Transition state halides

Section 4 9 The potential energy diagrams for separate elementary steps can be merged into a diagram for the overall process The diagram for the reac tion of a secondary or tertiary alcohol with a hydrogen halide is charac terized by two intermediates and three transition states The reaction is classified as a ummolecular nucleophilic substitution, abbreviated as SnI... 

Dehydrohalogenation of alkyl halides (Sections 5 14-5 16) Strong bases cause a proton and a halide to be lost from adjacent carbons of an alkyl halide to yield an alkene Regioselectivity is in accord with the Zaitsev rule The order of halide reactivity is I > Br > Cl > F A concerted E2 reaction pathway is followed carbocations are not involved and rearrangements do not occur An anti coplanar arrangement of the proton being removed and the halide being lost characterizes the transition state... 

Carbon is partially bonded to both the incoming nucleophile and the departing halide at the transition state Progress is made toward the transition state as the nucleophile begins to share a pair of its electrons with carbon and the halide ion leaves taking with it the pair of electrons m its bond to carbon... 

The 8n2 mechanism is believed to describe most substitutions m which simple pri mary and secondary alkyl halides react with anionic nucleophiles All the examples cited in Table 8 1 proceed by the 8 2 mechanism (or a mechanism very much like 8 2— remember mechanisms can never be established with certainty but represent only our best present explanations of experimental observations) We 11 examine the 8 2 mecha nism particularly the structure of the transition state in more detail in 8ection 8 5 after hrst looking at some stereochemical studies carried out by Hughes and Ingold... 

Rate IS governed by stability of car bocation that is formed in loniza tion step Tertiary alkyl halides can react only by the SnI mechanism they never react by the Sn2 mecha nism (Section 8 9) Rate IS governed by steric effects (crowding in transition state) Methyl and primary alkyl halides can react only by the Sn2 mecha nism they never react by the SnI mechanism (Section 8 6)... 

FIGURE 9 5 (a) Curved arrow notation and (b) transition state for electrophilic addition of a hydrogen halide HXto an alkyne... 

Enby 6 is an example of a stereospecific elimination reaction of an alkyl halide in which the transition state requires die proton and bromide ion that are lost to be in an anti orientation with respect to each odier. The diastereomeric threo- and e/ytAra-l-bromo-1,2-diphenyl-propanes undergo )3-elimination to produce stereoisomeric products. Enby 7 is an example of a pyrolytic elimination requiring a syn orientation of die proton that is removed and the nitrogen atom of the amine oxide group. The elimination proceeds through a cyclic transition state in which the proton is transferred to die oxygen of die amine oxide group. 

We have previously seen (Scheme 2.9, enby 6), that the dehydrohalogenation of alkyl halides is a stereospecific reaction involving an anti orientation of the proton and the halide leaving group in the transition state. The elimination reaction is also moderately stereoselective (Scheme 2.10, enby 1) in the sense that the more stable of the two alkene isomers is formed preferentially. Both isomers are formed by anti elimination processes, but these processes involve stereochemically distinct hydrogens. Base-catalyzed elimination of 2-iodobutane affords three times as much -2-butene as Z-2-butene. 

In fee absence of fee solvation typical of protic solvents, fee relative nucleophilicity of anions changes. Hard nucleophiles increase in reactivity more than do soft nucleophiles. As a result, fee relative reactivity order changes. In methanol, for example, fee relative reactivity order is N3 > 1 > CN > Br > CP, whereas in DMSO fee order becomes CN > N3 > CP > Br > P. In mefeanol, fee reactivity order is dominated by solvent effects, and fee more weakly solvated N3 and P ions are fee most reactive nucleophiles. The iodide ion is large and very polarizable. The anionic charge on fee azide ion is dispersed by delocalization. When fee effect of solvation is diminished in DMSO, other factors become more important. These include fee strength of fee bond being formed, which would account for fee reversed order of fee halides in fee two series. There is also evidence fiiat S( 2 transition states are better solvated in protic dipolar solvents than in protic solvents. 

Among the cases in which this type of kinetics have been observed are the addition of hydrogen chloride to 2-methyl-1-butene, 2-methyl-2-butene, 1-mefliylcyclopentene, and cyclohexene. The addition of hydrogen bromide to cyclopentene also follows a third-order rate expression. The transition state associated with the third-order rate expression involves proton transfer to the alkene from one hydrogen halide molecule and capture of the halide ion from the second ... 

There is another useiiil way of depicting the ideas embodied in the variable transition state theory of elimination reactions. This is to construct a three-dimensional potential energy diagram. Suppose that we consider the case of an ethyl halide. The two stepwise reaction paths both require the formation of high-energy intermediates. The El mechanism requires formation of a carbocation whereas the Elcb mechanism proceeds via a caibanion intermediate. 

Soft electrophiles will prefer carbon, and it is found experimentally that most alkyl halides react to give C-alkylation. Because of the n character of the HOMO of the anion, there is a stereoelectronic preference for attack of the electrophile approximately perpendicular to the plane of the enolate. The frontier orbital is ip2, with electron density mainly at O and C-2. The tpi orbital is transformed into the C=0 bond. The transition state for an 8 2 alkylation of an enolate can be represented as below. 

Mixed halide additions are most satisfactorily interpreted as proceeding via a halonium complex (1), in which the less electronegative halogen approaches from the less hindered a-side. The energetic preference for a pm-planar transition state leading to the diaxial product (2) is sufliciently great that the... 

The Grignard reagent attacks the unsaturated ketones (3) and (6) from the relatively unhindered ot- or jS-side, respectively, perpendicular to the plane of the conjugated system. An analogous transition state (10) leading to axially substituted 1,6-addition products (11) from A -3-ketones (9) with methylmagnesium halide was suggested by Marshall. ... 

Elimination bimolecular (E2) mechanism (Section 5.15) Mechanism for elimination of alkyl halides characterized by a transition state in which the attacking base removes a proton at the same time that the bond to the halide leaving group is broken. 

AC is interpreted as the difference in heat capacities between the transition state and the reactants, and it may be a valuable mechanistic tool. Most reported ACp values are for reactions of neutral reactants to products, as in solvolysis reactions of neutral esters or aliphatic halides. " Because of the slight curvature seen in the Arrhenius plots, as exemplified by Fig. 6-2, the interpretation, and even the existence, of AC is a matter of debate. The subject is rather specialized, so we will not explore it deeply, but will outline methods for the estimation of ACp. 

---