POCl3

[phalaris]

I have been unable to find a synthesis for phosphorus oxychloride.  Somebody mentioned that it could be made from PCl5 (which I do have a synth for), but there weren't any details.

PCl3 is made by bubbling chlorine gas through red phosphorus until the appropriate change in weight is noted.  PCl5 is produced the same way starting with PCl3 instead of phosphorus.

P4 + 6 Cl2 -> 4 PCl3

PCl3 + Cl2 -> PCl5

Actually, will PCl3 and hydrogen peroxide do the trick?

Hmm....

PCl3 + H2O2 -> POCl3 + H2O

Heats of formation in kcal/mol:

P4: -4.4
Cl2: 0
PCl3: -81.0
H2O2: -44.84
POCl3: -151.0
H2O: -70.41

These constants were taken from the _Handbook of Chemistry_ by Lange et al.

Let's see...

(-151.0 + -70.41) - (-81.0 + -44.84) = -95.57

Hmm...  95.57 kcal/mole heat generated.  Since  exothermic, does this mean it will be spontaneous?  I am still somewhat lacking in my understanding of thermodynamics.

I am also unsure as to how to determine the rate of reaction.

Will this work?  Do I have any side-products to worry about?

[phalaris]

I just read something about phosphorus halides reacting with water to produce phosphoric and hydrohalic acids.  Perhaps this could be done with sodium hypochlorite?

[KrZ]

Thats alot of work for something you could buy isn't it?  Not to stop you, I'm just saying, buying POCl3 might be easier than getting Red P.

[Bright Star]

POCl3 is tough to get.
It is THE pre-cursor to Saran Nerve Gas.

KrZ- I've been following your thoughts on this and I urge you to continue.   I am not an Organinc Chemist ... so I am no help. 

But, its not Like I have to urge you, eh?   

[KrZ]

What was the reason for not being able to use SOCl2?

[phalaris]

I read today that POCl3 is also a byproduct in the alcohol to alkyl chloride FGI when PCl5 is used as the acidic reagent.  I am not sure what happens to the hydrogen though.  Perhaps this?:

PCl5 + ROH -> POCl3 + HCl

KrZ:  Which reagent are you suggesting I substitute SOCl2 for?  I am not very familiar with this compound.

[KrZ]

I've read ref's using SOCl2 in place of POCl3 for acyl chloride formation in both LSA, and IAA.  So it should be a useful substituite for pretty much anything.  TIHKAL mentions a 1960 reference for LSA->acyl chloride->LSD, does anyone know what that reference is?  Is it included in the hard-copy?  Should I just go and buy that?  I don't really want it if he doesn't include the reference information...

[phalaris]

It has been said in earlier discussions that POCl3 is higher yielding than the SOCl2 method, but I really don't know anything about that.  I have read much praise of the POCl3 method for its high yields, relative safety, and the purity of the product obtained.  Something called "epimizeration" was mentioned several times with other reagents...  I have inferred this to be some sort of isomerization into inactive analogues (the so-called iso-LSD?).  Supposedly this does not occur with POCl3.  Does it occur with SOCl2?

The synth using POCl3 is very possibly not the easiest one, but it looks easy enough and can be done almost OTC.  In fact, I think that with some effort it would be possible to obtain every reagent in the synth OTC.  Hmm...

Back to the books...  later.

[KrZ]

Well if someone knows where that 1960 reference is we could check it out.  Also, I'd like to get some info on that ergotalkaloid extraction if anyone knows where to get Biol. Physiol. I can't seem to find it...

[phalaris]

What is this "Biol. Physiol?"  Is this the full title?  I have access to a very good library, and might be able to find it if given the author.

[KrZ]

This is what you need
 

quote:Ran through a bunch of references I've been meaning to look up anyway...over half of them in German...sigh...hopefully these (few English I managed to find) will help...here we go:

Bacteriology 1972, 112(2), 791.
-mycelium dried
                             -2 mL made alkaline w/ 0.2 mL 10% ammonia
                             -extracted w/ 2 mL chloroform
                             -chloroform evaporated to dryness under N2
                             -1 mL 1% succinic acid soln. added
                             (this is as far as they needed to go for a colorimetric detn.)

                             Arcamone et al. Biochim. Biophys. Acta, 1962, 57, 174.

                             -cooled culture extracted 2X @ pH 7.5 w/ equal vol. chloroform-isobutanol (4:1 v/v)
                             -alkaloids transferred from the solvent into 1% tartaric acid soln.(1/4 vol. used w/ 3X extractions)
                             -free base by repeated chlorofrom extractions @ pH 7.5, concentration of chloroform extracts and precipitation with
                             pet. ether

                             Robertson et al. J. Bacteriol., 1973, 114(1), 208. (same guys who worked on Robbers et al. paper...very similar
                             procedure)

                             -dried mycelium powdered
                             -2 mL culture made alkaline w/ o.2 mL 10% NH4OH
                             -alkaloids extracted w/ 2 mL chloroform
                             -chloroform evaporated to dryness @ room temp
                             -succinic acid (2%, 1mL) added to dried residue

                             The last reference I have refers to isolation of ergot alkaloids from Ipomoea violoacea:

                             Moekatis et al, Biochem. Physiol. Pflanzen, 1973, 164, 248.

                             Seeds:
                             -pulverized seeds defatted in pet. ether for 5 hrs.
                             -1 g of this material shaken 3X (each for 1 hr.) w/ 20mL of (2g tartaric acid in 30 mL H2O, 70 mL acetone) mix
                             -combined extracts heated on H2O bath (55°C) to expell acetone
                             -tartaric acid soln. shaken 3X w/ anhydrous ether, then basified (pH 8-9) w/ NH4OH
                             -from this soln' alks extracted 3X w/ 10 mL DCM
                             -combined extracts reduced to 1 mL and chromatographed

                             Roots, Leaves, Stems:

                             -pulverized material (15g) wetted w/ 3% NH4OH
                             -extracted w/ 200 mL DCM in Soxhlet for 6 hrs
                             -condensed to 20 mL & shaken 4X each w/ 10mL 2% tartaric acid
                             -total of 40 mL soln. extracted 3X each w/ 10mL anhydrous ether
                             -tartaric acid extract made basic w/ NH4OH (pH 8-9) & shaken 3X w/ 10 mL DCM
                             -total of 30 mL DCM extract condensed to 0.3 mL & chromatographed...

                             If you're interested, I came across a couple references to stationary and mobile phases used in chrom. Also came
                             across A LOT of references to controlling amount of alkaloid production in cultures...

                             -Teo

[KrZ]

That last one looked the best.  Ideally would be a detailed "ergot alkaloid" extraction, all the goodies you want without extra hassle to get only ergotamine.  The crude ergot alkaloids could all be hydrolyzed and the LSA collected, this would probably give the best LSA yields available from Claviceps Purpea.  It's definitely got to take some balls/brains to be able to run an efficent extraction on 10lbs of JLF's "Claviceps Purpea Batch #2".  Ever wonder why the second one is so much more expensive?  I wonder how much of THAT they've been selling ;-)

[KrZ]

WE definitely need this one too;

"Ergot Peptide Alkaloid Spectra of Claviceps-Infected Tall
Fescue, Wheat, and Barley" by James K. Porter, Charles W. Bacon, Ronald D.
Plattner, and Richard F. Arrendale.  J. Agric. Food Chem. 1987 (35) 359-361.
Edit: This article has been posted in

Post 480338

(Rhodium: "Claviceps-Infected Tall Fescue/Wheat/Barley", Tryptamine Chemistry)


CA: 77:P156333n : describes a method used to get 9.75g pure lysergamides from a 10 litre fermentation originally containing an estimated 15g.

*The Ergot Alkaloids; A. Stoll and A. Hofmann (THE);
Chapter 21, The Alkaloids, Manske (ed. ?) vol. VIII, pgs 725-779+.
Describes lots and lots and lots of chemical detail regarding
everything from biogenesis to complete chemical synthesis as a means
of confirming structure. Also has a section completely devoted to
"Derivatives of Ergot Alkaloids" in which the following processes
for synthesizing amides are discussed:
=> The azide process.
=> DMF-SO3 mixed anhydride method.
=> mixed Lysergic acid trifluoroacetic anhydride.
=> Lysergic acid chloride hydrochloride method.
=> N,N'- carbonyldiimidazole as condensing agent (Best IMHO).

there's also the Michael Valentine extraction, but I'd like to see some ref's before I go taking his word for it.

[LaBTop]

Tihkal mentions on page 492 (#26, LSD-25):

[...] The earliest syntheses of LSD involved the use of [...] or with the acid chloride as the active intermediate with POCl3, PCl5 or thionyl chloride (1963) or just phosphorus oxychloride (1973). [...] The POCl3 procedure is clean and fast,and is the preferred process today for the synthesis of a wide variety of substituted lysergamides.

The refs from 1963 which could be this ref are:

Frey, A.

Patent US3084164

(1963).

Observations on Direct and Cross Tolerance with LSD and d-Amphethamine in Man
Rosenberg, D.E., Wollbach Jr., A.B., Miner, E.J. and Isbell, H.
Psychopharmacologia 5, 1-15 (1963).

The Ergot Alkaloids. II. The Degration of Ergotinine with Alkali Lysergic Acid.
Jacobs, W.A. and Craig, L.C.
J. Biol. Chem. 104, 547-51 (1934) 

Post 436450

(Rhodium: "Discovery of Lysergic Acid", Tryptamine Chemistry)

Ergot Alkaloids. XLV. Substitution in the Ring System of Lysergic Acid. 3. Halogenation.
Troxler, F. and Hofmann, A.
Helv. Chim. Acta 40, 2160 (1957)

Synthesis and LSD-like Discriminative Stimulus Properties in a Series of N(6)-Alkyl Norlysergic Acid N,N-Diethylamide Derivatives.
Hoffman, A.J. and Nichols, D.E.
J. Med. Chem. 28, 1252-1255 (1985)

Post 480281

(Rhodium: "Some syntheses of LSD and analogs", Tryptamine Chemistry)

Esters of Indoles for the treatment of Mental Disturbances
Hofmann, A. and Troxler, F.

Patent US3078214

Feb. 19, 1963.

LT/

[KrZ]

In an ideal world, yes, POCl3, in take-what-you-can-get ClanChem...  I mainly just wanted to compare the two reagents to see what the overall benfit of a preperation/aquisition would be..

[rev drone]

phalaris,

POCl3 is produced by reacting PCl3 with O2, not H2O2 -- remember, this stuff's moisture sensitive.

------------------
-the good reverend drone

Ipsa scientia potestas est

[KrZ]

Looks like there is no need to worry anyway.  Obtained 100ml of POCl3 today for 45 bones.

[phalaris]

rev drone:  This is what I was referring to in the second post.  I then proposed that it be done with hypochlorite.  It turns out that the working synth I found involves the use of PCl5 and an alcohol:

PCl5 + EtOH -> POCl3 + EtCl

The organic chemistry textbook I read this in did not discuss what happens to the missing hydrogen.

I believe that the ethyl chloride produced in this reaction could be used to produce diethylamine via Hofmann alkylation, but I do not have any more details at this time.

I will report back after visiting the library.

[Slappy]

Bright Star: If you're not an "Organinc" chemist, then what the hell are you? I always thought that you were.

saran = plastic wrap
sarin = nerve agent

[phalaris]

What a relief!  I was afraid that I was wrapping my sandwiches in neurotoxins!