At oxygen

The nucleophilic reacbvity of the C-5 oxygen is well documented however, no quantitative data are available. A-2-Thiazoline-5-ones (212) react at oxygen with acetyl chloride or acetic anhydride (447. 452). benzoyl chloride (447). methyl or phenyl isocyanate (467). carbamoyl chloride (453, 467). or phosphorus derivatives (468, 428) in the presence of bases to give 213, 214, 215. or 216 (Scheme 109). Strong bases such as... 

Incorporating an oxygen atom into a three membered nng requires its bond angle to be seriously distorted from the normal tetrahedral value In ethylene oxide for exam pie the bond angle at oxygen is 61 5°... 

Their polar carbon-oxygen bonds and the presence of unshared electron pairs at oxygen contribute to the ability of ethers to form Lewis acid Lewis base complexes with metal ions... 

Protonation of this anion can occur either at the a carbon or at oxygen Protonation of the a carbon simply returns the anion to the starting aldehyde or ketone Protonation of oxygen as shown m step 2 of Figure 18 3 produces the enol... 

Electrophilic attack at oxygen is rare, alkylation normally occurring at nitrogen, but the 6-hydroxypyrido[2,3- f]pyrimidine (75) is methylated on oxygen in low yield (70CB1250), whilst the 6-cyano derivative (76) undergoes O-tosylation to (77) (75JHC311). 

Acylation of -ones and -diones appears to occur mainly at oxygen, but in the fused pyridazino[4,5-6]quinoline (312) the O-acyl derivative (313) was formed via an iV,0-diacyl derivative (72BSF1588). Reduced derivatives, however, are acylated at nitrogen. 

Hydroxythiophene also exists mainly in ketonic forms. Electrophilic reagents react either at oxygen or at C-5. O-Methyl and O-acetyl derivatives are obtained in alkaline solution, probably through intermediacy of the anion. In acidic solution, coupling with benzenediazonium ion, a characteristic phenolic reaction, is found to take place (Scheme 72). 

The mesomeric anion (157 Scheme 10) reacts readily with electrophilic reagents such as alkyl or acyl halides at N-2, C-4 and the exocyclic oxygen atom. The percentages of the different products formed are controlled by the HSAB principle. The acylium ion (hard) attacks preferentially at oxygen (hard), whilst the softer alkylating agents attack the nitrogen atom. 

In this case, the ti-MOs resemble those of butadiene. Relative to the butadiene orbitals, however, the acrolein orbitals lie somewhat lower in energy because of the effect of the more electronegative oxygen atom. This factor also increases the electron density at oxygen relative to carbon. 

A. J. Kirby, The Anomeric Effect and Related Stereoelectronic Effects at Oxygen, Springer-Verlag, New %rk, 1983. 

There is another mechanism for equilibration of the cation pairs A, Aj and B, Bj, namely, inversion at oxygen. However, the observed barrier represents at least the minimum for the C=0 rotational barrier and therefore demonstrates that the C-O bond has double-bond character. 

The alkylation reactions of enolate anions of both ketones and esters have been extensively utilized in synthesis. Both very stable enolates, such as those derived from (i-ketoesters, / -diketones, and malonate esters, as well as less stable enolates of monofunctional ketones, esters, nitriles, etc., are reactive. Many aspects of the relationships between reactivity, stereochemistry, and mechanism have been clarified. A starting point for the discussion of these reactions is the structure of the enolates. Because of the delocalized nature of enolates, an electrophile can attack either at oxygen or at carbon. 

Ruonnated carboxylic anhydrides and acyl halides as common acylating reagents to convert amines to amides and to acy late suitable heterocyclic nitiogen atoms have already been described in the first edition [10] Like in the acylation at oxygen, much synthetic activity was concentrated m the past few years on the denvatization of biomolecules by fluoroacylation reactions, that is, tnfluoroacetylation of amino sugars,... 

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