pomegranate
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benzoic acid to benzoyl chloride ; non benzotrichloride route to hippuric acid
ok, so i’m still digging around on the forums, just reading loosely related data;
http://www.sciencemadness.org/talk/viewthread.php?tid=9121
http://www.sciencemadness.org/talk/viewthread.php?tid=10256
also, it seems VWR doesn’t sell to individuals now; but, i haven’t went deeper into it.
BUT there doesn’t seem to be a direct mention of reaction conditions/procedure/guidelines, or success in
CHLORINATION OF BENZOIC ACID TO BENZOYL CHLORIDE
for acylation with glycine to hippuric acid. ( a little mention on that synth, is also appreciated )
i see routes that go from benzotrichloride; but am wondering about going from benzoic acid. benzaldehyde is watched and experimenting would add up
over time; and nothing simple on benzoic acid seems to afford it ( i think i read that around, but my mind isn’t on that now; just this process from
Cl2 generated and reacted with benzoic acid
(maybe “dumb” question, but can TCCA be added into a reaction mixture itself and generate Cl2 directly mixed with benzoic acid (i don’t know
what the intermediates / cyanuric acid would do; but i assume there would be reactions at the amines)
BUT ANYWAY ! ;
i don’t know if • bleach/NaOCl can be used
• if bleach with an HCl drip
• or just bubbling dry Cl2 into benzoic acid (what solvent, and temperature )
maybe iodine is easier for the bezoyl iodide and can be recovered from H2SO4 on alkali salt; and sublimation; if that salt is crystallized out of the
hippuric acid reaction mix (HCl step has me wondering if metathesis, HI would mess with the hippuric acid.
please just let me have some good info. and, at least realistic-theoretical procedural steps
thanks
[Edited on 14-9-2019 by pomegranate]
also; i don’t have good material sources, so i’m just trying to find good solutions. also excessive ring iodination ; is something that just came
to mind as something i don’t know about ; help is appreciated
i don’t know if a peptide coupling using a lithium reagent could link the glycine straight to the benzoic acid; because of there being a COOH group
on glycine, so maybe if it was first protected with 1,3-dioxolane first; it could happen; and then be de-protected; but that seems alot, and beyond
where i already have many questions .
alright, thanks again
[Edited on 14-9-2019 by pomegranate]
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mayko
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what is your goal here? to prepare hippuric acid? in what quantity?
al-khemie is not a terrorist organization
"Chemicals, chemicals... I need chemicals!" - George Hayduke
"Wubbalubba dub-dub!" - Rick Sanchez
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UC235
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Ingestion of benzoate salts results in excretion of hippuric acid in the urine. It is possible to prepare small amounts in this manner.
Check out Fieser in our own library, http://library.sciencemadness.org/library/books/Experiments_...
Section of interest begins on page 113.
Also, you are going about preparing acyl halides in entirely the wrong manner. Conventional chlorinating agents can't convert benzoic acid to benzoyl
chloride. They are for oxidative chlorination of materials, generally substituting a hydrogen.
What you need is a material that will preferentially remove OH and replace it with Cl. These are generally very moisture sensitive (as is the
resulting acyl halide). It is not an oxidizing reaction.
Traditional reagents for this are PCl5 and SOCl2. An acid anhydride can also react with dry HCl to produce an equimolar mix of acyl chloride and free
acid.
There are a number of incomplete experiments on this board for performing this reaction, one of the most promising being reaction with
perchloropropylene in the presence of a lewis acid. Perchloropropylene is an allylic trichloride with similar chemical characteristics to
benzotrichloride and should be able to react with a donor acid forming trichloroacryloyl chloride, HCl, and acyl chloride.
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pomegranate
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i guess i’m looking to be able to do 10s of grams, 50 grams, 100 grams; idk, i bet i’ll mess up with expectations in experiments and hope to have
a good supply or be able to whip some up, every now and then. and it’s good practice, i presume; so probably starting in the 10s of grams, with a
100g as a hopeful ability in reserve. idk
but getting it from pee , seems laborious; but still interesting; and nasty; but ok, right ? !
but i guess perchloropropylene is not easy to come by. i wonder if 2,3,3,3-Tetrafluoropropene, HFO-1234yf could be chlorinated, (or brominated easier)
to a similar compound, with 2 halogens on the 1-alkene ; but i would want to be absolutely sure the flourines weren’ leaving the hydrocarbon. i
don’t think i understand it, that the two hydrogens wouldn’t be merely substituted by bromines, for example.
but; besides eventually crafting a ketene/Ac2O reactor; i was wondering about production of COCl2 from CHCl3 ; and using it direct, in slow addition
of something to chloroform or visa versa (likely CHCl3 would volatilize through the gas line into the reaction , somewhat, right ? ); or running
through a tube that pulls SO2 in as well , to make SOCl2. or pulling Cl2 through a heated coke over cooler activated carbon and through a venturi of
SO2 i guess; all aspirated or something through a sufficient condenser setup and or cold trap; i assume the industrial details are available
somewhere; but that seems a further off achievement than the ketene/Ac2O setup. it seemed that COCl2 and SO2 was the cleanest way to reach SOCl2; and
COCl2 with GAA was the cleanest way to reach AcCl besides Ac2O and HCl. (and the CO2 from both could seemingly be brought back over the coke bed to
max CO production if C reactive sites are in exess , i guess.)
BUT
right now; i just wonder about the ease of reacting chloroform slowly and bringing the phosgene over into a reaction with benzoic acid; or with SOCl2
i guess, from a sulfur burner through a teflon stopcock in claisen connection which has the phosgene coming in from a 120 degree male male connector
to one par , through maybe a warm water condensor (maybe staged into a cool-ish water one; dripping into the benzoic acid flask; with i guess a reflux
and vacuum take off to a scrubber/bubbler or some setup into Na2CO3; to an aspirator or small low powered vacuum pump (maybe with a cold trap gefore
hand, if needed; or just a tube of sodium hydroxide, and then another bubbling in base before the pump. i wouldn’t want to run anything like that
unless i got info on the heat of COCl2 and SO2 reaction; so the claisen/stopcock meeting and/or the condensor wasn’t burst. i would guess that; the
SO2 could be metered by the teflon hole in the stopcock; and the phosgene; from the addition funnel. and the excessive SO2 from the exposed burner,
pulled out through a fume hood or vented away somehow.
what do you think? is this to naive ? is there a safe solvent to react the benzoic acid in ; and importantly; what forms COCl2 on demand safely from
CHCl3 ? would it be, dripping CHCl3 into a flask with a catalyst like aluminum and AlCl3 , with a dry oxygen source pulled in ? O3 makes a different
reaction right (and might travel up the pressure equalizer arm in the addition funnel to ill dangerous effect ? unless the addition funnel was non
equalizing, and had a drierite tube on the top; but then; the O3 would probably not be all reacted and end up in the flask, causing problem or maybe
making SO3, so that seems dangerous to start.) ?
i’m tired and going to bed, but i drew a sloppy picture, https://imgur.com/a/epsUYq6
[Edited on 15-9-2019 by pomegranate]
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Pumukli
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"what do you think? is this to naive ?"
Yes, it is.
You can't get benzoyl chloride but are mindstorming about phosgene and/or thionylchloride synthesis... And for what? To make hippuric acid???
COCl2 already killed at least one amateur chemist in the last few years. He also thought he could handle it safely, obviously couldn't. Do you think
you are different and you can do it? He surely thought so too.
You seem to be attracted to the most hair-rising routes, don't you?
What about easier acylating agents? E.g. benzoic acid anhydride? Or even methyl-benzoate? (An ester can be ammonolyzed. Maybe refluxing Me-benzoate
with glycine for a few hours would yield hippuric acid.) Or simply melting together benzoic acid and glycine would yield something. I don't know if
these routes are useful or not, surely not the cleanest ways but are less likely to end in a coffin.
Pardon me, but based on your questions it seems that you have to learn a lot before you try putting together a phosgene generator or anything like
that.
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pomegranate
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that is terrible; but, does anyone know what he did wrong, so no one thinks that’s the way to go ? did he make a large addition or something, or not
use a mask, and breath in chronic/acute amounts over the period of the reaction ?
i hope to learn small scale industrial semi labtop chemistry ; but accessing reagents for smooth synthesis in the beginnings would be great :/
the methyl benzoate one may be interesting to try; i read that methanol and benzoic acid condense to form it “Methyl benzoate is formed by the
condensation of methanol and benzoic acid, in presence of a strong acid.[1] [2]
Methyl benzoate reacts at both the ring and the ester, depending on the substrate. Electrophiles attack the ring, illustrated by acid-catalysed
nitration with nitric acid to give methyl 3-nitrobenzoate. Nucleophiles attack the carbonyl center, illustrated by hydrolysis with addition of aqueous
NaOH to give methanol and sodium benzoate.”
[1] Maki, Takao; Takeda, Kazuo. "Benzoic Acid and Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. https://doi.org/10.1002/14356007.a03_555
[2] John McMurry (2008). Organic Chemistry, 7th Edition. Thompson - Brooks/Cole. ISBN 1-4390-4972-6 Page 623
so i guess that is the fischer esterification
i was looking for info on amidification; and, found this:
“One-pot synthesis of amides by aerobic oxidative coupling of alcohols or aldehydes with amines using supported gold and base as catalysts”
https://orbit.dtu.dk/files/6576809/dlib.dtu.pdf
DOI: 10.1039/c2cc16768a
https://pubs.rsc.org/en/content/articlelanding/2012/cc/c2cc1...
supplementary files : http://www.rsc.org/suppdata/cc/c2/c2cc16768a/c2cc16768a.pdf
and there is this paper:
“A Heterogeneous Niobium(V) Oxide Catalyst for the Direct Amidation of Esters”
DOI: 10.1002/cctc.201500601
http://dx.doi.org/10.1002/cctc.201500601
supporting info : https://onlinelibrary.wiley.com/action/downloadSupplement?do...
( and; this article seems to be related ; i stumbled on it from an auto google search for the other one’s doi address with the http spaced (before
the address, from a pdf text copy format error); after it didn’t link to the url:
“Nb2O5·nH2O as a Heterogeneous Catalyst with Water-Tolerant Lewis Acid Sites”
https://doi.org/10.1021/ja110482r
https://pubs.acs.org/doi/abs/10.1021/ja110482r
supporting information : https://pubs.acs.org/doi/suppl/10.1021/ja110482r/suppl_file/...
it seems it is somewhat water tolerant) (<—edit: haha, i was frankenstiening this together from far spaced internet browser tabs; so my memory
forgot the exact saying and i gave my general idea of why i was looking at it :/ which was the verbatim phrase i forgot i remembered; after looking at
the description of the cool diagram and grabbing other links and reordering the paragraphs. heheha)
but
i was guessing that if the nucleophile was a strong organic lithium ; it would couple; and when i looked, i found this paper/article:
Indian Journal of Chemistry
Vol. 42B, October 2003, pp. 2641-2642
“A facile conversion of aromatic esters to amides by using lithium amide under mild reaction condition”
Dibakar C Deka*, Biswajit Purkayastha & Maumita Paul
http://nopr.niscair.res.in/bitstream/123456789/21737/1/IJCB%...
“One pot conversion of aromatic esters to amides has been achieved by use of lithium amides derived ill silu by reacting /1- butyl lithium with a
primary or secondary amine at 0° C in diethyl ether as the solvent.”
so; i guess it would need amino acid protection of the carboxylic acid end of glycine, before that reaction. idk ; and it would have to be cleaved by
something that wasn’t a base ; or reducer, hopefully , and hopefully not too strong an acid that it messes up the hippuric acid. ha ha
[Edited on 15-9-2019 by pomegranate]
[Edited on 15-9-2019 by pomegranate]
[Edited on 15-9-2019 by pomegranate]
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