From: ladasky@netcom.com (John J. Ladasky II)
Subject: Re: Azide Chemistry
Date: Mon, 31 Aug 92 01:02:34 GMT
Organization: Netcom - Online Communication Services (408 241-9760 guest)
Summary: more than meets the eye!

In article <useless number> saj@chinet.chi.il.us (Stephen Jacobs) writes:
>I wrote:
>>	O.K., I've got an o-chem question.
>>
>>	The paper, "Selective covalent binging of an Ethidium Analog to
>>Mitochondial DNA with Production of Petite Mutants in Yeast by Photoaffin-
>>ity Labeling" (Hixon SC et. al., J. Mol. Biol 92:319-329 [1975]), contains
>>a reference to a reaction that is not covered in my o-chem references.
>>
>>[description of chemical reaction deleted]
>>
>I've never seen this one before, and I'd be reluctant to try it, but what's
>going on is clear.  The primary amine is being diazotized.  Being aliphatic,
>it promptly decomposes to the carbonium ion; being benzylic (and that is
>important here) it lasts long enough to react with something external--in
>this case, to combine with the azide ions in the solution.  Neat, in a way.
>
>But hydrazoic acid is volatile, explosive, lethal in concentrations
>comparable to the concentrations at which HCN is lethal, and causes distress-
>ing circulatory problems (including monumental headaches) at low concentrations.
>
>I just wouldn't want to do it this way.  Could you maybe displace a benzylic
>chloride or tosylate with azide in DMSO or liquid ammonia?  Not totally safe
>either, but it scares me a lot less.
>
>The reaction given should affect tertiary amines MUCH slower than primary 
>amines (but not leave them totally untouched).
>
>                                         Steve

	First of all, thanks to both Steve and Howard Black for their help
with this reaction.  I've found a few references to the reaction, now that
I know the category of reactions to look for.

	To answer Steve's question: "Could you maybe displace a benzylic
chloride or tosylate with azide in DMSO or liquid ammonia?"  Well, the par-
ticular reaction in the paper to which I refer is the transformation of
ethidium bromide, a commonly-available fluorescent stain of nucleic acids.
The sodium nitrite reaction is a convenient, single-step modification of an
existing compound.  The authors probably chose to do it they way because
synthesizing ethidium from scratch would have distracted them from the 
biology which is, after all, the subject of their paper.

	BTW, here is the structure of ethidium bromide.  I find it inter-
esting, given that the reaction would seem to occur at both of the amino
groups, that the authors report reaction only at the amine marked with a
* below.  (I'm at home and don't have the article in front of me, so I'm
not sure how they know this.)  Perhaps writing out some resonance struc-
tures would help to explain?

	       ____	 ____
	  *   /    \    /    \
	H2N--<  ()  ----  ()  >--NH2
	      \    /    \    /
	       ----	 ----
		   \    /
		    ===N+ Br-
	       ____/    \
	      /    \     C2H5
	     <  ()  >
	      \    /
	       ----
		
	I am more interested in the general applications of adding azides
to molecules, however, so if synthesizing something from scratch, I would
certainly consider the safer method suggested by Steve.
-- 
=============================================================================
 John J. Ladasky II ("ii")				(ladasky@netcom.COM)
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