EXERCISE 1 Nucleophilic Aromatic Substitution (SNAr): Synthesis of 2,4-DNP

I. Introduction 2,4-Dinitrophenylhydrazine is one of the components of bradys reagent commonly used in the analysis of ketones and aldehydes. It is usually synthesize through the reaction of hydrazine sulfate with 2,4-dinitrochlorobenzene under Nucleophilic Aromatic Substitution (SNAr). (show general equation here) Nucleophilic substitution reactions of aryl halides occur when strong electronwithdrawing groups are ortho or para to the halogen atom, making the aryl carbon bonded to the halogen (ipso carbon) susceptible to the nucleophilic attack (Solomons & Fryhle, 2011). This is caused by the stabilized intermediate anion by resonance. Nucleophilic substitutions on an aromatic ring proceed by a two step mechanism: first is the addition of the nucleophile to the electron-deficient aryl halide, forming a resonance-stabilized negatively charged intermediate called a Meisenheimer complex (show mechanism here) and second is the elimination of the halide ion. (show mechanism here)

In the first rate-determining step, ipso attack by the nucleophile produces an anion with a highly delocalized charge stabilized by its resonance. In contrast when the substituents are in the meta position relative to the ipso carbon, delocalization of the electrons are hindered so 1-chloro-3,5-dinitrobenzene compound does not undergo SNAr reactions under the conditions employed (Vollhardt, Peter & Schore, 2011). To carry out the reaction in the experiment, heating, suction filtration and reflux are the essential techniques to be used. Followed by recrystallization and weighing prior to characterization.

The first part of the experiment involves the addition of water to hydrazine sulfate. H20 is added to ionize the hydrazine sulfate and thus, the nucleophile is generated. (Show reaction here) Sodium acetate is also added to buffer the mixture. It is then heated for further dissolution of the salt. After slight cooling it is filtrated using ethanol as the solvent. The filtrate is carried for the synthesis proper. The hydrazine solution is added with 2,4-dinitrochlorobenzene and undergoes reflux for one hour. After reflux, the solution is filtered and washed with cold water before washing with warm ethanol. This is for rapid recrystallization of the salts and for minimizing the trapping of impurities. The residue is dried and weighed before characterization. Reactions of 2,4-Dinitrophenylhydrazine to ketones and/or aldehydes to form 2,4Dinitrohydrazone is signaled by a yellow precipitate. (Show reaction here) The reaction can also be considered as an addition-elimination reaction: nucleophilic addition of the -NH2 group to the C=O carbonyl group, followed by the removal of a H 2O molecule. Specifically, when 2,4-Dinitrophenylhydrazine reacts with benzaldehyde and acetone, the following general reactions and mechanisms are observed: (show reaction for benzaldehyde)

(Show reaction for acetone) Crystals of different hydrazones have characteristic melting and boiling points, allowing the identity of a substance to be determined in a method known as derivatization (Shriner, etal., 1998). In this experiment, the student should be able to (1) synthesize 2,4Dinitrophenylhydrazine from 2,4-dinitrochlorobenzene, (2) Characterized the product through derivatization, and (3) write all the mechanisms involved in each reactions.

II. List of necessary chemicals and set-ups A. List of necessary chemicals

NAME and STRUCTURE

AMOUNT (g)

Purpose in the experiment

Physical properties

Hazards and precautions/ first aid

B. Set-Up

Figure 1.1. Reflux set-up

Figure1.2. Suction Filter set-up