Pyridine 1-oxides base-catalyzed

As mentioned already in CHEC-II(1996) <1996CHEC-II(8)411>, some tetrazolo[l,5- ]pyridines can react with their C(5)-C(6) and C(7)-C(8) double bonds as dienophiles in Diels-Alder reactions. A novel study again supported this recognition Goumont et al. described that 6,8-dinitrotetrazolo[l,5- ]pyridine 11 easily react with some 2,3-disub-stituted butadienes to give bis-cycloadducts 48 <2002T3249>. These products when treated with potassium /-butoxide undergo base catalyzed elimination of nitric acid followed by oxidation reaction to yield the fully aromatic tetracyclic compounds 49 (Scheme 14). 

Base-catalyzed addition of glycosyl oxides for anomeric O-activation has been extended meanwhile to trifluoroacetonitrile (see Scheme 9), to dichlor-oacetonitrile, to l-aryl-l,l-dichloroacetonitriles, and to ketene imines (46,51,52). Also 2-(glycosyloxy)-pyridine and -pyrimidine derivatives were readily prepared from the corresponding 2-halo precursors (78). However,... 

Base-catalyzed deprotonation of pjn idine 1-oxides should occur much more readily than in the pjrridines themselves and this prediction has been borne out by several workers. These compounds exhibit the same relative positional reactivity as do the pyridinium ions. For example, for 3-bromopyridine 1-oxide in 0.1 N NaOD-DjO the order is 2>6>4>>5, as would be expected on the basis of the net (it -t- a) electron densities at the various nuclear positions. For pyridine 1-oxide the relative rates of exchange in methanolic methoxide solutions at 50° are... 

While arylnitrile oxides dimerize in protic solvents and in pure pyridine (cf. 4.04.8.1.3.), they form bis(adducts) (191) and (192) via zwitterions (189) with pyridine in apolar solvents (Scheme 83) <89JHC757,90Gi>. Significantly, the cycloaddition of the nitrile oxide to pyridine to give (190) is not a concerted process. Heterocycles (191) undergo base catalyzed ring cleavage (Scheme 84). 

It has been pointed out (75TL213) that path A behavior might be more complex in some instances, and involve initial ylide formation followed by intramolecular proton abstraction (Scheme 202). The aryloxy quaternary salt (274), formed by reaction of pyridine 1-oxide with an arenediazonium salt, undergoes an interesting base-catalyzed rearrangement that is believed to take the course (path E) indicated (Scheme 203) (71JA3074). 

Cr3+ can also be integrated into the structures of layered double hydroxides. A mixed oxide, prepared by calcination of ZnCr-LDH-CCh, was used in combination with t-BuOOH for the ketonization of alkyl and of benzyl pyridines and for the oxidation of benzyl amines to give Schiff bases (67,68). In contrast to MgAl-LDHs, for example, these materials display hardly any basicity so that base-catalyzed side reactions such as aldol condensations are avoided. 

Rates of exchange with NaOMe/MeOH at 50°C of the 2-, 4-, and 6-positions of 3-chloropyridine N-oxide and of the 2-position of 3,5-dichlor-opyridine N-oxide, relative to the 2-position of pyridine N-oxide, were 1840, 0.37, 12.2, and 11,800, respectively. These showed that the normal carbanion mechanism applied and emphasized further the importance of inductive effects in base-catalyzed exchange. The activating effects of substituents (relative to a position in benzene, at 50°C) were calculated as 2-C1, 1800 4-C1, 9 2-N + 0, 3.8 x 109 4-N+0", 7.6 x 10s (69JOC1405). 

Rate Data for Base-Catalyzed Exchange of Pyridine N-Oxides under Standard Conditions"... 

Finally, rate coefficients for base-catalyzed exchange of pyridines under standard conditions (0.6 M MeOK in MeOD at 140°C) and for pyridine /V-oxides (0.1 M MeOK in MeOD at 50°C) are given, in terms of the log values, in Tables 9.2 and 9.3, respectively, along with Arrhenius data (74CHE1397). The wide variations in log A values are difficult to interpret, and similar variations occur with diazines (Chapter 10). 

Of the substituted pyridines, the halogenated derivatives have been the most intensively studied.144,145 Treatment of 3,5-dichloropyridine A-oxide at 74° with 0.1 A NaOD led to exchange in three positions of the molecule, whereas with 3-chloropyridine iV-oxide relative rates of exchange were position 2>6>4>5. In l-methyl-4-pyridone, 1,3,5-trimethyl-4-pyridone, and 3,5-dibromo-l-methyl-4-pyridone, deuteration in basic D20 at 100° gives 2- and 6-substitution.146 With the poly-azaindenes (45) -(47) already discussed in the acid exchange section,141 base-catalyzed deuteration occurs in the positions indicated 45 3 and 5 46 2, 3, 5, and 6 and 47 2, 5, 6, and 7. In other isolated heterocycles some selectivity is observed in base-catalyzed exchange, e.g., certain imidazoles,147 thiazole,148 isothiazole,148 benzothiazole,149 and benzoxazole.149... 

There are a few tetra- and pentacyclic analogues. Benzo analogues of 245 were prepared from pyridine-2,3-dicarboxylic acid anhydride and a tetralin derivative under conditions of the Friedel-Crafts reaction (85JCR(S)338). Pentacyclic compounds 258 (R = H or Me) were prepared from the bis adduct of anthranilic (or IV-methylanthranilic) acid to 1,4-benzoquinone, followed by cyclization in concentrated sulfuric acid (55JCS4440 66CB1991). 6-Methylquinoline-5,8-dione dimerized in the presence of ethanolic N-methyl-cyclohexylamine to 259 in very low yield and the dimerization is interpreted as two base-catalyzed addition reactions and three oxidation steps (71JCS(C)1253). 

Osmium-tetroxide-catalyzed dihydroxylation of sterically hindered olefins proceeds more efficiently with trimethylamine AA-oxide in the presence of pyridine. The base appears to catalyze not only formation of the osmate ester, but also its hydrolysis. 

There are two different ways of making 2-ethoxyoctane from 2-octanol using the Williamson ether synthesis. When pure (—)-2-octanol of specific rotation —8.24° is treated with sodium metal and then ethyl iodide, the product is 2-ethoxyoc-tane with a specific rotation of —15.6°. When pure (—)-2-octanol is treated with tosyl chloride and pyridine and then with sodium ethoxide, the product is also 2-ethoxyoctane. Predict the rotation of the 2-ethoxyoctane made using the tosy-lation/sodium ethoxide procedure, and propose a detailed mechanism to support your predictioa 14-43 Under base-catalyzed conditions, several molecules of propylene oxide can react to give short polymers. Propose a mechanism for the base-catalyzed formation of the following trimer. 

Whilst acetylenic alcohols can be employed directly in Cadiot-Chodkiewicz reactions [9], protection of the alcohol (usefully as the Thp ether) is necessary for Castro coupling [14]. A variation based upon these two processes involves coupling of terminal alkynes with 3-bromopropynol (10) in the presence of pyridine [15]. For primary alcohol products, oxidation to the aldehyde with nickel peroxide followed by base-catalyzed decarbonylation generates the new terminal acetylene e.g. Fig. 1.10. 

As foretold in the introduction, ring formation via attack on a double bond in the endo-trig mode is not well exemplified. The palladium(II) catalyzed oxidative cyclization of o-aminostyrenes to indoles has been described (78JA5800). The treatment of o-methyl-selenocinnamates with bromine in pyridine gives excellent yields of benzoselenophene-2-carboxylates (Scheme 10a) (77BSF157). The base promoted conversion of dienoic thioamides to 2-aminothiophenes is another synthetically useful example of this type (Scheme 10b) (73RTC1331). 

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