Two heteroatoms in the 1,2-positions

The 2-position in imidazoles, thiazoles and oxazoles is electron deficient, and substituents in the 2-position (480) generally show the same reactivity as a- or y-substituents on pyridines. 2-Substituents in azoliums of this type, including 1,3-dithiolyliums, are highly activated. 

Substituents in the 4-position of these compounds are also a to a multiply bonded nitrogen atom, but because of bond fixation they are relatively little influenced by this nitrogen atom even when it is quatemized (481). This is similar to the situation for 3-substituents in isoquinolines, cf. Chapter 3.2. In general, substituents in the 4- and 5-positions of imidazoles, thiazoles and oxazoles show much the same reactivity of the same substituents on benzenoid compounds (but see Section 3.4.3.9.1). 

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Neutral azoles are readily C-lithiated by K-butyllithium provided they do not contain a free NH group (Table 6). Derivatives with two heteroatoms in the 1,3-orientation undergo lithiation preferentially at the 2-position other compounds are lithiated at the 5-position. Attempted metallation of isoxazoles usually causes ring opening via proton loss at the 3-or 5-position (Section 4.02.2.1.7.5) however, if both of these positions are substituted, normal lithiation occurs at the 4-position (Scheme 21). 

Neutral azoles are readily C-lithiated by n-butyllithium provided they do not contain a free NH group (Table 7). Derivatives with two heteroatoms in the 1,3-orientation undergo lithiation preferentially at the 2-position other compounds are lithiated at the 5-position. 

Removal of two electrons from the formal cyclic 87r-electron structures serves to produce potential Hiickel 4n + 2 aromatic systems. The loss of one electron to form a radical cation was referred to in Section 2.26.2.1, and removal of a second electron by electrochemical oxidation, leading to dicationic structures, has also been achieved for a wide range of unsaturated compounds with heteroatoms in the 1,4 positions (70ZC147, 73JA2375). The oxidations are discussed further in Section 2.26.3.1.5, where tabulated data are presented. An interesting feature is the stability of certain salts of the dications, some of which have been isolated. 

The appearance of crown forms in tetroxocane and other compounds with heteroatoms in the 1,3,5 and 7 positions probably results from two stabilizing effects (a) a slightly lower eclipsing barrier for the —O—CHg— versus the —CH2—CH2 fragment in the crown there are eight partially eclipsed bonds which would benefit from relief of torsional strain (b) distorted crowns, i.e. the chair-chair and twist-chair-chair may suffer from higher dipolar repulsions than does the crown. Unfortunately, there are no conformational energy calculations available on any of the heterocyclic systems. 

The reactivity of cyclic aminomethylphosphines is of special interest due to the presence of two or more heteroatoms capable of quartemization in a 1,3-position. Besides the ordinary oxidation of tricoordinated phosphorus, mutual transformations and rearrangements are typical. 

Structurally, the azole N-oxides can be divided into two distinct types. In the 1,2-type (Scheme 1, upper row) the oxygen-substituted nitrogen atom and the heteroatom contributing two electrons to the aromatic Jt-electron sextet of the azole are situated in a 1,2-position. In the 1,3-type these atoms are situated in a 1,3-position (Scheme 1, lower row). 

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