Acyloxy groups reactivities

Rate constants and Arrhenius parameters for the reaction of Et3Si radicals with various carbonyl compounds are available. Some data are collected in Table 5.2 [49]. The ease of addition of EtsSi radicals was found to decrease in the order 1,4-benzoquinone > cyclic diaryl ketones, benzaldehyde, benzil, perfluoro propionic anhydride > benzophenone alkyl aryl ketone, alkyl aldehyde > oxalate > benzoate, trifluoroacetate, anhydride > cyclic dialkyl ketone > acyclic dialkyl ketone > formate > acetate [49,50]. This order of reactivity was rationalized in terms of bond energy differences, stabilization of the radical formed, polar effects, and steric factors. Thus, a phenyl or acyl group adjacent to the carbonyl will stabilize the radical adduct whereas a perfluoroalkyl or acyloxy group next to the carbonyl moiety will enhance the contribution given by the canonical structure with a charge separation to the transition state (Equation 5.24). 

Replacement of alkyl groups by substituents bearing nonbonding electrons renders the boron atom less electrophilic, and this, together with internal coordination from its own acyloxy groups, explains why the acyloxyboron intermediates become progressively less reactive towards protonolysis. 

Reactivity in this ring system is sufficient for facile hydrolysis (20°, 2 hr or 100°, 1 min) of the 2-, 4-, 6-, and 7-methoxypteridines in high yield and for easy substitution (75-90% yields) of the 7-methylthio group with methanolic hydrazine hydrate (65°, 15 min), dimethylamine (65°, 30 min), and ethanolic ammonia (125°, 6 hr). The 7-acyloxy intermediate in thionation of 7-oxopteridine with phosphorus pentasulfide is readily substituted (80°) to form pteridine-7-thione. The chloro group in 6-aryl-2,4-diamino-7-chloro-pteridine still reacts readily with hydrazine (100°, several minutes) in spite of the two deactivating amino substituents. 

Bimolecular reactions of aniline with /V-acyloxy-/V-alkoxyamides are model Sn2 processes in which reactivity is dictated by a transition state that resembles normal Sn2 processes at carbon. Electronic influences of substituents support a non-synchronous process which has strong charge separation at the transition state and which is subject to steric effects around the reactive centre, at the nucleophile but not on the leaving group. The sp3 character of nitrogen and disconnection between the amino group and the amide carbonyl renders these reactions analogous to the displacement of halides in a-haloketones. 

Like Af-alkoxy-Af-chloroamides, the S 2 reactivity of A-acyloxy-A-alkoxyamides is directly analogons to the 8 2 reactions of a-haloketones where the a-carbonyl groups are well known to enhance 8 2 reactivity Although there are no comparative rate data for reactions of amines or alkoxyamines, these arguments shonld apply to snbstimtion at the amide nitrogen in A-acyloxy-A-alkoxyamides. 

As it is well known, acyloxy, alkoxy, or phenoxy groups connected to sp2-hybridized carbon atoms in alkenes or aromatics are unreactive to nucleophilic substitution. However, after alkene ozonolysis such groups become attached to sp3-hybridized carbon atoms and become reactive. It was shown <1989TL1511> that such substitutions have to be carried out at 40 °C when they compete with thermolytic reactions of the ozonides, lowering the yields. However, if 2,3-dichloropropene and as- or /ra/rt-1,2,4-trichloro-2-butene are ozonized, one obtains stable ozonides 68a-70... 

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