Advanced organic chemistry Lab – Alkylation of Sodium Saccharin

Prelab work:

1. Aim: This Experiment aims to determine the nucleophilic attack of Sodium Saccharin (N
and O) which would be alkylated by iodoethane in DMF (N, N-Dimethylformamide) aprotic
solvent. There are 2 possible products of which would form from this reaction o-ethyl
saccharine (Kinetically favoured product) and N-ethyl saccharine (thermodynamically
favoured production) this experiment aims to determine the major product.

2.

3. Mass of Sodium Saccharine and Volume of Iodoethane with working out below

Amount of sodium saccharine used: 2.052grams

Working out: 10mmol = .01mol; formula = nm (number of mole) = Mass/Molar mass.
Mass = nM (number of mole) * Molar mass.
Mass = nM(0.01mol) * Molar mass (205.2g/mol)
Mass = 2.052g

Volume of Iodoethane used: 0.8mL

Working out: 10mmol = .01mol; Formula = nM (number of mol) = Mass/Molar mass.
Density = Mass/Volume.
Mass = nM (number of mole) * Molar mass.
Mass = nM (.01) * Molar mass (156.0)
Mass = 1.56g
Density = mass / volume; Volume = mass/density
Volume = mass (1.56g)/(1.950g/mL)
Volume = 0.8mL

4A. N is more thermodynamically favoured nucleophile.

Bond Enthalpy = E(Broken) – E(Formed)

N – Ethyl saccharine Bond Enthalpy:

Bond Enthalpy = E (No bonds broken) – E (N-C: 73)
Bond Enthalpy = 0 - 73
Bond Enthalpy = -73kcal/mol

O-Ethyl Saccharine Bond Enthalpy:

Bond Enthalpy = E (C=o: 179) – E (N=C: 147 + O-C: 86)
Bond Enthalpy = 179 – (147 + 86)
Bond Enthalpy = -54kcal/mol

N-Ethyl saccharin is a more stable and preferred product because its bond energy is -
73kcal/mol, which is lower than that of O-Ethyl Saccharin. As a result, N has a higher
nucleophilicity.

4B. Reaction mechanism

4C.

Determining ratio.

On the chemical shift, you'd start by identifying the important molecule. As in the 1H NMR
60deg 10 minutes experiment. Chemical shifts 3.8 (N-ethyl) and 4.5 (benzene) are important
(O-ethyl). The multiplicity is a quartet, indicating that it comes after ch3 (n+1). Finally, the
ratio is calculated by taking the integration and dividing it by the lowest integration, with
the lowest integration equalling 1 and the highest integration equalling the product
produced when the lowest integration equals 1. (Dr. Chris Schaller, 2020).
1:4.18 means that for 1 (O-ethyl) molecule produced there is 4.18 (N-ethyl) produced.

Melting point profile.

The melting point profile is used to quickly determine a product's purity. The melting points
of N-ethyl (95Co) and O-ethyl (211Co) (Zubrick, J. W, 1997) are dramatically different, and if
the final product melts at 95 +/- 3-5Co, it is not O-ethyl, which has a melting point of 211Co,
and the end product must be N-ethyl. After that, the final product is refined using IR and 1H
NMR.

4D.

IR trends

Title: JJ sodium saccharin

- The broad peaks at 3361.59 and 3487.63 indicates an OH and NH; which is a
tautomerisation of sodium saccharin. OH (3550 – 3200 broad) and NH (3350 – 3310
broad).

Title: 60Co @ 10mins

- There is a peak at 1686 showing a development of an amide bond (1700 – 1650)
which wasn’t presented in the IR of Sodium saccharin which stipulate a development
of N-ethyl product. However, there is a distinctive 3376.84 broad peak suggesting
residual OH molecules (3550 – 3200). Continuing, this displays the reaction is still
happening since higher temperatures are necessary for complete N-ethyl product to
be favoured.

Title: 60Co @ 30mins

- The 3376.85 is gone indicating there is no more residual OH molecules in the
product. Meantime, there is a new peak development at 2981.70 suggesting
formation of an aliphatic carbon (3100-3000), meaning there is a complete product
formation. There is an amide peak persisting, formation of peak 1196.26 indicates
formation of O-C ether (1200-1000). This could mean there is a mixture of N-ethyl
and O-ethyl products.

80Co@ 10mins and 80Co@ 30mins

- The peaks remain the same with a mixture of products O-ethyl saccharin and N-ethyl
saccharin with no new clear product development.

1H NMR 60Co @ 10mins

 - For every 1 O-ethyl product there is 4.18 N-ethyl formed. This is a significant high
amount considering that O-ethyl is kinetically favoured product.

1H NMR 60Co @ 30mins

- For every 1 O-ethyl product formed there is 4.48 N-ethyl formed. There isn’t
significant increase in product but as the time increases N-ethyl can be expected to
appreciate.

1H NMR 80Co @ 10mins

- There is now a ratio of 1:4.60, this displays a notable increment of N-product yield as
it is considerably higher in contrast to the product yield at 60Co @ 30mins and 60Co
@ 10mins. This maybe because N-ethyl is thermodynamically favoured product.

1H NMR 80Co @ 30mins

- The ratio is 1:5.37, There is a notable rise of N-ethyl product yield. This only shows as
the reaction temperature and time increases so will the yield of N-ethyl product.

Conditions of series of Yield of N- Yield of O-

reactions compounds Ethyl ethyl
60deg 10mins 1 4.18 1
60deg 30mins 2 4.48 1
80deg 10mins 3 4.6 1
80deg 30mins 4 5.37 1
Table 1: Reaction conditions of Sodium saccharin and its ratio of product yield.

Ratio of N and O product

6

5 f(x) = 0.369 x + 3.735

R² = 0.883617249099581
N-ethyl prodcut yield

0
0.5 1 1.5 2 2.5 3 3.5 4 4.5
Series of Compounds all equal 1

Graph 1: A linear relationship of ratio of products and series of compound all equal the
product yield of O-ethyl of 1.

%Yield
The experimental yield is not given to calculate a percent yield.
However, theoretical percent yield can be determined for each condition.

Conclusion:
Finally, a mixture of O-ethyl saccharine and N-ethyl saccharine is obtained as the final
product. However, compared to O-ethyl saccharine, N-ethyl saccharine will be the most
created. This is owing to the thermodynamic advantage of the N-ethyl product, which
requires less energy to produce and is more stable at lower energies. The product can be
identified by conducting a melting point test because there was no experimental melting
point. It can only be assumed that N-ethyl will have larger yield despite the fact that both
products would be created.

References:

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