Archive for the ‘synthetic’ Category:
Desiccator Fail
by azmanam on Jun 30 2009 (1416 Views)Found this in one of our desiccators yesterday.
No wonder the DrieRite’s always purple.
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by azmanam on May 13 2009 (1188 Views)
I read an interesting article in May’s issue of J. Chem. Ed. titled “Can Reaction Mechanisms Be Proven?” by Allen Buskirk and Hediyeh Baradaran of BYU. Intriguing. So I pop open the pdf and a Note from the Editor is boxed at the top of the page before the article starts. It says:
“Can Reaction Mechanisms Be Proven?” generated spirited responses from its reviewers. The reviews were approximately evenly divided, and all were of very high quality. The authors agreed with the editor’s proposal that the reviewers convert their reviews into rebuttals or affirmations of the authors’ position for publication along with the article, which has been revised based on the reviews. Most agreed to such a process and their comments appear here. We hope that publication of this paper and well-reasoned rebuttals such as those provided here will initiate a wide-ranging discussion. JCE will provide an online forum for further discussion of the issue. Our hope is that both faculty and students will contribute their opinions and ideas to this discussion. -JWM
Huh. You don’t usually hear about that happening too often. So now I had to read the article. It’s pretty fascinating, and I encourage you to read it all. I’ll summarize and give my thoughts below the jump
Re-issuing Classic Chemistry
by Jeremy on May 07 2009 (628 Views)I recently bought a 2009 re-issued copy of Pearl Jam’s first album “Ten,” originally released back in 1991. Those who know me well are also aware of my interest in Pearl Jam; I enjoy collecting demos or live versions of their music. Anyhow, their officially released re-issue contains a remixed version of their 1991 album and (in my opinion) parts of it sound distinctly different than the original mix. For you music buffs out there in internet land, Brendan O’Brien—the original producer—dumped the supplemental reverb applied to the original tracks in this newer version. As a result, the guitars and drums sound much cleaner and less wet (I recommend listening to both versions of “Why Go” or “Oceans” for a good example of the remixing).
Thinking about the whole concept of “re-issue” got me thinking about organic chemistry (big surprise). How often do scientists report fantastically optimized results, table the idea, and then revisit it at a later date (to make vast improvements)? Or better yet, how much “new” chemistry has derived from “re-issuing” processed developed in the late 19th or early 20th century? My PI calls refers to this particular phenomenon as, “teaching an old dog new tricks.” In writing my dissertation (an ongoing process) I had the pleasure of reading Lipshutz’s recent review about cuprate chemistry (Synlett 2009, 509-524; DOI: 10.1055/s-0028-1087923). This personalized narrative discusses the Lipshutz group efforts and contributions to the field of copper(I) hydride chemistry.
This article is of particular interest apart from discussing it at length in the ‘ol thesis. A few months back, I had a conversation with a colleague of mine who claimed that since Stryker’s contributions, “conjugate reduction chemistry has (basically) fallen to the wayside.” I recall laughing out loud at his remark. “What about Lipshutz or Riant or even Buchwald,” I asked. He claimed, with a sense of arrogance, that their work was “just a new twist on Stryker’s original work.” Based off of this logic, if someone successfully synthesized Taxol from table sugar in three steps, would it be considered a new twist on Nicolau or Holton’s contributions? Arrogance aside, this idea of “re-issuing” is a common phenomenon in research chemistry. It’s done frequently, often to the tune of 10-20 additional printed publications (apart from the seminal contribution). Perhaps, it’s these instances that call into question the process of “re-issuing” chemistry.
That said, re-issued chemistry can result in significantly new discoveries and improvements on original methods. Taking the conjugate reduction example, Stryker’s catalytic reactions, performed under a high pressure of H2, were plagued with over-reduced products. In switching the stoichiometric hydride source from hydrogen gas to PMHS, Lipshutz reported a vast improvement in reaction times and overall yields (Tetrahedron 2000, 56, 2779-2788; doi: 10.1016/S0040-4020(00)00132-0). This change has spawned a whole new area of carbon-carbon bond formation, particularly in the field of reductive alkylation reactions.
While I’m genuinely interested in the idea of inventing new and exciting reactions, the thought of tweaked processes resulting in “re-issued” chemistry is largely appealing (when done responsibly). A prominent neutron chemist once told me that real chemistry lies in unexplored places. “We want to be doing things that others aren’t,” he said. I agree. But on occasion, it’s necessary to explore the landscapes previously claimed by others for the betterment of the (scientific) community as a whole.
Elemental analysis
by Phil on Apr 19 2009 (1054 Views)What analytical data are necessary to characterize a new compound in organic synthesis? In the times before NMR, melting points, elemental analysis and IR used to be the available methods (and UV, if applicable). Nowadays, EA isn’t required by the journals anymore andv IR is probably going to disappear soon. Additionally, the significance of melting points is quickly decreasing because mostly people take the product as it comes off the column without recrystallizing it. Are we losing something there?
A number of people argue that the ability to get crystalline compounds is essential to be a good chemist, so recrystallization should always be done if possible. As a reward, you get EA-pure solids that are also easy to handle and may give you the occasional X-ray crystal structure (if you want to grow crystals). On the other hand, an additional effort is required: you need substantial amounts of material, which is no problem in a short synthesis, but can be a problem if it takes twenty steps to get to the product. If I have tediously made 50 milligrams of a material, I don’t really want to give ten away to be burned.
I wonder if elemental analysis is still a necessity today. In most cases you get all the information you need from NMR (identity and purity). What EA gives you is confirmation that your compound is pure as well as dry. Still, is it worth the trouble or just a waste of time? I suppose it all depends on the kind of research you’re doing. If you are “target-oriented”, as medicinal chemists like me are, I do not think it is worth it, as long as the final compounds being tested are pure. I suppose this is being sloppy, but I want to get a series of compounds in a reasonable amount of time. It might be a bit different in a total synthesis project, where the focus is on the pathway rather than the target compound per se.
Sunday Update from ACS in SLC
by Jeremy on Mar 22 2009 (484 Views)
On my flight into Salt Lake City, I was greeted to nasty turbulence, an overcast sky but a comfortable mid-50 degree temperature, which eventually turned to rain (there’s a chance of snow tonight).
So, what happened today?
The Inorganic/Medicinal Version of Brown. M. Frederick Hawthorne is slated to win the highly coveted ACS Priestley medal for his contributions to boron chemistry in SLC this week (March 24, 2009). In addition to synthesizing polyhedral borane clusters such as B12H122- in the 1950’s, he is noted for his boron neutron capture therapy (BNCT)—a promising technique in the war on cancer (see: J. Am. Chem. Soc. 2007, 129, 6507-6512). I realize this isn’t really news per se since C&EN covered it last June, but some of you might have missed it.
Smith’s Dithiane Chemistry. I caught most of Amos Smith’s talk about his lab’s recent efforts in the realm of dithiane transformations (you should be thinking “umpolong”). He did a nice presentation on multicomponent anion relay chemistry (“ARC”; for example see: J. Am. Chem. Soc. 2006, 128, 12368-12369 and Angew. Chem. Int. Ed. 2008, 47, 7082-7086) while making a cute comment that the resultant “protected” alcohols are easily removed with Philadelphia tap water. For those not familiar, the Smith lab has been applying hybrid umpolong/Brook rearrangement chemistry to synthesize cool “proof-of-concept” natural product-like molecules. Smith mentioned that this type of work has caught Jeff Johnson’s attention (hence the umpolong connection) evidenced by a fairly recent publication about the synthesis of zaragozic acid C (J. Am. Chem. Soc. 2008, 130, 17281-17283). I had to leave the talk a bit early, but from my vantage point I noticed a lot of male chemists slowly starting to assemble for M. Christina White’s talk. I was truly sorry that I missed it. Oh, in case you were wondering, I did not notice her trademark ostentatious belt buckle.
CAS and Nanotechnology. In the few hours I’ve been at the ACS conference, I’ve noticed that there’s an awful lot of material (no pun intended) on nanotechnology. While nanotechnology touches areas of pharma, materials and even the molecular automotive industry, the issue of classification is making its way through the chemical community. Roger Schenck (of CAS) did a fine presentation on the issue from Chemical Abstracts Service’s vantage point. CAS currently catalogs 80 sections of chemistry (#1 is pharmacology), and, according to Schenck, CAS is not planning on adding #81 (which would be nanotechnology) anytime soon. It seems that the issue will be tabled for a bit longer while the field continues to grow/evolve. For you history buffs out there, Schenck contends that nanotechnology probably began with Kroto’s C60 discovery (Nature 1985, 318, 162-163). Interesting tidbit: Kroto even mentioned that he’d “prefer to let this issue of nomenclature be settled by the consensus.”
Alright, I’m off to the expo social event. See you tomorrow.
Chemistry Lab Demonstrations: Homemade Breathylizers…Sorta
by azmanam on Mar 19 2009 (746 Views)Undergrads were on spring break last week, so no lab last week. This week, we performed the Jones oxidation of isoborneol to camphor. The crude product was put in the bottom of a Hirsch funnel with a cold finger, and the product was purified by sublimation. One of my favorite chemistry trivia facts is that the opposite of sublimation is deposition. Now you know.
I must say, I am really, really disappointed with the way this week’s demo turned out. Plan A was following a patent prep to immobilize Jones reagent on silica gel. That actually worked really well. No problems there. I had a nice orange granular solid. The next step was to pack it into 5″ pipets between glass wool and plain silica gel to create a tall, narrow column of Jones reagent. That also worked really well. I meant to take a picture of the setup before I dumped everything, but I was pretty down after it didn’t work and just poured it all into my chromium waste bottle. Sorry.
Anyway, the plan was to ask if anyone came to lab drunk that day (no one admitted they did), then have someone volunteer to swish around some Listerine for a while. Then attach a clean drinking straw to the pipet and blow. See, Listerine is 21% alcohol, so there’d still be some ethanol vapor in the breath which should flow past the Jones reagent. The Jones reagent will oxidize the ethanol to acetic acid and will itself be reduced. The reduced chromium reagent is greenish brown. With the pipet system, the orange color would slowly change over to green from the start to the finish. The amount of ethanol in a person’s breath (and therefore the BAC) can be determined by seeing how far up the column the green color extends. The more solid that is reduced to green, the more wasted the person.
I know there are several potential safety issues with this setup. Chromium is toxic and shouldn’t be ingested or released into the environment. The goal was to have only me handle the glass and only the student with clean hands touch the drinking straw – which was not ot be unwrapped until just before use. When I was testing this, I don’t know what was going on, but I could get no air pressure through the pipet. With breath not flowing through the pipet, there’s no chance of the Jones reagent being reduced, so no demo.
See, they really did used to use Jones reagent in breathalyzers. They don’t anymore because chromium is toxic, and well, lots of things can reduce chromium… not just ethanol. This leads to false positives. Now they use a fuel cell for better results. The best part of the Jones reagent story is that drunk people would blow through a solution of Jones reagent, which would reduce some of the chromium. A UV/Vis detector could measure the absorption of the solution before and after the test. The absorption is related to the amount of ethanol because the measured absorption (A) is equal to the product of the concentration of chromium (c), the path length of the cell (l), and a constant unique to chromium (ε). A =εcl. This relationship, ironically enough, is known as Beer’s law. That’s right. Beer’s law can be used to tell how drunk a person is.
Plan B was to have a row of test tubes with a solution of Jones reagent to which was added increasing amounts of ethanol. This would gradually change the color from yellow to greenish. A separate test tube with a solution of Jones reagent in lab would have an arbitrary amount of ethanol added to it. It could be titrated against the standards to show the color change and determine the level of drunkenness. Problem is the color change is very subtle in dilute solutions. Too subtle to really see. No demo again.
I won’t bore you with plan C, but suffice it to say – fail.
So finally, plan D. Same as plan B, but with a surrogate for Jones reagent… and a surrogate for ethanol. Basically none of the actual reagents, but would still give a color change. I went with acid/base chemistry. A row of test tubes was filled with an acidic solution of bromocresol green. The acidic solution is yellow. To each tube was added an increasing amount of sodium hydroxide so the color would gradually change to a deep blue. The first test tube was yellow, then gradually orange, then muddy brown, then blue. In fact, the series hit just about every color EXCEPT green (the image looks better. Mine was not nearly so nice. I was in a hurry). Anyway, then an arbitrary amount of NaOH was added to a separate tube with an acidic solution of bromocresol green and titrated against the standard.
It wasn’t a great demo, but it looked like it was supposed to look.
The Anomeric Effect
by azmanam on Mar 18 2009 (1316 Views)In a post several months ago, I was talking about sugars and mentioned:
Note that in the cyclic isomer of glucose – β-D-glucopyranose (left) – all 5 substituents on the pyran ring are in the low-energy equatorial position (actually, the lowest-energy conformation of glucose is α-D-glucopyranose, where one of the -OH substituents is in the axial position. It is stabilized by what is known as the anomeric effect)
To which Mitch commented:
In regards to the anomeric effect, no one else finds it strange that when there is no good stereoelectronic effect explanation all of a sudden hyperconjugation is the key?
First, a mea culpa. For unsubstituted glucopyranose, the β isomer is the lowest-energy isomer, and the α isomer is disfavored at a ratio of about 64:36. When the hydroxyl group at the acetal position is changed to a methoxy group, then the β isomer is the lowest-energy isomer at a ratio of about 67:33 – the selectivity reverses. (click images for larger throughout)
Second, my PhD research relies heavily on the anomeric effect, and I often get this ‘I don’t understand the anomeric effect’ response from people. They assume it’s all handwaving. I’d like to explain the anomeric effect and hopefully clear up some of the confusion surrounding it. Read more below the jump.
A Brief Analysis of Truvia
by Jeremy on Feb 20 2009 (4114 Views)
On December 18, 2008, the Food and Drug Administration ruled the natural sweetener Truvia “generally safe” for use in foods and beverages. Truvia (trade name Rebiana) is comprised of a diterpene called steviol glycoside, which is isolated from the extracts of the leaves of the plant Stevia rebaudiana bertoni. The herb Stevia—basically the leaves of the plant—has been available for years, so steviol glycoside is nothing new, per se. Cargill Food and Ingredient Systems now markets Truvia as a singular, “fully-characterized product” (Stevia, by comparison is a witch’s brew of anywhere from 40 to 200 compounds). More interesting data about Truvia can be found here. As a result of the FDA’s ruling, Coca-Cola Company will soon launch a new line of reduced-calorie drinks with the most prominent being a new version of Sprite called Sprite Green (comes in a nifty aluminum can).
Stevia was purportedly discovered by Moises Santiago Bertoni in 1887 while exploring the forests of Paraguay—Stevia rebaudiana’s natural habitat (see: Econ. Bot. 1983, 37, 74-82). Additionally, the plant had been identified in Korea, China and Japan (J. Med. Chem. 1981, 24, 1269–1271). Word spread about the plant and eventually Stevia made its way to the US (courtesy of the Department of Agriculture) in 1918 due to the growing interest in its strong sweetness. A wide array of physiological studies determined that the sweet sensation of Stevia derives from the presence the compound steviol glycoside. Since then, several studies have been reported on its structure and function of steviol glycoside including stereochemical analysis (J. Am. Chem. Soc. 1963, 85, 2305–2309) and metabolic analyses (J. Agric. Food Chem. 2006, 54, 2794–2798).
In the spirit the Truvia saga, I figured that I’d cover its first total synthesis of steviol methyl ester, which Mori and co-workers first reported (Tetrahedron Lett. 1970, 11, 2411-2414). Starting from the tricyclic methyl ester, Mori protected the aldehyde then installed ketone by way of a hydroboration-oxidation and ensuing Jones oxidation. Deprotection of the dioxolane was accomplished using aqueous acid in acetone followed by tandem acid-catalyzed aldol addition to furnish the 1,3-ketol, which was converted to the 1,3-dione via second Jones oxidation. Clemmenson reduction afforded the 1,2-ketol (I encourage you to push the arrows for that transformation), which was converted to the allylic alcohol by methylenation.
As is the case with most “new” sweeteners, Stevia has been the subject of criticism over toxicological effects. One study, conducted by John Pezzuto and co-workers at the University of Chicago, concluded that steviol is actually metagenic (PNAS 1985, 82, 2478-2482). However, the asterisk to this scientific study—“steviol is mutagenic toward S. typhimurium strain TM677” and not human cells—should clearly be taken into consideration when weighing the toxicity of the supplement as a whole. Just so we’re all on the same page, the “S” in “S. typhimurium” stands for salmonella—a bacterium.
All in all, I think it’ll pretty interesting to watch more information about Truvia find its way into the public eye.
