Question

Question to answer from the lab:

What aspect(s) of the approach taken is/are NOT especially green? What changes might be made to make the overall process greener?

The Lab

Experiment Summary

Polyethylene glycols such as PEG-400 are currently of great interest to organic chemists, since their application as reaction solvents is very intriguing (1). PEG-400 is non-volatile and nonflammable in nature, and also possesses important properties such as recyclability, ease of work-up, thermal stability and economical cost. In addition, the solvating capability of PEG-400 often makes a reaction system homogeneous, which allows molecular interactions to be more efficient. In this experiment, PEG-400 will be utilized as a “green” solvent for the reaction between an aromatic aldehyde and two equivalents of a diketone to form a condensation product. This takes place at room temperature and highlights a number of green chemistry principles (2).

Background

Green chemistry is the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances. Often referred to as a form of molecular-level pollution prevention, green chemistry relies on a set of twelve principles that can be used to design or re-design molecules, materials and chemical transformations to be safer for human health and the environment (2). Organic solvents (in particular volatile organic solvents (VOCs)) are used in the manufacturing and processing of almost all commercially available products. VOCs are typically small organic molecules, which are volatile, flammable and often toxic in nature. Studies have shown that use of large quantities of VOCs and their release in the atmosphere has led to a significant destruction of the protective ozone layer. With an increasing emphasis on using green chemistry principles in the chemical industry to employ safer and environmentally friendly compounds, there has been keen interest in finding alternative solvents to VOCs. PEG-400 (structure below) can be considered as a useful option in this regard (3).

In today’s experiment, PEG-400 is used as a recyclable solvent for the catalyzed condensation reaction between 4-nitrobenzaldehyde and 5,5-dimethylcyclohexane-1,3-dione (dimedone). Racemic proline (an amino acid) acts as an organocatalyst under these conditions toform a tetraketone product that exists in its dienol form 1 below, Scheme 1.

Tetraketones are important intermediates for the preparation of heterocyclic compounds (4) and various laser dyes (5). Several methods have been reported for the synthesis of tetraketones using NaOH (6), piperidine (4), proline (7), L-lysine in water (8), L-histidine in an ionic liquid (9), under grinding conditions (10), and in the solid-state (11). Recently, synthesis of tetraketones in PEG-400 was described (3).

In this reaction, both PEG-400 and racemic proline will be recycled making both of them reusable. Some of the green chemistry principles exemplified in this transformation are noted in the following table, Table 1.

Green Chemistry Principle	Application of Green Chemistry Principle in this Reaction
Pollution Prevention	Use of a non-volatile solvent that is recycled
Less Hazardous Chemical Synthesis	Use of a non-toxic, non-volatile solvent
Safer Solvents and Auxiliaries	Solvent and catalyst are non-volatile, non-toxic and can be both recycled
Design for Energy Efficiency	Reaction undertaken at room temperature (lower than traditional synthetic methods)
Catalysis	Use of an amino acid organocatalyst
Inherently Safer Chemistry for Accident Prevention	Reaction run at ambient temperature, reducing the risk of accidents

Experimental Procedure

1. In a hood, place the following in a 25-mL round-bottomed flask:

4-nitrobenzaldehyde (151 mg); 5,5-dimethylcyclohexane-1,3-dione (280 mg); (±)-proline

(57 mg) and PEG-400 (2 mL – use an automatic delivery pipette). ALTERNATIVELY,

use PEG-400/(±)-proline that was recycled by a previous student after their reaction.

2. Introduce a small stir bar and stir VIGOROUSLY at room temperature using a magnetic

stirring plate.

3. After 30 minutes, perform TLC on the reaction solution (stationary phase, silica gel; eluent, 2:1 hexanes:ethyl acetate). Be sure to include the following three spots on the TLC plate (left lane: 4-nitrobenzaldehyde; centre lane: 5,5-dimethylcyclohexane-1,3-dione; right lane: product mixture) and visualize the spots using ultra-violet light at 254 nm.

Perform TLC again after one hour of reaction time.

4. Remove the flask from the magnetic stirring plate and add ice-cold water to the reaction flask (10 mL). Return the flask to the stirrer/hotplate and stir for 10 minutes (a white precipitate will form).

5. Collect the crude product by vacuum filtration using a Hirsch funnel, rinsing any residual product from the reaction flask with no more than 5 mL of ice-cold water. Leave the solid under vacuum on the filter funnel until it is reasonably dry. Be sure to re-filter any solid that passes through the filter paper into the vacuum filtration flask.

6. Pour the filtrate from the vacuum filtration flask into a 50-mL round-bottomed flask and evaporate the water using a rotary evaporator. Place the recycled PEG-400/(±)-proline into a vial for future student use.

7. Recrystallize the crude solid product from a MINIMUM amount of absolute ethanol and rinse the solid with a small amount of ice-cold solvent (2 mL). Be sure to re-filter any solid that passes through the filter paper into the vacuum filtration flask. Record the mass, percentage yield and melting point of your dried product. Obtain an IR spectrum and ¹H NMR spectrum (CDCl₃ solvent).

Answer 1

Using ethanol as the crystallizing solvent is not green in the process. Ethanol is volatile, flammable solvent and hence use of it makes process non-green.

Ice-water was used to form precipitate of the product which means water can be used for re-crystallization of the product as like ethanol, water is also polar.

Water being non-volatile and non-flammable will turn the process greener.