User:Chem540f09grp9/Sandbox2 Taylor's Work

Free Energy Considerations

Table of A-Values

Substituent	A-Value	Substituent	A-Value	Substituent	A-Value
D	0.006	CH2Br	1.79	OSi(CH3)3	0.74
F	0.15	CH(CH3)2	2.15	OH	0.87
Cl	0.43	c-C6H11	2.15	OCH3	0.6
Br	0.38	C(CH3)3	>4	OCD3	0.56
I	0.43	Ph	3	OCH2CH3	0.9
CN	0.17	C2H	1.35	O-Ac	0.6
NC	0.21	CO2-	1.92	O-TFA	0.68
NCO	0.51	CO2CH3	1.27	OCHO	0.27
NCS	0.28	CO2Et	1.2	O-Ts	0.5
N=C=NR	1	CO2iPr	0.96	ONO2	0.59
CH3	1.7	COCl	1.25	NH2	1.6
CF3	2.1	COCH3	1.17	NHCH3	1
CH2CH3	1.75	SH	0.9	N(CH3)3	2.1
CH=CH2	1.35	SMe	0.7	NH3+	1.9
CCH	0.41	SPh	0.8	NO2	1.1
CH2tBu	2	S-	1.3	HgBr	~0
CH2OTs	1.75	SOPh	1.9	HgCl	0.3
		SO2Ph	2.5	Si(CH3)3	2.5

Applications

Predicting Reactivity

One of the original experiments performed by Winston and Holness6 was measuring the rate of oxidation in trans and cis substituted rings using a Chromium catalyst. The large tBu group used locks the conformation of each molecule placing it equatorial (cis compound shown).

Possible chair conformations of cis 4-tert-butyl-1-cyclohexanol

It was observed that the cis compound underwent oxidation at a much faster rate than the trans compound. The proposition was that the large hydroxyl group in the axial position was disfavored and formed the carbonyl more readily to relieve this strain. The trans compound had rates identical to those found in the monosubstituted cyclohexanol.

Chromium oxidation of cis 4-tertbutyl-1-cyclohexanol

Approximating Intramolecular Force Strength Using A-Values

Using the A-Values of the hydroxyl and isopropyl subunit, the energetic value of a favorable intramolecular hydrogen bond can be calculated.

Possible chair conformations and the favorable hydrogen bond available in the conformation where both hydroxyl substituents are equatorial

Limitations

A-Values are measured using a mono-substituted cyclohexane ring, and are an indication of only the sterics a particular substituent imparts on the molecule. This leads to a problem when there are possible stabilizing electronic factors in a different system. The carboxylic acid substituent shown below is axial in the ground state, despite a positive A-Value. From this observation, it is clear that there are other possible electronic interactions that stabilize the axial conformation.

Equilibrium representation of a chair flip of a Carboxylic Acid. The axial position is preferred due to favorable electronic factors, despite a steric bias favoring the equatorial position.