Pyridine 1-oxide reactivity

Little is known about the chemistry of pyridylfuroxans, but reaction of the [l,2,5]oxadiazolo[3,4-Z>]pyridine oxides (126) and (127) with activated methylene synthons provides pyrido[2,3-6]pyrazine-1,4-dioxides (130) in moderate yields (Beirut reaction) (Table 4, Scheme 21) <80M407, 82AF10). The actual reactive species is presumed to be the bis(nitroso)pyridine isomer (128). Direct oxidation... 

The ozonolysis mixtures still required reductive treatment to obtain high yields of aldehyde. The reduction was apparently necessary to destroy the pyridine oxide-ozone intermediates which were postulated above. It was possible, however, to eliminate the reduction step if the more reactive formaldehyde was added to destroy the reactive intermediates. The results obtained by treatment of several aliquots of an ozonolysis reaction mixture are shown in Table II. 

Electrophilic nitration and bromination of pyridine iV-oxides can be controlled to give 4-substituted products by way of attack on the free A-oxide. ° Under conditions where the A-oxide is 0-protonated, substitution follows the typical pyridine/pyridinium reactivity pattern thus, in fuming sulfuric acid, bromination shows P-regioselectivity. Mercuration takes place at the a-position, however mercuric-catalysed sulfonation produces the 3-sulfonic acid. ... 

A number of aromatic hydrocarbons react with pyridine when oxidized either with iodine or anodically. N-Arylpyridinium ions arc formed and the reaction is called pyridination. The reactive species is... 

In fact, the presence of ZnBrj is crucial to stabilize the electrogenerated cobalt(I) in acetonitrile and allows its reaction with ArBr. Even though the oxidative addition rate constants of ArBr to Co are smaller than that obtained in ACN/ pyridine, the reactivity of Co is not affected [41]. 

In peptide syntheses, where partial racemization of the chiral a-carbon centers is a serious problem, the application of 1-hydroxy-1 H-benzotriazole ( HBT") and DCC has been very successful in increasing yields and decreasing racemization (W. Kdnig, 1970 G.C. Windridge, 1971 H.R. Bosshard, 1973), l-(Acyloxy)-lif-benzotriazoles or l-acyl-17f-benzo-triazole 3-oxides are formed as reactive intermediates. If carboxylic or phosphoric esters are to be formed from the acids and alcohols using DCC, 4-(pyrrolidin-l -yl)pyridine ( PPY A. Hassner, 1978 K.M. Patel, 1979) and HBT are efficient catalysts even with tert-alkyl, choles-teryl, aryl, and other unreactive alcohols as well as with highly bulky or labile acids. 

We shall describe a specific synthetic example for each protective group given above. Regiosdective proteaion is generally only possible if there are hydroxyl groups of different sterical hindrance (prim < sec < tert equatorial < axial). Acetylation has usually been effected with acetic anhydride. The acetylation of less reactive hydroxyl groups is catalyzed by DMAP (see p.l44f.). Acetates are stable toward oxidation with chromium trioxide in pyridine and have been used, for example, for protection of steroids (H.J.E. Loewenthal, 1959), carbohydrates (M.L. Wolfrom, 1963 J.M. Williams, 1967), and nucleosides (A.M. Micbelson, 1963). The most common deacetylation procedures are ammonolysis with NH in CH OH and methanolysis with KjCO, or sodium methoxide. 

The reactivity of the amino radical has not yet been investigated. Alkaline hypochlorite oxidation, known in the pyridine series to yield azo derivatives (155,156). and photolysis of N,N-dichloro derivatives, which may be obtained by action of sodium hypochlorite on amino derivatives in acidic medium (157). should provide interesting insight on this reactivitv. 

Reactive halogen compounds, alkyl haUdes, and activated alkenes give quaternary pyridinium salts, such as (12). Oxidation with peracids gives pyridine Akoxides, such as pyridine AJ-oxide itself [694-59-7] (13), which are useful for further synthetic transformations (11). 

The use of dimethyl sulfoxide-acetic anhydride as a reagent for the oxidation of unhindered steroidal alcohols does not appear to be as promising due to extensive formation of by-products. However, the reagent is sufficiently reactive to oxidize the hindered 11 j -hydroxyl group to the 11-ketone in moderate yield. The use of sulfur trioxide-pyridine complex in dimethyl sulfoxide has also been reported. The results parallel those using DCC-DMSO but reaction times are much shorter and the work-up is more facile since the separation of dicyclohexylurea is not necessary. Allylic alcohols can be oxidized by this procedure without significant side reactions. 

Reaction Constants for the Reactivity of Substituted Pybidines and Pyridine 1-Oxides... 

The jS-position of pyridine 1-oxide is much less reactive than either the a- or y-position. This is shown for the displacement of the chloro group in structures 39 and 40 the relative rates are indicated (jS = 1) at... 

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