Experiment 5 Multistep Synthesis

Brittany Finger
Organic Chemistry Lab 1 SCH 211-02
December 5, 2018
I. ABSTRACT:

In this multistep reaction there are three reactions to be performed. In this experiment the
objectives were to synthesize cis-Norbornene-5,6-endo-anhydride by a Diels Alder reaction; cis-
Norbornene-5, 6-endo-dicarboxylic acid by a Nucleophilic Acyl Substitution; cis-Norbornene-5,
6-endodimethylester by Fischer Esterification. The products from each of the reactions were
analyzed by IR and MPR, the final product was also analyzed by NMR. The % yield for each
product of the multistep synthesis is 49.8% cis-Norbornene-5,6-endo-anhydride, 81.4% cis-
Norbornene-5, 6-endo-dicarboxylic, 63.6% 6-endodimethylester and the overall % yield is
25.8%.

Scheme 1. Diels Alder Reaction

Scheme 2. Nucleophilic Acyl Substitution

Scheme 3. Fischer Esterification

II. INTRODUCTION:

In this multistep synthesis there are three major reactions. There is the Diels Alder, Nucleophilic
Acyl Substitution, and Fischer Esterification. In multistep synthesis it takes many reactions to
achieve the desired product. Another important aspect are the yields for the reactions and in each
step you will lose some of your product. One of the biggest challenges is the yield of the final
produce, because not every reaction forms one product and that limits the yield. Purity is very
crucial too, because it is important for the product to be of high purity. But attempts in
purification usually result in loss of product. The product can affect the overall yield and that is
why yield and purity are usually in opposition of each other in regards to deciding when to
purify. Most of the time each step is not purified and the “crude” product is used. In addition,
purifications should be performed through all parts of the synthesis in order to obtain a final pure
product. Therefore, reactions that take a series of individual reactions are greatly valued.

The first part of the reaction was named after Diels and Alder and he received the Nobel prize in
1950 for this reaction. This reaction is a way to form C-C bonds and create a cyclohexane type
molecule and the starting materials for this experiment are alkene and diene. For Diels Alder
reactions it is important to be stereospecific and only one product is produced. The formation for
a product of this type of reaction is usually a cyclohexene ring in high yield and the reactants are
usually achiral and acyclic. The reaction is always done is one step and it always requires two
different functional groups, and they are almost always alkenes and alkynes. The reactions can
be done intermolecularly and intramolecularly. Also the diene in the reaction always has to be
cis, it cannot be trans.

Scheme 4: Diels Alder ex.

A Nucleophilic Acyl Substitution involves nucleophiles and acyl compounds. In this reaction the
nucleophile becomes the new acyl and that is why it is called a Nucleophilic Acyl Substitution.3
For example in carboxylic acid derivatives, the acyl group can be the leaving group.3 Notice how
the nucleophile becomes the new acyl group in the example. The tetrahedral intermediate can
then eject the leaving group. 1 This reaction occurs in a two step process.

Scheme 5: Nucleophilic Acyl Substitution ex.

The last part if the reaction is the Fischer esterification, it involves the reflux of a carboxylic acid
and an alcohol when there is a strong acid catalyst. It is an equilibrium reaction and product
formation happens in the presence of excess alcohol and acid depending on the reaction. The
equilibrium is influenced because of the removing of a product from the reaction mixture and the
excess of a reactant.4 In this reaction there was excess methanol that produced an ester formation.

Scheme 6: Fischer Esterification ex.

III. RESULTS & DISCUSSION:

Figure 1: IR of Endo-Anhydride

Table.1 IR of Endo-Anhydride
Range Bond
3000-2850 C-H
1710-1665 C=O
1500-1400 C-C (ring)
1335-1250 C-N

According to these peaks the product from the Diels Alder reaction is confirmed. The peaks
correlate with the structure of the product.

Figure 2: IR of Endo-Diacid
Table 2. IR of Endo-Diacid
Range Bond
3100-3000 C-H
3000-2850 C-H
1710-1665 C=O
1500-1400 C-C (ring)
1370-1350 C-H
1335-1250 C-N

According to these peaks the product from the Nucleophilic Acyl Substitution reaction is
confirmed. The peaks correlate with the structure of the product.

Figure 3: IR of Endo-Diester
Table 3. IR of Endo-Diester
Range Bond
3000-2850 C-H
1740-1720 C=O
1500-1400 C-C (ring)
1360-1290 O-N (symmetric)
1335-1250 C-N

According to these peaks the product from the Fischer Esterification reaction is confirmed. The
peaks correlate with the structure of the product.

Calculations:
Theoretical Yields

Theoretical Yield of Endo-Anhydride:

1 mol 1 mol 163.15 g endo−anhydride

40.8 mmol maleic anhydride × × × =6.66 g
1000 mmol 1 mol 1mol

Theoretical Yield of Endo-Diacid:

1 mol 1 mol 182.2 g endo−diacid

15.02 mmol endo−anhydride× × × =2.73 g
1000 mmol 1 mol 1mol

Theoretical Yield of Endo-Diester:

1 mol 1 mol 207.22 g endo−diester

9.17 mmol endo−diacid × × × =1.90 g
1000mmol 1 mol 1mol

% Yields:

1.99 g
% Yield of Endo-Anhydride: ×100=29.9 %
6.66 g

1.36 g
% Yield of Endo-Diacid: ×100=49.8 %
2.73 g

1.19 g
% Yield of Endo-Diester: ×100=62.6 %
1.90 g

Overall % Yield: ((0.299)(0.498)(0.626))= 9.32%

Table 4. Product Yield

Name Product Yield (g)
Endo-Anhydride 6.66
Endo-Diacid 2.73
Endo-Diester 1.90

Table 5. % Yields
Name % Yields
Endo-Anhydride 29.9%
Endo-Diacid 49.8%
Endo-Diester 62.6%
Overall 9.32%
Table 6. Melting Points
Name MPR℃
Endo-Anhydride 169-171℃
Endo-Diacid 174-174.5℃

Discussion Tables and Calculations:

All in all, the tables that are shown and the calculations conclude that I successfully finished the
experiment. Mistakes were made, but next time directions will be followed better.

Figure 4: NMR of Endo-Diester

At 6 ppm there is a triplet with an integration of 2 (CH2 group), indicating there is a carbon with
two hydrogens next to it. At 3.5 ppm there is a singlet with an integration of 6 (2 CH3 groups),
indicating there is no carbons with hydrogens next to it. A 3.4 ppm there is a triplet with an
integration of 2 (CH2 group), indicating there is a carbon with two hydrogens next to it. At 3.2
ppm there is a mutiplet with an integration of 2 (CH2 group), indicating there more than just
hydrogens next to it. At 1.5 ppm there is a mutiplet with an integration of 2 (CH2 group),
indicating there is more than just hydrogens next to it. The NMR shows all the chemical shifts
that make up the end product of endo-diester.
IV. EXPERIMENTAL:

Synthesis of cis-Norbornene-5,6-endo-anhydride:

Maleic anhydride (2.0 g, 0.02 mols) was placed in an Erlenmeyer flask (50-mL). The anhydride
was dissolved in of ethyl acetate (6 mL) while being heated on a hot plate. Hexane was added to
the solution (6 mL) and then was cooled in an ice-water bath. Crystals formed after being left in
the bath. Dry cyclopentadiene (2 mL) was added to the ice-cold solution of maleic anhydride.
The solution was swirled in an ice bath for a few minutes until it turned to a white solid. The
mixture was heated on a hot plate until the solid dissolved. Once dissolved, the solution was
cooled to room temperature and then cooled on an ice bath. The resulting solid was suction
filtered and washed with cold hexane. The endo anhydride that was isolated as a white
precipitate (2.45 g, 15.02 mmol, 29.9%): mp 169-171℃; IR 3000-2850, 1710-1665, 1500-1400,
1335-1250.1

Synthesis of cis-Norbornene-5, 6-endo-dicarboxylic acid:

Anhydride (2.45 g) was placed from the previous experiment into an Erlenmeyer flask (125-mL)
with distilled water (50-mL). A clamp was used to swirl the contents in the Erlenmeyer flask
over a hot plate till the contents dissolved/melted. The solution was heated until the oil dissolved
and then cooled for 30 minutes until it had reached room temperature. If the crystallization
needed encouragement, the surface of the liquid was touched with a stirring rod or the side of the
glass was scratched to initiate crystallization. The crystallization proceeded and was then put in
ice. The resulting solid was suction filtered and washed with cold water. The endo diacid
snowflake looking crystals that were isolated (1.67 g, 9.17 mmol, 49.8%): mp 174-174.5℃; IR
3100-3000, 3000-2850, 1710-1665, 1500-1400, 1370-1350, 1335-1250.2

Esterification:

Endo-diacid was weighed (1.17 g, 0.007 mols) and transferred into a round-bottomed flask (25-
mL) with the use of a powder funnel. Methanol (4.68 mL) and sulfuric acid (0.23 mL) was added
and swirling was used to dissolve the reactants. A boiling chip and a reflux condenser was added.
An hour of refluxing was done. The mixture was cooled in an ice-water bath and the contents in
the round-bottomed flask were transferred into the separatory funnel with water (6.0 mL). Tert-
butyl methyl ether was added (6.0 mL) and shook to extract the dimethyl ester in the ether layer
and he lower layer was then discarded. The ether layer was extracted with aqueous sodium
bicarbonate solution (6.0 mL) and sodium chloride solution (6.0 mL). The ether solution of the
diester was transferred to an Erlenmeyer flask. Anhydrous pelletized calcium chloride was added
(0.5 g) to the flask and swirled for 5 minutes. The dried solution was transferred into a round-
bottomed flask (50-mL). The tert-butyl methyl ether solvent was rotary evaporated. The result
for endo-diester was a clear liquid (1.19 g, 5.74 mmol, 62.6%): IR 3000-2850, 1740-1720, 1500-
1400, 1360-1290, 1335-1250; NMR 6.3-6.2 (t 2H), 3.7-3.6 (s 6H), 3.4-3.3 (t 2H), 3.3-3.2 (m
2H), 1.5-1.4 (m 2H).
V. REFERENCES

1. Sigma Aldrich [Link]

lang=en&region=US
December 6, 2018

2. Sigma Aldrich [Link]

lang=en&region=US
December 6, 2018

3. Chemistry Libre Books

[Link]
%3A_Organic_Chemistry_(McMurry)/Chapter_21%3A_Carboxylic_Acid_Derivatives
%3A_Nucleophilic_Acyl_Substitution_Reactions/21.02_Nucleophilic_Acyl_Substitution_Reacti
ons
December 6, 2018

[Link] Libre Books

[Link]
c_Chemistry)/Carboxylic_Acids/Reactivity_of_Carboxylic_Acids/Fischer_Esterification
December 6, 2018