chemist

Hey - sorry for the delayed response I wasn't really aware you'd asked me a question until it was brought to my attention by a lab mate - I'm not really active on this forum anymore - and also the others would prefer if you didn't give out *their* info as it pertains to this forum to other students - so that they can remain active on this forum... they don't want to be "expected" to answer student questions here but I will however take a stab at this question since this will not be a problem for me in the future and I'm quite certain that this is due for you by Monday.... Now.. since it's for comps and I'm your former TA I can't give you an exact answer but I can point you in the right direction and perhaps if you still don't understand someone else will come along and SOS... That being said... First of all if you must do the first reaction as described... then you will likely get attack from the face that has the least steric hindrance... use the Cram Chelation model in this case because you have an alpha alkoxy group.... but I would suspect that you'd get chelation to the alpha position bearing the methyl and therefore the reagent would attack accordingly.... however... there is not much of a differentiable difference between the methyl and the ethyl substituents so if you proceed as planned you will likely get a mixture no matter what you do... It's just that it should favor the methyl... but how much I couldn't tell you without actually running the reaction... Might I suggest TBS protecting the undesired location in order to facilitate attack from the intended face and with the intended regiochemistry.... For the second question... First determine what group will prefer to be axial and which will prefer to be equitorial... I would suggest using the charts given in the handouts early in the semester.... paying close attention to section on ring conformation and the sterics invovled.... Also remember that you have a bulky reducing agent... so therefore it will attack from an equitorial face - i.e. the hydride will be delivered to the equitorial position - to give the axial alcohol.... hope this helps good luck. p.s. if you get desperate and the others won't come along to help you can email me at my uni account which is listed on the first page of the old discussion syllabus...

Hello, I'd like to delete my account but recently found out that deleting accounts isn't an option here... I know that it is possible to ban members so - out of curiosity I was just wondering why it isn't possible to delete accounts too... I understand that deleting old posts of members that want to leave would be problematic but I've always wondered what forums do with the inactive accounts when they start piling up?

Hello, Well to each his own... not everyone is a good fit for everywhere... Could you please assist me with deleting my account whenever you get a chance? I sent a PM too - or at least I think I did - since I'm trying from my black berry and I never know exactly what I'm clicking the screen is so small... Thanks.

I was under the impression that I was ridiculed first...

lol! Whatever you say man... - "For simple unfunctionalized alcohols, oxidations can be done by an addition of an acidic aqueous solution containing chormic acid (known as jones reagent)" - Carey & Sundberg part B see link: http://books.google.com/books?id=cbDE0prX93gC&pg=PA748&lpg=PA748&dq=problems+with+jones+reagent+in+advanced+synthesis&source=bl&ots=p6AtZeOBkV&sig=JWNRmdMCJGNeXu9lqkoQJ-iNEqg&hl=en&ei=cmQgSu6WL4KctgP3hNSWBA&sa=X&oi=book_result&ct=result&resnum=6#PPA748,M1 simple unfuntionalized alcohols that is not what the typical synthetic chemist works with on a daily basis.. at least that's not the case around here.. but if you're trying to oxidize 2-butanol then by all means use Jones... oh and btw PCC was NOT made to improve selectivity.. tell me what alcohols would PCC be more selective for that Jones is not? lol! PCC and the others were made because Jones is not functional group compatible - it's too harsh - and people wanted a more mild oxidizer for their complex molecules... I've used PCC on 1 and 2 alcohols and alcohols with differing energetics... selectivity in this case is substrate level and has nothing to do with reagent level control. WTF are you talking about?! PCC will oxidize the same stuff as Jones it just tends to stop before causing problems to other functionality in your molecule that whereas Jones does not... - lol! I think you might have meant chemoselectivity and there isn't much of a relevant difference between these two reagents there as you're trying to oxidize a secondary alcohol so your issue is functional group compatibility despite what you think... Yeah KMnO4 as a catalyst or when being used with solid support etc will work but you're not gonna get that to work on yours for reasons so obvious you should already know them... This is starting to seem to me to be more your problem than the reactants... If you noticed I asked you how you did your work up.. you wouldn't see the carboxylic acid if you used water to quench your reaction.. It would be in the aqueous.. so unless you protonated and extracted accordingly - because you knew you had a COOH - then I don't know why you are expecting to see it on NMR... As for the SN2 I've gotten that to work on that exact substrate so you are doing something wrong.. but if you can't get that to work you can convert to mesylates and then use CN-, and if that doesn't work you can convert the mesylates to the Iodide... etc... but by all means go and try to oxidize that with KMnO4 in a solid support and see how many equivelants that takes.. lol! Merged post follows: Consecutive posts mergedIn addition to reading what Cary and Sundberg have to say about the functional group incompatibility of Jones... You may also want to check out this book scrolling down to page 4 section 1.1.5 Selection of Oxidant : http://books.google.com/books?id=O6USLyDIBOUC&pg=PA1&lpg=PA1&dq=Jones+reagent+in+organic+synthesis&source=bl&ots=7AAIPi7hik&sig=Uk5WkSSQVeB3vOnApVvl3OojoD0&hl=en&ei=pVAhSpGxNZSatAPPjKyZBA&sa=X&oi=book_result&ct=result&resnum=9#PPA4,M1 and also seeing this link scrolling down to page 246 section on oxidations: "Oxidation with acid solutions of chromic acid is unsuitable for alcohols which contain acid sensitive groups or other easily oxidisable groups such as olefinic bonds..." - http://books.google.com/books?id=xAc4AAAAIAAJ&pg=PA247&lpg=PA247&dq=using+Jones+Reagent+in+complex+organic+synthesis&source=bl&ots=nrUUsIAwVR&sig=JuQi2OVLdYWsq47HE2EXREljnfg&hl=en&ei=f1chSvT3CZSutgO4tYCUBA&sa=X&oi=book_result&ct=result&resnum=6#PPA121,M1 - remembering that Nitriles are acid labile - Duh! and see this as you still seem to be confused regarding the ease of hydrolyzing a nitrile - you do NOT need excess water.. that's only something they tell you in undergrad.. with all of the equivalents you said you added of the already aqueous Jones reagent in sulfuric acid that you heated and let stir for days.. lol! - see this link for more details: http://www.mhhe.com/physsci/chemistry/carey/student/olc/graphics/carey04oc/ref/ch20reactionsnitriles.html - search for the hydrolysis reaction of nitriles and you'll see that the conditions you describe are near perfect... so I think you might want to vamp up your lab skills and pay better attention during your work up to see that you are not discarding side products etc... sigh... Good luck.

Hello, These might be some useful links to start with: - http://www.soilminerals.com/Cation_Exchange_Simplified.htm - http://hubcap.clemson.edu/~blpprt/bobweb/BOBWEB23.HTM and - http://soils.tfrec.wsu.edu/webnutritiongood/soilprops/04CEC.htm hope this helps.. Good luck. : )

Wow to never have any problems with CrO3 you must really work with simple molecules.. It's quite common knowledge around here that CrO3 will eat your stuff and typically does require waaay more than 1.1 equivs for complex molecules and also has solubility issues etc... - see Carey and Sundbergy 4th ed page 748 approximately the 2nd to last paragraph down - for all the info you want on why Cr(VI) reagents can be problematic for complex molecules... if you're certain that you're not hydrolyzing and you don't want to change the synthetic route and you don't like any of the oxidations methods suggested you might just ask your boss how to do it... or crack open C&S part B flip to oxidations and start trying at random... Typically I've found that when problems occur with oxidations one reagent can be considered stronger than the other depending on the conditions.. In your case you're using Cr(VI) reagent which is a transition metal... Nitriles are a common common ligand for those.. so chelation, pi-back bonding etc can be all be things you have to consider when you're using a reagent that has a transition metal.. - see link: http://pubs.acs.org/doi/abs/10.1021/ja01000a024 - if you've got coordination that can be slowing the reaction progress and making the reagent less effective... this is part of the reason why some of these Cr based oxidizers don't work so great in complex molecules or molecules with functionality.... but I'd ask your boss if you're already talking to him and you're not finding outside help useful... just ask him... Edit: I wrote a bunch of other stuff that I deleted as everything I was saying in the longer post above is easily verified by the links and references listed below.. good luck. Merged post follows: Consecutive posts merged Oh and by the way... if you check Carey and Sundberg 4th ed part B page 751.. oh I'd say about the 1st paragraph down you'll find this sentence.... "KMnO4 is another powerful transition-metal oxidant has found relatively little aplication in the oxidation of alcohols to ketones and aldehydes. The reagent is less selective than Cr(VI), and overoxidation is a problem." You can read the rest for yourself... but you might want to run it by your boss because I think he might be confused.... Oxidizing reagents are NOT one size fits all... and you and your boss might also want to check out this article: http://en.wikipedia.org/wiki/Nitrile - and search keyword reactions of nitriles.... - pay special attention to the sentence that says "The hydrolysis of nitriles is generally considered to be one of the best methods for the preparation of carboxylic acids." - then just to solidify it I'd do a quick SciFinder search and pull up the experimentals for these hydrolysis reactions and you'll see that this is pretty common and could easily happen if stirring in heat and acid for "days" Good luck... Edit: you may also want to check out this link regarding oxidation of secondary alcohols with sodium and calcium hypochlorite: http://www.erowid.org/archive/rhodium/chemistry/ether2ester.hypochlorite.html - and then maybe search SciFinder for some others... Also.. just wondering but is your boss a classically trained synthetic chemist? That KMno4 things is kinda common knowledge as well. : ( Merged post follows: Consecutive posts mergedAnd you know really I know you really don't want to change the synthetic route but... glycerol HAS to be commercially available from Aldrich or Acros or something... Just buy that stuff.. they probably have one with the carbonyl already at the 3 position.. if not just oxidize that up with a reagent that is selective for just secondary alcohol i.e. NaOCl and Acetic Acid - check Carey and Sundberg part B and/or SciFinder for a reference to this reaction.... Then add PBr3 or something similar and then convert to the cyanos with CN- seems like the easiest way to do this if you are certain that you CN groups are the problem although I'm quite certain chelation/coordination and/or hydrolysis are the likely causes of your difficulties... Good luck...

Again... I'm not sure if you know what you're talking about.. that is what the regulator is for.. if you do this right the chlorine gas cylinder will come with it's own indication system... Furthermore: most bubblers are mineral oil - not mercury (think density here) - and you simply remove them from the system when doing something corrosive.. there are other ways to tell if you're getting gas through system - i.e. specialized gauges - http://www.ilpi.com/inorganic/glassware/vacline.html - search key word electronic gauge.... Not to mention you can run plenty of things through a schlenk line.. we use argon for example.... Nitrogen isn't commonly used in labs anymore.. Argon is preferred because it has a slower escape velocity... so again I'm not sure you know what you're talking about.. cos if I was to make an assumption about a synthesis lab I would assume that their inert atmosphere was Argon... Funny you're able to assume all of that without ever reading the paper... I thought you didn't have SciFinder.. if now you do then simply research oxidations with molecular chlorine and you'll find plenty of references for this procedure... In regards to the disposal of the cylinder.. I don't know how your chem stores works but here if you order a cylinder they deliver it with all of the required equipment.. then take it back and store it in chem stores for the next person to use.. i.e. these things can be shared department wide... so in a science department this isn't much of a problem... so again I'm not sure you know exactly what you're talking about... Well just because it's not stable doesn't mean he isn't getting the hydrolyzed product.. that is why it is important to know if he is getting back 100% yield of his S.M. Neither are the desired product but if he wants to trouble shoot this reaction he'll need to know for certain that he is getting back 100% or really close yield of his starting material and if not then where is it going... just because he sees starting material by NMR doesn't mean that he has 100% of the starting material back.. there is a huge difference between these two things... so again I'm not entirely sure that you know what you're talking about... so like I said before.. if he hasn't already.. he should check for hydrolysis... by first verifying what yield of S.M. he is getting back... if he has done that already and it's 100% yield or really damn close of S.M. then he has to try a different oxidizer if he is unwilling to change the synthetic route... funny I thought I had already mentioned that...

Actually this is incorrect for the oxidation procedure I'm quoting he WILL need the cl gas cylinder and special lines or the oxidation will not work predictably... If he is going to generate his own cl gas he may as well just use the bleach... that will likely give the same results.. but if he wants a "super oxidizer" he will want to use the cl gas procedure with the cylinder and a good functioning schlenk line... multiple system purges will be required before use etc... yes this is time consuming but sometimes these specialized reactions are and that's just the way it is... There should be no hazard involved for a trained chemist... Especially if he/she has access to a glove box etc... Although I personally would double and triple check to see if there is any hydrolysis taking place first as h2so4 and water is commonly used to hydrolyze cyano groups and the Cr03 procedure would have a lot of both floating around, he added heat, and left it for days.. seems like a likely possibility to me and something worth looking into before moving forward if he hasn't already... hope this helps... Good luck.. : )

Hello, I know that is a strong oxidizing agent but I think that might be part of your problem... CrO3 isn't exactly functional group compatible... and I've had solubility issues when using it that have led to no reaction... I suggested the others because they are pretty versatile and functional group compatible..... they are also pretty strong.... I've used them on neopentyl alcohols before with good results.... Also... Are you getting back 100% of your starting material? It might be hydrolyzing your cyano groups.. how are you doing your workup? If you're using water you may be loosing the material that is being hyrdolyzed into the aqueous layer... and cro3 is weird so you typically need waaaay more equivalents then you'd think to get it to work in addition to it destroying your stuff... you might have unreacted S.M. because you're not adding enough equivalents.... If you're certain you're not hydrolyzing then you could try calcium or sodium hypochlorite or Cl gas and acid... Also there is oxone.. but I would make double sure you're not hydrolyzing first... Those last few oxidation methods are pretty brutal... let me know if you need some references... if you do decide to try the cl gas you'll want to get a cylinder of it and you'll need special lines, a regulator etc.... good luck.. hope this helps.

Hello, have you tried (COCL2)2, DMS0 with Et3N at -78c? See: Jones,T.K; Reamer, R.A; Desmons et al J. AM. Chem Soc. 1990, 112, 2998-3017 Also check into: DMSO, EDC in TFA, pyr Hanessian, S; Lavallee, P. Can. J. Chem 1981, 59, 870-877 There is also the Dess-Martin Periodinane (DMP) that I use often... here are some good references for that - J. Am. Chem. Soc. 1983,48, 4155-4156 - J. Org. Synth. 1999, 77, 141-152 - J. Chem. Eng. News 1990, july 16, 3 *also note that DMP and precurser IBX can be sensitive to heat and shock so make sure you take care when dealing with these and look up an appropriate procedure on scifinder... - I haven't ever used any of these on your exact substrate before but let me know if neither seems useful after you scan the papers. We have a prof here that specializes in similar chemistry and I can ask him if he knows any specific procedures pertinent to your case. Good luck.. hope this helps... EDIT: I also just remember another good reference for use of DMP check out Evans, D.A.; et al J. Am. Chem. Soc. 1990, 112, 7001-7031 DMP in CH2Cl2, pyr was used pretty successfully in late stages of cytovaricin synthesis...

Hello : ) Just a few quick questions before trying to give you advice. 1. Are you good at math and physics and more importantly - do you like doing math and physics? 2. Are you artistic? 3. Do you prefer working with your hands in a lab or would you rather be doing something theoretical? 4. Do you like biology? 5. How do you feel about memorization?

Hello, Unfortunately the silyl enol ether is also unstable with gringnards - but you're on the right track. : ) Also adding fluoride in the acidic workup will not really help you here.. It will actually complicate things a lot... The problem is that as soon as you THP protect the alcohol you will have a mixture of diastereomers that you will have to purify via column chromatography before you can do the gringnard.. you cannot have any of the reactants or left overs from the quench / workup steps in your mixture when you attempt the gringnard.. Furthermore.. although it is tempting to find ways to combine reactions when you fist start out in synthesis it is never a good idea to do this because pushing on with crude and / or trying to add multiple steps in the same pot usually results in black gue... When I monoprotect a symmetrical diketone I have the symmetrical ketone with catalytic amounts of acid in a round bottom with molecular sieves.. then using an addition funnel I add a dilute solution of the protection group drop wise in the appropriate solvent - the ratios for this solution depend on the protecting group/solvent etc... Also.. the PCC is a realistic method.. often times harsh and/or acidic oxidizing agents can remove protection groups that are acid labile.. PCC is about 10cents more expensive per use than some of the other oxidizing agents because if your alcohol is secondary and stable it typically takes a lot more equivalents of these kinds of reagents therefore while the bottle is cheaper from aldrich in practice they are not cheaper per use... especially when they wreck your compound... : ( Merged post follows: Consecutive posts merged That sucks not having scifinder... I would go crazy without it and beilstein... those are like bibles to synthetic chemists...

Hello, Oh sorry that you don't have access to those.. if you want to check them out you can go to your university library and they should have scifinder there.. if not they should have some other way to access online journals... Then you just have to put in the info provided in the reference... To your question... THP is an okay protecting group.. but TBS or some other silyl protecting group would be better here because... THP can often get displaced by gringnards so that is another problem... Yes you will be removing it but until you do the disastereomers will be a problem... Unfortunately you will have to characterize and isolate each intermediate - god I wish this wasn't so.. but alas it is.. : ( if you do not do so it will not be possible to do the next reaction without major problems... I'd be happy to run through a procedure for the monoprotection for you... either by PMs or in another thread if you want - I'm not sure if I can do that here.. but if I can I'll post it here tomorrow if you want.. whatever is easier... hope this helps : ) congrats on deciding to become a synthetic organic chemist.. I'm in a PhD program for chemistry right now - so I might be bias - but I think it's a great career choice. : )

Hello, The monoprotection works.. I do these all the time.. here are some references I quickly found on scifinder... I have my own procedure that utilizes a dilution method but these are published and provide decent yields as well... Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), (11), 2117-22; 1989 72% yield Journal of the Chemical Society, Chemical Communications, (4), 364-5; 1993 52% CASREACT Justus Liebigs Annalen der Chemie, 665, 55-67; 1963 60% Merged post follows: Consecutive posts merged EDIT: Sorry still posting from the lab... you may also want to be careful about using the THP protection group if you're going to be following the synthetic route utilizing the 3-hydroxycyclohexanone because: 1. The THP will have a stereocenter once added 2. and even if the 3-hydroxycyclohexanone is not racemic - which would make it waay more expensive than PCC - you'll end up with a very nasty mixture of distereomers that will be a pain to separate and characterize... just a thought... Using PCC is more of a personal choice I guess.. I prefer to use it because it typically requires less equivalents.... plus my stuff tends to be really complicated so staying away from the harsher oxidizing/cheapo reagents is usually a good idea - but I'm not sure if in a theoretical situation the profs will care either way... hope this helps. : )

Hello, Please see this link to a chemdraw scheme I've made below: http://picasaweb.google.com/lh/photo/-SbDv9deQWE1E9kI1zT__w?authkey=Gv1sRgCJuh7bCx65-CUQ&feat=directlink sorry I didn't have time to figure out how to load this on the forum any other way.. let me know if you have any questions... hope this helps.. : ) EDIT: Sorry I threw that together quick.. I'm still at the lab.. but I should add that if your prof asks about a mixture of monoprotected and diprotected being formed you can tell him that the protection step can be done highly diluted to avoid that... or you can also use 3-hydroxycyclohexanone... protect the alcohol... do the gringnard... dehydrate the alcohol formed in the gringnard and then deprotect the other alcohol and oxidize back to the ketone with PCC... hope that helps..

Hello, Because you are dealing with a tertiary center and therefore automatically confined to an SN1 mechanism... for either route going from the alcohol to the chloride or the chloride to the alcohol you will go through the same carbocation intermediate. Thus to effectively convert the alcohol to the chloride it is necessary to have an excess of Cl- anion present compared to water molecules present (Le Chatelier's principle)... This overcomes the equilibrium issue that you are referring to.. When actually doing this reaction in the lab often times molecular sieves or anhydrous calcium chloride is added to remove the water thereby further driving the equilibrium towards the production of the desired product - the tertiary halide. As far as the other examples with SOCl2 etc.. they go through SN2 mechanisms and will not work on a tertiary alcohol... hope this helps. : )