Bondoc, Kristopher Jayson C.

15 March 2013
CH 48 B Instructor: Ronald Reyes

Real-Time Monitoring of an Esterification Reaction by Nuclear Magnetic Resonance Spectroscopy

Derived Data Tables

Table 1: NMR-monitoring for Methanol-TFA Esterification

H-alpha
time TFA H-alpha ester alcohol ln(H-alpha alcohol) ln(H-alpha ester)
30 100 30.25 9.07 2.204972264 3.409496184
50 100 34.5 3.61 1.283707772 3.540959324
55 100 34.85 3.18 1.156881197 3.551053137
60 100 35.56 2.53 0.928219303 3.571221411

red k-alcohol 0.0425

blue k-ester 0.0055
t1/2-alcohol 16.30934542
t1/2-ester 126.0267601

Table 2: NMR-monitoring for Ethanol-TFA Esterification

H-alpha
time TFA H-alpha ester alcohol ln(H-alpha alcohol) ln(H-alpha ester)
20 100 10.35 7.67 2.037316615 2.33698652
25 100 11.87 6.64 1.893111963 2.474014209
30 100 12.66 5.26 1.660131027 2.538447417
45 100 15.16 3.21 1.166270937 2.71866038
50 100 15.72 1.95 0.667829373 2.754933787
55 100 16.15 1.6 0.470003629 2.78192005

red k-alcohol 0.0448

blue k-ester 0.0122
t1/2-alcohol 15.47203528
t1/2-ester 56.81534267

Table 3: NMR-monitoring for Butanol-TFA Esterification

H-alpha
time TFA H-alpha ester alcohol ln(H-alpha alcohol) ln(H-alpha ester)
45 100 2.04 0.29 -1.237874356 0.712949808
55 100 1.93 0.27 -1.30933332 0.657520003
60 100 1.96 0.02 -3.912023005 0.672944473
75 100 2.02 0 #NUM! 0.703097511
80 100 2.01 0 #NUM! 0.698134722
85 100 2.1 0.08 -2.525728644 0.741937345

red k-alcohol 0.0177

blue k-ester 0.0009
t1/2-alcohol 39.16085766
t1/2-ester 770.163534
Table 4: NMR-monitoring for t-Butanol-TFA Esterification
 H-alpha
time TFA H-alpha ester alcohol ln(H-alpha alcohol) ln(H-alpha ester)
26 100 52.61 5.14 1.637053079 3.962906216
30 100 53.15 5.29 1.665818246 3.973118105
35 100 52.52 5.34 1.675225653 3.961194049
45 100 52.35 5.41 1.688249093 3.957951937
50 100 52.16 5.43 1.691939134 3.954315918
55 100 52.23 5.43 1.691939134 3.955657042
60 100 52.87 5.18 1.644805056 3.96783607

red k-alcohol 0.0006

blue k-ester 0.0002
t1/2-alcohol 1155.245301
t1/2-ester 3465.735903

Results and Discussions

In an esterification reaction, a carboxylic acid and an alcohol react together to form an ester. In general,
the esterification reaction proceed as follows:

R-OH + R’-COOH ---> R’-(COO)-R + water

alcohol + carboxylic acid --> ester + leaving group

Since the carboxylic acid TFA is present in excess, the rate law can be written as v = k[A], in which v = -
dA/dt. Integrating this will yield a linear equation, ln[A] = ln [A 0] – kt. This form of equation can now be
plotted so that the slope can be obtained. Also, knowing the value of k, one can arrive at the value of
the half-life, t1/2 = (ln 2)/k.

In this experiment, four different alcohols were mixed with excess TFA in order to see the changes in the
rates of a pseudo-first order reaction. For the first trial, methanol was used. The following plot was
obtained:

3.5
f(x) = 0.00552957816561087 x + 3.24861557851807
R² = 0.977585229103345
3

2.5
ln(H-alpha)

2 f(x) = − 0.0425361360986642 x + 3.46708176881072

R² = 0.995302412393247
1.5

0.5

0
25 30 35 40 45 50 55 60 65
Time (min)

This plot shows that the rate of reaction for the MeOH-TFA reaction that’s based on the consumption of
the alcohol reactant is k = 0.00425. On the other hand, the rate of reaction for MeOH-TFA reaction
that’s based on the production of ester is k = 0.0055. Ideally, the two rate values should be the same
because technically, the rate of consumption of the alcohol should be equal to the rate of the
appearance of the ester because it is ideal that the alcohol is converted fully to ester. However, since the
two experimental k values are not equal, it can be said that there might be side reactions for this
esterification process.

From Table 1, it can be seen that the amount of signal for the alpha hydrogen for ester is increasing as
time increases and the amount of signal for the alpha hydrogen for alcohol is decreasing as time
increases. These findings agree with the idea that as the reaction progresses, alcohol is consumed
(hence the signal goes down) and the ester is produced (hence the signal goes up).

In this aspect, it can be seen that H-NMR can monitor the rate of the reaction by monitoring the signals
of alpha hydrogen atoms for every species present. Basically, for this esterification reaction, since the
alcohol is consumed (TFA is virtually not changed because it is in excess), the proton signals will change.
For this case, the proton signals for the alpha hydrogen of the alcohol will go down because this alcohol
will lose its alpha hydrogen atoms when it forms the other end of the ester. Similarly, changes in the
proton signals for the ester will change. In this case, these signals will increase because ester molecules
are formed.

For the case of using the ethanol, the following plot was obtained:

3
f(x) = 0.0121922204628748 x + 2.14361879296435
2.5 R² = 0.963826820140659

2 f(x) = − 0.0447691183766759 x + 2.99461919655542

R² = 0.976243906426122
ln(H-alpha)

1.5

0.5

0
15 20 25 30 35 40 45 50 55 60
Time (min)

This plot shows that the rate of reaction for the EtOH-TFA reaction that’s based on the consumption of
the alcohol reactant is k = 0.0448. On the other hand, the rate of reaction for EtOH-TFA reaction that’s
based on the production of ester is k = 0.0122. Since the two experimental k values are not equal, it can
be said that there might be side reactions for this esterification process. Moreover, as compared to the
MeOH-TFA, EtOH-TFA reaction has improved reaction rates. The reactions occurred relatively faster.
This observation might be due to a more stable intermediate formed by the EtOH-TFA.

For the case of using butanol and t-butanol, the following plots were obtained, respectively:
 2 4.5
1 4
f(x)3.5
= − 0.000190754388691446 x + 3.97005662979885
f(x)0= 0.000944744202891489 x + 0.634781030178704 R² = 0.133541365658129
R² = 0.247590011531179 3
ln(H-alpha)

ln(H-alpha)
-1 40 45 50 55 60 65 70 75 80 85 90 2.5
f(x) = 0.0177334821651745 x − 2.6797253652986 2
-2 R² = 0.0337999310204272 1.5
f(x) = 0.000592939401063149 x + 1.64522209080155
-3 R² =1 0.115921749663218
0.5
-4 0
-5 20 25 30 35 40 45 50 55 60 65
Time (min) Time (min)

These plots show that the reactions weren’t able to produce substantial amount of yield as revealed by
their rate constants (see Table 3 and 4). This is because of the nature of the alcohol - they are bulky
enough and their molecular structures hinder the formation of the intermediate. For butanol, the
hydrocarbon chain is bulky as compared to methanol and ethanol. For t-butanol, methyl groups that
clumped around the alpha carbon hinder the formation of the a stable intermediate. And because
intermediates can’t be formed, in turn, the ester cannot be formed as well.

Conclusion

In this experiment, it was evident that H-NMR can be a monitoring instrument to see whether a reaction
happen. By utilizing the power of the H-NMR to detect changes in proton signals due to formation of
new bonds and new molecules by tracking the changes in particular signals at particular chemical shifts,
one can be able to get the rate constant for the reaction and this gives the idea on the amount of
products formed and reactants consumed per unit of time. Since there is also a C-NMR, the same
methodologies can be also utilized so that anyone can track a reaction which involves organic
molecules.

Sample Calculations

Rate constant
v = k[A] or -k[A] --> v = -dA/dt or dA/dt
Integrating this will yield a linear equation, ln[A] = ln [A 0] – kt or ln[A] = ln [A0] + kt

Half-life
t1/2 = ln(2)/k = ln(2)/0.0177 = 39.16 min

Reference
Organic Chemistry by John McMurry