[Hand15]

So over the past few weeks I've been trying to replicate the synthesis of Diazirine Photo-Crosslinkers reported in this paper (http://onlinelibrary.wiley.com/doi/10.1002/anie.201300683/abstract)

Everything went smoothly without problem except with the key diaziridination step. The reported yield was about 70%, but I got less than 10% yield! (yield inconsistent from one attempt to another).

At first I thought the reaction requires dry condition, so I set the reaction under gentle N2 stream so no outside air can come into my flask, but it seems that diaziridination works even in open air and aqueous solution (see: http://www.orgsyn.org/demo.aspx?prep=CV5P0897)

I followed the procedure as closely as possible. The only thing that I did not control well is the addition of hydroxylamine-O-sulfonic acid, which was supposed to be added over 30 minutes (I add HOSA under 5 min due to smaller scale of my reaction). I don't think that is the problem though. But is it?

Or is it the problem with my reaction set up? (See attachment) I suspect the N2 stream remove away all NH3 before the reaction is complete?

[wildfyr]

Diarizines (and really, any N=N bonded molecules) are rather sensitive to thermal degradation, so perhaps even in the dry ice/acetone bath your reaction is getting too hot. Thats why you add your hydroxylamine so slowly in the lit procedure. Why dont you try adding by syringe hanging through a septum since its a small volume, and that will allow you to add literally a single drop at a time.

Just so everyone can see

2-(3-(But-3-ynyl)-3H-diazirin-3-yl)ethanol (16). Anhydrous ammonia (20 mL) was condensed into a round-bottomed flask containing (ketone precursor) (2.52 g, 20 mmol) in an acetone-dry ice bath. The mixture was stirred at 35-40 °C for 5 h. The solution was cooled with dry ice, and a solution of hydroxylamine-O-sulfonic acid (2.59 g,
23 mmol) in anhydrous methanol (6 mL) was added over a period of 30 min. The acetone-dry ice bath was removed, and the mixture was refluxed with stirring at 35 °C for 1 h. The remaining ammonia was then allowed to evaporate overnight. The resulting slurry was filtered and the filter cake washed with several portions of methanol.
The combined solution was evaporated in vacuo. The residue of the diaziridine derivative was dissolved in dichloromethane (10 mL) and treated with triethylamine (3.5 mL). A solution of iodine (3.7 g, 28.8 mmol) in dichloromethane (10 mL) was slowly added with stirring until the appearance of a persistent orange-brown coloration. The mixture was chromatographed on a column of silica gel equilibrated with dichloromethane hexane
(4:1 v/v). After successive washing of the column with this solvent and then with dichloromethane containing 5% ether to give 2-(3-(but-3-ynyl)-3H-diazirin-3-yl)ethanol 16 (1.92 g, 70%).

[Hand15]

Diazirine is actually surprisingly stable. If you look at the next step after the diazirination, the diazirine product is actually heated up to reflux temperature.
One thing that I highly doubt is the part where it calls for stirring at 35-40 °C, do you think it should be -35-40°C (minus)? I did the reflux at -35 (boiling point of ammonia). I don't know whether it is safe to heat liquid ammonia to 35°C. 

I'm now trying to stir it at RT to see if i get some improvement.

[Enthalpy]

Stray light? Diazirines reportedly react to near-UV like 360nm, which both fluorescent lights and sunlight bring. Filament bulbs emit less UV, and red "inactinic" light was developed for such purposes.

[wildfyr]

Good point, definitely try to do this all covered in foil! They are quite UV-activatable. Also, just because the final diazirine is decently thermally stable doesnt mean any of the various intermediate compounds in this reaction are

[vnaanwani]

HEY,
I HAVE BEEN TO PREPARE DIAZIRINE FROM LAST FEW WEEK. BUT I AM NOT SUCCESSFUL YET, I AM USUING METHANOLIC AMMONIA INSTEAD OF UNHYDROUS ONE. WOULD YOU KINDLY TELL ME THE PROCEDURE TO CNDENSE THE AMMONIA.

[wildfyr]

Do you truly expect help typing in all capital letters? That is considered pretty rude on the internet, like shouting in someone's face.

[gedftsnd]

Diazirinenes can be stable and yes caps lock is a bit much

[PeterYW]

The factor most directly related to the yield is the amount of liquid ammonia. You cannot use a nitrogen stream to purge the system, as this will cause the liquid ammonia to leak out. Using a closed system and ensuring that every 1g of substrate is reacted in about 15 ml of liquid ammonia will greatly increase your yield.

[rolnor]

Very nice to see an apparatus like this, great! I would follow the procedure to the letter, thats always a good start. add the reagent slowly.