Co-authored by Athavan Alias Anand Selvam and Harshitha Suresh

Teaching organic chemistry to high school students can often be challenging, as many struggle with essential concepts like structural isomerism, reaction mechanisms, and IUPAC nomenclature. Unfortunately, the typical syllabus for organic chemistry seldom encourages lab-based activities, which could make these abstract concepts more tangible. Unlike inorganic chemistry, which is frequently explored through hands-on activities—such as experiments with acids, bases, and metal salts—organic chemistry rarely includes engaging lab exercises.

Introducing Synthetic Organic Chemistry to the High School Students

Facile Method to Synthesize an Organic Compound

To bridge this gap, we developed an activity that not only introduces students to synthetic organic chemistry but also immerses them in the experience of working as a chemist. In this lab, students learn to follow safety protocols, following lab manual, monitor reactions, yield calculation, and use thin-layer chromatography for reaction analysis. The activity centers around the Mannich Condensation reaction, a one-pot synthesis that can be conducted under mild conditions with straightforward reactants. It’s a fantastic opportunity for students to synthesize an organic compound in a classroom or lab setting, applying fundamental concepts like the mole concept in a real-world context. This reaction involves the combination of 3-pentanone, benzaldehyde, and ammonium acetate (Reaction Scheme 1) to produce 3,5-dimethyl-2,6-diphenylpiperidin-4-one—a compound with both ketone and amine functionalities.¹

In our experience, students not only enjoyed the synthesis but also gained a deeper appreciation for organic chemistry. Hands-on activities like this can significantly enhance student motivation and engagement, transforming their theoretical knowledge into practical skills through experiential learning.

Reaction scheme 1: Reactants and reaction condition to synthesize 3,5-dimethyl-2,6-diphenylpiperidin-4-one

Materials

• Erlenmeyer flask (250 mL)
• Measuring cylinder (20 mL)
• Hot plate or Bunsen burner
• Weighing balance (kitchen balance/laboratory balance)
• Ethanol
• 3-pentanone
• Benzaldehyde
• Ammonium acetate
• Printed materials for students and writing tools

Background

Procedure

Step 1: Begin with a clean 250 mL Erlenmeyer flask and add 20 mL of ethanol.

Step 2: Add the required amounts of 3-pentanone, benzaldehyde, and ammonium acetate to the ethanol. Heat the flask to 60°C, gently shaking it for five minutes until the reaction mixture becomes a pale-yellow solution. Take care not to allow the solution to boil.

Step 3: Cover the mouth of the flask with butter paper or aluminum foil, and leave the solution at room temperature (25°C) to allow white crystals to form. Crystals should appear within 6–12 hours.

Workup Procedure: Once the 3,5-dimethyl-2,6-diphenylpiperidin-4-one crystals have formed, decant and discard the excess yellow solution from the flask. Rinse the crystals twice with 20 mL of ethanol each time, carefully decanting and discarding the wash. Allow the compound to dry completely, then weigh it to calculate the yield.

Optional: If possible, students can also use thin-layer chromatography (TLC) to assess the purity of the product and learn about the TLC technique. Procedure for TLC: Dissolve very small amount of crystal (piperidone compound), benzaldehyde, and 3-pentanone separately in acetone and place each solution in a vial. Spot the solutions onto a TLC plate, and use a 1:1 mixture of hexane and ethyl acetate as the mobile phase. After developing the TLC plate, visualize the spots under short-wave ultraviolet (UV) light at 254 nm.

Figure 1. Images captured during the experiment by our students (a) crystals obtained after 12 hours, (b) decanting the excess liquid in the conical flask, (c) rinsing the crystals with ethanol, and (d) students recording their observation including thin layer chromatography.

We synthesize the compound by following the above procedure and the white crystals formed is shown in figure 1a. Later we rinsed with ethanol twice, dried and weighed the product formed. Based on the weight of the compound, we calculated the yield as shown below. Also, our students checked the purity of the compound using TLC by following the above procedure. We asked the students to draw the TLC plate results under UV (figure 1b) in their record notebook.

Yield Calculations

• Theoretical yield of 3,5-dimethyl-2,6-diphenylpiperidin-4-one = Mol. Wt. × moles expected = 279 × 0.1 = 27.9 grams
• The actual yield of 3,5-dimethyl-2,6-diphenylpiperidin-4-one = 22.6 grams
• Yield percentage = (actual yield ÷ theoretical yield) × 100 = (22.6÷27.9) × 100 = 81%

Conclusion

The reaction described above, between a ketone, an aldehyde, and ammonium acetate, is a classic example of the Mannich condensation. Due to the simple reaction conditions and straightforward workup, this activity is well-suited for high school students. We engaged our grade 10 students in this lab experiment under close supervision, and they thoroughly enjoyed the experience—from wearing personal protective equipment (PPE) to handling chemicals, glassware, and lab equipment like hot plates and weighing balances, which allowed them to feel like true scientists. Safety protocols were strictly followed; students were permitted to proceed only after wearing lab coats, gloves, goggles, and closed-toe shoes.

We recommend this simple, one-pot organic chemistry reaction as an excellent introductory lab activity for high school students. It offers hands-on experience in synthesizing organic compounds while reinforcing concepts like the mole, organic reaction naming, purification, and yield calculation. Additionally, teachers may choose to introduce thin-layer chromatography (TLC) as outlined in the procedure, providing students with a valuable analytical technique.

Safety

• Personal Protective Equipment (PPE): All students were required to wear lab coats, gloves, safety goggles, and closed-toe shoes throughout the experiment. These protective measures safeguarded them from potential chemical exposure or accidents.
• Proper Ventilation: Since organic solvents like ethanol can release fumes, the experiment was conducted in a well-ventilated area, ideally under a fume hood, to minimize inhalation risks.
• Chemical Handling: Students were instructed on safe handling and disposal practices for each reagent—3-pentanone, benzaldehyde, and ammonium acetate. They were advised not to directly inhale fumes, taste, or touch chemicals, and were guided to report any spills immediately.
• Supervised Heating: During the reaction, students were supervised while using a hot plate to heat the solution to 60°C. They were cautioned to avoid overheating or boiling the solution, as this could lead to splattering or unwanted reactions.
• Emergency Preparedness: Students were briefed on emergency procedures, including the location and proper use of safety equipment like fire extinguishers, eyewash stations, and safety showers.

Questions

Concepts

Time Required

Two 45-minute sessions on separate days

Preparation

To ensure a smooth setup and execution of the reaction, it is essential to prepare all
materials and reagents in advance. Teachers or the lab attenders can help students in
weighing the required quantities of 3-pentanone, benzaldehyde, and ammonium acetate
for each group to minimize errors and save time. Arrange glassware, spatulas, and
butter paper in ready-to-use condition to avoid delays caused by cleaning or rinsing.
Label each student group's conical flask with a permanent marker to prevent confusion,
and ensure all non-essential items, such as bags and water bottles, are kept away from
the workspace. If fume hood facilities are unavailable, convert this into a group activity
to better manage the lab environment and minimize mess. Maintaining the reaction
temperature at approximately 60°C (referred to as a "bearable heat" for students) is
critical for optimal results. Avoid boiling the mixture because 3-pentanone (boiling
point: 102°C) may evaporate, significantly reducing the yield. If hot plates are not
available for every group, a hot water bath (around 70°C) can be used as an alternative
for gentle heating. Additionally, emphasize the importance of using cold ethanol for
washing the crystals, as the product is partially soluble in ethanol, and warm ethanol
may dissolve the crystals, decreasing the yield. Students should wash the crystals gently
to avoid product loss.
To streamline the post-reaction process, direct students to weigh their conical flasks
(empty weight) before starting the experiment. This allows them to calculate the
product yield after drying the crystals without transferring them to another container,
reducing the risk of spillage or loss. For quicker drying, place the conical flask with
washed crystals in an oven at 80°C or use a hot water bath to evaporate residual
ethanol. To manage waste effectively, provide designated waste containers and instruct
students to transfer solutions into these containers as part of proper waste
management practices. These steps will ensure a smooth and efficient experiment while
helping students focus on learning key concepts.

Attribution

1. Noller, C. R.; Baliah, V. The preparation of some piperidine derivatives by the Mannich reaction. J. Am. Chem. Soc. 1948, 70(11), 3853–3855.

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