous potassium cyanide (Scheme 111) (05CB1603). This yielded a crystalline product, C17H12N2O, a Reissert compound (176) which afforded benzaldehyde and quinaldinic acid on acid hydrolysis (Scheme 111). Kaufmann (09CB3776) treated a 1 -methylquinolinium salt with aqueous potassium cyanide and observed 1,4-rather than 1,2-addition (Scheme 112), the Reissert-Kaufmann reaction. Reissert compounds are well known in the quinoline and isoquinoline series, but only rarely have even small yields been found in the pyridine series. On the other hand, cyanide ions add 1,4 with ease to pyridinium salts that have an electron withdrawing substituent at C-3. 

Bodor and Brewster (1983) first used the term CDS, in describing the use of dihydropyridine ester- (or amide)-linked prodrugs such as 27 (X-OH is the parent) which can partition readily into the CNS, there to be oxidized to pyridinium salts (28), which are effectively trapped in the biophase because of their extreme polarity, and which then undergo enzymic or chemical hydrolysis of the now very labile ester link to release active drug. 

The preparation of conjugated dienes from pyridines is exemplified by the transformation of 2-picoline into the sex pheromone (669) of Lobesia botrana, a major pest of vineyards (Scheme 154) (80TL67). Thus, the lithio salt of 2-picoline was alkylated by 2-(5-chloropentyl-oxy)tetrahydropyran, the resulting pyridine (665) N-methylated, and the pyridinium salt reduced by sodium borohydride. Quaternization of the 1,2,3,6-tetrahydropyridine (666) and Hofmann elimination gave the (7 , 9Z)-undecadien-l-ol (667) as the sole isomer. Protection of the alcohol and treatment of the corresponding ammonium salt (668) of the amine with lithium dimethylcuprate gave pure (669) after hydrolysis, acetylation and HPLC purification. 

A chloroacetylbenzo[6]thiophene is readily converted into the corresponding benzo[6]thiophene carboxylic acid by alkaline hydrolysis of its pyridinium salt.132 464... 

Hosie, L. Marshall, P. J. Sinnott, M. L. Failure of the antiperiplanar lone pair hypothesis in glycoside hydrolysis. Synthesis, conformation, and hydrolysis of a-D-xylopyranosyl and a-D-glucopyranosyl pyridinium salts. /. Chem. Soc. Perkin Trans. 2 1984,1121-1131. 

A two-electron reduction of activated pyridinium salt 178 forms an intermediate enolate 179, which, upon quenching with a number of electrophiles, yields dihydro l-pyridones 180 after hydrolysis. These compounds are notable because they contain a variety of groups a to the nitrogen (Table 5 Equation (94) <20050L435, 20060BC1071>. 

Generally, the structures of the 1,2,3,5-thiatriazoles (114) and (113 X = S) are inferred from the mode of synthesis. The structure of l,2,3,5-thiatriazoIo[5,4-a]pyridine 3-oxide (117) has been discussed in more detail. 2-Hydrazinopyridine is formed upon hydrolysis and the IR spectrum exhibits an NH stretching vibration at 3280 cm-1. This suggests the interesting possibility of tautomeric and zwitterionic structures (Scheme 8). Methylation with diazomethane gives the 1-methyl derivative which apparently is best formulated as the zwitterionic A4-thiatriazoline (118). UV spectroscopic properties of (117) (Amax 235, 290 and 342) and (118) (Amax 235, 290 and 345 nm) reveal a close structural similarity (63CB2519). A comparative NMR spectroscopic study of (117) and the A3-l,2,3,5-thiatriazo-line (119 R1 = H, R2 = Me) supports the description of (117) as a pyridinium salt (Scheme 9) (70CB1918). 

Dimethyl-3-formylselenophene was obtained by the Sommelet reaction on 2,5-dimethyl-3-chloromethylselenophene.60 2,5-Diformyl-selenophene has been prepared in two ways reaction of dimethyl-formamide with 2-lithio-5-formylselenophene (obtained from 2-formylselenophene and butyllithium) and hydrolysis of the nitrone from the reaction of p-nitrosodimethylaniline with the pyridinium salt obtained from 2,5-bischloromethylselenophene.76... 

Krohnke reactions. A halogen compound reacts with pyridine in ethanol to form a pyridinium salt (1), which is treated with p-nitroso-N,N-dimethylaniline and alkali to produce a nitrone (2), which on acid hydrolysis affords an aldehyde. 

The 1,4-conjugate addition of enamines to the 4-phosphorylated 1,2-dia-zabuta-1,3-diene (184) provides a route to substituted 1-aminopyrroles (185) which can be further converted into 1-aminopyrroles (186) by basic hydrolysis (Scheme 26). Moderate to good yields of 2,6-diphosphonylated-l,2-dihyd-ropyridines (187) have been obtained in a one-pot reaction from either 1,4-dihydropyridines or pyridinium salts (Scheme 27). ... 

---