Alpha-bromo-p-tolunitrile (Acros Organics)

DIBAH 1M (Aldrich)

Toluene (distilled over NaH)

HCl 1M

Dichloromethane (EMD)

Hexanes (EMD)

Di Water

Sodium Sulfate

Celite (Aldrich)

All glassware was stored at 110°C or at least 10 hours prior to the reaction.  Alpha-bromo-p-tolunitrile (2.99g 1.53x10-2mol) was added to a 250mL 3 necked round bottom flask fixed with a 25mL dropping funnel.  The assembled reactor was sealed with rubber septa, purged with Nitrogen (UHP) for 10 min, then dried with a heat-gun under vacuum.  Anhydrous toluene (~100mL) was added to the reactor via a solvent bridge.  The solution was then stirred and cooled in an ice bath.  After 30 minutes at 0°C, 1M DIBAH (17.6mL 1.76x10-2mol) was added to the dropping funnel.  The DIBAH was added dropwise from the dropping funnel into the nitrile solution.  Once all of the DIBAH was added to the flask, the contents were allowed to react with stirring at 0°C over the course of which the solution turned from colorless to light yellow.  After 3 hours, the solution was checked by TLC (80% dichloromethane 20% hexanes) spotted against the starting material and revealed that no nitrile remained.

Cold 1M aqueous HCL(~100mL) was added to the solution and allowed to stir at room temperature for 30 minutes over the course of which the solution turned colorless and white emulsion formed.  The entire content of the flask was filtered through Celite.  The two phases were then separated.  The organic phase was washed 3x50mL with 1M aqueous HCl.  Then all of the aqueous phase was washed 3x50mL with dichloromethane.  All of the organic solution was collected and dried over sodium sulfate.  The dried organic solution was concentrated then analyzed by HNMR in CDCl~3~ to be 98% p-bromomethyl benzaldehyde with a total mass of 2.74g (88% yield).

A solvent bridge is constructed using a syringe needle that is sharp on both ends that may penetrate two septum sealed containers.  External pressure is supplied to the reagent container and a normal syringe needle is used to relieve pressure build up in the receiving container.  Reagents flow cleanly through the solvent bridge with little to no contact with the ambient atmosphere.  I find that this method of transferring anhydrous reagents is easier and cleaner than using a syringe, especially for volumes greater than 5mL.

Separation of the aldehyde from unreacted nitrile and the overreacted primary amine product was very difficult.  It was therefore very important to make sure that the nitrile was completely consumed but not allowed to react with a second equivalent of DIBAH.  Because DIBAH is so moisture sensitive, a slight excess is necessary for the reaction to run to completion.  It is difficult to estimate the excess of DIBAH necessary to completely consume the nitrile without a bit of experience.  It is best to start off by adding only 1 equivalent of DIBAH and checking the reaction by TLC.  Excess DIBAH can be added about 0.05 mole equivalents at a time until TLC indicates that no nitrile remains.

If the reaction is run cleanly, no further purification is necessary.  However, the aldehyde recrystallized nicely in 100% hexanes.