scarmani (Hive Bee)
06-16-03 19:03
No 440423
      Question Regarding Shulgin's 2C-E Synthesis  Bookmark   

"A solution of 8.16 g of 2,5-dimethoxy-1-ethylbenzene in 30 mL CH2Cl2 was cooled to 0 C with good stirring and under an inert atmosphere of He. There was then added 11.7 mL anhydrous stannic chloride, followed by 3.95 mL dichloromethyl methyl ether dropwise over the course of 0.5 h. The stirred reaction mixture was allowed to come up to room temperature, then held on the steam bath for 1 h. The reaction mixture was poured into 1 L water, extracted with 3x75 mL CH2Cl2, and the pooled extracts washed with dilute HCl. The organic phase was stripped under vacuum yielding 10.8 g of a dark viscous oil. This was distilled at 90-110 C at 0.2 mm/Hg to yield a colorless oil that, on cooling, set to white crystals"

Dichloromethyl methyl ether is very toxic and carcinogenic, and stannic chloride is also toxic and incompatible with air (fuming heavily).  Therefore, a few questions:

1) What is a typical setup for performing reactions and handling reagents under inert atmosphere?  The plumbing / logistics are hard to envision.

Is the reaction performed in a closed system of glassware continously flushed with inert gas?  If so, does this require special-purpose glassware designed specifically to be used for such reactions (e.g. addition funnels, adaptors, etc.) that prevent the ambient atmosphere from entering the system?

Or, is the entire setup enclosed within a glovebox-like chamber that itself is filled and continuously flushed with an inert gas?

How does one perform stirring under an inert atmosphere?

References are made to syringes being used to transport & introduce air-sensitive reagents to reactions.  Is this the standard method of working with such reagents?

How does one use a syringe to add an air-sensitive reagent to a reaction without allowing air to be introduced into the reaction system?

2.  In this reaction, at what point is the inert atmosphere no longer required?  The default assumption is that it is at the point where the reaction mixture is quenched with water, and that the subsequent work up and extraction does not need to take place under inert atmosphere.

Is this correct...

Or does the inert atmosphere apply only to the initial addition of reagents?

Or, does it apply to both the reaction AND the following work-up?

Has anyone had experience with this sort of procedure?  If so, what possibly unexpected difficulties might it entail?

stop, drop & roll
(Chief Bee)
06-16-03 19:28
No 440432
      Working under an inert atmosphere
(Rated as: excellent)

This answers most of your questions:

Handling air-sensitive reagents | Aldrich Technical Bulletin AL-134 (../rhodium/pdf /anhydroushandling.pdf)

You seal all glassware joints with septa to keep oxygen and/or moisture out, and you introduce reagents with syringes, with which you pierce the septum and inject the liquid (adding solids under inert gas is a hassle, use a solution if possible). If you use an inert gas* then you let a very very slow stream of nitrogen or argon seep in* through a hose adapter and out through a needle stuck through the septum you have on the top of the condenser (or a side-arm of the flask). This "bleed capillary" is very important, or else the setup will fly apart if you let the gas pressure build up inside when adding reagents, if the rxn evolves gas and/or by the force of the inert gas stream.

A mag-stirrer is perfect for stirring under inert gas - there are gas-tight overhead stirrer adapters available but they cost as much as a cheap mag-stirrer... The inert gas is used until the reactants has been used up and/or until the reaction has been quenched, for example by adding water through a syringe.

* Optional in this case, the important thing is that you keep the air out, not much of the reagents will be destroyed by the small amount of air inside your apparatus, unless you live in the tropics.

* You need a very very slow stream, just enough to have a slight positive pressure inside, so that the outside air does not seep in, butonly the inert gas seeping out.