no_dream
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Copper catalyzed cyanations of benzyl chlorides with potassium ferrocyanide
There was published an interesting article on the synthesis of nitriles by cyanation of aryl halides. Standard methods use cyanide, this one uses
potassium ferrocyanide and a catalyst.
There are some more papers regarding this, and using palladium catalysts:
Microwave-enhanced and ligand-free copper-catalyzed cyanation of aryl halides with K4[Fe(CN)6] in water
Tetrahedron Letters 50 (2009) 4595–4597
A new palladium catalyst system for the cyanation of aryl chlorides with K4[Fe(CN)6]
Tetrahedron Letters 48 (2007) 1087–1090
Palladium-catalyzed cyanation of aryl halides using K4[Fe(CN)6] as cyanide source, water as solvent, and microwave heating
Tetrahedron Letters 49 (2008) 4693–4694
Pd-catalyzed cyanation of benzyl chlorides with nontoxic K4[Fe(CN)6]
Tetrahedron Letters 52 (2011) 5107–5109
Efficient cyanation of aryl bromides with K4[Fe(CN)6] catalyzed by a palladium-indolylphosphine complex
Tetrahedron Letters 52 (2011) 7038–7041
Copper catalyst:
Ligand-free CuI-catalyzed cyanation of aryl halides using K4[Fe(CN)6] as cyanide source and water as solvent
Tetrahedron 66 (2010) 1098–1101
An environmentally benign procedure for the Cu-catalyzed cyanation of aryl bromides
Tetrahedron Letters 46 (2005) 2585–2588
The main article of interest and its supplemental data is this:
Copper-catalyzed cyanation of benzyl chlorides with non-toxic K4[Fe(CN)6]
Tetrahedron Letters 53 (2012) 2825–2827
The Chinese claim "No other reagent apart from CuI, K4[Fe(CN)6] and toluene was used in the cyanation,
showing that the presented protocol is simple and practical. A series of benzyl chlorides were smoothly
cyanated in up to 85% yield under the optimal conditions."
That seems to be too good than true. The use toluene as solvent, and run the reaction at 180degC in a 40ml tube sealed with a septum in an oil bath
for 20 hours. My estimated pressure of the toluene vapors is in the order of 5 bar.
Some non-pressurized experiments took place. Copper(I) iodide was prepared by the method in Inorganic syntheses, vol.VI, p.3 and air dried. Potassium
hexacyanoferrate trihidrate (the yellow salt) was dehydrated on a hot plate for some hours at about 150-200degC. The dried salt was a light yellow
powder. Benzyl chloride, ethylene glycol was reagent grade, xylene was technical and toluene distilled.
Experimental
Run I:
0,1 molar
50ml toluene
12ml benzyl chloride
18,7g of pottasium ferrocyanide
6,8g CuI
Refluxed and stirred for 18 hours at atmospheric pressure. No product was isolated, but TLC showed a new compound.
Run II:
instead of toluene 80ml of ethylene glycol was used. Reflux for 6 hours. Some crystals formed in the condenser. No smell of benzyl chloride from the
post reaction mixture, so there was an complete conversion. After steam distillation milky distillate was obtained, but nothing separated after salt
addition. The distillate smelled a little like the chloride, but a new smell was also present.
Run III:
xylene instead of toluene to raise the reflux temperature somewhat. After filtration a dark organic phase was obtained, which retained its color after
washing with 10% thiosulphate. Xylene was distilled off, the residue vacuum distilled. Some 10mls of pink liquid came over at 110-120@70mmHg. Probably
benzyl chloride. At 140-160@80mmHg something brown came over, supposed to be the nitrile. Then the distilling flask dried out and the residue
decomposed forming iodine vapors.
The supposed nitrile was mixed with 3mls of con. sulfuric acid in a test tube and heated. No reaction was observed.
Because of a lack of a pressure equipment, no more experiments were conducted. Using a pipe bomb is certainly needed, but the stirring of the mixture
wouldn't be possible. A pipe bomb made from water pipe and cast iron pipe caps should withstand the pressure without problems. The long heating in an
oil bath could probably degrade the oil, at 200degC vegetable oil does smoke.
Anyway this reaction is a novel method, using non toxic materials and deserves more discussion. Because in was not mentioned, this post was written.
Attachment: mmc1.pdf (372kB)
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[Edited on 26-2-2013 by no_dream]
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Dr.Bob
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Very nice effort to reproduce their chemistry. The main issue I see is that they say that any oxygen present is detrimental, so purging the reaction
with nitrogen would be helpful. A simple sealed glass pressure tube should be able to handle those pressures, or a microwave type vial with a crimp
top. But the chemistry looks possible, although it would not surprise me if there was not a small amount of palladium in the copper (I) iodide,
which could be helping the reaction as well. That would not be the first time that trace heavy metals assisted a reaction.
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no_dream
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I don't know why they used toluene, if only for convenience or for some special properties. TO avoid the need of pressure work, i suppose some
methods:
1. Use a suitable non-polar high boiling solvent, for example tetralin(b.p 206degC) or maybe some high boiling hydrocarbon derivative - paraffin oil?
2. Use an excess of benzyl chloride as a solvent to make the mixture stirrable.
The choice of the solvent should not make the workup worse. Benzyl chloride boils at 180degC, the according nitrile at 233. Maybe an very high boiling
solvent could work, first the chloride would distill, then the nitrile and the solvent remains in the boiling flask.
The second approach is based on the standard alkali cyanide reaction. Would it be possible to use the ferrocyanide to produce CN- ions in the aq.
layer which would then react with the chloride maybe with an PTC or only water-alcohol-chloride biphasic system.
Production of free HCN gas would be highly undesirable.
If any method based on the ferrocyanide would at least work to some extent, it would be a great way to many subsituted aryl nitriles.
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bananaman
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Quote: Originally posted by no_dream  |
Anyway this reaction is a novel method, using non toxic materials and deserves more discussion. Because in was not mentioned, this post was written.
[Edited on 26-2-2013 by no_dream] |
Just one query, what is the end product of K4[Fe(CN)6] after the reaction?
Is it toxic?
As for the reaction, I tend to believe that some form of copper cyanide salt might be the main reagent performing the reaction. It would be nice if
the authors were to run an experiment using vaious forms of copper cyanide (without presence of K4[Fe(CN)6]). 
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Lambda-Eyde
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| Quote: Originally posted by bananaman |
As for the reaction, I tend to believe that some form of copper cyanide salt might be the main reagent performing the reaction. It would be nice if
the authors were to run an experiment using vaious forms of copper cyanide (without presence of K4[Fe(CN)6]). |
As in the Sandmeyer reaction?
This just in: 95,5 % of the world population lives outside the USA
You should really listen to ABBAPlease drop by our IRC channel: #sciencemadness @ irc.efnet.org
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bananaman
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Well, someone just had to try it out...... 
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Organikum
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| Quote: Originally posted by Dr.Bob | Very nice effort to reproduce their chemistry. The main issue I see is that they say that any oxygen present is detrimental, so purging the reaction
with nitrogen would be helpful. A simple sealed glass pressure tube should be able to handle those pressures, or a microwave type vial with a crimp
top. But the chemistry looks possible, although it would not surprise me if there was not a small amount of palladium in the copper (I) iodide,
which could be helping the reaction as well. That would not be the first time that trace heavy metals assisted a reaction.
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Purging the reaction with inert gas or just evacuating with vacuum as far the bp allows, sure thats no problem and vacuum might allevate the pressure
buildup on heating a little bit.
But nevertheless it calls for some installments if doing it on an interesting scale, 50 or 100g at least to have some material for further
experimentations.
What bothers me most the small scale they ran the reaction with, will it reproducible with more substrate?
And ok it works, how good will it work for to my displease they give the yield as detected by GC/MS, something what triggers all my alarms and a big
warning sign flashes as this says they had nothing in hands actually and raises the big big question WHY?
If I am to work on this, with asscheap starting materials, nothing not available cheapest by the kilo, why do I not pick at least two or three
examples, run them on a gram-level and isolate and analyze product?
I am afraid something stinks here.
Somebody trying it and proving it works would be better news, as it would bw great this really working (in a high-boiling solvent, or better in BzCl
as solvent).
/ORG
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