Sciencemadness Discussion Board
Not logged in [Login ]
Go To Bottom

Printable Version  
Author: Subject: TEMPO writeup
Metacelsus
International Hazard
*****




Posts: 2505
Registered: 26-12-2012
Location: Boston, MA
Member Is Offline

Mood: Double, double, toil and trouble

[*] posted on 9-5-2015 at 14:15
TEMPO writeup


I've written up my procedure used in Etaoin Shrdlu's challenge:
https://www.sciencemadness.org/whisper/viewthread.php?tid=45...



Attachment: TEMPO Writeup.pdf (3.6MB)
This file has been downloaded 1788 times





As below, so above.
View user's profile View All Posts By User
gdflp
Super Moderator
*******




Posts: 1320
Registered: 14-2-2014
Location: NY, USA
Member Is Offline

Mood: Staring at code

[*] posted on 9-5-2015 at 16:12


Nice job, the writeup looks good. Some thoughts on the yield:

The yield for the first step isn't terribly important because all of the reagents are cheap and readily accessible, it also doesn't look terribly time intensive.

The Clemmensen reduction looks like the yield killer though. Since the substrate is an amine, a Wolff-Kishner might be more appropriate. I realize that the hydrazine might have brought the reaction out of the OTC realm, but improving upon the process afterwards by using non-OTC but still accessible reagents may be good. It also rids the need to deal with mercury compounds, something which is always nice as proper cleanup of all of the glassware can be a pain.

The oxidation yield doesn't look bad and I can't think of anyway to really improve it. TEMPO is a typically a catalyst though, so large amounts are unnecessary, as long as the yields are in the 50% range it shouldn't affect small scale preps.

I may attempt this in a while, I have a lot of other reactions lined up though. If I do, I'll try it with the Wolff-Kishner, and I will post results. Overall though, great job!




View user's profile View All Posts By User
byko3y
International Hazard
*****




Posts: 721
Registered: 16-3-2015
Member Is Offline

Mood: dooM

[*] posted on 10-5-2015 at 07:03


Woof, hydrazine is actually OTC. You just need ammonia and hypochorite to prepare it. Then you can do W-K reduction via hydrazine, alkali and ethylene glycol. TMP can be easily distilled of the solution. However I have no idea about how much of hydrazine would also come out.
Btw, you can't check whether you've got 4-oxo-TEMPO or TEMPO by melting point - they both have the same melting point near 35-38°C (just like unsaturated derivatives). And all the N-oxo derivatives have red color. There's pretty much the only easy way to find what compound you've got - to convert your TMP into freebase. While triacetoneamine and possible dimers are solid at room temperature (r.t.), TMP is a liquid at r.t. Possible unsaturated derivatives are also liquid, but they have a slightly higher boiling point. To really check if there's any double bounds present you can use permanganate - it does not react with amines having no hydrogen on α-carbon, but easily oxidizes double bounds (I don't think halogens will work well here).
View user's profile View All Posts By User
smaerd
International Hazard
*****




Posts: 1262
Registered: 23-1-2010
Member Is Offline

Mood: hmm...

[*] posted on 10-5-2015 at 07:37


Really nice work here Cheddite! I remember when you first started on this. It's nice to see that you have had success.

I'm actually pretty interested in this simply for the 2,2,6,6-­‐tetramethylpiperidine intermediate. TEMPO is useful but that looks like a lovely OTC stericly hindered base! It is a shame about the clemmenson giving low yields but something tells me someone could optimize that a bit.

My only suggestion would be to assume your readers are lazy and show the percent yields.

edit - also given the choice... I'd much rather work with a clemmenson than do anything involving distilling hydrazine at home. Mercury salts are scary but yea.

[Edited on 10-5-2015 by smaerd]




View user's profile View All Posts By User
Chemosynthesis
International Hazard
*****




Posts: 1071
Registered: 26-9-2013
Member Is Offline

Mood: No Mood

[*] posted on 10-5-2015 at 07:45


I agree that this was excellent work. I'll have to download the actual writeup later. I would have gone with a W-K, but I can't complain too much as I didn't do any work. (https://www.sciencemadness.org/whisper/viewthread.php?tid=45...)

I don't mean to detract at all from a MP determination, which I recommend, but I do see another test for differentiating TEMPO from 4-oxo-TEMPO, and that would be using your presumed TEMPO in a reaction (do it!) then testing the presumed 2,2,6,6-Tetramethylpiperidine (TMP) byproduct with bisulfite, looking for the appearance of visible adduct from an unreduced ketone.
View user's profile View All Posts By User
DJF90
International Hazard
*****




Posts: 2266
Registered: 15-12-2007
Location: At the bench
Member Is Offline

Mood: No Mood

[*] posted on 11-5-2015 at 06:00


Firstly, congratulations on your synthesis of TEMPO and winning the first Etaoin Shrdlu challenge.

Overall, I think your write-up is very good. However I think the introduction should be extended to include a brief summary of the work performed by others en route to TEMPO. Klute invested a fair amount of time and effort in the preparation of triacetonamine, and in my opinion it is this intermediate which provides most difficulty. Summarising this in a concise manner and highlighting the potential pitfalls sets the stage for discussion of your own work. I appreciate that a link is provided at the end of the publication, but I think it should be discussed more rather than being a point of reference.

You should also include a reaction scheme to show your intended route, and discuss the pros and cons of it. You chose that route for a reason, and it'd be good to see how you justify it. You may wish to compare and contrast other potential routes (which fall under the nature of the challenge).

After the introduction, it'd be nice to have a high-level summary to state what you achieved before digging into the details, e.g. "TEMPO was successfully prepared in XX %th yield from cheap and readily available precursors in three steps".

The rest of my criticism falls down to formatting. I'll bullet point these for your consideration:

> The text of your publication should be "fully justified"; this will make it flush with both the left and right margins.

> You've written the introduction using double-spaced lines (a la thesis), but then revert to single spacing. Be consistent, and perhaps consider 1.5 line spacing as a balance between the two.

> In your materials list, only the first part of a compounds name should be capitalised, e.g. Ammonium chloride, Hydrochloric acid.

> Values and units should be separated by a space. You've done this for most things apart from concentrations, which should read e.g. 12 M Hydrochloric acid. Additionally there is a "ph" which should be "pH". Consistently the unit of volume is written as "ml"; this should be "mL"

> Consider the number of significant figures required for e.g. masses. I suspect two decimal places are sufficient.

>When stating the amount of substance added, it is helpful to also include how many molar equivalents this is, e.g. "Ammonium chloride (XX g, XX eq.) was added".

> When describing the workup, you often say "was extracted with 3 5 mL portions of [solvent]". This is ambiguous and should be written either as "was extracted with three 5 mL portions of [solvent]" or "was extracted with 3 x 5 mL [solvent]" or was extracted with [solvent] (3 x 5 mL)". Note that the "x" should be a multiplication symbol and not the letter "x" as I have used.

Finally a few technical points:

> When you recrystallise your triacetonamine, you mention that the mixture is concentrated and cooled to 0 *C prior to filtering. Something important that you have omitted is to what volume the mixture was concentrated (any solid formation?) and also how long the mixture was "aged" at 0 *C. Your yield may be higher if you age it for 1 hr compared to 15 min (depending on rate/extent of crystallisation).

> During the Clemmensen work-up, you neutralise with sodium hydroxide and filter off the zinc oxide. Is there any reason why you did not add an excess of hydroxide to solubilise the solids as zincate? This would allow you to streamline the process by omitting the filtration step.

Please remember that these comments are intended to be constructive and generally highlight only minor flaws in your work.

[Edited on 11-5-2015 by DJF90]
View user's profile View All Posts By User
Hexavalent
International Hazard
*****




Posts: 1564
Registered: 29-12-2011
Location: Wales, UK
Member Is Offline

Mood: Pericyclic

[*] posted on 11-5-2015 at 11:38


Congratulations on your work! TEMPO is a useful reagent but is indeed difficult to procure by the amateur.

Aside from the points addressed above, I would like to add the following suggestions. All are intended in a purely constructive fashion.

1. It is more meaningful when literature melting points are quoted alongside your experimental data. You must assume that the reader is lazy and will not search himself for the literature values, so you should aim to include them after your own.

2. Although you mention details of your reagents in the experimental section, i.e. "zinc powder", it may be helpful to have these quoted in your reagents list prior to this. It may also be helpful to clarify that the use of anhydrous solvents is unnecessary. Although this may be insinuated in the experimental section, it may be helpful to make this explicitly clear in your reagents section.

3. This is a personal thing, but I find the wording of your introduction a trifle informal for this kind of writing, although it naturally depends on who your intended audience is.

4. This relates somewhat to DJF90's comments regarding weighings - some are quoted to 2 dp, yet others are quoted to 3 dp. Choose one level of precision, and stick to it throughout.

5. Rf values quoted from TLC don't provide much useful information to the reader, unless they are taken under exactly the same conditions as, and discussed with, the literature values. The differences in Rf values recorded indicate that the reaction has proceeded, but mean nothing in terms of actual quantitative purity.




"Success is going from failure to failure without loss of enthusiasm." Winston Churchill
View user's profile View All Posts By User
aga
Forum Drunkard
*****




Posts: 7030
Registered: 25-3-2014
Member Is Offline


[*] posted on 11-5-2015 at 11:51


The comments on the cosmetics of the presentation are valid, yet this is undeniably Excellent work.

Well done, congratulations on the synthesis and winning the Challenge.

A great example of how Doing stuff rather than just talking about it Wins every time.




View user's profile View All Posts By User
Boffis
International Hazard
*****




Posts: 1723
Registered: 1-5-2011
Member Is Online

Mood: No Mood

[*] posted on 11-5-2015 at 16:27


Nice work Cheddite, I liked the write and won´t pic nits either.

I´ve been thinking about having a go at this for some time now.
View user's profile View All Posts By User
j_sum1
Administrator
********




Posts: 5764
Registered: 4-10-2014
Location: Unmoved
Member Is Offline

Mood: Possessor of a tidy and organised lab. Now to mess it up again.

[*] posted on 11-5-2015 at 17:49


Nor will I pick nits. Lovely work.
I saved it with the intent of showing my (high school) students. The actual content will fly straight over their heads and they will read little. But it showcases well many of the things I have been trying to instil in them for their practical write-ups. Such things as:

Writing in the third person past tense
Selection of photos and diagrams that have good explanatory power
Captions for photos and diagrams
Appropriate use of technical terminology
Appropriate level of detail in description of procedures
and so on.

Sometimes actually seeing these things speaks a whole lot more than having someone tell you.
So thanks.
As an aside, if I ever need some TEMPO (which is unlikely at least for a while) I now know what to do to get it.
View user's profile View All Posts By User
Magpie
lab constructor
*****




Posts: 5939
Registered: 1-11-2003
Location: USA
Member Is Offline

Mood: Chemistry: the subtle science.

[*] posted on 12-5-2015 at 08:28


I'm uninformed as to the value of TEMPO to the home chemist. However, this seems like a significant accomplishment, especially since it has been done with OTC reagents. Nice work!

I want to add that the comments of DJF90 are very constructive and their incorporation would help the readability significantly. I commend DJF90 for having the balls to provide these comments which many will just refer to as knit-picks. I'm assuming that we promote quality writing among those who post here. There are many young contributors here. What they learn about report writing is just as valuable as learning chemistry, assuming that some day they want to be professionals.




The single most important condition for a successful synthesis is good mixing - Nicodem
View user's profile View All Posts By User
DJF90
International Hazard
*****




Posts: 2266
Registered: 15-12-2007
Location: At the bench
Member Is Offline

Mood: No Mood

[*] posted on 12-5-2015 at 08:56


Quote: Originally posted by Magpie  
I commend DJF90 for having the balls to provide these comments which many will just refer to as knit-picks.


Thanks, but theres no need for that Magpie. As I see it, the prepublications section is a place to post procedures for review by other members, so that improvements can be made to the manuscript. Its called pre-publications for a reason. Anyone that just says "nice job" is not doing the author justice; they have not taken the time to properly review what has been written. It ultimately falls to the author what (if any) comments/suggestions they take on board.
Quote: Originally posted by Magpie  
I'm assuming that we promote quality writing among those who post here. There are many young contributors here. What they learn about report writing is just as valuable as learning chemistry, assuming that some day they want to be professionals.


This is largely why I provided my input. As a professional I have written a thesis, project reports and client updates, and have a good feel for what is required. The comments I have made are largely based on this experience - it is the "right way" to do it. I had imagined that Cheddite Cheese will one day be writing his own thesis/reports, and the sooner he can get in the correct format, the easier it'll be for him.

One final note - just because we are doing chemistry as a hobby does not mean we have to be amatuers about reporting our results. Some of us here are (or aspire to be) professional chemists - for this reason I prefer the term "independant researcher" to "amatuer chemist"
View user's profile View All Posts By User
CuReUS
International Hazard
*****




Posts: 928
Registered: 9-9-2014
Member Is Offline

Mood: No Mood

[*] posted on 23-5-2015 at 01:16


some notes for increasing the yield
1.I noticed that the oxidation of TEMP to TEMPO gave higher yields(96%) when the 4-keto group or any other electron withdrawing group was present compared to just TEMP.so it would be good if the oxidation was done first,followed by a wolf-kishner reduction
http://www.ncbi.nlm.nih.gov/pubmed/18066874

2.one member said that the reduction step was killing the yield.this paper looks promising (yield-99%).could someone get it.
http://www.heterocycles.jp/newlibrary/libraries/journal/19/1
View user's profile View All Posts By User
aga
Forum Drunkard
*****




Posts: 7030
Registered: 25-3-2014
Member Is Offline


[*] posted on 23-5-2015 at 10:25


Quote: Originally posted by CuReUS  
2.one member said that the reduction step was killing the yield.this paper looks promising (yield-99%).could someone get it.
http://www.heterocycles.jp/newlibrary/libraries/journal/19/1

I was about to, then saw an endless list of papers.

Which one is it ?




View user's profile View All Posts By User
Boffis
International Hazard
*****




Posts: 1723
Registered: 1-5-2011
Member Is Online

Mood: No Mood

[*] posted on 23-5-2015 at 15:24


I presume its this one:

p1-5



Attachment: R-1982-01-0001.pdf (109kB)
This file has been downloaded 850 times

View user's profile View All Posts By User

  Go To Top