Sciencemadness Discussion Board - Chlorobutanol synthesis

Chlorobutanol synthesis

blazter - 15-12-2002 at 10:01

A while ago i stumbled across a fairly easy looking synthesis for a chemical known as chlorobutanol. Seems that it was being discussed as a possible chemical for a tranqulizer dart. Anyways after sorting out the fragmented directions at http://www.rhodium.ws/chemistry/chlorobutanol.txt
i figured that all i needed was generic bleach, acetone, lye, denatured alcohol and a bit of equipment. First of all the chloroform was easily produced by mixing some acetone with ~1gal of bleach (again following directions at rhodium). After letting the bleach/acetone sit overnight the excess water was poured off until there was about 50/50 chloroform water left at the bottom of the beaker. This was then distilled, the distillate was cloudy but after sitting for a while it separated into chloroform and water layers. I think i got a pretty shitty yeild of only around ~30ml, but that would be plenty for this purpose.

Then some acetone was distilled to remove any traces of oils and crap. about 100 ml of denatured alcohol was also distilled with some anhydrous MgSO4 in hopes that it would be more or less anhydrous (I'm not sure how successful that was).

Anyways, the actual synthesis was pretty smooth, 45ml distilled acetone and 5ml chloroform was measured out and chilled separatly to about -5C in a snow/salt bath. About 1.5 gram drain open lye was massed (it's not 100% pure and contains what i beleive are carbonates).

The chilled acetone and chloroform were mixed, the NaOH added, and i turned on my homemade overhead stirrer in a 250 ml beaker, all in the ice bath. The solution was stirred for about 2 hours and when time was up it had a milky with a slight yellow tint to it.

It was difficult to filter out the insoluable bits because it was extremely fine and took about 3 passes through doubled up coffee filter paper (some extra acetone was added to make up for evaporation and to ensure it would be free flowing). The clear yellowish/greenish liquid was distilled to remove excess acetone (heating stopped at around 90C). The remaining oil was poured into ice cold water and stirred rapidly until what looked like crystals had formed. Now this is where the substance starts acting a little weird. A very tiny bit seemed to form well defined crystals but the vast majority seemed to be like bits of solidified wax.

Anyways, this was filtered and let to dry overnight. At this point the 'camphourous' odor was very distinctive which leads me to beleive that what i have is indeed the stuff described at rhodium. The solids were dissolved in warm ethanol (very soluable!) took less than 50 ml and that was too much i think. This was left to evaporate in a shallow dish and better crystals were formed in time. They were needle like for the most part and had a tendency to form parallel to the surface they were crystallizing on.

My guess is that there is ~5g final product but it is still oily and seems to almost be reverting back to the oil as it sits in a vial. Could this be due to water being left in the crystals? Also, when i accidently came in contact with some of crystals i didnt note any local anestetic effect which was described. I'm really not crazy about ingesting it myself as the crystals seem to be a bit off white and therefore probably impure. Could this be at all useful as a poison dart for small animals or such?

madscientist - 15-12-2002 at 18:35

Chlorobutanol: Cl₃CC(CH₃)₂OH: Colorless to white crystals with characteristic odor and taste. Soluble in alcohol and glycerol; slightly soluble in water; readily soluble in ether, chloroform, and volatile oils. Melting point (anhydrous form) 97C; melting point (hemihydrate) 78C; boiling point 167C; sublimes easily.

I recommend doing a melting point test. If the melting point is somewhere between 75C and 100C, I'd think it's safe to assume that you have chlorobutanol that is pure enough to be used as a poison dart for small animals.

Interesting

Polverone - 15-12-2002 at 23:28

I've never noticed that particular synthesis before. I will have to try it when I can get to my materials again. I found it interesting that one of the procedures said that no cooling is necessary. The base-catalyzed reaction of acetone and chloroform has often been described as explosively violent in texts on industrial and laboratory hazards. Maybe it's only a problem on a large scale.

Marvin - 17-12-2002 at 03:18

madscientist, that is very bad advice, alow a 25 degree melting point range simply becuase it could be one or the other? Chemicals in lit normally have a 2C or so melting point range, and sharp melting points (somewhere in the given range) are attributed to fairly pure products. I suggest dehydrating it before crystalisation, if you suspect the hydrate is being formed. I'd like however to turn my attention to the text which includes major fundamental errors, of which I'll concentrate on one howler.

[Begin Rant]
Rhodiums page contains a lot of very good info, but whoever wrote part of this text has made major obvios mistakes.

Quote,
7. It was found that re-crystallizing the product from ethanol gives a much
cleaner product. The original product contains excess water, and is somewhat
oily to the touch. Dissolve the product in the minimum amt of ethanol and
allow to evaporate dry as a thin layer on a "large" glass plate. Scrape off
the re-crystallized chlorobutanol with a razor blade or other sharp straight
edge. Store the chlorobutanol in a closed dark container, as it sublimes
easily.
[Vitriol]
This is, and I use this expression rarely, utter shit. The process this describes may well make the crystals look whiter, but they will be less pure than before, not more. The reason they look whiter is the very action of scraping them off the glass turns them into a finer powder, in which the real colour of the chemical shows up less. You can see this in scratch tests of minerals. You take a dark grey rock, scratch the surface and the fine powder is only light grey.

The whole point of recrystalisation is to remove impurities less soluable and more soluable than the product you want. You need a solvent that the product is not very soluable in, and ideally should have a wide solubility range with temperature.

You add just less of the solvent than will dissolve hot all of the powder, and FILTER. The solid is then thrown away. The filtrate is alowed to cool, and the ppt is filtered off, being purer than it was before. The filtrate, containing only a small amount of of the product, together with its contained second lot of impurities is then DISCARDED.

Frequently a mixture of solvents has to be used to provide moderate solubility at high temperatures and sparing solubility cold, with or without extra cooling, for example ice. Frenquently a prep will say 'dried with', in which case the filtrate from the first step often has a small amount of a dehydrating agent, eg MgSO4 added, and then after a while it is refiltered, and the cooling started. Another common sight is for example 'recrystalised from ethanol (charcol)' in which case activiated charcol is added in the same way, usualy to remove coloured, or resinous materials. This is fractional crystalisation, and exactly what preps. are talking about when they say 'product was recrystalised from' in the lituriture becuase they know every graduate chemist, and most other people besides known exactly what they are talking about.

A mistake as huge and as basic as this throws the whole text into doubt. Oily crystals are common and are usually becuase they are very impure. If the yeild is only 25% wrt chloroform, then that leaves a an awful lot of side products, and an untold amount of rubbish from the excess acetone alone, such as polymers, aldol condensation products that form when acetone is treated with base, to contaminate the product.

I have nothing against people making and taking chemicals, despite local laws, but people that dont have the skills, dont do any reading themselves and simply take a method off the internet which could have been, and often has been written by a clueless highschool wannabe, and is then willing to eat the product deserves everything they get.
[/Vitriol]

On the subject of this, I see nothing to recommend it as a tranquiliser. It says its a local anaesthetic, not to be confused with general anaesthetics, and has mild hypnotic properties. Find more out about this, but darts tipped with this are likley to do nothing other than possibly numb the affected area based on the available information.

It says this sublimes easily, in which case this might provide a much better way of purifying it (after, not instead of recyrystalisation), if anyone decides that they cant live without eating some or for topical use with themselves or animals.
[End Rant]

good rant

Polverone - 17-12-2002 at 06:09

If you look at the cyanide synthesis procedure hosted on Rhodium's site you will find evidence not just of incompetence on the author's part but outright fabrication. Unfortunately, Rhodium doesn't have time to proofread everything that he hosts. Thanks for pointing out the the author's missteps in this procedure. It looks like I'll be looking for an academically credible synthesis before I go ahead with it.

Hermes_Trismegistus - 9-1-2004 at 21:59

Found a lovely little spinny picture of the molecule on the bottom of this page.

http://www.globalchemsources.com/clbutanol.htm

found some contraindications for use in humans

http://www.lotusbirth.com/doc/FEB2003Lotusbirth-162.htm

CHLORETONE, 0.2%. Earthworm anesthetic. Dissolve 2g chloretone in 1000 ml pondwater. Chloretone is 1, 1, 1-trichloro-2-methyl-2-propanol, or chlorobutanol, and is available from Ward's Natural Science Establishment.

CHLORETONE, 5%. Anesthetic for freshwater metazoans. Dissolve 50g chloretone in 1000 ml water.

http://www.lander.edu/rsfox/310suppliesLab.html

blazter - 10-1-2004 at 21:05

After digging through some old vials which had been accumulating, I stumbled upon the old chlorobutanol sample which had been sitting around. Since the new webcam was working at the time I decided to snap a pic. The rusty discoloration on the vial is actually a rust stain on the outside and not part of the actual material. Also, you can see where it has been subliming and recrystalizing on the side of the vial. It is too bad that the resolution is so low, because the crystal shape looks a bit like a snowflake. The semi liquid bottom fraction can also be seen which is what the text refers to as "oily crystals". Since I really have no data to effective recrystalizations, there it sits, though someday I may attempt to do something with it. I suspect that there may be more contamination than desired product in it though.

Impure_Chlorobutanol.jpg - 15kB

recrystallization

Hermes_Trismegistus - 11-1-2004 at 13:08

Merck index lists it as being freely soluble in WARM water, slightly soluble in cold water. (however I did pull info from two sources)

martindale "extra pharmacopoeia lists a solubility of 1:1 in alchohol perhaps that would be a better choice.

[Edited on 14-1-2004 by Hermes_Trismegistus]

Storing Chloretone, chlorobutanol.

Hermes_Trismegistus - 14-1-2004 at 15:13

STABILITY: the half-life at 25 for chlorobutol(chloretone) in a solution buffered at pH 3 was calculated to be 90 years, whereas at pH7.5 it was 0.23 year.

Similarily for the decomposition in aqueous sol'n when heated for 30 min at 115 degrees was calculated to be 13% at pH 5 and 58% at pH 6.
--- A.D. Nair and J. L. Lach, Journal of the American Pharmaceutical Association, scient. Edn., 1959, 48, 390.

A 0.5% sol'n of chlorobutol with a pH of 5 to 6 lost 10% of its potency when stored for six weeks at between 25 and 30 degrees. Neutral or alkaline sol'n's were less stable.
--- N.V. Patwa and C.L. Huyck Journal of the American Pharmaceutical Association, 1966, NS6, 372.

[Edited on 14-1-2004 by Hermes_Trismegistus]

guaguanco - 14-1-2004 at 15:27

Quote:

Originally posted by Hermes_Trismegistus

http://www.lotusbirth.com/doc/FEB2003Lotusbirth-162.htm

Excellent. Should any unruly earthworms head my way, I'll know what to do.

bbartlog - 18-10-2014 at 14:34

I've been thinking about pursuing an analogous synthesis, using 2-butanone (methyl ethyl ketone, MEK) as a substrate instead of acetone.

Couple of questions:

- can anyone see an obvious problem with this? It looks to me like 2-butanone should be pretty similar to acetone in terms of its susceptibility to nucleophilic backside attack, but I have not been able to find an example of someone actually doing this synthesis.

- does anyone know where I can find melting point information for 1,1,1-Trichloro-2-ethyl-2-propanol (or would it properly be named 1,1,1-trichloro-2-methyl-2-butanol?)? Would be nice to obtain some rudimentary verification by way of melting point that I've actually obtained the target material, but I can't find that information either.

[Edited on 18-10-2014 by bbartlog]

Ninja - 9-12-2014 at 09:22

Quote:

I've been thinking about pursuing an analogous synthesis, using 2-butanone (methyl ethyl ketone, MEK) as a substrate instead of acetone.

I once read a paper that described a similar synthesis with levulinic acid, so i should work with butanone. I am truly sorry that a cannot give any references, but i could'nt find them again. It is NOT a sedative.
THE ADDITION PRODUCTS OF METHYLETHYL KETONE WITH CHLOROFORM, BROMOFORM AND IODOFORM
This might be a sedative.

[Edited on 9-12-2014 by Ninja]