Subject:

ORGANIC CHEMISTRY 1, 65202

Student Name:
Yvonne Du

Lab partner:
Kevin Nguyen

Lab Report Title:

OC1 Experiment 4 - Laboratory Report

Date submitted:
11th May 2020

Declaration:
I, the undersigned, declare that this report is my own work except where the contributions or assistance of
others has been properly acknowledged by UTS rules.
I have kept a copy of the report.

Name:​ Yvonne Du

Signature: Date​: 11th May 2020

Receipt for submission of report

Name: ______________________________________________________________________
Experiment Number: ◻
Report Received by: ___________________________________________________________
Date: __/__/__
ABSTRACT
Experiment 4, Preparation of N-(4-butoxyphenyl)acetamide; ​S​N​1​ and ​S​N​2​ reactions of halohydrocarbons aims to
synthesise N-(4-butoxyphenyl)acetamide through the reaction of N-(4-hydroxyphenyl) (paracetamol) and 1-bromobutane
with sodium hydroxide (base). The reaction of Part A follows the Williamson Ether Synthesis and utilises the ​S​N​2
mechanism, beginning with the formation of an alkoxide or phenoxide which then reacts with a haloalkane to produce an
ether. Part B of experiment 4 aimed to observe how different halohydrocarbons react and can favour the ​S​N​1​ or ​S​N​2
nucleophilic substitution mechanism. The results had illustrated a percentage yield of 68.1% and a melting point of 118​°C,
showing the impurities and unreacted paracetamol.

INTRODUCTION
Halohydrocarbons define compounds consisting of one of more carbon-halogen bonds, where the halogen atom/s replace
the hydrogen and bonds to the carbon atom via covalent bonding. Developed in 1850 by Alexander Williamson, the
experiment conducted focuses on the nucleophilic substitution of halohydrocarbons via ‘Williamson Ether Synthesis’, an
organic reaction that involves the formation of an ether from a halohydrocarbon and deprotonated alcohol (UTS OC1
Laboratory Manual, 2020). An ether is a compound group that consists of an Oxygen atom surrounded by two alkyl
groups.

This reaction followed a nucleophilic substitution S​N​2 mechanism. S​N​2 reactions begin with the formation of an alkoxide
or phenoxide from aliphatic or aromatic alcohols. The alkoxide or phenoxide ion then reacts with a primary haloalkane in
order to form an ether. Figure 1 below illustrates the general mechanism on the reaction:

Figure 1: General mechanism of the Williamson Ether Synthesis

Particular to Experiment 4, N-(4-hydroxyphenyl)acetamide (Paracetamol) and 1-bromobutane were reacted to form
N-(4-butoxyphenyl)acetamide as a product. NaOH is utilised as a base, its role being to deprotonate the paracetamol.
Figure 2 depicts the mechanism used for this experiment:

Figure 2: Synthesis of N-(4-butoxyphenyl)acetamide

Part B of Experiment 4 involves testing for both S​N​1 and S​N​2 mechanisms. The first set of reactions consist of six different
halohydrocarbons which were then reacted with silver nitrate in ethanol. These structures vary from primary to tertiary
and a benzene ring which favour the S​N​1 substitution reaction. In the latter half of the Part B experiment, four different
halohydrocarbons reacted with sodium iodide in acetone, ultimately favouring the S​N​2 mechanism.

The aim of this experiment was to conduct a Williamson ether synthesis reaction with paracetamol and 1-bromobutane
(Part A) and exhibit how various halohydrocarbons react and can favour the S​N​1 or S​N​2 nucleophilic substitution
mechanism (Part B).

METHOD
The method outlined in ‘Experiment 4: Preparation of N-(4-butoxyphenyl)acetamide; S​N​1 and S​N​2 reactions of
halohydrocarbons’ was utilised, and can be located in the Organic Chemistry 1 Laboratory Manual. Due to certain
complications, the experiment was performed by laboratory demonstrators and was filmed as a virtual practical, watched
by students. Several amendments were made to Part A of the experiment. This was due to the methodology in the
laboratory manual not being thorough in regards to obtaining the product. The missing steps in the laboratory manual and
video were:
- Washing the filtered solid product twice with 50mL of ice-cold water to remove any impurities
- Providing the weight of the empty sample vial
- Carefully utilising a funnel to transfer the sonic into an empty pre-weighed sample vial.
- Determining the weight of the dried product (after the product has cooled to room temperature)
- Determining the mass of the product in grams
RESULTS: ​PART A

The Melting Point

M.P of N-(4-butoxyphenyl)acetamide = 118​°C
Literature obtained melting point = 112​°C​ (SciFinder 2018)

IR Spectrum

Figure 3: IR Spectrum of Paracetamol

Figure 4: IR Spectrum of Butoxy phenylacetamide

Thin-Layer Chromatography (TLC)

At the start of the TLC process, there are two visible spots in the
reaction mixture, one being the reactant paracetamol and the
other being the product. This confirms that the reaction has gone
to a completion as the reactant has converted and formed the
product. Further refluxing is required to allow all of the reactant
to undergo product formation. Indication that the reaction has
gone to completion can be determined from the absence of the
paracetamol and the appearance of the product.

Retention factor (Rf) = distance travelled by substance (mm) / distance travelled by solvent (mm) = d / s
R​f​ (Paracetamol) = 0.34
R​f​ (Product) = 0.47

Theoretical and Percentage Yield

Compound Molar Mass (g/mol)

Paracetamol 151.16

1-bromobutane 137.02

N-(4-butoxyphenyl)acetamide 207.27

Moles (Paracetamol) = 3.75 / 151.163 = 0.02480815 = ​0.025mol​ (provided in lab manual)

Moles (1-bromobutane) = 3.63 / 137.02 = ​0.028mol​ (provided in lab manual)
Limiting Reagent = Paracetamol
Mole ratio = 1:1

Theoretical Yield = Moles (limiting reagent) x Molecular weight (product)

= 0.02480815mol * 207.27g/mol
= 5.14g (2dp)

Actual Yield = 3.5g of N-(4-butoxyphenyl)acetamide obtained

Percentage Yield = Actual yield / theoretical yield * 100

= 3.5 / 5.14 * 100
= 68.1% (3 significant figures)
RESULTS: PART B

Table 1: Reactions of chlorides with silver nitrate (AgNO3 ) in ethanol (S​N​1 instances)

1-chlorobutane - Slow reaction

2-chlorobutane - Slow reaction

2-chloro-2-methylpropane - Immediate reaction

- The solution turned into a white cloudy precipitate at approximately 14
seconds

Chlorobenzene - Slow reaction

Allyl Chloride - Immediate reaction

- The solution turned into a white cloudy precipitate at approximately 5
seconds

Benzyl Chloride - Reacts in approximately 3 minutes

- White cloudy precipitate formed after resting

Table 2: Reactions of bromides with sodium iodide (NaI) in acetone (S​N​2 instances)

1-bromobutane - Reacts in approximately 2 minutes

2-bromobutane - Slow reaction

2-bromo-2-methylpropane - Slow reaction

Bromobenzene - Slow reaction

DISCUSSION
The aim of part A Experiment 4 was to form N-(4-butoxyphenyl)acetamide through the use of a William Ether Synthesis
reaction by reacting paracetamol with 1-bromobutane. Conducting this experiment had resulted in a yield of 3.5g and a
percentage yield of 68.1%. The loss of the final product could have been attributed to the fact that the reaction did not run
to full completion and thus, more of the final product could not be obtained. This is further elaborated through the results
of the thin-layer chromatography which showed both Paracetamol (reactant) and N-(4-butoxyphenyl)acetamide (final
product). This once again advocates the idea that the reaction did not undergo full completion. The difference in the
obtained melting point (118​°C​) and the literature value (112​°C​) further suggesting that there was a level of impurities
present in the final product.

Additionally, the formation of by-products was inevitable, possibly affecting the yield of our final product. The possible
formation of water, dibutyl ether and other alkenes can be minimised in further experiments by ensuring that the product
is thoroughly dried during the oven process and ensuring that the reaction goes to a full completion (the absence of
paracetamol and appearance of the product is an ideal indication that the reaction has gone to a completion.

Part B of Experiment 4 involved testing for both S​N​1 and S​N​2 mechanisms as it aimed to exhibit how various
halohydrocarbons react and favour respective substitution mechanisms. As observed in table 1 of the results section, the
first group of reactions of chlorides with silver nitrate in ethanol, 2-chloro-2-methylpropane, allyl chloride and benzyl
chloride all reacted to form a silver halide precipitate. Due to the reasoning that the aforementioned compounds favour the
S​N​1 mechanism, this ultimately explains why 1-chlorobutane, 2-chlorobutane and chlorobenzene did not react/had a slow
reaction. 1-chlorobutane is a primary haloalkane and 2-chlorobutane is a secondary haloalkane, justifying why it did not
react within the first twenty minutes as S​N​1 mechanisms favour tertiary haloalkanes. Benzyl chloride reacted in
approximately three minutes. This could have been due to contamination of other samples or an unknown source, or could
have just had a slower reaction time.

Table 2 of the results section exhibited the latter group of reactions consisting of four bromides reacting with sodium
iodide in acetone. Only 1-bromobutane had reacted with the sodium iodide, forming a sodium bromide precipitate after
approximately two minutes. This was attributed due 1-bromobutane being a primary carbocation and is minimally affected
by steric hindrance, favoured especially in an S​N​2 mechanism. 2-bromobutane forms a secondary carbocation thus
explaining the slow reaction observed in table 2. Tertiary carbocations such as 2-bromo-2-methylpropane and
bromobenzene have a significantly higher steric hindrance than 1-bromobutane and is therefore unlikely to react in an S​N​2
mechanism.
DISCUSSION QUESTIONS: PART A

1. N-(4-butoxyphenyl)acetamide can form via the S​N​2 mechanism. Sodium hydroxide (NaOH) acts as a base and is
required to deprotonate the phenol group in N-(4-hydroxyphenyl), otherwise known as paracetamol, resulting in
the transition state sodium 4-acetamidophenolate, as seen in figure x below. The nucleophilic phenol group reacts
with the electrophile, 1-bromobutane, resulting in the Br- anion becoming the leaving group and reacting with the
Na+ cation to form NaBr. Paracetamol reacts with 1-bromobutane as it is a primary haloalkane and thus, has little
steric hindrance.

2. Alkene and dibutyl ether can form as by-products in the synthesis of N-(4-butoxyphenyl)acetamide.
1-bromobutene and dibutyl ether forms as a result of 1-bromobutane reacting with the strong base NaOH, ensuing
an E2 reaction and thus forming 1-butene. Additionally, 1-bromobutane can further react with sodium hydroxide
to form 1-butanol, forming dibutyl ether as a by-product. The formation of these by-products can be reduced via
the usage of a Grignard reagent to form alkoxide ions which will in turn, reduce the chances of by-product
formation.

3. It is essential to mix the paracetamol with sodium hydroxide before adding 1-bromobutane due to the notion that
the Williamson Ether Synthesis requires a deprotonated alcohol. The sodium hydroxide acts as a base which
deprotonates the paracetamol, ultimately making it nucleophilic (heat can be applied to encourage solubility). This
allows for the nucleophilic paracetamol to react with 1-bromobutane (electrophile) in order to complete the
William Ether Synthesis reaction.
4. Based on the lecture on the Williamson Ether Synthesis reaction, it is not feasible that
N-(4-butoxyphenyl)acetamide could be prepared using the alternative reaction route as there is too much steric
hindrance on the targeted carbon atom which will ultimately reduce the possibility of an S​N​2 reaction from
occurring. Furthermore, the alternate route consists of a secondary carbocation, thus, will form different products
as a result of competition with S​N​1 reactions.

5. Labelled Paracetamol IR spectrum:

6. The paracetamol has successfully been converted to the product N-(4-butoxyphenyl)acetamide as there is an
absence of the O-H stretch in the IR spectrum. Additionally, the C-O bonds are strengthened due to the
delocalisation of the lone pairs of electrons. This is due to the deprotonation reaction, which ultimately affects
phenols when undergoing reactions. The conversion is further demonstrated due to the presence of an ether as
indicated by the C-O stretch.
DISCUSSION QUESTIONS: PART B

7. The following compounds are listed in decreasing order of their observed reactivity towards silver nitrate in
ethanol: ​2-chloro-2-methylpropane < 2-chlorobutane < 1-chlorobutane​. The S​N​1 mechanism favours a tertiary
carbocation over primary and secondary, as primary and secondary forms unstable carbocation intermediates and
thus do not react. Hence, 2-chloro-2-methylpropane has the most reactivity towards silver nitrate in ethanol, being
a tertiary carbocation. 1-chlorobutane (primary carbocation) and 2-chlorobutane (secondary carbocation) are thus
not as reactive.

8. The following compounds are listed in decreasing order of their observed reactivity towards iodide ions in
acetone: ​1-bromobutane, 2-bromobutane, 2-bromo-2-methylpropane​. 1-bromobutane when reacted with
sodium iodide in acetone favours the S​N​2 mechanism due to having little steric hindrance (crowding) at the site of
the reaction. The general order of reactivity for S​N​2 mechanisms favour primary > secondary > tertiary.
1-bromobutane is a primary carbocation and thus has the highest reactivity towards the sodium iodide.
2-bromobutane (secondary) and 2-bromo-2-methylpropane (tertiary) are thus, not as reactive as there is an
increase in steric hindrance.]
 9. There were differences in reactivity observed between the two primary haloalkanes 1-chlorobutane and allyl
chloride (3-chloropropene) towards silver nitrate in ethanol. The most prominent sentiment being that
1-chlorobutane is an alkane, whilst allyl chloride is an alkene. Alkenes are known to be more reactive than
alkanes as they are unsaturated (having double bonds) and contain pi bonds, making them more susceptible to
reactions as the bonds are easily broken (sp2 hybridisation). Alkanes have no pi bonds, but rather, have sp3
hybridisation (sigma bonds) which require more energy to break. This concept can be visualised when conducting
the experiment as the allyl chloride exhibited an immediate reaction when reacted with silver nitrate in ethanol, as
opposed to 1-chlorobutane which concluded with a slow reaction.

10. Benzyl chloride is more reactive than chlorobenzene. The major difference between the two aromatic compounds
is that chlorobenzene has a chlorine atom directly attached to the benzene ring as opposed to benzyl chloride,
where the chlorine atom is attached to a CH2 alkyl group and is therefore, indirectly attached. As a result of this
nature, the lone pair of electrons of the chlorine atom (on the benzyl chloride) is readily available for reaction
(does not get involved in resonance with benzene ring). Chlorobenzene, when losing a chlorine atom, will become
unstable and thus, will tend to not lose its Cl atom, resulting in it being less reactive. This concept can be
identified when conducting Part B as benzyl chloride reacted in 3 minutes in juxtaposition to chlorobenzene
which had portrayed a slow reaction.

CONCLUSION
The aim of Part A of the Experiment 4 was to conduct a Williamson ether synthesis reaction with paracetamol and
1-bromobutane, whilst Part B was conducted to exhibit how various halohydrocarbons react and can favour the S​N​1 or S​N​2
nucleophilic substitution mechanism. The yield of the final product concluded to be 3.5g, thus confirming that the
synthesis of N-(4-butoxyphenyl)acetamide was successful. This was further exhibited by the TLC and IR spectroscopy
results. The percentage yield obtained gave a value of 68.1%. This could have been affected by several factors including
not enough drying time, or the reaction did not undergo a full completion, resulting in some of the product being lost. Part
B on the other hand successfully demonstrated various halohydrocarbons undergoing S​N​1 and S​N​2 reactions respectively.
REFERENCES
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