Linalool is a fragrance compound that gives floral/spicy notes. I read about this reaction on P 269 of 'Perfumery and flavoring synthetics' by Bedoukian (1986). A synthesis of linalool is carried out by a little known step that treats methyl heptenone with sodium acetylide. This is a way to functionalize at a carbonyl, kind of like a grignard reaction. It says:

"Finally, linalool (I) was synthesized by Ruzicka and Fornasir through a very interesting series of reactions. Employing a reaction discovered earlier by Nef, they condensed methyl heptenone (V) with sodium acetylide and obtained dehydrolinalool (VI). The acetylinic linkage was reduced with sodium to the ethylenic linkage to give dl-linalool (I)."

Fragrance Guru Luca Turin says in his book:

"Smelling solid, especially crystalline, perfumery materials is often misleading. As Charles Sell of Quest International explained to me, crystal growth pushes impurities that do not fit into the crystal out of the way, i.e. towards the surface of the crystal. This means that when you open the can you are smelling the stuff far less pure than it actually is.".

This is well worth remembering for those of us making crystalline compounds and then smelling them.

Throughout my first two years of PhD, if I needed to weigh out solids before transfer I would use plain white paper in varied size. While I still do this, I learned from my time at MIPS that they keep an old chemical catalog book next to their balance and tear out a page each time they want to weigh a few mg of compound. This paper is thinner and easy to tear into shape. It is also 'shinier' and compounds are easy to remove by tapping with a spatula.
I shared this trick with my colleagues when I returned to RMIT. A postdoc who works in the organometallics lab next door says that he uses parafilm backing paper for exactly this purpose. He does this so often in fact that those in his group routinely dispose of the parafilm just to use the paper. I laughed as I have often used the parafilm and thrown out the paper!
Therefore, I present three good options for compound weighing & transfer. Each may be suitable depending on quantity, properties and preciousness of the compound.

Other websites have discussed the use of TLC stains. My post here shares one example of a reaction that was successfully visualized using KMnO4 dip.
As part of a project to prepare homologues of a drug, 2-Methyltetrahydrofuran was reacted with HBr for a ring opening to give a hydroxyl at one end and bromine at the other. However these products readily  dibrominated and any of the free alcohol compounds left recyclized on contact with silica. Therefore acetic anhydride was added to the reaction and the ring opened product thus immediately acylated. The two products obtained (drawn below) were viewable by NMR in what looked like an 80:20 ratio. The mixture had a fruity, apple-like aroma, with a distinct C-Br bond smell that was absent in the 2-MeTHF start material which smelled minty/ethereal.

Using "Merck TLC Silica gel 60 F254", this TLC was run in 3:1 hexanes/EtOAc. As these compounds had no chromophore, they were not visible in a UV box. A number of stains were tried, including iodine vapours which sometimes gave faint spots. KMnO4 which at first gave no spot was re-tried. When heated gently with a hair dryer (not a heat gun) two spots for the compounds became visible! If the hair dryer was not switched off within 2 seconds of the appearance of the spots, they vanished, presumably due to entering the vapour phase and disappearing into the air. If the hair dryer was stopped at the right moment, the TLC remained visualizable for 2 or more hours (see photo). These spots were in the same location as those seen from the iodine chamber, however these compounds departed the plate before the iodine could effectively stain them.
This project was abandoned to focus on other pursuits, but if I revisit it I'd like to try dry column vacuum chromatography (DCVC) to separate the compounds. While they looked to be separable it must be remembered that each spot is a racemic mixture of two compounds as a chiral centre has been created at the point on the alkyl chain with the methyl group.

I have often thought that the most toxic material in a synthesis lab is the silica. The body can expel organic solvents in a few days as they will be soluble in one tissue or another. Silica won't dissolve unless heated to 180 °C or placed in acid/base. This means once it is in your body, it stays there and if it lodges itself in the lungs it becomes a nucleation point for tumors.
A colleague from another University showed me this neat way to load silica into a column without breathing any of it in.
Get a new 500 mL acetone squirt bottle, cut the top off and use a small rubber septum for the lid. Then fill it with silica and label the bottle. When dispensing into a column, the lid makes a seal which prevents airborne particles from escaping. Put the lid back on loosely as you turn the container upright to prevent a small puff of silica into the air.

I had an email exchange with Jeff Johannes at Astra-Zeneca back in Feb 2013 on using methanol for flash columns. We agreed that it was worth posting on a noticeboard, so I post it here now.

Jeff:
Thanks for these emails (solvent of the week), I have been enjoying them each week. I would like to ask you about this statement:

“Methanol can be added to solvents for flash chromatography but don't use more than 10% or it will start to dissolve the silica.”

Is it really true?  I used to think this in grad. school, but since moving to a job in the pharmaceutical industry for the last 6 years we routinely run 20 or even 30% MeOH in DCM to purify really polar compounds without accumulating silicon dioxide in our samples.  Is there a published paper on the solubility of silica in MeOH?

Matthew:
Hi Jeff, Thanks for your thoughts and it's a very good question. :)
I have not come across any peer reviewed papers on the matter. I base my comment of not exceeding 10% MeOH on flash columns on general views. I like to keep solvent of the week short so that it appeals to a wide audience and does not take up too much of people's day.

I think you are right that there are many exceptions to the 10% rule

• Dissolve is really the wrong word as silica is not really what we would call "miscible" in MeOH. I've tried to gloss over this by saying "start to dissolve" to avoid opening the can of worms in the short solvent of the week email
• My more senior colleague with the most flash column experience in our group tells me that any more than 10% MeOH and he gets amorphous white solids in his test tubes. I believe this happens readily but not because the silica was miscible and crashed out on the other side but because some grades of silica have a more broad particle size distribution than others and possibly more than the pack specifies. MeOH has a way of loosening the smallest particles from the packing and bringing them down to the frit where if they are small enough and under pressure they can pass through. Another description is that MeOH disturbs the silica into a thixotropic gel-like solution with poor particulate separation.
  
• I believe you are on to something about getting away with a higher percent MeOH in chlorinated solvents like DCM/chloroform. Depending on the compounds present MeOH can become slightly acidic which allows the smallest most amorphous parts of the silica to pass into solution for the briefest of moments and I reckon the DCM stabilizes MeOH a bit against becoming acidic.
• A higher grade of consistent particle size silica is probably less prone to this effect (at Universities we use cheap, old or reactivated shit).
• I have certainly tried TLCs in 20% MeOH and I find that it disturbs the silica away from the aluminium plate, rendering the TLC unreadable. This of course is different to a packed column.

Opinions on this matter are often passed down in a haphazard way. It is very useful of you to point out to our group your experience of using 20 or 30% MeOH in DCM for columns. Can you tell us what sort of compounds this has worked with?

We are also curious of your preferred method of deactivating silica for sticky compounds? We often use formic acid or triethylamine.

Jeff:
Hi Matthew, thanks for writing back. One big difference that typically exists between academic and big pharma labs is that we exclusively use ISCO chromatography systems, which includes the ISCO columns which are pre-packed in a plastic cartridge and generally pretty good quality. The silica gel in these pre-packed columns is pretty good and they have good frits. So the combination of higher quality silica and better frits may greatly reduce the amount of silica that comes through. When I was in grad school it was just a cotton plug and sand holding back that silica gel!

The DCM-MeOH is quite common for purifying really polar heterocycles (usually with unprotected NH or OH groups) or really basic amines.  For really sticky basic amines, a very small percentage of concentrated NH4OH in H2O can be added to the DCM-MeOH system.  Sticky acids are less common (we don’t make a lot of acidic compounds since they tend to be highly plasma protein bound) but I have used AcOH as an additive with some success.

In terms of TLC plates (usually silica on glass in the labs I’ve been in), I have heard that using a high percentage of MeOH is bad, especially for prep TLC, because the MeOH can start to dissolve the binder. I did follow this advice in grad school, and I haven’t had to run prep TLC in my industry job yet J.  But I’ve never really done a proper experiment to test this.

This conversation could be the basis for a really good paper. You know one of those that people have pinned to their bulletin boards, like Clark Still’s 1978 flash chromatography paper. You make really good points about the quality and size dispersion of the silica as an important factor, and also which solvent the MeOH is paired with. I think that the pore size of the frit that is used is also critical.

Matthew:
Hi Jeff, thanks for your thoughts on columns. They are very useful to our group. :)

I've just read Clark Still's 1978 Flash Chromatography. I'd be honoured if our email exchange is pinned below it on the bulletin board.

Jeff:
Hi Matt, I’m glad that our discussion helped the group. And I would be honored to have our emails pinned near Clark Still’s paper!

We have very limited access to freezer space to store chemicals in our lab. This bizarre photo shows that some freezer items have become even harder to access!

About 2 years ago when I was in first year PhD, I thought to myself that for many recrystallizations I wanted a temperature in between room and fridge. Crystals usually grow better when solutions are cooled more slowly and I knew of expensive devices to achieve this, but I also remembered seeing a product on sale at Aldi which cooled wine. After speaking to my lab manager and describing the product and its low price, he agreed that if it came up for sale again he would buy it for our lab. Sure enough, in December 2011 (the start of summer), Aldi offered an 8 bottle wine cooler for just AU$80. I told the lab manager and the product was purchased! I had to modify it by removing some shelves and creating a flat surface on others, but ever since then it has done exactly what I predicted it would do: grow crystals! It has temperature control to between 8 and 18 °C but most of the time we leave it on 8 °C. It also has an anti-vibration feature which is meant to protect wine but is also exactly what is needed for great crystals. In the image above, I am using it to get more crystals out of the mother liquor from a previous recrystallization and in this case I placed a seed crystal which has grown into a bushel. It runs on 70 W and when completely empty I have been able to fit a 2 L erlenmeyer flask which yielded 100 g of crystals.

If you have an Aldi near you you might want to keep an eye on their catalogue for a similar product, especially near summer as this makes lab work so much easier at a low price.

I had a compound that I was preparing on a 10-50 g scale and kept getting one spot with a consistently lower Rf which when present would stop my compound from recrystallizing. I heard about this method from a colleague who gave me a copy of Daniel Sejer Pedersen's 2001 Paper in Synthesis (Synthesis, 2001, (16), 2431-2434). Daniel has further detailed this technique on his blog.
I made the closest adaptation I could with our existing glassware and it worked great. In this photo 13 g of crude compound is loaded onto 40 g of silica. It took 300 mL to see any trace of the compound and after 500 mL I increased the solvent polarity from 70% hexanes : 30% EtOAc to 50% hexanes : 50% EtOAc to recover 12 g of compound that recrystallized easily. I have since managed to upscale to 25 g with exactly the same setup.
I used DCM to load my compound to the silica and care had to be taken when removing the DCM which bumps violently on the rotavap even when the vacuum is lowered with care, so you might want to use a splashguard with cotton in it. The dry loaded silica is then distributed evenly over the wide column of clean silica using a glass funnel. The Synthesis paper suggests placing a filter paper on top of the loaded silica when pouring solvent. I tried once with this and once without and found that in my case I got a more evenly spread pour with no paper but by using a wide mouthed beaker moved in a circular fashion as poured. It is true what it says in the paper that when a compound comes through a foaming is seen in the solvent. It would definitely be better to have a separatory funnel on the bottom with a vacuum inlet near the neck as this would more conveniently control the release of each fraction.

Not my fume hood and caused by persons unknown in my lab at RMIT on 11-Feb-2013, this really placed a drag on my 3rd year of PhD. I spent three months as a visitor at Monash Institute of Pharmaceutical Sciences while repairs were to be made and then one month in America for conference/holiday. When I returned, it still wasn't fixed. This made my PhD harder to get. It's amazing I got so much work done this year!
Please note: Unfortunately, RMIT does not provide a fumehood to each researcher. The fumehood in this photo does not belong to any one person.