NATIONAL UNIVERSITY

HO CHI MINH UNIVERSITY OF TECHNOLOGY

FACULTY OF CHEMICAL ENGINEERING
SUBJECT: EXPERIMENTAL DESIGN & DATA ANALYSIS

EFFECT OF TEMPERATURE AT DIFFERENT

STAGES OF TIME ON ETHYL ACETATE
HYDROLYSIS IN SODIUM HYDROXIDE SOLUTION
(USING R TO EXAMINE THE DISTRIBUTION OF THE
DATASET AND BUILD A SIMPLE REGRESSION MODEL)

Instructor : Dr. Nguyễn Tiến Dũng

Members :
Nguyễn Quốc Phong 1752414
Trương Đào Hải Đăng 1750077
Trần Hạ Vy 1850063
Lương Bội Linh 1850023

Ho Chi Minh City, 29th December 2020

CONTENTS

CHAPTER I - AN OVERVIEW OF COMPONENTS & REACTIONS 3

1. Properties of chemical reactants and products 3
1.1 Ethyl Acetate 3
1.2 Sodium Hydroxide 4
1.3 Acetic Acid and Sodium Acetate 5
1.4 Ethanol 6
2. Hydrolysis 7
2.1 The concept of Hydrolysis 7
2.2 Mechanism of different types of catalyzed hydrolysis of Ethyl Acetate 7
2.3 Hydrolysis of Ethyl Acetate in Sodium Hydroxide solution method 8

CHAPTER II – STATISTICAL METHODS 10

1. Regression Analysis 10
1.1 Linear Regression 10
1.2 Simple Linear Regression 10
2. Quantile-Quantile plot 11

CHAPTER III – PROBLEM AND ANALYSIS USING R 12

1. Problem 12
2. Analysis using R (details, discussions and conclusion) 12

CHAPTER IV – REFERENCES 17

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LIST OF FIGURES

Figure 1.1 Structure of an Ethyl Acetate molecule 3

Figure 1.2 Solid Sodium Hydroxide and its crystalline molecular structure 4
Figure 1.3 Structure of an Acetic Acid molecule 5
Figure 1.4 Structure of an Ethanol molecule 6

Figure 2.1 Mechanism of the acidic catalyzed hydrolysis of Ethyl Acetate 8

Figure 2.2 Mechanism of the basic catalyzed hydrolysis of Ethyl Acetate 8

Figure 3.1 Dataset of Ethyl Acetate hydrolysis 12

Figure 3.2 Q-Q plot of the relationship between Time and IC 14
Figure 3.3 Q-Q plot of the relationship between Temperature and IC 15
Figure 3.4 Q-Q plot of the relationship between (Time & Temperature) with IC 16

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CHAPTER I - AN OVERVIEW OF COMPONENTS & REACTIONS

1. Properties of chemical reactants and products

1.1 Ethyl Acetate
Ethyl Acetate (systematically ethyl ethanoate, commonly abbreviated EtOAc, ETAC or
EA) is an organic compound with the formula CH3COOCH2CH3. This colorless liquid has
a characteristic sweet smell (similar to pear drops) and is used in glues, nail polish
removers, and in the decaffeination process of tea and coffee.

Figure 1.1 Structure of an Ethyl Acetate molecule

Ethyl Acetate is synthesized in industry mainly via the classic Fischer esterification
reaction of Ethanol and Acetic Acid.
CH3COOH + CH3CH2OH ⇄ H2O + CH3COOC2H5
The reaction can be accelerated by acid catalysis and the equilibrium can be shifted to
the right by removal of water. (The sign “⇄” notes that this is a reversible reaction).
It is also prepared in industry using the Tishchenko reaction, by combining two
equivalents of acetaldehyde in the presence of an alkoxide catalyst:
2CH3CHO → CH3COOC2H5
Ethyl acetate is used primarily as a solvent and diluent, being favored because of its low
cost, low toxicity, and agreeable odor. For example, it is commonly used to clean circuit
boards and in some nail varnish removers. Coffee beans and tea leaves are decaffeinated
with this solvent. It is also used in paints as an activator or hardener. Ethyl acetate is
present in confectionery, perfumes, and fruits. In perfumes, it evaporates quickly,
leaving only the scent of the perfume on the skin. In the laboratory, mixtures containing
ethyl acetate are commonly used in column chromatography and extractions. This
substance is rarely selected as a reaction solvent because it is prone to hydrolysis,
transesterification, and condensations.
Ethyl acetate is the most common ester in wine, being the product of the most common
volatile organic acid – acetic acid, and the ethyl alcohol generated during the
fermentation. The aroma of ethyl acetate is most vivid in younger wines and contributes
towards the general perception of "fruitiness" in the wine.
Overexposure to ethyl acetate may cause irritation of the eyes, nose, and throat. Severe
overexposure may cause weakness, drowsiness, and unconsciousness. Humans exposed
to a concentration of 400 ppm in 1.4 mg/L ethyl acetate for a short time were affected
by nose and throat irritation.

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1.2 Sodium Hydroxide and its solution
Sodium Hydroxide is a white solid and ionic compound consisting of sodium cations
(Na+) and hydroxide anions (OH−). This is a highly caustic base and alkali that
decomposes proteins at ordinary ambient temperatures and may cause severe chemical
burns. It is highly soluble in water and readily absorbs moisture and carbon dioxide
from the air.

Figure 1.2
Solid Sodium Hydroxide and its crystalline molecular structure

Pure sodium hydroxide is a colorless crystalline solid that melts at 318 °C (604 °F)
without decomposition, and with a boiling point of 1,388 °C (2,530 °F). It is highly
soluble in water, with a lower solubility in polar solvents such as ethanol and methanol.
The dissolution of solid sodium hydroxide in water is a highly exothermic reaction
where a large amount of heat is liberated, posing a threat to safety through the possibility
of splashing. The resulting solution is usually colorless and odorless. As with other
alkaline solutions, it feels slippery with skin contact due to the process of saponification
that occurs between NaOH and natural skin oils.
Historically, sodium hydroxide was produced by treating sodium carbonate with
calcium hydroxide in a metathesis reaction. (Sodium hydroxide is soluble while calcium
carbonate is not.) This process was called causticizing
Ca(OH)2(aq) + Na2CO3(s) → CaCO3 (precipitate) + 2NaOH(aq)
Sodium hydroxide is industrially produced as a 50% solution by variations of the
electrolytic chloralkali process. Solid sodium hydroxide is then obtained from this
solution by the evaporation of water.
As a fluid solution, NaOH demonstrates a characteristic viscosity, 78 mPa·s, much
greater than water (1.0 mPa·s) and near that of olive oil (85 mPa·s) at room temperature.
The viscosity of NaOH, as with any chemical, is inversely related to its service
temperature; meaning viscosity decreases as temperature increases, and vice versa. The
viscosity of sodium hydroxide plays a direct role in its application as well as its storage.
Sodium hydroxide is used in many industries: in the manufacture of pulp and paper,
textiles, drinking water, soaps, detergents, and as a drain cleaner. In industry, sodium
hydroxide is used as an additive in drilling mud to increase alkalinity in bentonite mud

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systems, to increase the mud viscosity, and to neutralize any acid gas (such as hydrogen
sulfide and carbon dioxide) which may be encountered in the geological formation as
drilling progresses. Food uses of sodium hydroxide comprises washing or chemical
peeling of fruits and vegetables, chocolate and cocoa processing, caramel coloring
production, poultry scalding, soft drink processing, and thickening ice cream.

1.3 Acetic Acid and Sodium Acetate

Acetic acid, systematically named ethanoic acid, is a colourless liquid organic
compound with the chemical formula CH3COOH. It has a distinctive sour taste and
pungent smell. It is an important chemical reagent and industrial chemical, used
primarily in the production of cellulose acetate for photographic film, polyvinyl acetate
for wood glue, and synthetic fibres and fabrics.

Figure 1.3 Structure of an Acetic Acid molecule

In solid acetic acid, the molecules form chains, individual molecules being
interconnected by hydrogen bonds. In the vapour at 120°C (248°F), dimers can be
detected. Dimers also occur in the liquid phase in dilute solutions in non-hydrogen-
bonding solvents, and a certain extent in pure acetic acid, but are disrupted by hydrogen-
bonding solvents. The dissociation enthalpy of the dimer is estimated at 65.0-66.0
kJ/mol, and the dissociation entropy at 154–157 J mol−1 K−1. Liquid acetic acid is a
hydrophilic protic solvent, similar to ethanol and water. It is miscible with polar and
non-polar solvents such as water, chloroform, and hexane. With higher alkanes (starting
with octane), acetic acid is not miscible at all compositions, and solubility of acetic acid
in alkanes declines with longer n-alkanes.
Prior to the commercialization of the Monsanto process, most acetic acid was produced
by oxidation of acetaldehyde:
2CH3CHO + O2 → 2CH3COOH
For most of human history, acetic acid bacteria of the genus Acetobacter have made
acetic acid, in the form of vinegar. Given sufficient oxygen, these bacteria can produce
vinegar from a variety of alcoholic foodstuffs. Commonly used feeds include apple
cider, wine, and fermented grain, malt, rice, or potato mash. The overall chemical
reaction facilitated by these bacteria is:
C2H5OH + O2 → CH3COOH + H2O
Species of anaerobic bacteria, including members of the genus Clostridium or
Acetobacterium can convert sugars to acetic acid directly without creating ethanol as
an intermediate. The overall chemical reaction conducted by these bacteria may be
represented as:

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 C6H12O6 → 3CH3COOH
These acetogenic bacteria produce acetic acid from one-carbon compounds, including
methanol, carbon monoxide, or a mixture of carbon dioxide and hydrogen:
2CO2 + 4H2 → CH3COOH + 2H2O
Sodium acetate, CH3COONa, also abbreviated as NaOAc, is the sodium salt of acetic
acid. This colorless deliquescent salt has a wide range of uses. Sodium acetate is used
in the textile industry to neutralize sulfuric acid waste streams and also as a photoresist
while using aniline dyes. It is also a pickling agent in chrome tanning and helps to
impede vulcanization of chloroprene in synthetic rubber production. In processing
cotton for disposable cotton pads, sodium acetate is used to eliminate the buildup of
static electricity. As the conjugate base of acetic acid, a solution of sodium acetate and
acetic acid can act as a buffer to keep a relatively constant pH level. This is useful
especially in biochemical applications where reactions are pH-dependent in a mildly
acidic range (pH 4–6).
For laboratory use, sodium acetate is inexpensive and usually purchased instead of
being synthesized. It is sometimes produced in a laboratory experiment by the reaction
of acetic acid, commonly in the 5–8% solution known as vinegar, with sodium
carbonate, sodium bicarbonate, or sodium hydroxide.
1.4 Ethanol
Ethanol (ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) has the
chemical formula C2H6O. Its formula can be also written as CH3CH2OH or C2H5OH
and is often abbreviated as EtOH. It is a volatile, flammable, colorless liquid with a
slight characteristic odor. It is a psychoactive substance and is the principal active
ingredient found in alcoholic drinks.

Figure 1.4 Structure of an Ethanol molecule

Ethanol is considered a universal solvent, as its molecular structure allows for the
dissolving of both polar, hydrophilic and nonpolar, hydrophobic compounds. As the
substance also has a low boiling point, it is easy to remove from a solution that has been
used to dissolve other compounds, making it a popular extracting agent for botanical
oils. Furthermore, ethanol is found in paints, markers, and personal care products such
as mouthwashes, perfumes and deodorants. However, polysaccharides precipitate from
aqueous solution in the presence of alcohol, and ethanol precipitation is used for this
reason in the purification of DNA and RNA. Because of its low freezing point
(−114.14°C) and low toxicity, ethanol is sometimes used in laboratories (with dry ice

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or other coolants) as a cooling bath to keep vessels at temperatures below the freezing
point of water. For the same reason, it is also used as the active fluid in alcohol
thermometers.
Ethanol for use as an industrial feedstock or solvent is made from petrochemical
feedstocks, primarily by the acid-catalyzed hydration of ethylene:
C2H4 + H2O → CH3CH2OH
Ethanol in alcoholic beverages and fuel is produced by fermentation. Certain species of
yeast metabolize sugar, producing ethanol and carbon dioxide. The chemical equations
below summarize the conversion:
C6H12O6 → 2CH3CH2OH + 2CO2
C12H22O11 + H2O → 4CH3CH2OH + 4CO2

2. Hydrolysis
2.1 The concept of Hydrolysis
Hydrolysis is a type of decomposition reaction where one of the reactants is water.
Typically, water is used to break the chemical bonds in the other reactant. Hydrolysis
may be considered the reverse of a condensation reaction, in which two molecules
combine with each other, producing water as one of the products. When we consider
“Organic hydrolysis” reactions, we mostly bear in mind that those are reactions between
water and an ester.

2.2 Mechanism of different types of catalyzed hydrolysis of Ethyl Acetate

Hydrolysis of Ethyl Acetate can occur in both acidic and basic medium as described
below.
* In an acidic solution:
+ Step 1: Since we only have a weak nucleophile and a poor electrophile we need to
activate the ester. Protonation of the ester carbonyl makes it more electrophilic
+ Step 2: The oxygen in the water molecule functions as the nucleophile attacking the
electrophilic C in the C=O, with the electrons moving towards the oxonium ion, creating
the tetrahedral intermediate.
+ Step 3: Deprotonate the oxygen that came from the water molecule to neutralise the
charge.
+ Step 4: Make the -OCH3 leave, but need to convert it into a good leaving group first
by protonation.
+ Step 5: Use the electrons of an adjacent oxygen to help "push out" the leaving group,
a neutral methanol molecule.
+ Step 6: Deprotonation of the oxonium ion reveals the carbonyl C=O in the carboxylic
acid product and regenerates the acid catalyst.

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 Figure 2.1 Mechanism of the acidic catalyzed hydrolysis of Ethyl Acetate
* In a basic solution:
+ Step 1: The hydroxide nucleophile attacks at the electrophilic C of the ester C=O,
breaking the π bond and creating the tetrahedral intermediate.
+ Step 2: The intermediate collapses, reforming the C=O results in the loss of the
leaving group the alkoxide, RO-, leading to the carboxylic acid.
+ Step 3: This is a very rapid equilibrium stage where the alkoxide RO- functions as a
base deprotonation of the carboxylic acid RCOOH.

Figure 2.2 Mechanism of the basic catalyzed hydrolysis of Ethyl Acetate

2.3 Hydrolysis of Ethyl Acetate by Sodium Hydroxide solution method
*Reason of choosing this project:
This topic is selected with the aim of comparing the practical data from a scientific
research with the theoretical yields to determine the relationship between the reaction
time and temperature in defining the conversion of ethyl acetate in its hydrolysis with
sodium hydroxide using R analysis program.
*Main reaction:
In the data analysis using R, we consider the reaction in basic conditions as follows:
CH3COOC2H5 + NaOH → CH3COONa + C2H5OH
As the reaction proceeds, each hydroxide ion disappeared in the formation of ethanol
removes one molecule of ethyl acetate, therefore, the concentration of the reactants
decreases. Previous research shows that equimolecular concentration of both reactants

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yield high conversion this can be also seen from the reaction stoichiometry. Now we
need to illustrate the effect of temperature to the conversion, noting that both reactants
should be as close to same temperature as possible before starting the experiment.
*Suggested methods:
(1) Volumetric titration independently in which the composition of reaction mixture is
analyzed by withdrawal of samples after equal intervals of time.
(2) Conductometric measurement technique based upon the composition measurement
at different time and temperature.

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CHAPTER II - STATISTICAL METHODS
1. Regression Analysis
In statistical modeling, regression analysis is a set of statistical processes for
estimating the relationships between a dependent variable and one or more
independent variables. Regression analysis is primarily used for two conceptually
distinct purposes. Firstly, it is widely used for prediction and forecasting, where its
use has substantial overlap with the field of machine learning. Secondly, in some
situations, regression analysis can be used to infer causal relationships between the
independent and dependent variables. Importantly, regressions by themselves only
reveal relationships between a dependent variable and a collection of independent
variables in a fixed dataset.

1.1 Linear Regression

The most common form of regression analysis is linear regression, in which a
researcher finds the line (or a more complex linear combination) that most closely
fits the data according to a specific mathematical criterion.
In linear regression, the relationships are modeled using linear predictor functions
whose unknown model parameters are estimated from the data. Such models are
called linear models. Most commonly, the conditional mean of the response given
the values of the explanatory variables is assumed to be an affine function of those
values; less commonly, the conditional median or some other quantile is used. Like
all forms of regression analysis, linear regression focuses on the conditional
probability distribution of the response given the values of the predictors, rather than
on the joint probability distribution of all of these variables, which is the domain of
multivariate analysis. Linear Regression is generally classified into two types:
“Simple Linear Regression” and “Multiple Linear Regression”. In this project, we
focus on the simple type.

1.2 Simple Linear Regression

Simple linear regression is a statistical method for obtaining a formula to predict
values of one variable from another where there is a causal relationship between the
two variables.
*Straight line formula: Central to simple linear regression is the formula for a straight
line that is most commonly represented as (y=mx+c) or (y=a+bx). The variables x
and y are those whose relationship we are studying. We give them the following
names:
+ x: independent (or predictor or explanatory) variable.
+ y: dependent (or response) variable.
It is convention when plotting data to put the dependent and independent data on the
y and x axis respectively.

2. Quantile-Quantile plot (Q-Q plot)

In statistics, a Q–Q plot is a probability plot, which is a graphical method for
comparing two probability distributions by plotting their quantiles against each other.

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First, the set of intervals for the quantiles is chosen. A point (x, y) on the plot
corresponds to one of the quantiles of the second distribution (y-coordinate) plotted
against the same quantile of the first distribution (x-coordinate). Thus the line is a
parametric curve with the parameter which is the number of the interval for the
quantile.
If the two distributions being compared are similar, the points in the Q–Q plot will
approximately lie on the line (y=x). If the distributions are linearly related, the points
in the Q–Q plot will approximately lie on a line, but not necessarily on the line (y=x).
Q–Q plots can also be used as a graphical means of estimating parameters in a
location-scale family of distributions.
The main step in constructing a Q–Q plot is calculating or estimating the quantiles to
be plotted. If one or both of the axes in a Q–Q plot is based on a theoretical
distribution with a continuous cumulative distribution function (CDF), all quantiles
are uniquely defined and can be obtained by inverting the CDF. If a theoretical
probability distribution with a discontinuous CDF is one of the two distributions
being compared, some of the quantiles may not be defined, so an interpolated quantile
may be plotted. If the Q–Q plot is based on data, there are multiple quantile estimators
in use. Rules for forming Q–Q plots when quantiles must be estimated or interpolated
are called plotting positions.
A simple case is where one has two data sets of the same size. In that case, to make
the Q–Q plot, one orders each set in increasing order, then pairs off and plots the
corresponding values. A more complicated construction is the case where two data
sets of different sizes are being compared. To construct the Q–Q plot in this case, it
is necessary to use an interpolated quantile estimate so that quantiles corresponding
to the same underlying probability can be constructed.

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CHAPTER III - PROBLEM AND ANALYSIS USING R
1. Problem
In laboratory, a group of Bach Khoa students tests the hydrolysis reaction of Ethyl
Acetate at 3 stages of temperature 25, 40 and 50 degree Celsius combining with three
different reaction time 1, 5, and 10 minutes respectively in Sodium Hydroxide
solution to determine the effect of which components affect to the reaction and figure
out their relationship. The dataset is shown below.
Figure 3.1 Dataset of Ethyl Acetate hydrolysis

*Goals of testing:
(1) Do temperature and time have a strong linear relationship with the
instantaneous conversion of this hydrolysis reaction?
(2) Predict at the temperature of 35 degree Celsius in 8 minutes, what is the
instantaneous conversion value?

2. Analysis using R (details. discussions and conclusion)

#List all the Time & Temperature data then create a loop
for each of them

> x1=x1=c(1,5,10)
> x1=rep(x1,3)
> x2=c(rep(25,3), rep(40,3), rep(50,3))

#To create a table for easier following

> data=data.frame(x1)
> data=cbind(data,x2)

#List all the instantaneous concentration (Y)

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 > y=c(0.52,0.61,0.67,0.48,0.52,0.53,0.49,0.51,0.52)

#To link y to the data table

> data=cbind(data,y)

#To check the linear relationship between the Time and

the Instantaneous Concentration to build a simple
regression model

> lm(y~x1)
> result1=lm(y~x1)
> summary(result1)

#Then RUN to see the result

#Y=0.4942+0.0084X
(R-squared=0.2853;S=0.0554; p-value = 0.1385>0.05)→ The time does not affect
the Instantaneous Concentration (IC), therefore, we cannot trust this regression
model.

#Use the Quantile-Quantile graph to double check the

decision (figure 3.2)

> plot(result1)

Figure 3.2 Q-Q plot of the relationship between Time and IC

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#To check the linear relationship between the Temperature
and the Instantaneous Concentration to build a simple
regression model

> lm(y~x2)
> result2=lm(y~x2)
> summary(result2)
#Y=0.6889-0.0039X
(R-squared=0.4833;S=0.0471;p-value=0.0376 < 0.05)→ We can trust this linear
regression.
#Then, we use Q-Q graph to double check (figure 3.3)

> plot(result2)

Figure 3.3 Q-Q plot of the relationship between Temperature and IC

#To check the linear relationship between the

(Temperature and Time) with the Instantaneous
Concentration to build a simple regression model

lm(y~x1+x2)
result3=lm(y~x1+x2)
summary(result3)
#Y=0.6441+(0.0084X1)+(-0.0039X2)
(R-squared=0.7685; S=0.0341; p-value=0.0124 < 0.05), we
can trust this regression model.

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#Double-check by using Q-Q graph plot (see the graph on
page 16)

> plot(result3)

Figure 3.4 Q-Q plot of the relationship between (Time & Temperature) with IC
#Based on figure 3.4, we can see that there are almost
standardized residuals place around the sketched line of
this linear regression model.

#To predict the Instantaneous Conversion at 35 degree

Celsius after 8 minutes of reacting

> predict(result3, data.frame(x1=8, x2=35)

#The predicted result claims to be 0.5743 (Y=0.5743).

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CHAPTER IV - REFERENCES
1. [Simple R]

“Using R for Introductory Statistics”

John Verzani

2. [Researchgate]

“Kinetics of Alkaline Hydrolysis of Ethyl Acetate by Conductometric Measurement

Approach Over Temperature Ranges 298.15K to 343.15K”

Department of Chemical Engineering, Uni Politècnica de Catalunya-UPC, Spain

3. [Lecture]

“Experimental Design and Data Analysis course”

Dr. Nguyễn Tiến Dũng, HCMUT, Department of Applied Maths

4.[National Library of Medicine website]

“Understanding the Hydrolysis Mechanism of Ethyl Acetate Catalyzed”

Elkin Tilvez, Gloria I Cárdenas-Jirón, María I Menéndez, Ramón López

END

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