devongrrl - 22-10-2009 at 12:58
I ws musing today about the synthesis of Phenacyl chloride
by Friedel Crafts acylation of benzene by chloroacetyl chloride in the presence of a lewis acid.
Chloroacetyl chloride is pretty nasty being a strong lachrymator not to mention toxic and damn corrosive.
Would it be any easier reacting 2-hydroxy-1-phenylethanone with thionyl chloride in the presence of pyridine to replace the OH group with a Cl ?
Of course I am aware that thionyl chloride brings its own risks to the party.
Which route would you all follow ?
chemoleo - 22-10-2009 at 14:17
In the case of the bromine derivative, you can also directly brominate acetophenone - although you will obtain a mix where the phenylring, as well as
the CH3 is brominated - so it'd have to be purified.
There's a Chemische Berichte article on this if you are interested.
Barium - 22-10-2009 at 17:24
devongrrl , I'd choose the Friedel Craft acylation any day of the week. Chloroacetyl chloride isn't worse to handle than acetyl chloride, which is
pretty ok.
chemoleo, do you mean that acetophenone cannot be selectivly brominated at the alpha position?
entropy51 - 22-10-2009 at 17:44
For Friedel-Crafts route, see Note 1 in this Org Syn prep
devongrrl - 22-10-2009 at 23:44
Chemoleo, I'd very much like to see the Berichte article if you have a link please.
DJF90 - 23-10-2009 at 02:46
I wouldnt expect the ring to be brominated in acetophenone - the acyl group is a fairly strong electron withdrawing group by mesomeric effect, making
the ring less reactive than in benzene, which as we all know, will not react with bromine unless in the presence of a halogen carrier (its too
kinetically stable). If you do proceed to try bromination, remember to perform the reaction under acid conditions... using base will yeild benzoic
acid via the Haloform reaction.
Out of interest, what do you want phenacyl bromide for? If its an intermediate then perhaps there is a nicer/higher yeilding/more facile route you
could take.
[Edited on 23-10-2009 by DJF90]
devongrrl - 23-10-2009 at 06:09
I was merely discussing Phenacyl chloride , it was chemoleo that brought up the bromine derivative.
garage chemist - 23-10-2009 at 08:41
Chemoleo, I'd also think that adding bromine to acetophenone would give phenacyl bromide in high selectivity. Look in "The War Gases" by Mario
Sartori, it's described there under bromoacetophenone.
Phenacyl chloride can also be made from acetophenone and chlorine in high yield, it's described in this book too.
Ketones are highly activated towards halogenation in the alpha position, and if there is only one alpha carbon with at least one hydrogen on it the
halogenation will be selective.
The halogenations of ketones are catalysed by strong acids, such as the byproduct hydrogen halide, and are therefore autocatalytic.
If you add bromine to a solution of excess acetophenone in DCM, initially nothing happens. After a time anywhere from a few minutes to a few hours,
the solution suddenly becomes colorless. Upon adding more bromine, every drop reacts immediately.
This can be dangerous to the inexperienced chemist who adds too much, or even all, of the necessary bromine to the ketone thinking that the reaction
is slow. When it finally kicks in, the sudden exotherm and gas evolution can be strong enough to explosively propel the reaction mixture out of the
flask and even shatter the apparatus if the pressure cannot escape rapidly enough.
I think this happened to someone here who was brominating butyrophenone with a dodgy bromine-generating mixture...
chemoleo - 25-10-2009 at 15:17
Well I know where you guys are coming from - but the Chem Berichte article is unequivocal on that (in german) - direct bromination yields two products
where one is soluble in EtOH, the other in chloroform.
But I guess the guys did that in polar solvents, I haven't read it in detail enough to see whether that is so. Nonpolar solvents should minimise
electrophilic substitution on the ring.
Attachment: Phenyacylbromide emmerling chem berichte.pdf (160kB)
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