C Solution phase studies

The approach o f the behaviour o f our compounds in solution was carried out by NMR. Mainly ’^C gated *H-decoupled, at room temperature, was the technique employed to develop the study o f alkyl to oxygen bond. An indirect

methods based in the relationship between the three bond coupling constant and the torsion angle 'P(H-C-O-C), Karplus equation, was applied to study the conformation of the formates derivatives. The results have been displayed in Table 2.6.

Com pound ^Jl3a-0> O-C IH ^dl3C(=0)-lII

rMM 3' Y(H-C-O-C) V I (degrees) 2.10 3.9 225.5 61.0 2.11 3.2 223.2 43.5 2.12 4.6 223.5 4.6 2.13 3.2 223.4 43.8 2.14 3.2 223.4 43.2 2.15 4.3 223.3 0.6 2.16 4.6 223.4 0.0 2.17 3.5 223.4 41.3 2.18 2.7 224.5 2.76

*The uncertainty in Jjac-jnis ± 0.5 Hz while f o r Jnc-iH it is ± 0 . 2 Hz.

Experimental values fo r the three bond coupling constants ^Juc-ih thought the

ester bond and the one bond coupling constant ^Juc-ih measured at room

temperature. On the right, appeared the torsion angle W(H-C-O-C) fo r the energy minima conformations suggested by MMS.

Table 2.6

A range of formates 2.10-2.18 has been synthesised and their NMR spectra measured. The compounds suggested to have eclipsed conformations show a larger ^Joc-m than the compounds suggested to have staggered conformations, as expected from previous results. The eclipsed conformation can be assigned to those compounds showing three-bond coupling constants o f 4.3- 4.6 Hz and for compounds suggested to prefer staggered conformations, 2.7-3.4 Hz is the coupled constant measured. The range of coupling constants is smaller than that for methoxy compounds"^^ (around 3.5Hz).

It has been reported that the main factor affecting the value for the three bond coupling constant is the torsion angle. Using a procedure first suggested by Dorman, Bauer, and Roberts^^, it should be possible to link the measured ^Jbc-ih

in compounds calculated to have a single populated conformation, to the torsion angle Y(H-C-O-C) calculated for such compounds.

Thus for compound 2.15, the perfect stereotype of an eclipsed conformation, a coupling constant 4.32 Hz goes with a 0° torsion angle H-C-O-C. Compound 2.18 is calculated to have a 60° torsion angle and = 2.76 Hz. Compound 2.10 showed a coupling constant o f 3.9 Hz (see Figure 2.25), an average of two times ^Jôo” and ^Ji8o° whence we calculate the value of 6.18 Hz for the three bonds coupling constant for a 180° torsion angle Y(H-C-O-C) The introduction of these values in the expression for the general Karplus equation gave the empirical Karplus equation calculated for formates:

= 3.32

V — 0.8

V

2.06

^Compound 2.10 180

Coupling constant fo r compound 2.10. Formula employed to calculate the three bonds coupling constant fo r 180 \

Figure 2.25

Figure 2.26 shows the Karplus plot for formates (Equation 2.1) and for comparison Anderson’s Karplus plot"^^ for ethers, and with these, experimental values measured for acetates and formates.

The Karplus plot for formates is based on experimental values so matches well. Acetates values are slightly off the formate plot by at most 0.9 Hz, so extrapolation from such a Karplus plot to esters in general will have to be done carefiilly.

Such Karplus plots highlight the problem o f the smaller range of coupling constant values for esters compared with the ethers. The formate Karplus plot is

flat, with the coupling constant much less sensitive to the torsion angle than it is in the quite steep curve found for ethers. Another consequence o f this is that the difference between the 0° and 180° coupling constant values, i.e. for eclipsed and anti conformations o f formates, is also small, viz. less than 2 Hz.

Karplus curve for Ethers and Formates

10 I ' £ 6 Ù Torsional angle T(H-C-O-C) (degree) Karpins Equation for Ethers Karplus Equation for Eorniates • I'or mat es experimental values Acetates experimental values

Expansion of the Kaqilus curves for Ethers and Formates 8 7 N 6 w 5 X 4 Ù 3 2 1 0 r - --- ^ 6 - f? - 0 10 20 30 40 50 60 70 80 90 Torsional angle T(H-C-O-C) (degree) Karplus equation for Ethers - Karplus equation for Formates # Formates experimental values Acetates e>q)erimental values

Representation o f the Karplus ecpiation fo r ethers and form ates with the experimental values obtained fo r acetates and form ates.

2.3,3 Cis-trans equilibrium in the acvl-to-oxygen bond

With the gauche/Qcli^sed-anti equilibrium o f the alkyl-to-oxygen bond well-studied for acetates or formates, the second conformational objective is the study of the acyl-to-oxygen bond in formates.

Many authors have concentrated on reproducing empirical results by a,b calculations. Hartree-Fock, Correlated models (Moller-Plesset models), and Density Functional Models with large basis sets have been the preferred methods for groups active in the field^^’^"^.

NMR7^’80’^1’^^ has been the method o f choice for studying the acyl-to- oxygen bond equilibrium in solution. Typical information such as chemical shifts, ^Jc-H and ^Jc-h, and dynamic NMR changes have been exploited in the detection ad characterisation of the different populated conformations.

Not much information had been retrieved from the crystallographic database, since few formates have been found. Our approach therefore used mainly two methodologies. Firstly, Molecular Mechanics and ab initio (HF, DFT) calculations have been used to study the gas phase. Our aim was to show which conformation energy minima are likely to be populated according to various force fields, to obtain information about certain structural parameters (bond length and bond angles) and finally, to collect information about the electronic structure of the acyl-to-oxygen bond, previously suggested as an important factor in explaining the preference for the cis conformation in the equilibrium. Secondly,

the cis-trans equilibrium was studied in solution by NMR at various

temperatures, to establish the thermodynamic parameters.

2.3.3.a Solid state studies

As reported in section 2.3.2.a, only 19 formates have been found in the crystallographic database search. 18 of them showed a cis conformation with an average torsion angle 0 (R -0 -C = 0 ) equal to 2.1°, and one of them, SAJWAB^^, adopts a trans conformation (see Figure 2.26).

Other important information available from the crystal structure is the bond length, and this rigid parameter seems to suffer little distortion due to the lattice forces. The average bond length observed in the 18 c/v-formates is 1.186 Â for C = 0, and 1.328

A

cii o