R Population of

transisomer (%) AG (kcal/mol) (kcal/mol) -CH] 0.9" 2.15’ ' 9.9 -CH2CH3 V 1.67'' 10.4 -CH(CH] ) 2 3" 1 36" 10.4 -C(CH])3 24" 0,47" 8.7 -C(CH3)3 14" 0.57*' 9.0 C6H5 20^ 0.43*' 8.5 -2,6-(CH3)2-C6H5 3" 1.14*' 10.6 1

a- Soh enl (1:1, v: v) DMF: Acetone, b- Solvent (3:1, v:v) Acetaldehyde:Acetone.

Populations, free energy differences and energy harriers for formates by NMR. Table 2.5

The cv.v-conformation is always preferred, however, the population o f the Z/w/.s-isomer increases with the size o f the alkyl substituent. This clearly shows steric repulsion between the R group and the carbonyl, favouring the trans- conformation where R now interacts with the small formyl hydrogen atom (see Figure 2.18).

_ 0

0

II

R

Intetxictions R group-carhonyl responsible o f the increasing in the population conformation o f the t r a n s - f w w c r with the size o f group R.

There is an interesting solvent effect on the equilibrium. In tert-hutyX formate, increasing the polarity of the solvent increases the population of the more polar /ra«5-conformation, in agreement with earlier I.R. studies^^.

Finally it has been suggested that there is an important cross-conjugation effect through the oxygen, between the formate and the phenyl groupé % in phenyl formate. This effect disappears with the introduction of two methyl groups in positions 2 and 6 of the phenyl ring due to the different orientation of the ring.

2.3.1 Results and discussion

The analysis o f formates has been divided into two main parts:

1- The alkyl-to-oxvgen bond. In section 2.3.2, we study the gawc/ze/eclipsed- anti equilibrium. As with the acetates, we report conclusions either for the solid state (by CCDB search), for the gas phase (using MM3 and ab initio calculations) and for solution (by NMR).

2- The acvl-to-oxygen bond. In section 2.3.3, we investigate the cis-trans equilibrium. Little information was found in the CCDB search (since formate is not a popular protecting group), but MM3 and ah initio calculations, and solution studies by NMR provide interesting data.

2.3.2 Gauche/eclivsed-anti equilibrium in the alkvl-to-oxygen bond

2.3.2.a Solid state studies

Recourse to CCDB for formates did not produced the same extensive information as in acetates. Only 19 torsion angles were retrieved in a general search. With the same restrictions used for acetates (secondary carbons, cyclic organic compounds with at least 5 or 6 membered rings, including compounds with oxygen atoms in the skeleton o f the ring), examples decreased to ten. This is too small a sample for a proper statistical analysis and a confident exclusion of

lattice force effects on the averages observed but, some information can be reported. The ten torsion angles were divided in two groups;

1-Compounds with either equatorial or axial formate, and no adjacent equatorial substituents. Five compounds are in this group and the average torsion angle 'F(H-C-0-C(=0)) is 34,8° ( Figure 2.19). From the data reported for acetates, it is not surprising to find staggered conformations.

CHO Ring

Ring

R-H, Substituent

Figure 2.19

2-Compounds with an equatorial substituent on one side only o f the formate, which is either equatorial or axial. Five examples were found and the average torsion angle was 25.0° (see Figure 2.20). Since the interactions of formate with the substituent side and the hydrogen side are different, orientation towards the latter and staggered conformations are expected.

CHO

Ring Ring

R - H or substituent

Figure 2.20

One example of acyclic compounds was found. The compound with the CCDB Refcode C E L F rf^ shows a torsion angle 'F(H-C-0-C(=0)) o f 0.9° (see Figure 2.21). This value might seem surprising for an acyclic compound, but

examination o f the overall structure showed the arrangement in the space o f the atoms fits the stereotype o f eclipsed conformations reported by Anderson"^^. The central framework o f the structure shows an anti,anti arrangement, and the position o f the substituents on either side o f the formate group, see Figure 2.21, leads to an eclipsed torsion angle

H 2 D 04 06 D N2 03 05: O I D FI C l D NID. H I D 02 C2 02 D HI % % N1 Cl C2 D F I D o i 05 0 3 D 06 0 4 D H2 CHO NO CH CH NO NO CHO

Crystal structure o f the compound from CCDB^. (Reproduced by PLUTO program)

2.3.2.b Gas phase studies

The alkyl-to-oxygen bond has been widely studied in acetates, and in formates, the results are not expected to be very different.

The analogous model compounds have been chosen as for the acetates since this set covers a wide range o f conformational possibilities from eclipsed to staggered to anti, and they are mainly cyclohexane derivatives.

The MM3 program was used since specific parameterisation for formates is included in the force field and examples o f application to simple formates have been reported by Allinger^^. The dihedral driver was used to seek energy minima and to obtain the energy barrier to the interconversion of eclipsed and anti conformations. Our attention is concentrated here, on the torsion angle Y(H-C-0- C(=0)). The results and the nomenclature in formates are shown in Figure 2.22.

Compounds fitted into three groups depending on the torsion angle 'F(H- C-0-C(=0)):

1- Compounds 2.12, 2.15 and 2.16 Eclipsed torsion angles are observed for this group. They have an anti-anti arrangement o f the central framework, A-C-C(OR)-C-B, with substituents A and B, actually methyl groups, big enough to turn the torsion angle close to perfect eclipsing.

2- Compounds 2.11, 2.13, 2.14 and 2.17. These are expected to show staggered conformations with torsion angles around 40-45% as a result o f different interactions of the formate group with hydrogen atoms on either side.

3- The final group comprises compounds 2.10 and 2.18, expected to have perfect staggered conformations with 60° and 180° torsion angles.

Y (H ^ - 0 -C ( = 0 ))