Problem P6. 2,3-Dihydro-5,6-diphenylpyrazine

An imine is a functional group or chemical compound containing a carbon–nitrogen double bond. Some imine compounds can sometimes be referred to as Schiff bases. Imines may find utility in a wide range of contexts, including the development antimicrobial, antiviral and anticancer agents. Imines are also common intermediates in enzymatic reactions and are used as common ligands in coordination chemistry. They are also used in nanotechnology for water treatment, encapsulation and functionalized magnetic nanoparticle production.

In this experiment you are asked to synthesize 2,3-dihydro-5,6-diphenylpyrazine (DPP) through an imine formation reaction, starting from benzil and ethylenediamine.

Chemicals

Substance Name State GHS Hazard Statement

C14H10O2 Benzil Solid H315, H319, P302 + P352, P305 + P351 + P338 H2NCH2CH2NH2 Ethylenediamine Liquid H226, H302 + H332, H311, H314, H317, H334, H412, P210, P273, P280, P301 + P330 + P331, P302 + P352, P304 + P340, P305 + P351 + P338, P308 + P310 C2H5OH Ethanol Liquid H225, H319, P210, P305 + P351 + P338

Glassware and equipment

 1 Round-bottom flask, 250 mL  1 Stirring bar  1 Pipette, 10 mL  1 Reflux condenser  1 Beaker, 100 mL  1 Crystallization dish, 500 mL

 1 Büchner funnel  1 Büchner flask  1 Filter paper  1 TLC development tank  1 TLC sheets  1 UV lamp  1 Magnetic stirrer with a hot plate  1 Ice-water bath

Procedure

1. Dissolve 10 g of benzil in 30 mL of ethanol (95%) by heating in a 250 mL round bottom flask. Add 4.5 mL of 68% ethylenediamine (or an equivalent quantity of ethylenediamine in different concentrations).

2. While stirring, heat the mixture in a water bath under a reflux condenser for 45 minutes (See Figure P4.1 for reflux condenser apparatus).

3. If crystals have not formed in the flask, immediately transfer the hot supersaturated solution into a 100- or 150-mL beaker. The difficulty of removing the crystals from the flask is thus avoided.

4. Often crystallization occurs at once when the solution is poured into the beaker, and sufficient heat is evolved to cause the alcohol to boil. Cool to room temperature. Finally, place in an icebath (For detailed recrystallization see P5.8).

5. The loss due to solubility in cold alcohol is negligible. Filter the crystals, and wash them with a little alcohol. Dry the product using a suction filter (For vacuum filtration apparatus see P5.7).

6. Weigh the dried product and calculate the percent yield.

7. Determine melting point (highly purified DPP melts at 161.5162.5 C), and reserve a little amount of product for TLC analysis.

8. Perform TLC analysis using the recrystallized product and reference benzil (See P5.12 for a sample procedure of TLC analysis).

9. Report the Rf values of each compound and check the purity of the recrystallized DPP.

Question

P6.1. What is the product when DPP is oxidized?

P6.2. Is the oxidation product of the DPP aromatic?

P6.3. Which of the following reactants or methods could be used for the oxidation of DPP?

☐ 2,3-Dichloro-5,6-dicyanobenzoquinone (DDQ) ☐ Heating in air ☐ Et3N ☐ Na2CO3 ☐ Slight heating under vacuum

P6.4. What are the hybridizations of nitrogen (b) and carbons (a and c) in DPP?

P6.5. Draw the structures of the products when 1,3-propanediamine and 1,4-butanediamine were used instead of ethylenediamine.

Solution:

P6.1. The oxidation product of DPP is 2,3-diphenylpyrazine.

P6.2. The oxidation product 2,3-diphenylpyrazine is an aromatic compound since:  all the atoms of the pyrazine ring are sp2 hybridized and  the pyrazine ring obeys Hückel’s rule. P6.3. The following marked reactants or conditions could be used for the oxidation of DPP.

☒ 2,3-Dichloro-5,6-dicyanobenzoquinone (DDQ) ☒ Heating in air ☐ Et3N ☐ Na2CO3 ☐ Slight heating under vacuum

P6.4.

P6.5.

Products with 1,3-propanediamine and 1,4-butanediamine