Propionic anhydride

[Ford Prefect]

Propionic anhydride IS probably the most watched chemicals in the United States, meaning us bees could do well by finding an alternate means of acquiring it. I've got a couple thoughts, but this chemical is definitely due for some brainstorming. As I see it we've got a couple decent options...


Ala Drone, either by:

1)

"Propionic anhydride is made from a propionate salt like
calcium propionate by adding bromine or even chlorine."


or...

2)

"Alternatively, propionate esters are hydrolyzed,
the acid component isolated, and combined
with acetic anhydride and allowed to reflux, with
the product being fractionally distilled."

and also:

3)

By the hypochlorite oxidation of MEK then dehydration with ketene.

2CH3CH2CO2H + CH2=C=O -> (CH3CH2CO)2O + CH3CO2H

http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/propionic.acid.html

http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv1p0330


Yus, ketene is nasty but then so are the ultapotent fentanyl analogs you mothfuckers would surely be making if you got your paws on sum prop. anhydride. ;)


...and lastly, a patent for propionyl chloride which I haven't had time to read over in much depth quite yet: www.freepatentsonline.com/4093638.html


Thoughts bees?

[incorporated]

If propanoyl chloride can be acquired, it's doable. I don't know if it's easy to come by, but it's not listed so:

CH3-CH2-COCl + H2O + Pyridine > Propanoic acid

Propanoic acid + Base (to deprotonate the acid's hydroxyl) + Propanoyl Chloride > Propanoic anhydride.

[stateofhack]

Nice thinking, the last one seems to be the most OTC, but Ketene is nasty ass stuff :(

calcium propionate and the such watched? People can't be that stupid?

[Ford Prefect]

What about maybe the first half of the third with the second half of the second?

I like the hypochlorite oxidation quite a bit as it is very OTC and a seemingly facile method. But could the acid then be "combined with acetic anhydride and allowed to reflux, with the product being fractionally distilled" as suggested by Drone? It'd require AA, but you'd be skipping the part where you get a pulmonary edema. Or am I way off track? I'm not sure if I understand the mechanism at work there.

[JoePedo]

I'm curious... unlike, say, lysergic acid, is there really anything preventing just smoking the proprionate salt of the norproprionate precursor off tinfoil and letting thermal condensation do the rest???

Anyways...

1. Tear matchbooks.

2. Start fire.

3. ???

4. Fentanyl!!!

[Irukanji]

I'm curious... unlike, say, lysergic acid, is there really anything preventing just smoking the proprionate salt of the norproprionate precursor off tinfoil and letting thermal condensation do the rest???

Anyways...

1. Tear matchbooks.

2. Start fire.

3. ???

4. Fentanyl!!!

The ??? is the hard bit....

But hypochlorite is available in anything from 100mls to a weekly delivery of 20,000L

[eesakiwi]

50% Propionic acid is a easy OTC product.

Getting it to an Anhydride state is the next step.

[Ford Prefect]

50% Propionic acid is a easy OTC product.

Getting it to an Anhydride state is the next step.

Alright! So we've established that it can be bought or made OTC. This thread is now definitely about the dehydration of propionic acid.

Our choices so far...

1) Ketene: which'd probably look something like this... http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv3p0164
High yielding, but one would have to set up a ketene genny (not THAT dangerous).

2) Thermal condensation or possibly extractive distillation: http://www.freepatentsonline.com/5167774.html
I haven't had a chance to Merck any of this, but if somebody wanted to post some info on prop. acid it'd be helpful.

3) By heating with acetic anhydride: mentioned by Drone in the Hive and a related reaction is touched upon in the discussion section of the org syn link in option one. Anybody feeling like finding Michael, Ber., 34, 918 (1901)?

4) Dehydrating agents?

EDIT: a couple ketene generators...

www.jgp.org/cgi/reprint/18/1/69.pdf
http://jchemed.chem.wisc.edu/JCEsoft/CCA/CCA5/MAIN/1ORGANIC/ORG12/KETENE/MOVIE.HTM
http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv1p0330

[stateofhack]

There ya go:

Monograph Number: 7917
Title: Propionic Acid
CAS Registry Number: 79-09-4
CAS Name: Propanoic acid
Additional Names: methylacetic acid; ethylformic acid
Molecular Formula: C3H6O2
Molecular Weight: 74.08.
Percent Composition: C 48.64%, H 8.16%, O 43.19%
Line Formula: CH3CH2COOH
Literature References: Occurs in dairy products in small amounts. Can be obtained from wood pulp waste liquor by a fermentation process using bacteria of the genus Propionibacterium: Wayman et al., US 3067107 (1962 to Columbia Cellulose). Prepn from ethylene, carbon monoxide and steam: Reppe, Angew. Chem. 1956, 46; Larson, US 2448375 (1948 to du Pont); from ethanol and carbon monoxide using a boron trifluoride catalyst: Loder, US 2135448; US 2135451; US 2135453 (all 1939 to du Pont); by oxidation of propionaldehyde: Hasche, US 2294984 (1942 to Kodak); from natural gas by the Fischer-Tropsch process; as a byproduct in the pyrolysis of wood; by the action of microorganisms on a variety of materials in small yields. Very pure propionic acid can be obtained from propionitrile. Toxicity study: H. F. Smyth et al., Am. Ind. Hyg. Assoc. J. 23, 95 (1962).
Properties: Oily liquid. Slightly pungent, disagreeable, rancid odor. d420 0.99336. mp -21.5°. bp760 141.1°; bp400 122.0°; bp100 85.8°; bp1.0 4.6°. nD25 1.3848. Flash pt, open cup: 136°F (58°C). Viscosity (cp) at 15°: 1.175; at 25°: 1.020; at 30°: 0.956; at 60°: 0.668; at 90°: 0.495. Surface tension in dynes/cm at 15°: 27.21. Ka at 25°: 1.34 ´ 10-5. Misc with water. Can be salted out of water solns by the addn of CaCl2 or other salts. Sol in alcohol, ether, chloroform. Azeotrope with water, bp 99.98°, contains 17.7% acid; with toluene, bp 110.45°, contains 3% acid; with o-xylene, bp 135.4°, contains 43% acid; with ethylbenzene, bp 131.1°, contains 28% acid. LD50 orally in rats: 4.29 g/kg (Smyth).
Melting point: mp -21.5°
Boiling point: bp760 141.1°; bp400 122.0°; bp100 85.8°; bp1.0 4.6°; bp 99.98°; bp 110.45°; bp 135.4°; bp 131.1°
Flash point: Flash pt, open cup: 136°F (58°C)
Index of refraction: nD25 1.3848
Density: d420 0.99336
Toxicity data: LD50 orally in rats: 4.29 g/kg (Smyth)

Derivative Type: Barium salt monohydrate
Additional Names: Barium propionate
Molecular Formula: C6H10BaO4.H2O
Molecular Weight: 301.48.
Percent Composition: C 23.90%, H 4.01%, Ba 45.55%, O 26.53%
Properties: Powder, usually with slight odor. Poisonous! Freely sol in water; slightly sol in alcohol.

CAUTION: Potential symptoms of overexposure to propionic acid are irritation of eyes, skin, nose, throat; blurred vision, corneal burns; skin burns; abdominal pain, nausea, vomiting. See NIOSH Pocket Guide to Chemical Hazards (DHHS/NIOSH 97-140, 1997) p 266.
Use: Esterifying agent; in the production of cellulose propionate (thermoplastic) and other propionates, e.g., calcium propionate, used as mold inhibitors and preservatives; in the manuf of ester solvents, fruit flavors, and perfume bases.
Therap-Cat: Antifungal.

[Irukanji]

EDIT: a couple ketene generators...



So essentialy platinum wire/electrolysis, or copper/heat method. Wouldnt the heat cause it to spontaneously ignite?

Electricity = sparks. Sparks = boom.
Heat = heat. Heat = boom.

Which is gonna work, and how do you explain the boom?

[nshanin]

I'm curious... unlike, say, lysergic acid, is there really anything preventing just smoking the proprionate salt of the norproprionate precursor off tinfoil and letting thermal condensation do the rest???

Anyways...

1. Tear matchbooks.

2. Start fire.

3. ???

4. Fentanyl!!!

If only. Otherwise we'd just throw random amines and GAA into a fire. That this doesn't work with lysergic amides should probably have set off some alarms.

Heat = heat.

Aaaaah, I forgot to factor that in! :eek:

[Ford Prefect]

So essentialy platinum wire/electrolysis, or copper/heat method. Wouldnt the heat cause it to spontaneously ignite?

Electricity = sparks. Sparks = boom.
Heat = heat. Heat = boom.

Which is gonna work, and how do you explain the boom?

Yup. It sounds like its the pyrogenic decomposition that is responsible for the formation of the ketene. But I'm definitely liking this method less and less the more I read on it. Looks like a major fucking pain.

Here's another genny anyways- http://www.freepatentsonline.com/1879497.pdf

Pedo: you really think we might just condense sum vapors?

EDIT: Also...

To a stirred solution of propionic acid (2 mmol) and methanesulphonyl chloride (1.05 mmol) in dry THF (10 ml) at -15°C under nitrogen was added triethylamine (3.5 mmol) in THF (5 ml) slowly over 20 minutes. After stirring 1 hour at -15°C the reaction mixture was allowed to warm to room temperature. The reaction mixture was filtered through Celite and the solvent was evaporated off under reduced pressure. The anhydride was isolated by short-path distillation (yield: 85 %, bp: 70-72°C / 20 Torr (lit. bp: 67.5°C / 18 Torr)).

/

To a stirred solution of phthalic acid (0.332 g, 2 mmol) in dry THF (12 ml) was added triethylamine (0.202 g, 2 mmol) under nitrogen. The reaction mixture was cooled to - 20 °C. After stirring for 15 minutes, methanesulphonyl chloride was added (0.24 g, 2.1 mmol) followed by triethylamine (0.404 g, 4 mmol) in THF (5 ml) over 15 minutes. The reaction mixture was stirred at -15°C for 2 hours. The product was isolated using method A (0.275 g,, 93 %, m.p. 130-131°C)

http://www.erowid.org/archive/rhodium/chemistry/anhydrides.html

Obviously methanesulphonyl chloride is not a chemical one'd like to chill with, but at least its another option. And I guess it COULD be synthesised...

SO2 + Cl2 -> SO2Cl2
CH4 (g) + SO2Cl2 (g) -> CH3SO2Cl + HCl (g)

:(

[nshanin]

Yup. It sounds like its the pyrogenic decomposition that is responsible for the formation of the ketene. But I'm definitely liking this method less and less the more I read on it. Looks like a major fucking pain.

Here's another genny anyways- http://www.freepatentsonline.com/1879497.pdf

Pedo: you really think we might just condense sum vapors?

EDIT: Also...

To a stirred solution of propionic acid (2 mmol) and methanesulphonyl chloride (1.05 mmol) in dry THF (10 ml) at -15°C under nitrogen was added triethylamine (3.5 mmol) in THF (5 ml) slowly over 20 minutes. After stirring 1 hour at -15°C the reaction mixture was allowed to warm to room temperature. The reaction mixture was filtered through Celite and the solvent was evaporated off under reduced pressure. The anhydride was isolated by short-path distillation (yield: 85 %, bp: 70-72°C / 20 Torr (lit. bp: 67.5°C / 18 Torr)).

/

To a stirred solution of phthalic acid (0.332 g, 2 mmol) in dry THF (12 ml) was added triethylamine (0.202 g, 2 mmol) under nitrogen. The reaction mixture was cooled to - 20 °C. After stirring for 15 minutes, methanesulphonyl chloride was added (0.24 g, 2.1 mmol) followed by triethylamine (0.404 g, 4 mmol) in THF (5 ml) over 15 minutes. The reaction mixture was stirred at -15°C for 2 hours. The product was isolated using method A (0.275 g,, 93 %, m.p. 130-131°C)

http://www.erowid.org/archive/rhodium/chemistry/anhydrides.html

Obviously methanesulphonyl chloride is not a chemical one'd like to chill with, but at least its another option. And I guess it COULD be synthesised...

SO2 + Cl2 -> SO2Cl2
CH4 (g) + SO2Cl2 (g) -> CH3SO2Cl + HCl (g)

:(

I'm sure tosyl chloride would substitute well.

[incorporated]

50% Propionic acid is a easy OTC product.

Getting it to an Anhydride state is the next step.

If this is true, then your next step is:

Under water, in a shallow dish, cut 40 g of white phosphorus into small pieces with a knife. Displace the air in a 250-mL Florence flask with dry carbon dioxide. Add each piece of phosphorus to the flask by removing it from the water with tweezers, drying quickly by pressing between several layers of paper towel, and immediately placing in the flask. Be extremely careful that you do not ignite the phosphorus by friction from the paper towel, or by dropping it against the next of the flask. As soon as all of the phosphorus has been added, set the flask up for simple distillation with addition. Instead of a separatory funnel on the Clasien adapter, seal the straight arm with a 1-hole stopper or a thermometer adapter. Into the hole place a straight length of glass tubing far enough into the flask such that it is just above the level of the phosphorus. Do not run water through the condenser. The receiving flask should be held under a shower of cold water, and in a cold water bath, for example under a running faucet, and in a bowl that can overflow into the sink. There will be substantial quantities of waste chlorine gas, if you are using a vacuum adapter to connect the condenser to the receiver, attach a hose to it so it may direct the gas elsewhere. If not, you will figure something out, or you will suffocate.
A moderately rapid current of dry chlorine gas is passed over the white phosphorus; phosphorus trichloride will form with the evolution of heat and light. Some crystals of phosphorus pentachloride may begin to clog the condenser, these can be dislodged by gently heating the condenser, or by increasing the flow of the chlorine to generate more heat. If some white phosphorus begins to distill over, reduce the flow of the chlorine, or try to cool the reaction flask by briefly immersing it in cold water. The phosphorus trichloride thus collected is purified by distillation. (1)

And then:

Replacing the -OH group using phosphorus(III) chloride, PCl3

Phosphorus(III) chloride is a liquid at room temperature. Its reaction with a carboxylic acid is less dramatic than that of phosphorus(V) chloride because there is no hydrogen chloride produced.

You end up with a mixture of the acyl chloride and phosphoric(III) acid (old names: phosphorous acid or orthophosphorous acid), H3PO3.

For example:

Again, the ethanoyl chloride can be separated by fractional distillation. (2)

Refs: 1 (http://www.roguesci.org/megalomania/synth/synthesis4.html), 2 (http://www.chemguide.co.uk/organicprops/acids/pcl5.html)

[nshanin]

^ Source meh peeceeellthree.

[Ford Prefect]

HEY. Propionyl chloride looks just as good. Could save us a step (just gotta replace tha -OH with a -Cl) aaand we'd have a few more options to work with. Thionyl chloride, PCl3, PCl5, or...

Into the described flask, there is introduced:

850 g hexachloropropene (3.42 moles)
222 g propionic acid (3 moles)
1 g zinc chloride

The reaction mixture is heated to 150° C. The propionyl chloride formed is withdrawn by distillation after the temperature at the head of the column reaches 80° C. This temperature is reached after 11/2 hours of heating. During the following 21/2 hours, there is recovered 225 g propionyl chloride.

US Pat. 4093638

Still nowhere near OTC though.

[JoePedo]

The ??? is the hard bit....

"pass smoke through propionic acid???"

If only.

Only, dude.

Otherwise we'd just throw random amines and GAA into a fire.

Umm... the matchbooks were a source of elemental phosphorous, not a source of vinegar.

However, formation of acetamide from destructive distillation of ammonium acetate is actually known and in fact common procedure.

That this doesn't work with lysergic amides should probably have set off some alarms.

Umm, dude? Shulgin doesn't mention PO3 per se, but he does quite explicitly mention the related mineral anhydride in terms of sulfuric anhydride.

So, yes... it is quite known and sourced. Since you sort of changed topics at random, too... mere thermal condensation to create LSD works just fine, actually. There are no problems with it whatsoever, it is merely a fact that heating diethylammonium lysergate (or other lysergate or free lysergic acid) causes degredation at about the exact same rate that cooking LSD over an identical open flame does. This does not mean that the actual thermal condensation is ineffective or at all nonviable in itself.

However, as to the topic you actually quoted... yes, the use of mineral anhydrides to create lysergic anhydrides for various lysergic amide synthesis does work. Read Tihkal sometime, dude.

:)

[Ford Prefect]

...PCl3...

"A round flask fitted with a stirrer and reflux condenser contained 37 g (0.5 mole) of propionic acid, 40 ml of dry benzene, and 29 g (0.21 mole) of phosphorus trichloride; the reaction mass was stirred at 55-62?C for 1 hour. The mixture was then cooled to 30?C and phosphorous acid was separated off. To the remaining benzene solution 25 ml of dry benzene was added, the mixture was shaken, and the residual phosphorous acid was separated off."

hxxp://www.erowid.org/archive/rhodium/chemistry/propionic2ephedrone2ephedrine.html

This sounds good, I'm pretty happy with this. Other solvents would probably prove suitable provided they're rather dry 'n PCl3 is cheap and although listed schedule three by the chemical weapons convention probably not terribly hard to acquire provided one is dealing in small amounts.

And if not, I guess theres always scraping matchbooks... P4 + 6 Cl2 -> 4 PCl3

Thx for the leads incorporated/joe.

[Ford Prefect]

Bump/double post. Thoughts on propionyl chloride from propionic acid and benzoyl chloride?

[Irukanji]

If only. Otherwise we'd just throw random amines and GAA into a fire. That this doesn't work with lysergic amides should probably have set off some alarms.



Aaaaah, I forgot to factor that in! :eek:

:)

You know what heat does to unstable shit.....

[Irukanji]

"pass smoke through propionic acid???"


What sort of smoke? Or do you mean basically hot carbon dust? Since smoke is basically that....unless you mean all the different CO/CO2/etcetc....in which case you just need to find which one and your set. And obtain propionic acid....

Or.....we grow that shit....

http://en.wikipedia.org/wiki/Propionibacterium_acnes

Possible? It produces the stuff, much like yeast makes EtOH

[nshanin]

Bump/double post. Thoughts on propionyl chloride from propionic acid and benzoyl chloride?

Phthaloyl chloride is cheaper (don't quote me on this) and has twice the molar amount of acid chloride as your benzoyl chloride. According to SM, most acids are converted to their corresponding acid halides with phthaloyl chloride, but an exception was made to "more stable" acids, which I assumed to mean aryllic acids. So the question I have is what sorts of aryllic acids can be converted to their halides with phthaloyl chloride, which may just be more stable than your typical aryllic acid considering the intramolecular hydrogen bonding that is absent in the halide and present in the acid (at least with the ortho isomer).