12 Heterocyclic Chemistry are considerably more strained than cyclohexane.One might think that increased fexibility would be beneficial but in these cases although puckering reduces angle strain,many pairs of eclipsed H atoms are alsc created in adjacent CH,groups.These may further interact across the ring,causing compression if they encroach within the normal van der Waals'radii of the atoms involved (this additional strain is called strain).However,as more atoms are introduced and the ring size expands,these problems are reduced,and the molecules even- tually become essentially strain free. These considerations may also apply to fully reduced heterocycles where or more Nor atoms replace ring carbons,but it must noted that a change in element also means a change in electronegativi ty and a change of bond length.Thus in hetero analogues of cyclohexa- ne,for example,as C-N and C-O bonds are shorter than C-C bonds, there are ncre ased 1,3-(flagpole)interactio ns in the chair forms,ren dering axial substitution even less favourable. Furthermore,for multiple replacements,lone pair electrons on the heteroatoms may interact unfavourably and limit certain conformations. In fact,interactions between one pairs are the main reasc barriers to rotation,particularly in N-N bonds compared to C-C single bonds. Anomeric Effect When a ring system contains an O-CH-Y unit,where Y is an elec- tronegative group (halogen.OH.OR'.OCOR'.SR'OR'or NR'R") one ofth oxygen lone nay adopt a trans antiperiplanar relation ship with respect to the C-Y bond (Box 1.14).In this orientation the orbital containing the lone pair overlaps with the antibonding o orbital (*)of the C-Y bond and 'mixes in'to form a pseudo n-bond.This is called the anomeric effect.When Y is For Cl(strongly electronegative) Box 1.14 Anomeric Effect 12 Heterocyclic Chemistry are considerably more strained than cyclohexane. One might think that increased flexibility would be beneficial, but in these cases, although puckering reduces angle strain, many pairs of eclipsed H atoms are also created in adjacent CH, groups. These may further interact across the ring, causing compression if they encroach within the normal van der Waals’ radii of the atoms involved (this additional strain is called ‘transannular strain’). However, as more atoms are introduced and the ring size expands, these problems are reduced, and the molecules even￾tually become essentially strain free. These considerations may also apply to fully reduced heterocycles, where one or more N or 0 atoms replace ring carbons, but it must be noted that a change in element also means a change in electronegativi￾ty and a change of bond length. Thus in hetero analogues of cyclohexa￾ne, for example, as C-N and C-0 bonds are shorter than C-C bonds, there are increased 1,3- (flagpole) interactions in the chair forms, ren￾dering axial substitution even less favourable. Furthermore, for multiple replacements, lone pair electrons on the heteroatoms may interact unfavourably and limit certain conformations. In fact, interactions between lone pairs are the main reason for increased barriers to rotation, particularly in N-N bonds compared to C-C single bonds. Anomeric Effect When a ring system contains an O-CH-Y unit, where Y is an elec￾tronegative group (halogen, OH, OR’, OCOR’, SR’, OR’ or NR’R’’), one of the oxygen lone pairs may adopt a trans antiperiplanar relation￾ship with respect to the C-Y bond (Box 1.14). In this orientation the orbital containing the lone pair overlaps with the antibonding o orbital (o*) of the C-Y bond and ‘mixes in’ to form a pseudo n-bond. This is called the anomeric effect. When Y is F or Cl (strongly electronegative)