Lab Experiment in Azo Dye Preparation

Lab Experiment in Azo Dye Preparation Objective: The preparation of azo dyes is a standard reaction in the sophomore organic chemistry lab.� Its adaptation to a parallel synthesis format is straightforward and the assay is trivial.� Since the dyes vary widely in color, the diversity of this parallel synthesis becomes obvious.� In addition to parallel synthesis, the more standard sophomore organic topics of diazotization, electrophilic aromatic substitution and various analytical techniques enter into the discussion. The experiment as described below is written to allow the student to obtain pure compounds that can be characterized by NMR and other analytical techniques.� If only a color test is desired, the latter purification steps can be omitted. The reaction at Miami University was carried out in the Organic Chemistry Lab for Majors second semester course, CHM 255.� The work was done on a parallel synthesis apparatus, the FirstMate from Argonaut Technologies.� The experiment as described is apparatus independent and can be adapted to the equipment footprint of the individual lab. References: 1. 1. Marina Caldarelli, Ian R. Baxendale and Steven V. Ley, Green Chemistry, 43, April, 2000. 2. 2. Another approach, allowing isolation of the diazonium ions on an ion exchange resin is reported in James Merrington, Mark James and Mark Bradley, Chem. Commun., 2002, 140.� We prefer the former approach for our sophomore lab and describe it herein, but the latter has been tested and found to be effective as well. Safety Considerations: Due diligence should be exercised in this reaction, as in all reactions.� The scale of the work is such as to minimize wastes, but products should be discarded as organic waste.� The polymerbound nitrite ion species should be made fresh, but can be stored for months as required.� It should not be exposed to heat and should not be capped airtight.� Diazonium ions should be used immediately.� Stored compounds can decompose, sometimes violently. Reaction: Ar

NH2

+

HNO2

Ar

N

N

Ar' N Ar'

Ar N

The library synthesis is made possible by generation of nitrous acid from polymer-bound nitrite ion.

The choices of anilines are: NH2

NH2

NH2

NH2

NO2

OCH3

NO2

The co-reactants can be chosen from among the following: OH OH

OH

N

N

This affords a potential library of 20 dyes (regiochemistry of substitution is well controlled).� Not all reactions are reported to work and the array of colors is not impressive.� Colors vary with pH when the isolated dyes are formed.� Our choice was to follow the paper and evaluate the following dyes:

OH

pH = 0 yellow pH = 14 yellow

N N

OH

pH = 0 orange pH = 14 yellow-orange

N N

H3CO OH

pH = 0 yellow pH = 14 red

N N

O2N OH NO2

pH = 0 yellow pH = 14 orange

N N

OH

N N

O2N

pH = 0 orange pH = 14 blue

HO

pH = 0 yellow pH = 14 violet

N N

O2N

N

pH = 0 pink pH = 14 yellow

N N

N

pH = 0 red pH = 14 orange

N N

O2N

N NO2 N N

pH = 0 red pH = 14 orange

N

pH = 0 orange pH = 14 orange

N N

O2N

N

N N

no product isolated

H3CO

The reaction pairs to form these azo dyes is obvious.� It is not clear why the final entry is not successful, and we see no reason not to examine expanding the library, but in the sophomore lab context, this small library may be enough. Experimental Procedure: Preparation of polymer bound nitrite (occasionally this can be purchased, but is quite expensive). Amberlyst A-26 strongly basic ion exchange resin was stirred overnight at room temperature in 2M HCl (large excess).� The resin was filtered on a Buchner funnel and washed with distilled water until the filtrate was neutral. The resulting solid was suspended in a 2M aqueous solution of sodium nitrite and stirred for one hour.� The polymer bound nitrite was isolated by filtration, washed with distilled water and allowed to air dry. Diazonium Ions � since these are immediately reacted, they should be prepared in parallel fashion, i.e., one vessel per prospective reaction.� Into each vessel was placed one gram of the polymeric nitrite ion prepared above.� At 0C is added a solution of 50mg aniline in 2mL of 37% HCl (a stock solution of each aniline can be prepared at this concentration and metered into

the appropriate vessel).� The slurry is agitated for five minutes and a solution of the diazonium ion isolated by filtration.� Coupling (Once again using stock solutions) 50mg of the phenol, naphthol or dimethylaniline in 4mL 10% NaOH (the aniline derivatives should also include 250mg pyridine).� The reactions proceed with stirring and solid precipitates formed rapidly.� The precipitates are the crude azo dyes. Purification Reactions with phenol Dissolve product in methanol.� Add Dowex(OH) resin to absorb the colored dye.� Release the azo compound by washing the filtered resin with acetic acid.� Cool the solution and add 10% NaOH until the pH=7.� Upon cooling, the pure azo compound precipitates. Reactions with naphthols Products do not dissolve in methanol.� They can dissolve in dichloromethane and eluted on a small column of silica gel.� Collecting the deepest colored band affords, after evalporation, the pure azo compounds. Reactions with dimethylamino compounds The products are also dissolved in dichloromethane, washed with acid to remove pyridine and subjected to chromatography in the same way as the naphthols. Color analysis The dyes are slurried with aqueous solutions at the appropriate pH and the color dissolved.� Some dyes are sparingly soluble, addition of a small amount of acetonitrile aids dissolution.

NMR spectra (200 MHz) of the products are shown below as isolated from the chromatography or the ion exchange.� They are recorded in deuterated acetone, hence an acetone peak and often a water peak.� A few other extraneous peaks are observed, but the overall purity in the aromatic region is clear.