Cs-X bonds

Conceptually the most simple syntheses of complex molecules involve the joining of structural units in which all functional groups and all asymmetric centres are preformed. This technique can usually only be applied to compounds in which these units are connected by —C—X— bonds rather than C—C. It is illustrated here by the standard syntheses of oligonucleotides, peptides, and polydentate macrocyclic ligands. 

Aryl halides are less reactive than alkyl halides m reactions m which C—X bond breaking is rate determining especially m nucleophilic sub stitution reactions... 

The group moment always includes the C—X bond. When the group is attached to an aromatic system, the moment contains the contributions through resonance of those polar structures postulated as arising through charge shifts around the ring. 

Table 5 Comparison of C—X Bond Lengths for Parent Heterocycles and their Dibenzo Derivatives...

Cycloadditions including a cyclic S atom and an exocyclic C=X bond are known in the dithiazole series, e.g. as shown in Scheme 44. 

Polarographic studies on haloisoxazoles in anhydrous DMF containing R4N" were performed and the magnitude of the half-wave potentials were recorded. Cleavage of the C—X bond was faster in phenylhaloisoxazoles than in halobenzenes. Substitution patterns affected the reduction (79ZOB1322). 

For the antiaromatic three-membered heterocycles, experimental data are available only for thiirenes (and there is some doubt about the true antiaromaticity of thiirenes). Bond lengths have been calculated, however, for these antiaromatic 47r-systems (80PAC1623). In comparison with the corresponding saturated heterocycles, the C—X bond lengths are increased by 0.05 to 0.17 A and the C—C bond length is decreased by 0.2 A. 

Synthesis of heterocycles by forming C—X bonds by radical reactions is not a generally applicable method, and seems not to be useful for making small rings. However, the attack of thiol radicals on double bonds can be a practical synthetic route, such as in the conversion of 1-hexene-7-thiol to thiepane (Section 5.17.3.3.1). 

The anomeric effect is also present in acyclic systems and stabilizes conformations that allow antiperiplanar (ap) alignment of the C—X bond with a lone-pair orbital of the heteroatom. Anomeric effects are prominent in determining the conformation of acetals and a-alkoxyamines, as well as a-haloethers. MO calculations (4-3IG) have found 4kcal/mol as the difference between the two conformations shown below for methoxy-methyl chloride. ... 

These effects are attributed to differences in the c-donor character of the C—C bonds as a result of substitution. Electron-attracting groups diminish the donor capacity and promote syn addition. An alternative explanation invokes a direct electrostatic effect arising from the C-X bond dipole. 

I > Br > Cl > F. In nucleophilic aromatic substitution, the formation of the addition intermediate is usually the rate-determining step so the ease of C—X bond breaking does not affeet the rate. When this is the ease, the order of reactivity is often F > Cl > Br > I. This order is the result of the polar effeet of the halogen. The stronger bond dipoles assoeiated with the more eleetronegative halogens favor the addition step and thus inerease the overall rate of reaetion. 

Fonnation of C-X bonds is not normally a problem but the Grignaid route can occasionally be useful when normal halogen exchange fuls. Thus iodination of Me3(XH2CI cannot be achieved by reaction with Nal or similar reagents but direct iodinadon of the conesponding Grignaid effects a smooth conversion ... 

Synthetieally, the most important reaetions of this type are the eleavage of the =C—X bond and the formation of a new =C—H bond. 

Compounds that have the same number of carbon atoms can be compared by adding the number of C-O, C-N, and C-X bonds in each and then subtracting the number of C—H bonds. The larger the resultant value, the higher the oxidation level. 

Alkyl halides contain a halogen bonded to a saturated, sp3-hybridized carbon atom. The C-X bond is polar, and alkyl halides can therefore behave as electrophiles. 

Allylic and benzylic C—X bonds are about 50 kj/mol (12 kcal/mol) weaker than the corresponding saturated bonds and are therefore more easily broken. 

E1 Reaction C-X bond breaks first to give a carbocation intermediate, followed by base removal of a proton to yield the alkene. 

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