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Sauron
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Glucose or Glycerose -> DINA -> Derivatives
Please skip down the thread if you are more interested in Diisonitrosoacetone (DINA) for its own sake than in what you can make out of it.
Sartori rather teasingly mentions these in passing but they are indeed interesting compounds with unique reactivity.
Ethyl oxamate is the ethyl ester of oxamic acid and therefore really we are talking about the ethyl ester of oxamic amide readily prepared from oxalic
acid.
This compound when treated with phthaloyl chloride is converted to chloroformyl cyanice or cyanoformyl chloride or so says E.Ott in Chem.Ztg. 50 448
(1926) as cited by Sartori p.58.
ClC(=O)CN
which is an oily liquid of rather high boiling point 126-128/750 mm. It occupies a chemical niche between the two symmetricvasl carbonyl compounds
phosgene and carbonyl cyanide.
Phosgene while of great industrial importance is as we all know, a serious laboratory hazard due to its great volatility (bp 8 C) and toxicity, and
most especially its insidious nature. It can produce lethal lung damage at concentration which are not irritating to the eyes or nose and throat,
symptoms do not appear for half an hour or so. Many other equally toxic compounds of similar volatility are much less hazrdous simply because no one
can stand to be around them, they are immediately irritating.
Carbonyl cyanide is extremely reactive with water, explosively forming HCN and CO2. Thus it requires special handling in a dry box or inert
atmosphere.
Carbonyl cyanide reacts with alcohols to produce cyanoformate esters just as phosgene reacts with alcohols to produce chloroformate esters.
It is reasonable to speculate that cyanoformyl chloride might well also react with alcohols to produce cyanoformate esters and undergo other similar
reactions. I will look into this, and the properties of this mixed carbonyl.
--------------------
I'm afraid that in this instance scholarship leads to confusion rather than claridication.
The preparation mentioned by Sartori in THE WAR GASES was from E. Ott in Chem.Ztg, 50, 448 (1926). So far I have not been able to obtain this.
However, Appel et al in Angew.Chem. Intl.Ed 22, 785 (1983) claim first preparation of cyanoformyl chloride by a different process, confirming
structure by reactions as well as spectroscopy and giving bp 20 C. Their product could be stored at -78 C but, at ambiet temperatures
disproportionated slowly and irreversibly into phosgene and carbonyl cyanide - the symmetrical carbonyls.
Their evidence is compelling and so we must assume that Ott's product from chlorination of ethyl oxamate with phthaloyl chloride was not cyanoformyl
chloride at all, but something else - and probably of higher MW based on the reported bp 126-128/750 torr,
I wonder what it might have been? Until I can examine Ott's article I don't know what evidence he offered for his structural assignment. Elemental
analysis was routine in those days.
The logical step would be to replicate Ott's work and identify the product unambiguously. Who knows? It may be more interesting than what he thought
he made at the time.
[Edited on 5-6-2007 by Sauron]
[Edited on 10-6-2007 by Sauron]
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Sauron
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Carbonyl Cyanide
Org. Syn Coll.Vol. 4, p 877; Coll.Vol. 5, p 1007; Coll.Vol. 6, p 268
The first article describes preparation of the dibromomalononitrile which as you might expect is a nasty lachrymator and needs to be handled in a good
hood. Also the dimerization to tetracyanoethylene, a commercially available product. Caution: tetracyanoethylene slowly gives off HCN.
A simplified procedure for this step is described in Note 1 of the second paper.
The second paper concerns the opoxidation across the double bond of the tetracyanoethylene with hydrogen peroxide to form tetracyanoethylene oxide.
The final paper describes the scission of the intermediate with n-Butyl sulfide to give the title carbonyl cyanide compound and a byproduct, the two
are readily seperated. The procedure is subject of a referenced JACS article and a US patent, q.v.
The overall preparative scheme si summarized below.
[Edited on 26-5-2007 by Sauron]
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roamingnome
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compunds compounds everywhere, but not a drop to drink...
`God save thee, ancient Mariner !
From the fiends, that plague thee thus !--
Why look'st thou so ?'--With my cross-bow
I shot the ALBATROSS.
.......
i enjoy your weekly helping of what appears to me random entries from vogel
im sure we all have a scope set on some target....
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Sauron
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Well, NONE of this is in Vogel.
Here's some necessary nomenclature brushup for some of what's ahead.
Mesoxalic acid - usually used to refer to the ketomalonic acid but sometimes to dihydromalonic acid, the hydrate form. Available
commercially as diethyl ester or disodium salt.
Tartronic acid - reduction product of ketomalonic acid with sodium amalgam. 2-hydroxymalonic acid.
Oxomalonic acid - alt. name for ketomalonic acid
+++THIS IS A VOGEL FREE ZONE+++
[Edited on 29-5-2007 by Sauron]
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tupence_hapeny
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Could it be something like a cyano-dichlorocarbene (http://en.wikipedia.org/wiki/Dichlorocarbene) either Cl(x)C-O-CN or something similar (Cl2C-CN)? In the reference given their is a reaction scheme
with phenyl cyanate, which I assume it would be something like... However, their is no mention of an alkali - so this may not even be possible...
See also http://en.wikipedia.org/wiki/Reimer-Tiemann_reaction
tup
[Edited on 28-5-2007 by tupence_hapeny]
We are all the sum of our experiences, and our reactions to the same
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Sauron
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Just an Aside on Cyanoform
It's reeally pretty pointless to speculate till we have the Ott paper to read, and can see what support he had (if any) for his claim to the
structure.
Ott (in 1926) lacked the advantage of instrumental methods we take for granted today. While few home chemists will have an NMR, at least some of us do
have IR, UV-Vis, GC, HPLC, and even MS. Second hand equipment is affordable, still works well, and is a great convenience when face with a structural
ambiguity.
Prior to the advent of the method of Linn et al, the only prep of carbonyl cyanide was by a touchy pyrolysis of the diacetyl derivative of DINA
(diisonitrosoacetone) as described in:
Über das Carbonylcyanid (I. Mitteil.)
R. Malachowski, L. Jurkiewicz, J. Wojtowicz
Ber. 70 1012 (1937)
a paper I have requested but not yet received.
DINA is familiar subject matter on this forum, see the thread of same name. It is easily prepared from acetonedicarboxylic acid, itself not quite so
easily prepared from citric acid. Org.Syn. describes this method as multistep, nonreproducible, low yield and with risk of explosion.
Not my idea for a first choice procedure.
Meanwhile I have found another use for the intermediate in the Linn method, dibromomalononitrile. It is used to prepare potassium tricyanomethide,
which can then be converted to "cyanoform" proper. This is a very interesting substance, not very stable at RT in free form, and certainly not
existing in the simplistic (CN)3CH structure suggested by the unfortunate trivial name. In fact it is dicyanoketeneimine.
[Edited on 31-5-2007 by Sauron]
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Sauron
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Looking again at the original precursor to carbonyl cyanide: DINA
Di-isonitrosoacetone
Also known as
1,3-dioximinoacetone
Mesoxaldehyde dioxime
Some of the alternative nomenclature is enlightening, for "isonitroso" to the contrary, this compound IS an oxime. Notice that two carbons are lost in
the preparation from acetonedicarboxylic acid and sodium nitrite. These are lost as CO2, the nitrite attacks the alpha-carbons and the carboxyl groups
decompose. That's all done in the cold and in aqueous soln. von Pechmann was the first to report this, see Ber., 19, p 2564-2567 (1886).
Mesoxaldehyde? Homolog of glyoxal, one carbon higher. That carbon being a hydrated carbonyl. The nonhydrated form would be oxomalonaldehyde. (I doubt
this is stable, it likely collapses to acrolein.) Oxidizes to mesoxalic acid aka ketomalonic acid. Now, if we could prepare the di-amide form of this
acid and dehydrate the amides we'd have carbonyl cyanide.
For that matter, if we dehydrate DINA we'd also have carbonyl cyanide, and oximes dehydrate more readily than do amides.
TCT dehydrates oximes. In DMF I believe. Sounds like a novel and highly publishable prep of carbonyl cyanide to me - if it works.
Furthermore, if you could make mesoxaldehyde you could treat it with 2 mols hydroxylamine and have a new route to DINA.
I have not yet seen any alternative prep for DINA - only the NaNO2/acetonedicarboxylic acid route. DINA is an important colorimetric reagent for OPAs
and under investigation as a human ACEase reactivator (therapeutic agent against OPA poisoning.) Incidentally for some perverse reason it is also
known by the acronym DIA.
BTW carbonyl cyanide = oxomalononitrile
So why can't we oxidize malononitrile to this compound?
Diethyl malonate ("malonic ester") is oxidized in 75% yield by N2O4 gas to diethyl oxomalonate. This is a very mild oxidation. If the conditions don't
bother the ester why should they perturb the nitrile groups?
Ccarbonyl cyanide direct from malononitrile in one step.
The NOx must be DRY as the product reacts violently with water or moisture releasing HCN and CO2.
Here's three proposed novel rxn schemes:
Firs from DINA easily made fron citric acid in two steps
Second from off the shelf malononitrile
Third from the diamide of ketomalonic acid (oxomalonic acid)
This acid is best made from the oxidation of malonic ester with N2O4 or, by oxidation of 1,3-diacetylglycerol with conc nitric acid in the cold. There
may be a way to get from the ester to the amide directly with ammonium hydroxide, ammonium carbonate or urea.
[Edited on 29-5-2007 by Sauron]
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Sauron
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Looking again at DINA and the parent carbon skeleton, since it is clear that DINA is in fact a dioxume then the parent carbonyl compound is
mesoxaldehyde aka 1,2,3-propanetrione - the simplest possible tricarbonyl compound and one of great theoretical interest.
A review of the literature, which spans more than a century, reveals that this dialdehyde can be prepared from D-glucose by several means.
Treatment of D-glucode with sodium hydroxide and lead acetate converts the sugar to "triose reductone", which can then be oxidized with selenium
dioxide to 1,2,3-propanetrione. Don't let the biochem jargon throw you, triose reductone is simply 2,3-dihydroxypropenal, in other words a glycol
derivative of acrolein and a close relative of glyceraldehyde. How convenient that the selenous acid oxidizes the hydroxyls but leaves the aldehyde
untouched. Mesoxaldehyde from glucode in two easy steps!
From Can.J.Chem 33 (1955) by Bauer and Teed:
Abstract: Triose-reductone-C14 was obtained by treating D-glucose-1-C14 with sodium hydroxide in the presence of lead acetate at elevated
temperatures. Carbon atoms four, five, and six, as well as carbon atoms one, two, and three, of the D-glucose molecule are shown to contribute to the
triose-reductone yield. The formation of triose-reductone was found not to be accompanied by glycerol formation. Mechanisms for fragmentation of
reducing sugars are discussed in the light of these findings
-------------
D-glucosazone (from D-glucose and phenylhydrazine) upon periodate oxidation gives 1 mol of mesoxaldehyde-bis-phenylhydrazone along with 2 mols formic
acid and 1 mol formaldehyde. Fructose of course gives the same osazone as glucose so could be oxidized to same products in like fashion.
------------------
Similarly, oxidation of sucrose with nitric acid gives mesoxalic acid
I have not yet examined the older German literature on this subject, which is extensive. It is not yet clear which if any of these might provide a
practical preparative alternative to the preparation of DINA from citric acid but glucose or sucrose is even more OTC than citric acid and these
methods may be no more onerous than the preparation of the requisite acetonedicarboxylic acid.
The aldehyde could be stored as its tetramethyl or tetraethyl acetal, (1,1,3,3-tetraethylacetone) and converted to DINA with hydroxylamine.
I will report back as requested paper arrive and I have a better idea of what is involved.
--------------------------
I obtained two related procedures for NaOH degredation of D-glucose and the workup of triose reductone from its lead salt. The reaction is fast and
easy,and the workup straightforward but the purification by recrystallization from water entails serious losses. I think this can be improved upon.
Anyway as is the degredation of 2.5 Kg D-glucose (cheap and OTC) will yield c.100 g of the reductone and after the highly efficient and selective
selenium dioxide oxidation, about same qty of the mesoxaldehyde. This is probably best kept as its sodium bisulfite adduct.
I have requested the original 1933 article pioneering this prep but it in in German while the ones I have are in English.
Reductone is closely related to Ascorbic acid and also was utilized in the synthesis of folic acid so it is a biochemical of great significance. Once
again we are talking about 2,3-dihydroxyacrylaldehyde, one of the biologically active enediols.
[Edited on 31-5-2007 by Sauron]
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Sauron
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Mesoxalic Acid Rather than Mesoxaldehyde?
Just a quick survey of methods to get to the acid or its esters rather than the aldehyde.
Oxidation of sucrose or glucose with conc nitric acid is a very old technique for producing oxalic acid (starches also work) but mesoxalic acid
(ketomalonic acid) is also produced. From 1 Kg of the sugar about 200 g oxalic acid and 100 g of mesoxalic acid are produced and are easily seperated,
the latter as its sodium salt. About 10 L conc HNO3 are needed. Byproducts are NOx (lots) and sodium nitrate. Sodium carbonate is employed.
The NOx chiefly nitrogen peroxide could be condensed and stored for use in oxidation of diethyl malonate to diethyl ketomalonate or simply run into
conc nitric acid to produce fuming nitric acid.
Detailed optimized instructions are given in
CCCXXIV.—The oxidation of sucrose by nitric acid
Frederick Daniel Chattaway and Hinton John Harris
J. Chem. Soc., Trans. 1922, 121, 2703
Now available in References
Other methods:
-- reating dimethyl or diethyl malonate with liquified dried N2O3 or N2O4 for several hours in presence of a small cat. amount of Na metal
Org.Syn and references therein. In particular Curtiss, JACS 35, 477 (1906)
-- Electolytic reduction of D-tartaric acid alkiline soln
Chem. Zentr. 1922, III, 871 (likely also in Chem.Abstracts)
-- treatment of dibromomalonic acid with barium hydroxide soln (baryta water) or sodium metal
Ueber halogensubstituirte Malonsauren und deren Derivate
Berichte der deutschen chemischen Gesellschaft
Volume 35, Issue 2, Date: Mai-August 1902, Pages: 1813-1821
M. Conrad, H. Reinbach
-- ozonization of malonic acid to tartronic acid followed by oxidation
Dobinson, Chem. and Ind. (London) 1959, 853
-- Action of conc HNO3 in the cold on 1,3-Diacetin (glycerol diacetate} The problem with this is that commercially available Diacetin while cheap is
always a tech grade mixture of 1,3- and 1,2-isomers.
-- Treatment of alloxan with aqueous barium hydroxide, or action of lead acetate soln on caffuric acid. I mention this only as a historical note as it
has little preparative value unless you have access to a lot of these purines
Deichsel, J. Prakt. Chem. [1] 93, 194 (1864)
Many of these are now available in References
Remember that the methylene in malonic acid is highly activated and that the literature often uses the term mesoxalic acid to mean either the hydrated
form hioxymalonic acid, or the ketomalonic acid, and that these are readily interconvertible. Indeed ketomalonic acid aborbs moisture from the air if
left in an open vessel, and the hydrated form loses water if distilled from P2O5 in vacuo.
[Edited on 1-6-2007 by Sauron]
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Sauron
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Procedure for Degradation of D-Glucose to 2,3-dihydroxyacrylaldehyde (Triose Reductone) and Selenium Dioxide Oxidation of Reductone to
1,2,3-Propanetrione (Mesoxaldehyde)
D-Glucose 250 g is dissolved in 3.75 L water. The following are added:
Lead acetate 135 g
KCN 30 mg
Copper acetate 500 mg
Stirred and heated in a stream of N2 to 92 C
85 g NaOH in 250 ml water added and mixture shaken 2-3 minutes/ Acidified with glacial acetic acid 40 ml and quickly cooled.
Lead salt of reductone isolated by centrifugation, washed succesively with water, acetone and ether, and dried in vacuo. 125 g, Pb content 58.8%.
The lead salt suspended in 500 ml dry acetone and treated with H3PO4 85% 45 ml and shaken 30 min at RT. Lead phosphate filtered off and acetone soln
of reductone concentrated in vacuo then chilled to -15 C.
Crystals collected by filtration and dried in vacuo. Material (mp 149 C (decomp) is pure enough for use in the next step, q.v.
Optionally purified by sublimation at 5 microns with a bath temp of 60-80 C. Obtained 8.5 g pure triose reductone mp 153 C.
Oxidation
10 g reductone in 100 ml water is shaken one hour with 6 g SeO2 in 100 ml water then allowed to stand overnight. Selenium 4.5 g is filtered off.
The mesoxaldehyde may be characterized as its bisphenylhydrazone by reacting with aq.phenylhydrazine acetate, the mp should be 175-176 C.
The dialdehyde is probably best stored as its bisulfite addition product or converted directly to the dioxime with hydroxylamine.
[Edited on 1-6-2007 by Sauron]
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Ozone
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'Evening!
I think the question is how to do this without *extensive* side rxns (I would very much like to read this paper).
OK, in summary: When treated with alkali and heat we shoud establish a Lobry-Van Eckenstein equilibrium between glucose, fructose and mannose. This
treated with lead acetate (Pb(OAc)4??) should yield your 2,3-dihydroxypropenal (and a bunch of other crap). Subsequent oxidation with SeO2 could yield
the tricarbonyl, and crap.
Possible problems involve:
1. a multitude of products resulting from the hexose alkaline degradation pathways including your desired, open-ring precursor and polymer.
[edit] But the Pb salts are terribly insoluble--if they are made with yout product *very* quickly, there is a real chance of this working.
2. LTA can do multiple cleavages here owing primarily, to constant tautomeric shifts in diol loci under alkaline conditions.
[edit] Ah, maybe the Cu chelates the diols to prevent some of the tautomerism!
3. the small parts will *really* want to condense (especially whilst alkaline) to give more polymer.
[edit] But, there is an assload of lead, see 2, above. I want to find some alternative to LTA, if large scale route is to be realized. [edit] SWAG,
here, but what about KIO3/KMNO4?
4. The final product will be highly reactive (perhaps a reactive intermediate--has this ever been isolated, and if so, at reasonably high T?).
I know I can get to reductone(s) via Maillard reaction with *any* amine or amino acid, under mild conditions. The problem is very similar though--a
multitude of products and brown shit. Maybe the final product can be distilled as it is made to prevent some of this. I wonder if it could dimerize
into the wild 1,2,3,4,5,6 cyclohexaketone(sic)?
Do you have the primary literature (I don't have access to this particular journal).
If this can be done, even to the diol, you've probably got something $^).
What the hell,
O3
[Edited on 31-5-2007 by Ozone]
-Anyone who never made a mistake never tried anything new.
--Albert Einstein
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Sauron
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Hi @O3, how's your arm?
The procedure above for reductone is from Can J Chem and can be had from References (I just got it there.) They built 14C labelled reductone to settle
some mechanistic disputes and used Cocker's procedure, his paper from J.Chem.Soc is also in Refs. Cocker based his method on the original investigator
von Euler but skipped the rigorous and lossy sublimation.
Most of von Euler's key papers are difficult to access (in Akiv.Kemi Mineral.Geol.) but this one from Annalen contains on pp 83-84, his procedure (in
German) which is very obviously the basis for Cocker and the rest.
[Edited on 1-6-2007 by Sauron]
Attachment: Volume 505, Issue 1 p 73-87.pdf (735kB)
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Ozone
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Thanks for asking (and for the paper--it will be some time for me to translate it).
Still quite painful (they focused on the bones and ignored soft tissue damage at the joint). Better though!
Do you have: From Can.J.Chem 33 (1955) by Bauer and Teed?
Sweet!
O3
-Anyone who never made a mistake never tried anything new.
--Albert Einstein
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Sauron
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Preparation of D-Glucosazone and Its Periodate Oxidation
Somewhere upthread I think I mentioned periodate oxidative degradation of D-glucosazone results in 1 mol of 1,2-diphenylhydrazone of mesoxaldehyde
(solid, sparingly soluble in water) along with 2 mols formic acid and 1 mol formaldehyde.
As a possible prep route to the free aldehyde this hinges on the recovery of the free 1,2,3-propanetrione and its conversion to the 1,3-dioxime, DINA.
Like glyoxal, the trione will rapidly polymerize if not used at once or converted to bisulfite addition product. Or some similar technique.
Charles Huebner of the University of Wisconsin pioneered the study of periodate oxidation in a long series of papers in JACS. Here are two of them,
One specifically on oxidation of the glucosazone, and the other on the oxidation of glucose proper which makes it clear why the use of the osazine is
required with this reagent (sodium periodate).
Here's a procedure:
20 g D-glucose in 15 g glacial acetic acid and 5 ml water mixed with a solution of 30 g phenylhydrazine in 320 ml abs EtOH. A clear yellow solution is
obtained. After 3 hours standing the solution deposited yellow crystals, which after washing with water weighed 15 g. Two days further standing gave
an additional 4 g and after working up the mother liquor by concentration an additional 2 g is recovered. Total 21 g D-glucosazone. mp 206-207 C
14.05 g D-glucosazone is dissolved in 3 L warm dioxane, cooled rapidly to 25 C. 500 ml 0.425 M sodium periodate soln added along with 1.5 L water.
Almost immediately orange needles of 1,2-bis-phenylhydrazone of mesoxaldehyde start seperating out. The reaction is 85% complete in 30 minutes and at
1 hr the crystals are filtered from the mixture and washed with water.. About 11.5 g obtained. mp 196-197 C.
The only bad news is the need for dioxane as solvent. Huebner says 60/40 dioxane water is best choice for a mix that dissolves both the periodate and
the glucosazone.
Sounds like maybe a job for a PTC.
[Edited on 1-6-2007 by Sauron]
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Sauron
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Other route to reductone?
Looking a second time at "triose reductone":
Recognizing the relationship between this enediol-aldehyde and acrolein, I am moved to wonder how we can build this from acrolein or a close relative.
Org.Syn. has a nice prep of propiolaldehyde acetal from acrolein and bromine. The resulting 2,3-dibromopropanal is converted to its acetal with
triethyl orthoformate, then dehydrogenated with PTC to the triple bonded acetal.
I am thinking, why not hdrolyze the dibromo compound to dihydroxy? Or failing that, make the enediol from the propiolaldehyde acetal?
Org.Syn. Coll.Vol. 6, p.954
Acrolein is no joy to work with, but its acetal is not so bad. Perhaps the dibromopropanal or its acetal is commercially availanle.
[Edited on 5-6-2007 by Sauron]
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Sauron
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Another Alternative, No Dioxane Needed
In studying the osazone preparation, I noticed a comment in one of the articles that glycerol or glyceraldehyde behaves like a sugar. That is,
glyceraldehyde phenylhydrazone oxidizes the adjacent hydroxyl to a katone and phenylhydrazine (if present in excess as it always is in this
preparation) condenses with it. So, the osazone of glyceraldehyde.
Now, only a matter of oxidizing the third and only remaining hydroxyl to an aldehyde and what we have is the 1,2-diphenylhydrazone of mesoxaldehyde.
Racemic glyceraldehyde is easy to make from commercially available acrolein acetal, by KMnO4 oxidation of the double bond and hydrolysis of the
acetal. (Org.Syn.)
I will hunt around for confirmation that glyceraldehyde gives an osazone with phenylhydrazine, and give the details. This might obviate the problem of
needing all that dioxane as solvent for the periodate oxidation of glucosazone.
----------------
All right, the literature confirms the existance of an osazone from glyceraldehyde, identical to the 1,2-bisphenylhydrazone from periodate oxidation
of glucose. Therefore we can build this from acrolein acetal in three steps. No dioxane required. Acrolein acetal is a commercial product or, of
course, one can make their own acrolein if they are foolish enough.
The reaction scheme is shown below.
[Edited on 3-6-2007 by Sauron]
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Sauron
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Acrolein Acetal (Glycerol) to Mesoxaldehyde
I haven't drawn in the final two steps to the trione mesoxaldehyde, because I haven't decided finally on their order. nor defined them very well
procedurally. They are the oxidation of the 3-hydroxyl to carbonyl probably with SeO2 or dil HNO3, and the removal of the two hydrazone groups. Any
suggestions, particularly for the latter, will be most welcome.
Incidentally that osazone's parent compound which isn't glyceraldehy any longer and is not quite mesoxaldehyde yet, is none other than
3-hydroxypyruvaldehyde.
[Edited on 5-6-2007 by Sauron]
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Sauron
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Glycerin Oxidation with OTC Peroxide
There's another variation on same theme:
Glycerol is oxidized at ice-bath temperature (5 C) with 6% H2O2 and ferrous sulfate catalyst to glycose syrup, an equilibrium mixture of
DL-glyceraldehyde and its isomer 1,3-dihydroxyacetone. It is not necessary to seperate these components because they both give same osazone which just
as in the previous procedure is the diphenylhydrazone of hydroxy pyruvaldehyde. This is oxidized to mesoxaldehyde and liberated.
Glyceraldehyde by the way is the simplest aldose and dihydroxyacetone the simplest ketose. Their stereochemical configurations are the basis of the D
and L system in the familiar Fischer projection of carbohydrtae structure and their isomerization through a common enediol is the simplest case of the
Lobry de Bruyn-von Eckenstein Rearrangement. It is also of vast biochemical importance.
Dihydroxyacetone slowly dimerizes to 2,5-dihydroxydioxane-2,5-dimethanol which is commercially available (Aldrich). It is the active ingredient in
artificial tanning agents (e.g. "Man Tan") and is produced by aerobic fermentation of glycerin. There's a review of its biotech production in Chemical
& Engineering News.
Closely related substances:
Hydroxypyruvic acid which can be prepared from collodion by the method of Wills (Ber. 24, 400-407 (1891). This is degradation by NaOH and lead acetate
in same manner as that of glucose described upthread.
All of these oxidative methods tend to be finicky requiring close temperature control in absence of which yield will suffer. I recommend jacketed
flasks and recirculating chiller with good thermostatic control.
Of course the preparation of acetonedicarboxylic acid is just as finicky. We could break down and actually buy that acid but where's the fun in that?
[Edited on 5-6-2007 by Sauron]
Attachment: Just_Ber19_1205.zip (389kB)
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Sauron
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Except for the first method shown (NaOH/Lead Tetraacetate degradation of lucose) all of these routes to mesoxaldehyde make use of osazones
(glucosazone or hydroxypyruvaldehyde osazone etc.) and the recovery of the final product depends on facile and efficient removal of the
phenylhydrazone moieties. Until now I had only a vague notion (to put it mildly) of how or even whether this was possible. It turns out that simply
warming with hydrochloric acid splits the osazone and the substrate is recovered. Thus glucosazone splits to glucosone. I have not yet found details
on time, temperature, acid concentration or other conditions. But if necessary I can work these out for myself with (readily made) glucosazone.
Another methods effects this split with pyruvic acid but the reference may be hard to access.
L.Brull, Ann.Chim.Applicata 26, 415 (1936)
I think this is an Italian journal.. There's an umlaut on the uin the author's name. But the language of the journal title is not German.
--------------------
It turns out that liberating the product from the phenylhydrazo groups may not be completely necessary as those groups can be directly replaced by
oximino groups - a reversible process. As our target is mesoxaldehyde and DINA is its 1,3-dioximino derivative this is rather convenient.
Just, Ber. 19 1205-1207 (1886)
von Pechmann, ibid., 20, 4539-2544 (1887)
I have these articles and will post them here shortly.
The trick will be to get from the osazone (1,2-bis-phenylhydrazone) to the 1,3-bis-phenylhydrazone and then protecting the 2-position before
exchanging the phenylhydrazones for oximini groups. This will be interesting.
---------------------
Old von Pechmann knew his stuff. In addition to the "standard" DINA preparation from acetonedicarboxylic acid, he also prepared the
1,3-bis(phenyldiazo)acetone from the same compound using two mols of phenyldiazonium chloride to attack the highly activated methylene groups of this
beta-keto acid. A double decarboxylation ensues just as when sodium nitrate reacts. It is noteworthy that these groups, tautomeric with phenylhazro
groups, can very likely be exchanged with oximino groups. You wouldn't want to make DINA this way, it would be the long way round the block - but you
could do if you wished.
H.von Pechmann et al, Ber. 24, 3255
[Edited on 5-6-2007 by Sauron]
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Sauron
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Prep Scale Production of Dihydroxyacetone and Hydroxypyruvaldehyde
264 g diacetin, 149.4 g Na2Cr2O7.2H2O and 460 cc glacial acetic acid are charged in a flask with stirring and a solution of 227 g conc H2SO4 in 375 cc
glacial acetic acid is added over an 8 hour period at 20-25 C.
When addition is completed 55.5 g hydrated sodium acetate is added and the mixture stirred an additional 2 hours. The precipitate is filtered off and
washed with acetic acid. The combined filtrate and washings are evaporated to dryness at the pump, and the residue taken up in ether, washed
thoroughly with satd NaCl, dried over anhydr
sodium sulfate, and the solvent removed under reduced pressure. Product is distilled under reduced pressure, the fraction boiling at 130-150 C/8mm is
collected. Upon redistillation, main fraction boils at 134-136 C/8mm and amounts to 112 g dihydroxyacetone diacetate.
Note: diacetin (glyceryl diacetate) is an approx equal mixture of 1,3 and 1,2 isomers. Only the 1,3-diacetate gives dihydroxyacetone. Assuming 132 g
of the 1,3 isomer was present in the starting material the 112 g yield is quite good.
Saponification with sodium carbonate will give the free dihydroxyacetone which can be converted to hydroxypyruvaldehyde by either of two methods:
a. Dihydroxyacetone osazone
b. Oxidation with Cu(II) salt, saturated solution in water at RT. The second procedure is detailed here.
Copper acetate or copper sulfate solutions are employed.
1 mol (90 g) dihydroxyacetone in 180 ml water is treated with 2.25 mol finely divided cupric acetate at room temperature for 5-7 days until the
calculated amount of copper oxide has precipitated and a grayish ppt of copper oxalate begins to appear. Excess Cu++ is then destroyed by the careful
addition of calculated amount of 10% oxalic acid soln.
After filtration the soln is concentrated to a small volume at 35 C/17mm. Successive portions of abs. ethanol were added and product evaporated at 17
torr. Product was then dissolved in absolute ethanol and precipitated with ether. The combined alcohol-ether solutions were saved for later workup.
This process was repeated. Substances insoluble in water and absolute ethanol were removed. The product was
dried in vacuo at 70 C. Yield of hydroxypyruvaldehyde 87%.
Amorphous yellow solid mp 155-160 C. This is the trimer. The
monomer is reformed in aq soln on long standing at RT or 10 min on water bath at 60 C.
[Edited on 6-6-2007 by Sauron]
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Sauron
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As mentioned upthread commercial diacetin is a mixture of 1,2 and 1,3-glyceryl diacetates and usually contains some triacetin as well. But it is only
the 1,3-isomer that can be converted to dihydroxyacetone.
In a 1955 note in Naturwiss. the suggestion was made to employ Darzens' synthesis (Compt.Rend. 225, 942 (1947)) of 2-nitropropanediol, a nitroalkane,
from condensation of nitromethane and 2 eq formaldehyde with sodium methoxide in methanol as base. (The later authors found that methanolic NaOH also
worked.)The nitroalkane glycol is then acetylated to the 1,3-diacetate and reduced to 2-aminopropanediol, and the 2-position converted back to
hydroxyl with NaNO2. There is little room for doubt that this unambiguously gets the job done. Whether it is worth the bother compared to using
commercial diacetin and accepting lower yields of dihydroxyacetone, is an open question.
Darzens acetylated the nitropropylene glycol, treated it with aq oxalic acid and reduced that to the 1,3-diacetin.
Two variations on the reduction are given, one employing Pd catalyst and the other a Ni-Mg alloy (possibly one of the Raney nickels).
In a 1913 paper in Ber., Schmidt et al proposed and demonstrated the preparation of both diacetin esters in pure form by acetylating glycerin
chlorohydrins and bromohydrins.
Seperating the 1,2 and 1,3 diacetins is very difficult because their bp's are only 7 C apart and would require very high reflux ratios and a very
efficient column, making for a slow, tedious, energy intensive fractionation. In the absence of a spinning band column, I would rather do this by prep
HPLC, and that is also expensive. So synthesis is a viable option.
[Edited on 7-6-2007 by Sauron]
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Sauron
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Modified Darzens Sceme for 1,3-Diacetin
[Edited on 7-6-2007 by Sauron]
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Sauron
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Well, we've looked at five different literature routes and in reviewing these some conclusions pop out.
1. The routes from glucose are low yield. They do have the virtue of getting us unambiguously to mesoxaldehyde though. Of the two, the NaOH/Lead
Tetraacetate degradation is probably more practicable for more members than the alternative, simply because people might not be able to get
phenylhydrazine.
2. I don't think many members want to work with acrolein so we can skip that scheme.
3. That leaves the two routes from glycerol, one direct and one via Diacetin.
The hydrogen peroxide (6%) oxidation catalyzed by ferrous sulphate is efficient and productive but finicky. If temperature and addition rate are not
done just so, the mix will neither turn yellow nor set to a gel you you will know you have screwed the pooch.
But, this is a quite OTC method and worth attention.
The chromic acid oxidation of Diacetin is likewise very productive and not so finicky. And it is also quite OTC.
Both of these produce glycerose syrup. This is an equilibrium mix of the two trioses, gluceraldehyde and dihydroxyacetone - the simplest aldose and
the simplest ketose.
The next step is same for both. Copper acetate oxidation to hydroxypyruvaldehyde. Once again very OTC as anyone can buy or make cupric acetate.
The product is, I believe a tautomer of triose reductone (2,3-dihydroxyacrylaldehyde) and therefore ought to be oxidized to mesoxaldehyde by SeO2
easily. No overoxidation.
Confirmation of this is going to mean wet lab time, also required to figure out how to mask the middle carbonyl of mesoxaldehyde so I can react the 1
and 3 positions with hydroxylamine to obtain DINA.
The glyderol/Diacetin methoda are therefore my routes of choice. I may try the others, as well, but these are the ones I recommend as most suitable
and productive for most others.
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Sauron
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Eureka! Easy 1,3-Diacetin for Oxidation to DihydroxyAcetone
I found an alternative way to make pure 1,3-diacetin, that is simpler than the nitromethane-formaldehyde route.
1,3-dichloro-2-propanol ("1,3-dichlorohydrin") is commercially available and anyway is easy to prepare from glycerol and dry HCl. See Org.Syn.)
It reacts with anhydrous sodium acetate to give 1,3-diacetin in good yield. See p.1081 of Ober Diaeetine und andere G1yeerinabkSmmlinge, attached.
Thanks to Fractional, a helpful new member from Holland, here is a much better translation of the pertinent part than anything I could render in my
halting imprecise chemical German:
V. Diacetin from s-Dichlorohydrine
It seemed desirable to verify the composition of the diacetines by syntheses. The chlorohydrides seemed suitable starting materials, since they have
repeatetly been used with success for the synthesis of glycerol-esters. It could be shown that the substance assumed to be alpha,gamma-diacetine could
indeed be synthesised from symmetrical dichloro-hydrine, as expected.
20g dichloro-hydrine were intimately mixed with 25.5g water-free and finely powdered sodium-acetate and heated to 150 degC in a sealed tube for 8
hours. The air in the tube had been replaced by CO2. The contents of the tube were put in ether, filtrated, and the filtrate was distilled in vacuum.
At a pressure of 18mm 4g of a substance were first obtained at 86 degC, which probably was unreacted dichloro-hydrine, although the boiling point was
slightly too high. Further 4g were obtained at slowly rising temperature. Eventually a fraction with more or less constant boiling point was obtained.
The total amount of this substance after repeated fractioning was 15g with a boiling point of 148...152 degC at 12 mm, and analytically it was found
to be identical to the substance assumed to be alpha,gamma-diacetine.
0.2602g yielded 0.4534g CO2 and 0.1638g of H2O
Total (?) C 47.52 H 7.05%, calibrated for C7H12O5 (?) C 47.71, H 6.87%
s-dichloro-hydrine reacts only very slowly with silver-acetate in a water-bath. After heating for 5 hours 80% of the dichloro-hydrine remained
unreacted (b.p. 76...80 degC at 11mm. With pure dichloro-hydrine the observed b.p. at 11mm was 76 degC.
I think this makes the diacetin oxidation route the #1 best choice.
Required:
Step 1. Glycerin 1,3-dichlorohydrin
Glycerol
anhydrous HCl
Step 2. 1,3-Diacetin
anhydrous NaOAc
Ether
Step 3 1,3-Dihydroxyacetone
Sodium Dichromate
Glacial acetic acid
Conc Sulfuric Acid
Sodium carbonate
Step 4 Hydroxypyruvaldehyde
Cupric Acetate
Step 5 Mesoxaldehyde (1,2,3-propanetrione)
Selenium Dioxide
Step 6 DINA (mesoxaldehyde 1,3-dioxime)
Hydroxylamine hydrochloride
And there you have it, DINA from Glycerine.
If you buy your Dichlorohydrin you eliminate one step. If you buy your diacetin you eliminate teo steps. If you buy dihydroxyacetone dimer you cut out
three steps.
Perhaps it is a bit more work than the citric acid to acetonedicarboxylic acid to DINA via sodium nitrite method.
It may even be more work than the NaOH/LTA degradation of glucose, or the periodate oxidation of glucosazone.
But it gives much more satisfactory yields than any of those and is I think worth the extra bother.
Also it is highly OTC.
[Edited on 10-6-2007 by Sauron]
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Sauron
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My entire synthetic strategy in this route from glycerin depends on the workability of the final oxidation of hydroxypyruvaldehyde to mesoxaldehyde by
the use of selenium dioxide, a rapid but mild oxidizer that is documented in the literature as reagent of choice for converting triose reductone
(2,3-dihydroxyacrylaldehyde) to mesoxaldehyde without oxidizing the carbonyl function already present.
I firmly believe that hydroxypyruvaldehyde is tautomeric with 2,3-dihydroxypyruvaldehyde.
Both are C3H4O3
One is HO-CH2-C(=O)-C(H)=O
Other HO-C(H)=C(-OH)-C(H)=O
Draw them, see what I mean. Of course they are tautomeric and so in solution they are equilibrium and so, SeO2 ought to oxidize one as well as the
other. To same product. Depending on the nature of the equilibrium the rates might differ.
Comments please.
If for some reason this hypothesis proves invalid, how to get from hydroxypyruvaldehyde to mesoxaldehyde?
One way would be to prepare the tris(phenylhydrazone) and in the process, the hydroxyl group will be oxidized. This would be a reasonable way to store
the mesoxaldehyde anyway. It is a known compound having been prepared by H.von Pechmann 110 years ago so the mp is known. The mesoxaldehyde is
recovered by splitting off the phenylhydrazines with HCl or by means of another polycarbonyl (pyruvic acid being the usual reagent.)
This will suffice for he nonce as a fallback plan.
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