chem-wintergreen-synthesis-lab/main.tex

\documentclass[letterpaper]{article}

\usepackage[T1]{fontenc}


\usepackage{geometry}
\geometry{margin = 1in}
\usepackage{setspace}

\usepackage{chemfig}

\usepackage[style = chem-acs]{biblatex}
\addbibresource{references.bib}

\usepackage{graphicx}
\usepackage{float}
\newfloat{scheme}{htbp}{los}
\floatname{scheme}{Scheme}
\floatname{chart}{Chart}
\newfloat{graph}{htbp}{loh}

\usepackage{tabularx}


\usepackage{chemformula} % Formulas using \ch{}
% or
\usepackage[version = 4]{mhchem} % Formulas using \ce{}


\setcounter{secnumdepth}{-1}

\newcommand*\mycommand[1]{\texttt{\emph{#1}}}

\usepackage{authblk}
\author[1]{Shivam Tripathi}
\author[1]{Keshav Anand}
\affil[1]{Plano East Senior High School, Plano, TX, United States}

\title{Acid-Catalyzed Tandem Hydrolysis--Esterification of Acetylsalicylic Acid 
from Commerical Asprin Tablets to Form Methyl Salicylate}
% Use the \date command for email address(s) of corresponding authors


\begin{document}

\maketitle

\begin{abstract}
Methyl salicylate was synthesized from commercial aspirin tablets via an acid-catalyzed 
  tandem hydrolysis–esterification sequence. Acetylsalicylic acid (ASA) was extracted 
  from the tablet matrix into methanol and reacted under reflux with a catalytic 
  volume of \ce{H2SO4}. This one-pot method facilitates simultaneous deacetylation 
  and Fischer esterification, bypassing the isolation of a salicylic acid intermediate. 
  The resulting methyl salicylate was isolated via aqueous quenching and 
  liquid--liquid extraction. Crude product purification was achieved through 
  neutralization with saturated \ce{NaHCO3} and drying over anhydrous \ce{MgSO4}. 
  This synthesis demonstrates an efficient, high-yield conversion of a common 
  pharmaceutical precursor into a high-value fragrance ester, highlighting 
  fundamental principles of equilibrium-driven organic transformations and 
  multistep one-pot synthesis.
\end{abstract}


\section{Introduction}

Acetylsalicylic acid (ASA), \ch{C9H8O4}, is a synthetic organic derivative of salicylic acid 
and is commonly known as aspirin~\cite{Fijakowski2022}.\\
\begin{figure}[ht]
  \centering
  \vspace{1em} % Adds space above the molecule
  \chemfig{*6(-=-(-O-[:-30](=[:-90]O)-[:+30]CH_3)=([:60]-[:90](=[:150]O)-[:30]OH)-=)}
  \vspace{1em} % Adds space below the molecule
  \caption{Chemical structure of ASA}
  \label{fig:asa-structure}
\end{figure}

Commercial aspirin is commonly synthesized from salicylic acid through Eq~\ref{eq:aspirin-syn},
and the two molecules differ by an ester group (\ch{-OCOCH3})~\cite{Sneader2000}.
\begin{equation}
    \ce{C7H6O3 + C4H6O3 ->[H2SO4] C9H8O4 + CH3COOH}
    \label{eq:aspirin-syn}
\end{equation} \\
Another common derivative product of salicylic acid is methyl salicylate, \ch{C8H8O3}, commonly referred to 
as wintergreen oil. Methyl salicylate is commonly used in edibles (e.g. gum, mints), perfumes, and pain-relief 
ointments (e.g. Icy Hot, BenGay)~\cite{Guo2022}. Methyl salicylate also differs with salicylic acid by a single ester group and 
has simply been esterified differently than ASA.\\

\begin{figure}[ht]
  \centering
  \vspace{1em} % Adds space above the molecule
  \chemfig{*6(-=-(-OH)=([:60]-[:90](=[:150]O)-[:30]O-[:+90]CH_3)-=)}
  \vspace{1em} % Adds space below the molecule
  \caption{Chemical structure of methyl salicylate}
  \label{fig:methyl-salicylate}
\end{figure}

Due to the similarity between the two molecules, ASA can be reacted to synthesize methyl salicylate~\cite{Hartel2009}. 
The purpose of this experiment was to convert acetylsalicylic acid obtained from 
commercial aspirin tablets into methyl salicylate through acid-catalyzed esterification 
in methanol under reflux conditions.


\section{Results and discussion}

\subsection {Extraction and Solvation of ASA}

The synthesis began with the mechanical breakdown of commercial aspirin tablets (500~mg ASA/tablet) using a mortar and pestle. The resulting powder was digested in an excess of methanol for one hour with constant stirring.  \\

The heterogeneous mixture was subsequently clarified via filtration through a cellulose-based filter. This step effectively isolated the soluble ASA and miscible plasticizers from the insoluble structural excipients and pigments (Table~\ref{tbl:solubility}).

\renewcommand{\arraystretch}{1.5} % Adds vertical space between rows
\begin{table}[ht]
  \caption{Methanol Solubility/Miscibility Profile of Tablet Components}
  \label{tbl:solubility}
  \centering
  \begin{tabularx}{\textwidth}{l X l}
    \hline
    \textbf{Component Category} & \textbf{Specific Ingredients} & \textbf{Solubility in $\text{CH}_3\text{OH}$} \\
    \hline
    \textbf{Active Ingredient} & Acetylsalicylic Acid (ASA) & Soluble \\
    \textbf{Binders / Fillers} & Corn Starch, Powdered Cellulose & Insoluble \\
    \textbf{Coating Agents} & Carnauba Wax, Shellac, Hypromellose & Insoluble / Sparingly \\
    \textbf{Plasticizers} & Propylene Glycol, Triacetin & Miscible \\
    \textbf{Pigments / Lakes} & Titanium Dioxide, D\&C Red \#7, FD\&C Blue \#2, FD\&C Red \#40 & Insoluble \\
    \hline
  \end{tabularx}
\end{table}


\subsection{\ce{H2SO4} Catalyzed Tandem Hydrolysis--Esterification}

The conversion of ASA to methyl salicylate proceeds via a one-pot tandem sequence (Scheme~\ref{sch:mechanism}). Concentrated \ce{H2SO4} serves as a Brønsted acid catalyst, activating the carbonyl groups toward nucleophilic attack by methanol, and as a dehydrating agent to shift the equilibrium.

\begin{scheme}[H]
  \centering
  \small
  \setchemfig{atom sep=2.0em, compound sep=5em, nodesep=2pt}
  
  % Wrapper to ensure vertical alignment of the three main components
  \begin{tabular}{ccc}
    \chemname{
      \chemfig{*6(-=-(-O-[:-30](=[:-90]O)-[:+30]CH_3)=([:60]-[:90](=[:150]O)-[:30]OH)-=)}
    }{\footnotesize Acetylsalicylic Acid}
    & 
    \parbox{2.5cm}{\centering $\xrightarrow[\Delta]{\ce{CH3OH, H2SO4}}$} 
    & 
    \chemname{
      \chemfig{*6(-=-(-OH)=([:60]-[:90](=[:150]O)-[:30]O-[:+90]CH_3)-=)}
    }{\footnotesize Methyl Salicylate}
  \end{tabular}

  \vspace{1.5em}
  \caption{Tandem deacetylation and Fischer esterification sequence.}
  \label{sch:mechanism}
\end{scheme}

The transformation encompasses two concurrent equilibrium-driven processes:

\begin{enumerate}
    \item \textbf{Acid-Catalyzed Solvolysis:} The acetoxy group undergoes transesterification with methanol to yield salicylic acid and methyl acetate (Eq~\ref{eq:solvolysis}).
    \item \textbf{Fischer Esterification:} The carboxylic acid is esterified by the methanol solvent (Eq~\ref{eq:fischer}).
\end{enumerate}

\begin{equation}
    \ce{R-OCOCH3 + CH3OH <=>[H+] R-OH + CH3COOCH3}
    \label{eq:solvolysis}
\end{equation}

\begin{equation}
    \ce{Ar-COOH + CH3OH <=>[H+] Ar-COOCH3 + H2O}
    \label{eq:fischer}
\end{equation}

To drive the reaction toward the methyl salicylate product, a substantial stoichiometric excess of methanol was employed, utilizing Le Chatelier's principle to overcome the reversible nature of the esterification.

\subsection{Work-up and Purification}

Following reflux, the reaction was quenched in ice-cold distilled water. Methyl salicylate ($\rho \approx 1.17$ g/mL) was isolated as the organic phase via liquid--liquid extraction. Residual acidic species (\ce{H2SO4}, \ce{CH3COOH}) were neutralized using saturated \ce{NaHCO3}:

\begin{equation}
    \ce{H2SO4(aq) + 2NaHCO3(aq) -> Na2SO4(aq) + 2CO2(g) + 2H2O(l)}
\end{equation}

The organic extract was dried over anhydrous \ce{MgSO4} and filtered to yield the pure essential oil.

\subsection{Outline}

The document layout should follow the style of the journal concerned. Where
appropriate, sections and subsections should be added in the normal way.

\subsection{References}

References should be given in the normal way in \LaTeX{}. If you are using
\textsf{biblatex} (as recommended) then you can use the full range of citation
commands it provides. If you choose to use classical Bib\TeX{}, the
\textsf{natbib} package will be loaded and you can use it's commands.

\subsection{Floats}

New float types are set up in the preamble. The means graphics are included as
follows (Scheme~\ref{sch:example}). As illustrated, the float is ``here'' if
possible.
\begin{scheme}
  \centering
  Your scheme graphic would go here: PDF graphics are recommended.
  %\includegraphics{graphic}
  \caption{An example scheme}
  \label{sch:example}
\end{scheme}



The use of the different floating environments is not required, but it is
intended to make document preparation easier for authors. In general, you
should place your graphics where they make logical sense; the production
process will move them if needed.

\subsection{Math}

If packages such as \textsf{amsmath} are required, they should be loaded in the
preamble. However, the basic \LaTeX\ math(s) input should work correctly
without this. Some inline material $1 + 1 = 2$ followed by some display. \[ A =
\pi r^2 \]

It is possible to label equations in the usual way (Eq.~\ref{eqn:example}).
\begin{equation}
  \frac{\mathrm{d}}{\mathrm{d}x} \, r^2 = 2r \label{eqn:example}
\end{equation}
This can also be used to have equations containing graphical content. To align
the equation number with the middle of the graphic, rather than the bottom, a
minipage may be used.
\begin{equation}
  \begin{minipage}[c]{0.80\linewidth}
    \centering
    As illustrated here, the width of \\
    the minipage needs to allow some  \\
    space for the number to fit in to.
    %\includegraphics{graphic}
  \end{minipage}
  \label{eqn:graphic}
\end{equation}

\section{Experimental}

The usual experimental details should appear here. This could include a table,
which can be referenced as Table~\ref{tbl:example}. Notice that the caption is
positioned at the top of the table.
\begin{table}
  \caption{An example table}
  \label{tbl:example}
  \centering
  \begin{tabular}{ll}
    \hline
    Header one  & Header two  \\
    \hline
    Entry one   & Entry two   \\
    Entry three & Entry four  \\
    Entry five  & Entry five  \\
    Entry seven & Entry eight \\
    \hline
  \end{tabular}
\end{table}

Adding notes to tables can be complicated. Perhaps the easiest method is to
generate these using the basic \texttt{\textbackslash textsuperscript} and
\texttt{\textbackslash emph} macros, as illustrated (Table~\ref{tbl:notes}).
\begin{table}
  \caption{A table with notes}
  \label{tbl:notes}
  \centering
  \begin{tabular}{ll}
    \hline
    Header one                            & Header two \\
    \hline
    Entry one\textsuperscript{\emph{a}}   & Entry two  \\
    Entry three\textsuperscript{\emph{b}} & Entry four \\
    \hline
  \end{tabular}

  \textsuperscript{\emph{a}} Some text;
  \textsuperscript{\emph{b}} Some more text.
\end{table}

The example file also loads the optional \textsf{chemformula} and
\textsf{mhchem} packages, so that formulas are easy to input:
\texttt{\textbackslash ce\{H2SO4\}} gives \ce{H2SO4}. The two have similar
syntax but authors may prefer one or the other.

The use of new commands should be limited to simple things which will not
interfere with the production process. For example, \texttt{\textbackslash
mycommand} has been defined in this example, to give italic, mono-spaced text:
\mycommand{some text}.

\section*{Acknowledgements}

Please use ``The authors thank \ldots'' rather than ``The authors would like to
thank \ldots''.

\section*{Supporting information}

A listing of the contents of each file supplied as Supporting Information
should be included. For instructions on what should be included in the
Supporting Information as well as how to prepare this material for
publications, refer to the journal's Instructions for Authors.

The following files are available free of charge.
\begin{itemize}
  \item Filename-1: brief description
  \item Filename-2: brief description
\end{itemize}

\printbibliography

\newpage

\rule{0.05in}{1.75in}%
\begin{minipage}[b][1.75in]{3.25in}
  \sffamily
  \frenchspacing

  Some journals require a graphical entry for the Table of Contents. This
  should be laid out ``print ready'' so that the sizing of the text is correct.

  The space available depends on the journal: J. Am. Chem. Soc. allows 3.25 in
  by 1.75 in and requires sanserif text. Some journals want different sizes:
  you can easily adjust here.
  
  The two rules either side of the content are there to help judge the height
  of your material: they may be deleted once not required.
  
\end{minipage}%
\rule{0.05in}{1.75in}

\end{document}