Does anyone know of a practical way of forming acetophenones from benzaldehydes? Substitued acetophenones are said to often posses appreciable smells
as their corresponding 2-butanones.
What came to mind is the addition of a methyl grignard reagent on the aldehyde, followed by the oxidation of the resulting phenyl-1-ethanol to the
acetophenone.. Org syn says these reactions aren't always straight forward, and in some casesa re low yielding or prone to formation of by-products.
Apparently organo-titanium and dialkyl zinc reagents can be used too, but I would prefer sticking with a grignard if possible.
I would like to know if anyone has an ideas involving less strict reaction conditions than grignards?PainKilla - 22-7-2008 at 19:15
How about formation of the cyanohydrin followed by reduction/oxidation?Klute - 22-7-2008 at 19:52
Nice, i hadn't thought of that. But I don't have any cyanides, and don't really feel confortable using any...not_important - 22-7-2008 at 21:13
Then how about reacting it with acetic anhydride in a Perkin reaction, decarboxylation to the styrene, and add water?
If that sounds interesting you might wish to look at
doi:10.1016/j.tet.2007.08.034
Tetrahedron
Volume 63, Issue 45, 5 November 2007, Pages 11070-11077
Arun K. Sinha, Vinod Kumara, Abhishek Sharma, Anuj Sharma and Rakesh Kumar
An unusual, mild and convenient one-pot two-step access to (E)-stilbenes from hydroxy-substituted benzaldehydes and phenylacetic acids under microwave
activation: a new facet of the classical Perkin reaction
While they use phenylacetic acids it might work satisfactory with acetic acid.Nicodem - 23-7-2008 at 01:39
One way of benzaldehyde to acetophenone homologation is by carbene insertion using diazomethane:
Ar-CHO + CH2N2 => Ar-CO-CH3 +N2
There are a few old papers describing the reaction. However, preparing and working with diazomethane is not considered particularly "practical".Klute - 23-7-2008 at 05:23
Thank you all for your comments. It seems the grignard is finally the best option then, I do not posses enough Ac2O to try out all the derivatives I
want, but do have enough magnesium. I was thinking of generating the reagent using Painkilla's excellent MeBR generation, to avoid that costy MeI.
I kind of felt diazomethane would work, I must haev read about it in a book or such, but I was searching under "diazomethane methylation benzaldehyde"
and obviously didn't find anything.
EDIT: Well, another idea appeared from a review on the preparation of p-nitroacetophenone requested by Quino, the acylation of diethyl malonate with
p-nitrobenzoyl chloride, followed by hydrolysis and decarboxylation. thenyields can be brought up to 99% under the adequate solvent conditions!
The respective benzoyl chlorides can be produced by chlorination of the benzaldehydes, and then reacted with the mono-anion of diethylmalonate (they
use the ethylmagnesium anion), I could just aswell try the sodium anion.
[Edited on 23-7-2008 by Klute]Ritter - 23-7-2008 at 05:38
Quote:
Originally posted by Nicodem
One way of benzaldehyde to acetophenone homologation is by carbene insertion using diazomethane:
Ar-CHO + CH2N2 => Ar-CO-CH3 +N2
There are a few old papers describing the reaction. However, preparing and working with diazomethane is not considered particularly "practical".
Working with diazomethane (if not a trained chemist in a well-equipped lab setting), especially in quantities in excess of a few grams, is not the
easiest or least expensive way of killing yourself but it is on the list of such options.
To give you some idea of the hazards associated with this reagent, Aeroject in CA practices diazomethane chemistry at scale in remote-controlled
bunkers. See http://www.thomasarchibald.com/adobe/diazomethane.pdf.
My opinion of this material is that it should be discussed only in the Energetic Materials forum.not_important - 23-7-2008 at 05:57
see
Quote:
Gutsche, C.D. “The Reaction of Diazomethane and Its Derivatives with Aldehydes and Ketones” ; Org. React. (N.Y.) 1954, Vol. 8, P. 364.
Also note that Perkin reaction can be done with the acid under certain conditions. Also the related Knoevenagel condensation can use diesters of
malonic acid, which would require a double decarboxylation.S.C. Wack - 23-7-2008 at 05:57
If the corresponding benzoic acids are stable to considerable heat, perhaps oxidation and reflux with equal amounts of iron and acetic acid would be
interesting though not the highest-yielding. Diazomethane might give an unbeatable yield if done properly.
EDIT:
Quote:
Originally posted by Ritter
My opinion of this material is that it should be discussed only in the Energetic Materials forum.
Maybe you should start a new thread on it.
[Edited on 23-7-2008 by S.C. Wack]Klute - 23-7-2008 at 06:08
I haev realized that the chlorination of benzaldehyes to the benzoyl chlorides might not be applicable to the substrates I plan on using, mainly
phenolic and alkoxy-benzaldehydes, which would surely be ring chlorinated to a large extent during that reaction...
I could use thionyl chloride after oxidation of th ealdehydes for small scale reactions, if the sub benzoyl chlorides can be easily distilled under
25torr, but it just seems a pity to oxidize the aldehydes
I do not have the adequate glassware to handle diazomethane unfortuanly, I'm sure this would be the most direct option if done cautiously..
BTW, I meant sodium and ethylmagnesium anion, not salt. Sorry for the confusion. I will correct this in the above post.
S.C.Wack, the reduction of the benzoic acids with iron and AcOH, to produce the aldehydes? Actually I have the corresponding aldehydes at hand
already, but not the acids.
[Edited on 23-7-2008 by Klute]S.C. Wack - 23-7-2008 at 06:28
Quote:
Originally posted by Klute
S.C.Wack, the reduction of the benzoic acids with iron and AcOH, to produce the aldehydes?
??? Of course not. You seemed interested in acetophenones, so there you go. Known for ketones from both aliphatic and aromatic acids. Not a great
method because it needs a lot of heat and other groups on the ring interfere, and higher acids give better yields. Friedel made acetophenone in 1857
from dry distillation of Ca acetate and benzoate, and this is probably not a huge improvement.
[Edited on 23-7-2008 by S.C. Wack]Klute - 23-7-2008 at 07:53
Ah, ok. I thought that was a simple reduction and didn't really undersatnd the point. Thank you for pointing this out.Ritter - 24-7-2008 at 04:40
Quote:
Originally posted by S.C. Wack
Maybe you should start a new thread on it.
[Edited on 23-7-2008 by S.C. Wack]
Too unstable & toxic.Ephoton - 25-7-2008 at 02:27
from what I have read diazomethane is only unstable to friction if in pure state. when in
ether it is no were near as unstable.
the ether having a low evap temp makes as a great buffer for the diazomethane as
when the diazomethane evaporates so does the ether making for a dilution to the
emitions given off of any operations useing the solution.
Maby oneday I will have the chance to make and use this wonderfull reagent Klute - 25-7-2008 at 04:55
Well, this reagent is very commonly used in research labs, especially with fatty acids caracterisations and peptides, but requires special equipment
and care. I really don't think it's the kind of chemical that only has it's place in energetics sections, considering it's great use and applications.
The problem with ether solution and groud glass joints is that any little amount of solution diffusing throught he joint by capilarrity will quickly
evaporate, leaving a conc. diazomethane on a high surface material, which can be enough to cause detonation, or the slightest twist on the joint.
Don't get me wrong: it certainly isn't the kind of chemical to use on amateur setting if one isn't already familiar and trained for the use of this
compound.kmno4 - 25-7-2008 at 17:30
Quote:
Originally posted by Nicodem
One way of benzaldehyde to acetophenone homologation is by carbene insertion using diazomethane:
Ar-CHO + CH2N2 => Ar-CO-CH3 +N2
There are a few old papers describing the reaction. However, preparing and working with diazomethane is not considered particularly "practical".
Acetophenone reacts with diazomethane giving another homolog:
Ar-CH2-CO-CH3 and - propably- cyclic ether (disubstituted, at the same carbon with Ar and CH3, ethylene oxide). CH2N2 reacts very unselectively and
many products should be expected.
[Edited on 26-7-2008 by kmno4]Nicodem - 28-7-2008 at 05:56
True, but the reaction is not so fast and the acetophenones can be made the main product - at least according to the papers I saw (should check the
review Not_important refers to, since I don't know where I have the original papers). For example, Chemische Berichte, 97 (1964) 1470-1481
claims quantitative conversion of o-methylthiobenzaldehyde to o-methylthioacetophenone with diazomethane (I have not read it yet).
Also this a bit newer paper (where a safer reagent than diazomethane is used) might contain some newer references about the reaction (but I don't have
the time to go to the library now):
New methods and reagents in organic synthesis. 11. Reaction of trimethylsilyldiazomethane with aromatic aldehydes
Hashimoto, Norio; Aoyama, Toyohiko; Shioiri, Takayuki. Heterocycles, 15 (1981) 975-979.
Abstract: Me3SiCHN2 reacts with RCHO (R = Ph, substituted phenyl) in the presence of Et3N in MeOH to give I and II, as well as RCOMe, RCH2COMe, and
III. The products depend on the solvent and the substituent on the arom. ring.Ephoton - 30-7-2008 at 02:41
I never liked the idea of useing nitroso compounds to make diazomethane.
purely because you have to purchase them or something from some were that is not a normal shopping habit for some one not doing something way more
interesting than the average person.
the only way around this to synthesis alkali nitrites via some kind of high temp nastiness.
I always like the idea of chloroform, hydrazine sulfate and caustic as a way to make
diazomethane.
setup in full reflux setup with gas head on top.
make sure you have a second neck to drip in the diazomethane (I think long time since I read it.)
I can dig up reffs if any one is interested I have them on my server some were .
so many things can be done with diazomethane for organic chemistry its not funny.
ideas or questions on both for me would be
what happens when I add diazomethane to a tri hydroxy benzaldehyde
(ie 3 ,4 ,5 hydroxy benzaldehyde).
does the hydroxyl groups methylate compleatly first or does the aldehyde
get formed into a ketone.
if so how many hydroxyls get converted to methoxy groups before it touches the
carbonyl group.
I think in my books diazomethane comes to mind in the same class as ketene.
a short cut through the old school foundry lab idea.
as most people who have made one or the other would know they all
come with there price.
but I dont think a person who has learned about this subtance properly has
a reason to fear it any more than ketene.
in the patent I have I remeber it stating that the method they used to make diazomethane
was perfectly safe with ground glass joints.
there method did not use any kind of dilutent either the diazo that came off of the the reaction
was pure and all through a ground glass setup.
what happens when you add it to an alkali metal DJF90 - 30-7-2008 at 06:23
IIRC Diazomethane is made using ground glass apparatus, but the joints are FLAME POLISHED.S.C. Wack - 30-7-2008 at 07:23
I have a couple pieces (a three way and a Liebig) of flawless Wheaton Clear-Seal, they're pretty neat but I wish I had a complete set. I don't think
that they are polished, they are made in a different way altogether.
There is high yielding preparation of acetophenone from benzaldehyde and diazomethane in the literature, and other related preparation of further
methylated products. All in the conditions I guess. The fine print.
[Edited on 30-7-2008 by S.C. Wack]kmno4 - 30-7-2008 at 13:15
Quote:
Originally posted by S.C. Wack
There is high yielding preparation of acetophenone from benzaldehyde and diazomethane in the literature (...)
Yes, namely ?ziqquratu - 30-7-2008 at 22:58
Diazomethane is dangerous, but like anything can be handled properly if you take care. In our lab, we make it from Diazald, using a Buchner flask as
the generator and a pasteur pipette as the bubbler (we have two sets of the extremely expensive Aldrich polished-joint glassware, but for whatever
reason we don't bother with it).
Basically (and from memory) - Sep funnel in rubber stopper in Buchner, add KOH(aq) to Diazald (aq or EtOH, can't remember offhand). Sidearm connected
via vinyl tubing to pasteur pipette which is immersed in reaction mixture,
The MOST important things to take note of are:
- Glassware should be scrupulously clean
- Sharp edges MUST be avoided. The pipette is OK so long as it ALWAYS stays immersed. The reason, I'm told, is that the edges can induce small
crystals to form (of what, exactly, I'm not sure, but I'm going on what I've been told, and I've seen an explosion for no reason other than a small
fracture in the sidearm), which are liable to explode
- Control the addition very carefully, so as not to get an exotherm, and if you get layers forming, block your ears and run away!
- ALWAYS USE AN EXPLOSION SHIELD!
I can check with some people who do it slightly more often, if anyone's interested.Klute - 31-7-2008 at 00:32
Thank you for the details ziqquratu, it would be great to have the the opinion of people regularily using it, especially if the polished-joint
glassware isn't mandatory!benzylchloride1 - 13-8-2008 at 14:06
I have found a good way of producing acetophenone derivatives with fairly common chemicals. Oxidation of ethylbenzene and substituted ethylbenzenes by
ammonium persulfate with a catalytic amount of silver nitrate produces acetophenone derivatives. A microscale and a scaled up procedure can be found
on page 394-398 of Microscale Organic Laboratory by Mayo, Pike and Butcher, 2nd edition. Ethylbenzene can be made by the catalytic hydrogenation of
styrene which can be easily prepared by the pyrolysis of polystyrene (Styrofoam) in a pyrex glass distillation set. I have not run this experiment yet
with ethylbenzene, but I have tested the reagents on styrene which oxidizes it to benzaldehyde and probably benzoic acid. Klute - 13-8-2008 at 15:04
Thank you for sharing. I remeber trying this syteme for oxidation of toluene and benzyl alcohols to their aldehydes, also the Fe2+/Cu2+ one with mixed
results. What kind of yields did you get with styrene? did you isolate your aldehyde?
Unfortunaly, this can't be of much use for producing substitued acetophenones from their corresponding benzaldehydes.JohnWW - 13-8-2008 at 21:38
Acetophenones (acetophenone itself is methyl phenyl ketone) from benzaldehydes sounds similar to the well-known benzoin condensation, in which
benzoin, C6H5CH(OH)C(=O)C6H5 is produced from the condensation of two molecules of benzaldehyde with formation of a new C-C bond, catalysed by the CN-
anion. It was discovered in 1903. Other catalysts for it have been found, e.g. thiamine and some other aliphatic and aromatic amines. It is to be
noted that benzoin has a chiral (optically active) C atom; the racemic mixture would probably be produced.
However, any such reaction of something else, e.g. another aldehyde, with benzaldehyde (or its substituted derivatives) itself, with a suitable
catalyst such as CN-, would be liable to produce a mixture containing benzoin (or its derivatives).
[Edited on 15-8-08 by JohnWW]Klute - 14-8-2008 at 04:55
Hum, great idea actually, I might try making benzoin derivatives and see hwo they smell, if they smell.. IIRC, the condensation requires cyanide
caatlysis, though? I'll have a look again. Thansk for the idea!Klute - 13-9-2008 at 18:47
I stumbled on an article on a-alkylcinnamic acids, were they prepare various derivatives. This gave me an idea for preparing acetophenones from
benzaldehdyes, through the benzalacetones:
-Aldol condensation of the aldehydes with acetone (which I have already done with a series of aldehydes, very simple and high yielding reaction):
Ar-CHO + Me2CO --NaOH--> Ar-CH=CH-COCH3
-Haloform reaction to the cinnamic acids:
Ar-CH=CH-COCH3 --NaOCl--> Ar-CH=CH-COOH
>80% yields, very easy reaction.
The cinnamic acids could also be prepared by the Perkin reaction.
-Bromination of the double bond to the dibromides:
Ar-CH=CH-COOH --Br2--> Ar-CHBr-CHBr-COOH
They perform the reaction in CCl4, I'm sure DCM will substitute very well. 75-90% yields.
-Double halogeno-elimination decarboxylation to the phenylacetylenes:
Ar-CHBr-CHBr-COOH ---KOH/EtOH--> Ar-CCH
70% yield.
The phenylacetylenes can then be hydrated to the acetophenones:
Ar-CCH ---H2O--> Ar-CO-CH3
I found a few mentionnings of this hydration, it cna be done using formic acid apparently. Ideally, mercuric salts should be used, but I ratehr use
something else. I'll keep on looking around, perhaps a simple dilute H2SO4 reflux would do the trick.
That's a farily long reaction scheme, but if it avaoid diazomethane... The yields are mostly on the high side, and the bromination and
decarboxyaltion/elimiantion can be done one-pot, perhasp even the hydration aswell (neutralize the KOH with H2SO4, reflux and distill).
I don't think there will be any demethyaltion of the alkoxy aldehdyes.
The phenolic aldehdyes might be a little more tricky, they could oxidize during the haloform, and the arene might be sufficently activated to cause
some ring-bromiantion when forming the dibromides... An eventual protection could be possible.
I could also form the respective bromostyrenes from the dibromides, and see how they smell. Straight b-bromostyrene is a classical academic
preparation..
Forming the acetylide anion and alkylating it with alkyl halide sounds like an interesting approach to, I think NaH would be enough to form the anion.
Could also prepare b-ketoalcohols by adding the anion to a ketone, and hydrating the alkyne. If the conditions are rought enough the b-alcohol could
dehydrate to form a aromatic a,b-unsaturated ketone? i could always do this in a seperate step in any case...
Any thoughts, ideas, suggestions?
EDIT: ref:
Some alpha-Alkylcinnamic Acids And Their Derivatives
Marston Taylor Bogert and David Davidson J. Am. Chem. Soc.; 54(1), 334 - 338 (1932)
DOI: 10.1021/ja01340a050
[Edited on 14-9-2008 by Klute]kmno4 - 14-9-2008 at 06:42
It is a long way and total yield <20%.
"Similar" way could be:
benzaldehyde--oxidation-->benzoic acid
benzoic acid+acetic acid--catal.decarboxyl.-->acetophenone
or via calcium salts.
Your "multistep idea" reminds me making benzophenone from benzaldehyde (without Grignard).smuv - 14-9-2008 at 16:48
You can oxidize to the benzoic acid and then treat with 2eq of methyl lithium. After acidic workup the acetophenone is directly obtained. Of course
I have no idea if you are equipped for this.
You can make the nitrile and hit it with methyl magnesium bromide. Acetophenone after hydrolysis.chemoleo - 14-9-2008 at 17:55
Although it is not based on benzaldehyde as a starting compound, but benzoic acid, acetophenone could be made by ketonisation decarboxylation from an
equimolar mix of dry Na-benzoate and NaAc, similar to the production of acetone from CaAc2, or benzophenone from Na-benzoate on its own.
This approach was also discussed here with unrelated compounds https://sciencemadness.org/talk/viewthread.php?tid=9717 , and also in some other threads which I can't find.
Attached also a paper on ketonisation decarboxylation of various carboxy acids - I think I got from one of those threads I couldn't find.
I'm not too found of pyrolysis reactions to be honest. I might give it a try on the cheapest aldehdyes though, but I'd prefer other routes.
I am equipped for organometallic reactions, although I don't have any lithium or alkyl lithium at hand. BuLi isn't something I would like to keep in
the fridge next to my food. The grignard on the benzonitrile is pretty interesting though. A direct grignard on the aldheyde is said to be pretty low
yielding..
This could be a good way of using any over-oxidized aldehydes. I could also give it a try on vanillin and a few of it's derivatives.
I think there is a way of obtaining directly the esters from the aldehdyes by oxidating them in presence of the alcohols, i could then form the amide
and dehydrate to the benzonitrile with sulfamic acid.
Or , the benzoic acids could be directly converted into the nitriles via urea/sulfamic acid.
Then a grignard as usual, followed by hydrolysis of the iminium salt. Simple
Somehow it hurts me to oxidize those poor aldehdyes, I think I will get a few substitued alkoxybenzoic acids, and dealkylate/realkylate them a bit..
There is also the possibility of forming the acetophenones by FC alkylation with the acids and PPA with a Dean Stark. I've been wanting to try this
alkylation out for a while, but I am somewhat limited on the subtitued arenes. I suppose I could try it out on phenol, guiacol, etcFlip - 15-9-2008 at 15:52
Now here is an idea worth exploring...
Why don't you form the epoxide by trimethylsulfoxide and then obtain the ketone by hydrolysis?
DMS + CH3I --> TMS(+)
1. benzaldehyde + TMS(+) --> styrene epoxide
2. styrene epoxide + h2so4 --> acetophenone
I believe you might actually get a mixture of products tho.. the ketone as well as the aldehyde.. still.
[Edited on 9/15/08 by Flip]smuv - 15-9-2008 at 18:18
I beleive you can make nitriles from aldehydes via NH3 and I2 (if you dont want to go through the low yielding sulphamic acid/urea route).
If you want to directly acylate; the hosch and nencki reactions could be useful for highly activated aromatics (phenols) in leu of the friedel-crafts.
EDIT: Got another idea (probably more academic than practical). Form a thioacetal (if that's the proper name) with propane-1,3-dithiol; deprotonate
it; alkylate with MeBr; hydrolyze. This might work with ethylene glycol or other diols but classically its done with the di-thiol as a way to make
alkanes (reductive elimination via CTH).
[Edited on 9-15-2008 by smuv]chemoleo - 15-9-2008 at 18:37
Quote:
[qutoe]I'm not too found of pyrolysis reactions to be honest. I might give it a try on the cheapest aldehdyes though, but I'd prefer other routes.
Not sure if you are aware of it, but the production of benzene worked quite well that way from Na-benzoate and NaOH (https://sciencemadness.org/talk/viewthread.php?tid=8027 check the first post by Axt). I don't see why it shouldn't work with i.e. acetophenone.
Admittedly you'd have to separate undesired products (such as di-phenyl, benylphenone etc) but distillation should be appropriate for that.
Most importantly, benzoic acid is readily available, and so is acetic acid, and both are cheap... not much to lose, don't you think?Klute - 15-9-2008 at 21:32
Well, acetophenone itself I don't really care, I'm aiming at the subtitued ones. So I could use p-hydroxybenzoic acid, p-methoxy and the other few
pretty cheaply, but the others I would have to use the aldhedyes I have, which bothers me a bit.. But I agree it's worth a try. I guess phenolic
compounds might be prone to excessive side reactions?
I will have a look in the trimethylsulfoxide route,as it seems intersting, and maybe the acetal alkylation route: propanedithiol is pretty expensive:
60E 25mL.... Remember these are my personal fundings!
Smuv, have you any further info on the NH3/I2 nitrile preparation?S.C. Wack - 16-9-2008 at 03:55
I can save smuv the search because I have this at my fingertips, I was just looking at a different benzaldehyde->benzonitrile conversion last
Saturday [JCS 1564 (1965), IIWC], and have these all together in my mind at least. BTW the JCS paper gave high yields of nitrile from benzaldehydes,
but it may be a little less economical, using hydroxylamine HCl, sodium formate, and 98-100% HCOOH, though yes these aren't exactly expensive things
and iodine is not cheap.
Anyways - Hive post 421248 in living color, Vitus' post of Tet. Lett. 42, 1103 (2001). (BTW in a later article [JOC 68, 1158 (2003)] with one of same
authors, the nitriles were unisolated intermediates to amides in high yield, by addition of 35% H2O2 after the mixture became colorless.)
Attachment: 421248.zip (37kB) This file has been downloaded 572 times
Klute - 16-9-2008 at 10:15
Thank you very much S.C Wack, very helpfull!S.C. Wack - 28-9-2008 at 20:34
Quote:
Originally posted by kmno4
Quote:
Originally posted by S.C. Wack
There is high yielding preparation of acetophenone from benzaldehyde and diazomethane in the literature (...)
Yes, namely ?
According to volume 8 of Organic Reactions, which is advisable reading on the subject,
Ber. 40, 479 (1907) (97%)
Ann. 433, 64 (1923) (quantitative).
BTW according to Coyne, Clear-Seal joints are shaped on a mandrel while hot, and not ground.Klute - 6-10-2008 at 09:27
I have located an article mentionning the preparation of substitued acetophenones after double-decarboxylation (like not_important mentionne don the
first page) of an acylated diethyl malonate (well, decarboxylation of the benzoylacetic acid). The reaction is referenced from a J. Prakt. Chema
rticle availble at Gallica.
Attachment: benzoylacetate.pdf (2.5MB) This file has been downloaded 605 times
S.C. Wack - 13-10-2008 at 18:45
Might as well throw out there another preparation of benzonitriles via hydroxylamine since I found another [Chem. Ind. 1873 (1961)] in my notes
similar to the one that I already mentioned. This one uses acetate and GAA instead of formic and formate but the yields are lower, 50% from piperonal,
67% from anisaldehyde, 80% from vanillin. The point is that I have a feeling that even cheaper methods using hydroxylamine HCl and perhaps mineral
acids in cheap solvent might be in the literature. It is in the literature for a small number of aliphatic aldehydes for sure.Klute - 13-9-2009 at 07:57
Ok, i appears the acylation of diethyl malonate anion looks like the most attracting method.. according to J. Am. Chem. Soc., 1946, 68 (7), pp
1386–1388, high yields of the methyl ketones are obtained after decarboxylation using sulfuric and acetic acids.. I have seen another ref where
propionic acid is used.
The acetoacetic esters can be used in place of diethyl malonate.
The acyl chlorides are availbale from the benzaldehydes by oxidation with H2O2, KMnO4, etc, followed by reaction with SOCl2, or by direct chlorination
of the benzaldehydes, although I afraid this will lead to nuclear chlorination with activated aldehydes (vanillin, etc)
This is on my to-do's list, as soon as I get the lab running back again!
Targeted acetophenones: 2-methoxy, 2-hydroxy, 4-methoxy, 4-hydroxy, 3-methoxy-4-hydroxy, 3,4-dimethoxy, and possibly ethoxy derivatives!zed - 14-9-2009 at 15:53
Flip.
The treatment of styrene epoxides, with acid, might be likely to produce phenylacetadehydes, rather than acetophenones.
Such reactions usually proceed through cleavage of the epoxide ring, via addition of H20, followed by dehydration of the resulting 1,2-diol.
Since, the benzylic ion is most stable, it is from there, that the OH group is most likely to be removed. The resulting unstable intermediate should
then rearrange to form the Phenylacetaldehyde, not the acetophenone.
This is analogous to the formation of Phenyl-2-propanones, via the treatment of epoxides, produced by by the action of Peroxide/Formic Acid, on
propenyl benzenes.
.......................................................................................................................................
Klute,
The pathway to ketones via pyrolysis/distillation of salts of carboxylic acids(Fe, Ca, or Pb), has been well discussed. And, while somewhat less than
elegant, it is straightforward.
I have read accounts that suggest performing the pyrolysis under vacuum is helpful for improving yields, as it aids in removing the formed ketones
quickly from the reaction mix.
Some suggest that yields as high as 70% may be obtained.
[Edited on 14-9-2009 by zed]Klute - 17-9-2009 at 15:04
Just realized there is a Org SYn preparation for o-nitroacetophenone using the benzoyl chloride/diethyl malonate route!
The yields look very good! Can't wait to try this out.. I still have to figure out the best way of oxidizing the benzaldehydes to the acids without
permangante or chromate salts.. H202 I'm scared might do a Dakin or Bayer villiger reaction forming the phenol.. NaOCl might chlorinate the
activated aromatique.. I will surely be starting with vanillin.. ANy suggestions?Klute - 19-9-2009 at 19:51
Ok, shortened the reaction path a little. I remebered reading about reacting benzaldehyde with TCCA to form benzoyl chloride. Indeed, Nicodem poste
dsome info on this in the acetic anhydride thread (p.20). Well, that french patent only claims 48% yield with benzaldehyde, and there musn't be any amino or hydroxy
substituants.. I'm afraid an activated aromatic like 3,4-dimethoxybenzaldehdye or p,o-methoxybenzaldehydes will get chlorinated on the arene..
So I was thinking of oxidizing the benzaldehydes to the acids using NaOCl and cat. Ni (II) salt (ref posted somewhere on the board, can't bother to
find it, it nearly 6 am and I still haven't slept yet), then forming the acyl chlorides with SOCl2.
Well, it seems SOCl2 can directly convert the benzaldehydes to benzoyl chlorides, Nicodem posted a article. Unfortunaly it's a terahedron, and science
direct is down for the moment.. So I will request it later.. Hopefully the yields are good, and activated aldehdyes can be used! Bam, two steps to
the acetophenones! Exactly what I needed..not_important - 20-9-2009 at 10:07
...
So I was thinking of oxidizing the benzaldehydes to the acids using NaOCl and cat. Ni (II) salt (ref posted somewhere on the board, can't bother to
find it, it nearly 6 am and I still haven't slept yet), then forming the acyl chlorides with SOCl2.
...
The Cannizzaro reaction comes to mind. Easy. Very little waste. Treat your benzaldehyde with base. Yields approximately 50% Benzoic acid....50%
Benzyl Alcohol.
Reoxidize your Benzyl Alcohol.
Wiki has an interesting reference.
I'm inclined to think that air should oxidize benzaldehydes directly to benzoic acids, under mild conditions. But, I don't have a ready reference.
Mostly, I've spent time searching, for an easy methods to achieve the opposite......Reducing Carboxylic acids to Aldehydes.
[Edited on 22-9-2009 by zed]Ephoton - 22-9-2009 at 01:01
I always liked the idea of making diazomethane from hydrazine, chloroform and caustic.
very easy for the home chemist too make.
whats an explosive but a few hundred yards away with an extension cord to
turn the heat off .
