Org Prep Daily

May 24, 2013

Oil pump desanguination – brilliant!

Filed under: procedures — milkshake @ 3:38 pm

I just had the fastest and most enjoyable pump oil change of my career, thanks to a colleague. We use large Welsh DuoSeal belt-driven pumps installed in metal cabinets under the hoods and these beasts are rugged, dependable – but so heavy: They take over 3 liters of oil to fill and the whole damned thing weights about 50 kilos. The oil drain valve is inconveniently located right near the bottom so the pump cannot be easily drained inside the cabinet. The normal oil change procedure requires disconnecting the vacuum hose and dragging the pump out. I would prop the pump on an empty solvent barrel, put oil collection bucket beneath the drain valve and keep draining, tilting, flushing, draining, filling, cursing. Lifting the pump requires two pairs of hands, the oil drips everywhere, and given the large and awkward shape of the (very heavy) re-filled pump that has to be finally coaxed back in and over the cabinet lip, the vacuum hose reattached and the inadvertent vacuum leaks fixed, it is a pretty unpopular job – a job that keeps getting postponed for as long as is possible, while pumps are left sloshing with tired crud that has the look and smell of burnt molasses. But not much longer!

Prodded by his injured back and by desperation, my colleague conceived a brilliant apparatus –  he took a large (4L) Erlenmeyer filtration flask closed with a stopper with a tube through it. To the tube he attached a cheap vinyl transparent tubing (like you would use for water in reflux condensers) and connected it to the oil drain valve at the bottom of the pump so that he can aspirate the spent oil by vacuum. Turns out, if the oil is warm (from a pump that has been run, so it is less viscous), it can by sucked out through the drain valve into the Erlenmeyer filtration flask under house vacuum in few minutes. After one fill with flushing oil, 2 min pump run and another suction-assisted drain and final re-fill, the entire oil changing operation can be completed in less than 15 minutes. No mess, no need to take the pump out, no need to disconnect the vacuum hose from the pump.

Our biologists of course claimed credit for the pump oil change idea, for having used this kind of setup previously when sucking off liquor from cells in multi-well plates. But I am afraid the true origin of this oil change breakthrough is rather more disturbing. You see, my colleague is leaving for medical school in few weeks and in preparation, he has already taken the anatomy labs. As I was sucking out gallon of alarmingly dark rotten muck from my pump with his gadget, he calmly observed that the really good, top-of-the-line embalming machines can aspirate blood while at the same time pumping formaldehyde solution back into the empty veins: The happy operator just needs to correctly insert the inlet and outlet tubes into the still body, turn on the flush routine and wait until the aspirate finally starts coming out clear…

April 1, 2013

It curdles if you don’t stir it

Filed under: mechanisms — milkshake @ 5:07 pm

IMG_3480

Trityl group on sulfur is unstable to LiAlH4 reduction. It falls off as triphenylmethyl anion – that’s where the gorgeous blood-red color is coming from. (Unlike trityl cation, which is canary yellow). I did not know about this S-trityl instability – my Greene book (3rd edition) for example mentions only the electrochemical reduction at highly negative potentials – and so I presume it is not as widely known.

In my hands, sulfur de-tritylation with LAH happens both with primary and secondary thiols protected as trityl thioethers. The rate of trityl loss seems structure-dependent: metal coordinating groups (such as OH, amino) in the vicinity of sulfur accelerate the LAH-promoted de-tritylation to a point that it cannot be avoided even under mild reaction conditions. In such cases all that remains to be done is completing the de-tritylation by overnight reflux and isolating the free-thiol product from the Al basic salt cake after the usual Fieser workup. The thiol actually ends up stuck within the salt cake as a thiolate; the filtrates contain only triphenylmethane.

Trityl-S group seems to be reasonably stable to borane-THF at room temperature.

Update: Trityl-O reductive cleavage to trityl anion is also facile, it takes place at room temperature with potassium naphthalenide solution in THF

 

October 29, 2012

Uroboros

Filed under: industry life — milkshake @ 6:56 am

I have been making water-soluble polymers with biomedical applications for the last 16 months and it is quite satisfying: Our macromolecules are usually well behaved – they extract into organic phase. They precipitate as a snow-white fluffy crystalline solid, on a kilo scale. They even have beautiful NMR spectra. Unfortunately, such was not the case with the frothy mixture in the picture. I had to isolate the material from a solution in concentrated HCl (0.3L), with extra sludge of inorganic salts and assorted gunk that included gram quantity of dimethyl sulfide.

The usual process would be: dilute, filtrer, dialyze. But dialysis is a slow and rather frustrating business and we don’t even have bags giant enough for removing few mols of salts and HCl. So I was delighted to learn that tangential flow filtration is a turbo-alternative to a dialysis – instead of steeping a swollen dialysis sausage bag (that can burst overnight) for days and waiting for the diffusion to run its course, the tangential flow filtration setup visibly labors for you: the pump pushes the mixture against a semi-permeable membrane, water and other small molecular weight material leak out, the macromolecular fraction stays in. The purification is done in few hours.

The peristaltic pump in the picture circulates the crude mixture at moderate pressure and high flow rate (20 psi, 1.7 L/min) from the beaker to bottom of the column; the stuff that flows out at the top is fed back into the beaker in a closed loop. The column consist of a bunch of spaghettini-like capillaries that are coated with a semipermeable membrane. The spaghettini are housed in a plastic pipe casing. It is inside these capillaries that the mixture rushes through at high speed over and over again – water and small molecule material that leaks out through the walls of the capillaries collect in the casing and flow into waste (the sidearm and the transparent bottle). One has to keep adding water into the beaker quite often because with a good column + pumping rate/pressure the mixture gets concentrated rather quickly.

The time to end the purification is when chromatography (GPC) can no longer detect small-molecular weight impurities. Of course with a whopping excess of HCl at the beginning, one doesn’t need to run GPC to confirm that all low-molecular weight material is gone – a pH paper will tell you that. (A sniff test for dimethylsulfide presence is also fast … and revolting…)

September 5, 2012

S-tritylthioacetic acid

Filed under: procedures — milkshake @ 6:53 pm

Neat mercaptoacetic acid 24.0g (260 mmol, about 18 mL) was added in one portion to a solution of trityl chloride 58.0g (208.0 mmol) in benzene 200mL (non-anhydrous, ACS grade). The flask was equipped with a gas outlet Drierite tube and the mixture was stirred for 17 hours: The HCl gas evolution ceased at this point and a heavy white material precipitated out from the reaction mixture. The reaction mixture was stirred under mild vacuum (50 Torr) for about 20 minutes to remove dissolved HCl. The solids were collected by filtration, washed with a small volume of benzene (2×10 mL) and with copious amount of hexane, then dried by suction.

The crude product (57.7g) was dissolved at reflux in benzene 250mL (100C oil bath) and the solution was left undisturbed for 1 day at ambient temperature. The supernatants were decanted off and the obtained crystalline mass was suspended in a small volume of benzene. The solids were collected by filtration, washed sequentially with benzene, cyclohexane and hexane and dried by suction, then on highvac. Y= 54.19g (78% based on Trit-Cl) of white coarse chunky crystals.

1H(CDCl3, 400MHz): 9.96(very br s, 1H), 7.32(m, 6H), 7.19(m, 6H), 7.12(m, 3H), 2.93(s, 2H); 13C(CDCl3, 100MHz): 176.1, 144.0(3C), 129.6(6C), 128.2(6C), 127.1(3C), 67.4, 34.6; TLC: CHCl3-MeOH 10:1 detected with UV and CAM, Rf=0.6

Note: The thiol reactant does not need to be present in excess but mercaptoacetic acid is cheap and its odor is quite tolerable – and adding more helps to improve the crude product purity and yield. This base-free thiol tritylation proceeds faster in more polar solvents like dichloromethane or dichloroethane but the reaction is then accompanied by a promptly vigorous HCl evolution and could be difficult to control on large scale. In benzene, the product gradually precipitates from the reaction mixture in a fairly pure form – this makes aqueous workup and evaporation unnecessary.

Benzene as a reaction solvent can be replaced with benzotrifluoride PhCF3 (400mL for a 58g scale experiment. Cooling on ambient water bath, 4 hours at RT) but PhCF3 alone does not work for recrystallization of Ph3CSCH2CO2H because the product is poorly soluble in it. Also, attempts at replacing benzene with toluene for recrystallization provided product of somewhat inferior purity so two recrystallizations from toluene (2 x 0.5L) were required.

Update: 2-mercaptopropionic acid can be tritylated without a base under similar condition but at elevated temperature: PhCF3 as a solvent, R.T. to reflux (distilled off a small volume of solvent until HCl evolution ceased, then at R.T. overnight. The precipitated crude product was collected by filtration, washed with hexane, dried and re-crystallized from PhCF3 to yield a pure product in 85% yield). 1H(CDCl3, 400MHz): 7.47(m, 6H), 7.29(m, 6H), 7.22(m, 3H), 3.05(q, 7.2 Hz, 1H), 1.211(d, 7.2Hz, 3H); 13C(CDCl3, 100MHz): 179.6, 144.3(3C), 129.8(6C), 128.1(6C), 127.1(3C), 68.4, 42.6, 18.6; TLC: CHCl3-MeOH 10:1 detected with UV and CAM, Rf=0.65

August 2, 2012

Shake and pray

Filed under: lab destruction, procedures — milkshake @ 6:16 pm

There is a pop-chem procedure on YouTube that I find astonishing – it beats the Diet Coke and Mentos trick hands down:

A guy loads NaOH dry solid pellets, about 1 inch high, into a plastic bottle, and adds about 2-3 inch thick layer of dry ammonium nitrate granules. Then he fills the bottle with ethyl ether and adds a good chunk of lithium metal foil. He screws the cap on and swirls the mix around. God have mercy.

This man is not building a home-made ANFO for roadside bombing. It is not going to be a Molotov cocktail enhanced with a metal/oxidizer, or perhaps a crude rocket. He is making a batch of meth by the Shake and Bake method. As he ads a pack of ground pseudoephedrine pills, he squirts in a small amount of water, caps the bottle and starts shaking real fast. The water initiates a vigorous and pretty much uncontrollable reaction of the lithium metal with ammonium nitrate. The solids in ether gradually liquify and become a bottom layer sludge – this all is accompanied by evolution of  copious amounts of ammonia and hydrogen. So he shakes this thing by hand and he periodically vents the ammonia by loosening the cap  when the plastic bottle bulges up too much. Eventually the reaction slows down, the majority of lithium metal gets dissolved and the leftover lithium pieces floating on top of ether attain a bronze/copper hue, this marks the completion of the reduction. The ether layer is decanted into a small plastic bag, saturated with HCl gas (evolved from another soda bottle with sulfuric acid and NaCl) and the hydrochloride salt crashes out and is collected on coffee filter and dried. The yield is about 1-2 grams of a hilbilly-grade crank in form of a white powder, from one large pack of pseudoephedrine pills, about 2 hours start to finish. No glassware anywhere.

The method does not scale – attempts at running bigger batches end in self-immolation. A common error is adding too much water at the beginning, which leads to uncontrollable takeoff:  the whole ether/ammonia/NaOH/NH4NO3/Li brew squirts out. One can try and keep the lid on an a bulging soda bottle by a sheer force but as the Li metal floats on top and fast reaction makes the chunks of lithium pretty hot,  they tend to burrow through the plastic wall and an impressive stream of flaming goodness rushes out with them, delivering bright red and yellow-colored ether flames accelerated by ammonium nitrate and lithium metal all over the place. As one skin graft patient observed “I haven’t seen stuff burning this fast before”.

The Shake and Bake meth is a twist on the classic method using Li metal with anhydrous liquid ammonia/ether. The outdoor storage ammonia tanks are now getting watched and additives are introduced into agriculture-grade NH3(l) so as to ruin its usefulness for dissolved metal reduction. Hence the soda bottle modification for ammonia generation in situ. No need to go to fields, now you can cook in the safety of your home…

Note: It would be easy for a manufacturer to add some organic soluble iron compound like Fe(acac)3 or ferrocene to the ether-based starter fluid  and likewise a small pinch of FeSO4 to the ammonium nitrate in cold packs and lye/drain opener. A finely divided iron promptly decomposes Li metal solution in ammonia to lithium amide and so it would make these materials useless for home brewing.

January 30, 2012

Potassium hydride self-ignition

Filed under: lab destruction — milkshake @ 1:40 pm

I had a rather bad fire last Friday. I was washing a large jacketed glass reaction vessel used for polymer scale-ups, after pouring the reaction mixture out, and a tiny particle of potassium hydride (from this poorly quenched reaction) that was adhering to the bottom of the reaction flask ignited just as I was giving the flask a proper acetone rinse. So I had a flaming flask in my hands + burning hands + flaming sink in front + a whole bunch of wash bottles ablaze next to me (plastic wash bottles peeing their burning solvents around…) A colleague promptly put the fire out with a mid-sized CO2 fire extinguisher before the flames spread any further. There was no damage to the lab, my fingers or the reaction mixture but it was a pretty scary situation – considering how fires in organic labs can get out of control so fast.

Potassium hydride pyrophoric nature is well documented in the literature; from my limited experience I would say KH is quite comparable to potassium metal in its tendency to flame up. But there are some aspects that make KH more treacherous than K metal: KH in paraffin or mineral oil is docile and only when the oil or wax is washed off the pyrophoric nature becomes apparent. Also, the KH appearance (a grayish-white powder) is less dramatic than shiny low-melting globules of K metal and one cannot easily guess whether KH is fully consumed or quenched by the sediment appearance if the reaction produces inorganic precipitate of its own. Also, I noticed that some alcohols react with KH in THF surprisingly sluggishly while reaction of other alcohols is prompt – I believe the solubility of the K-alkoxide in THF plays a role and the KH particles may get coated by a poorly soluble material and laze about the bottom – and then at some later point flame up when least expected.

Since K-alkoxides have significant reactivity advantages over Na and Li alkoxides in alkylation reactions[2], and since the easy-to-handle KH formulation in paraffin wax is now commercially available, it is likely that KH will get used increasingly more often in place of NaH. Despite its innocuous appearance KH is less tame than NaH;  having unreacted KH excess present in the reaction mix makes it prone to auto-ignition during the workup if the reaction was not quenched with care.

Note 1: I was impressed how good is CO2 extinguisher for large solvent fires – and it leaves no mess behind. I don’t think a dry powder extinguisher would have worked nearly as well.

Note 2: Taber et. al.: Tet. Letters 51 (2010), 3545-6

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