Experiment 22: THE SOLVENTLESS ALDOL-TYPE CONDENSATION

Objectives:  To synthesize an ,  unsaturated ketone from an aldehyde and a ketone using solvent-free conditions.  To purify the product through a recrystallization.  To identify and analyze purity through TLC and melting point analysis.  To analyze the product using IR spectra.

Before coming to lab…  Review these techniques: Recrystallization TLC Analysis Melting Point Analysis

ALDOL CONDENSATIONS  Aldol condensations are nucleophilic additions of an enolate ion, which are strong nucleophiles, to another C=O group under basic conditions.  Protonation gives the aldol product.  Once formed, the aldol product undergoes dehydration in base.  Abstraction of an a proton gives an enolate that can expel an –OH ion to give a conjugated product.  Dehydration is usually exothermic because it leads to a very stable conjugated product.

CHEMICAL EQUATION 3,4-dimethoxy benzaldehyde 1-indanone Aldol Product

MECHANISM Base removes  proton to form enolate ion. Resonance stabilized enolate forms carbanion, which attacks C=O of aldehyde When new C-C bond forms, C=O  bond breaks, electrons stay with oxygen. Oxygen anion removes proton from water, releasing –OH. Acidic  proton is removed by –OH. Electrons form new  bond.

TYPICAL ALDOL CONDENSATION  A typical aldol condensation reaction is carried out in an organic solvent, such as ethanol, requiring eventual waste disposal.  Isolation of the product requires a much more involved work up, not to mention the hazards to the experimenter and the environment due to waste disposal.  Another challenge is that solution phase reaction is reversible, so low product yields may result.

GREEN CHEMISTRY CONCERNS  One of the main themes of greener chemistry is to cut down on the use of solvent, and hence cut down on solvent waste. The best way to do this is simply not to use any solvent at all.  Workup is generally easier since as the reaction proceeds, the product separates from the melt as a solid, making work up much less complicated.  Another benefit is that unlike a solution phase reaction, the solid-state reaction is irreversible, resulting in higher chemical yields.

EXPERIMENTAL PROCEDURE (Synthesis)  Place aldehyde and ketone in large test tube.  Crush solids with glass rod until liquefied.  Add NaOH. Mix and scrape sides of test tube until pale green solid forms.  Continue to react for 15 minutes at room temperature.

EXPERIMENTAL PROCEDURE (Purification and Product Isolation)  Place test tube in a 90 o C water bath.  Add 90:10 PROPANOL/WATER and heat until solid dissolves.  Suction filter.  Transfer solid to PREWEIGHED WATCH GLASS AND PLACE IN OVEN 15 MINUTES to dry.  Obtain final product mass and calculate % yield.  Proceed to PRODUCT ANALYSIS (TLC, mp, IR).

Table 22.1 Theoretical yield (g) Determine limiting reagent first, then calculate theoretical yield. HINT: Don’t round too soon! Actual yield (g) % yield Melting range ( o C) Start temperature dial on setting of 5. Back down one tic mark ~ 150 o C and watch closely. Record T i -T f range. Compare to literature value to determine purity of product. Product Appearance Record the physical state and color of product.

Table 22.4 Atom Economy (%) Calculate based on reactants ONLY! Review Experiment 13 for calculation. Experimental Atom Economy (%) Calculate based on reactants ONLY! Review Experiment 13 for calculation. “E product ” Review Experiment 13 for calculation. Cost Per Synthesis ($) Costs of stock bottles of compounds on p Remember to use reactants and catalyst in this calculation! Cost per Gram ($/g) CPS/actual yield (g)

Table 22.2 Compound TLC R f values StandardSample 1-indanone R f values are UNITLESS! R f values are 2 decimal places ONLY! 3,4-dimethoxybenzaldehyde Aldol Product

Product Analysis (IR)

Table 22.3 Functional Group Base Values (cm -1 ) 1-Indanone3,4-dimethoxy -benzaldehyde Aldol Product Frequency (cm- 1 ) Frequency (cm- 1 ) Frequency (cm- 1 ) sp 3 CH stretch sp 2 CH stretch C=O stretch C-O stretch aromatic C=C stretch (2) aldehyde CH stretch (2)

SAFETY CONCERNS  Solid NaOH is very corrosive! Immediately flush skin with water if any gets on your skin!  Propanol is very flammable! Use extreme caution during purification!

WASTE MANAGEMENT  Place all liquid waste in container labeled “LIQUID ORGANIC WASTE”.  Place all solid waste in container labeled “SOLID WASTE”.  Place all used TLC capillaries and melting point capillaries in broken glass container, NOT TRASHCAN!  Leave TLC chambers with lids off in your lab drawer.

CLEANING  Clean all glassware with soap, water, and brush, followed by a rinse with wash acetone before returning to lab drawer.  DO NOT return any glassware to lab drawer dirty or wet!