Synthesis
moleculeoftheday | October 8, 2008Stick that TBDMS on Monday and helplessly flailing around, looking for a way to get your alcohol back? Have a little TBAF:
TBAF is one of the most common sources of fluoride ion for silyl deprotection. You usually get a 1M solution in THF with a little water, too. It can be a pain to get rid of when you're not working with big, greasy, drug-like molecules and you're working with water-soluble molecules like RNA.
moleculeoftheday | October 6, 2008Just like boc protects amines, TBDMS protects alcohols.
TBDMS chloride will protect alcohols. The silicon-oxygen bond is pretty strong, and the silicon-fluorine bond is even better. This provides a protecting group that's pretty robust - fluoride reagents are typically used for removing the silyl ether. More on that shortly...
moleculeoftheday | August 19, 2008Sodium borohydride is intermediate to the jackhammer that is LAH and the pussycat that is cyanoborohydride.
Borohydride is just on the cusp of reducing protons to hydrogen. In acidic solution, it'll bubble off hydrogen, in basic solution, it's stable enough that Aldrich sells the stuff.
moleculeoftheday | July 22, 2008A lot of reactions with nucleophiles' rates are determined by how good a leaving group you have. For leaving group reasons and others, DMAP is a great organocatalyst:
I am a sucker for non-pharmaceutical chemicals with their own domains, so please enjoy dmapcatalyst.com.
moleculeoftheday | June 16, 2008That was probably the longest break ever. I'm trying to do better, but writing up multiple papers and grant applications, along with a pretty intense summer travel schedule just haven't augured well for the blogging. Onward and upward: tetrazole.
Tetrazole is one of those molecules I didn't believe existed off paper the first time I saw it. Lots of electronegative atoms in a row (usually nitrogens and oxygens) typically indicates something unstable, if not explosive, but aromaticity does its work here, and tetrazole works well. So well, in fact, that it works in that mild-as-mothers-milk…
moleculeoftheday | May 5, 2008Automated solid-phase synthesis of biomolecules defines 20th century biology. I previously covered a protecting group that is ubiquitous in DNA synthesis, but the Nobel was actually awarded for peptide chemistry.
Fmoc is sort of to amino acids what DMT is to DNA. In amino acid synthesis, you take off stepwise protecting groups (fmoc) with base and release your peptide with acid, but in DNA, you take off stepwise groups (DMT) with acid and release your DNA with base.
Fmoc, like DMT, is useful because you can watch it come off because it's colored (well, Fmoc absorbs UV, DMT cation is kool-aid…
moleculeoftheday | May 1, 2008Chlorinated solvents are great solvents. The polarizability of chlorine, moderate electronegativity, moderate volatility, lack of acidic protons or reactivity - it all adds up to a great reaction medium. However, they usually are toxic.
Carbon tetrachloride, CCl4, used to find a lot of use, even in dry cleaning, but it's toxic, especially to the liver. Chloroform, CHCl3, is a little less toxic. And dichloromethane, CH2Cl2, is less toxic still.
A friend of mine used to joke that we'd use methyl chloride if only it weren't a gas.
moleculeoftheday | January 21, 2008Everyone knows that many organic solvents won't mix with water (or, more generally, some polar solvents won't mix with some nonpolar solvents). What you might not know is that some highly fluorinated liquids aren't very polar at all, but they won't dissolve in water or many organics.
In fact, you can mix certain organic solvents, the fluorous stuff, and water, and end up with three phases! The company in that link has made a business of using perfluorinated tags to stick on your molecule, which in turn stick to a perfluorinated solid support (you later wash off your stuff with something that…
moleculeoftheday | December 12, 2007So people gush over bmim and get the guaranteed publications for including "ionic liquid" in the title of their article. Ionic liquids are far from the newest fad, though, they've been around for nearly 100 years!
93 years ago, Paul Walden reported that ethylammonium nitrate actually melts just north of room temperature. Ionic liquids are hot now, but did you know they were about a century old?
moleculeoftheday | December 3, 2007When you take organic chemistry, you learn about methyl iodide for putting on a methyl group. Eventually, though, if you stick with chemistry, you need an alkylating agent for grown-ups.
There's a lot of good ones, including dimethyl sulfate, methyl triflate (PDF), and the ever-so-toxic "magic methyl," methyl fluorosulfonate.
Part of being a grown-up, though, is settling down with an alkylating agent, and aside from the odd dirty weekend with some of the more exotic compounds, it's trialkyloxonium salts for me:
We used to have coffee together in the morning, but the methanol got to me...
moleculeoftheday | November 5, 2007As I've mentioned in the past, chemists often need to reduce a molecule by adding hydrogen. A medicinal chemist might get to an azide by way of an amine, or a food chemist might want to get to a saturated fat (or, although it's less and less popular, a trans fat).
Adding hydrogen can be done with a catalyst and, well, just hydrogen gas. It's a gas and flammable under a huge range of concentrations. Even gasoline only burns in a narrow range in air - don't go sticking a lit stick in your gas tank, but it would just snuff it out. This is why molotov cocktails work. The gas-soaked rag will burn…
moleculeoftheday | October 17, 2007Thiophene is a simple five-membered sulfur-containing heterocycle - it's the sulfur analogue of furan.
It's an interesting heterocycle in its own right but it's probably best known as a contaminant in benzene - almost all the bottles you get a hold of today proclaim they're "thiophene free."
It wasn't always the case, as chemists who were trained more than a decade or two ago will tell you. My advisor in undergrad told me stories about having to remove the thiophene from benzene, which entailed shaking the benzene with concentrated sulfuric acid in a giant separatory funnel. Pressure builds…
moleculeoftheday | September 28, 2007As I noted in a recent entry on strychnine, NMR is important. Sometimes reference compounds like yesterday's molecule, TMS, will help you out.
This is all well and good for most organic chemists - TMS will go into just about any organic solvent. It won't work so well in water, however, so there's a second, water-soluble chemical shift reference: enter TSPA:
TSPA has a chemical shift of 0, just like TMS, and it's soluble in water - good for biochemists, who have to work in water (with at least a little of its deuterated buddy).
TSPA is probably even more controversial than TMS - it won't…
moleculeoftheday | September 27, 2007As I alluded to in a recent entry, NMR has been vital to science in recent decades - it's used in characterizing chemicals, cells, people, textiles - just about anything people have managed to figure out how to get into a strong enough field.
Like many organosilicon compounds, tetramethylsilane has a very low "chemical shift" - this is where its usefulness comes in - TMS has a shift of exactly zero, so you can use it as an internal reference.
A lot of people dislike TMS because it's just another thing you have to get rid of. Fortunately, it's barely a liquid - it boils just above room…
moleculeoftheday | September 18, 2007Integral to organic chemistry is hydrogenation - sometimes you need to make a functional group something a little less oxidized. For example, an azide or a nitrile can become an amine.
Often, we just use hydrogen for this! Metals like palladium can work some real magic doing the heavy lifting here. Process chemists hate hydrogen gas, though, and rightly so - everyone knows about its tendency to explode. It's worse, though - most hydrocarbons have a flammable range of about 1-8% in air - any more, and there's just not enough oxygen to support combustion. Any less, and you don't get enough heat…
moleculeoftheday | September 4, 2007Chorismate lies along a biosynthetic pathway in plants that leads to the aromatic amino acids.
A bit further up the pathway is shikimate, which is present in many organisms but especially abundant in star anise, and a precursor to Tamiflu (see also)
moleculeoftheday | August 22, 2007This reagent is one of my favorite ones for replacing an alcohol with an iodine.
Eric Kool's lab has made good use of it to iodinate the 5'-OH after automated synthesis of a DNA strand.
moleculeoftheday | August 3, 2007CS2 is kind of a neat molecule - it's the sulfur analogue of carbon dioxide.
It has more in common with other small organic solvent molecules than it does with dry ice (although it will react in some of the same reactions as CO2). Purportedly it doesn't smell at all when pure, or sort of ethereal (one commenter claimed awhile back sp2 sulfur in general didn't smell). However, there's usually some stanky impurities in there.
It's also crazy flammable.
moleculeoftheday | July 11, 2007The drought of chemical drawing software continues - here is the story. Every so often I see how Linux is doing and use it exclusively for a week or two. It is actually a usable desktop environment now, unlike a few years ago, but there isnt anything to draw decent structures. Today I set up XDrawChem, which is the basic idea of ChemDraw or ISIS, but less pretty and functional. I know I could get ChemDraw running on wine, but I can't find the disks. Anyway, onward and upward...tosyl chloride.
I have previously mentioned toluenesulfonic acid on the blog. Its acid chloride, tosyl chloride, can…
moleculeoftheday | July 10, 2007Palladium is really neat stuff. It has an almost absurd affinity for hydrogen - it's one of a few metals we can use as something other than a salt or complex (i.e., just the metal). Pd on C is just carbon dust covered with 5 or 10% Pd metal (you can't see it - it's very expensive copier toner looking stuff).
Pd can transfer H2 to unsaturated functional groups. It can also break down molecules without actually "burning" them - your catalytic converter actually has a good deal of Pd in it. Ford lost a load of money some time back investing in Pd expecting to need to stock up (when cats were…