Sciencemadness Discussion Board

Green Synthesis of 3-methyl-heptan-3-ol from common materials

ScienceHideout - 27-2-2016 at 19:38

Hi guys! I did it! There has been a lot of interest in making tertiary alcohols, and after spending the day in my lab and doing some intense research, I picked up on a few tricks. Therefore, I am posting the first draft of my paper with the intent to make revisions and get it published here in the SM publication library! The yield is awful, but the purpose of this experiment is not to mass produce loads of tertiary alcohol, but rather to show that there are techniques for the home scientist to make tertiary alcohols via Grignard without having any ridiculously dry solvents or ether. PLEASE let me know what you think and if there are any ways I can make it better.

As far as the characterization of this compound, I do not think that it would be feasible to run an NMR on this compound. The best analytical instrument that I have everyday access to is a Waters LCMS, but this molecule is not heavy enough to get a good looking peak. If you have any other ideas, let me know and I may try them out sometime!

Attachment: Green synthesis of 3-methyl-heptan-3-ol.pdf (847kB)
This file has been downloaded 2134 times

j_sum1 - 27-2-2016 at 20:08

I am no expert on this so someone else will have to critique the technical aspects of your report. However...

1. This looks like a fantastic accomplishment. Well done. I hope you are really pleased.
2. Great to see original work being done and posted in prepub.
3. Positive identification of the compound is obviously critical. Are you able to do a melting point test? It will at least get you somewhere towards identification.

ScienceHideout - 27-2-2016 at 20:19

Quote: Originally posted by j_sum1  
I am no expert on this so someone else will have to critique the technical aspects of your report. However...

1. This looks like a fantastic accomplishment. Well done. I hope you are really pleased.
2. Great to see original work being done and posted in prepub.
3. Positive identification of the compound is obviously critical. Are you able to do a melting point test? It will at least get you somewhere towards identification.


1) I am very pleased :)
2) Thanks, this technique is not widely known and I feel like it should be, because it is really practical especially for the home chemist.
3) CRC claims the m.p. is -83 or so. That means not even a dry ice/acetone bath will work. I would have to use liquid nitrogen, and unfortunately that might just freeze it regardless.

HeYBrO - 27-2-2016 at 21:27

I have only skimmed through it so far but you must actually post results and discussion after your experimental. Also, writing an equipment less procedure stream lines reading and presentation (also editing). The reason for this is that any competent chemist should be able to follow a basic procedure. You have done this in section 3.1 in this style (the right way imo, always write to your instructors specifications) then changed later. also, keep your significant figures consistent and make sure to add the molar quantities after the gram amounts. You could even say (as example) "Magnesium powder (x grams , y mmol) was added to 1- bromobutane (z, grams , u mmol)". so you don't need to say they were measured or anything. Good job, just needs to some adjusting to keep a consistent style throughout.

also, how would placing magnesium under vacuum dry it? surely you would need to heat it to dry it properly.

nice work and good effort!! :)

[Edited on 28-2-2016 by HeYBrO]

BromicAcid - 27-2-2016 at 22:17

Concentration of sulfuric acid in the synthesis in section 3.1? I would have assumed concentrated just because that is what most people have laying around but then during your wash of your organic layer you specify 80% concentration.

I like your procedure, sure the yields are the best but as you point out it is more accessible than a standard Grignard and that is the spirit of this forum. Glad to see this all documented. Excellent work, so much seems to be discussed in other threads with so few people actually experimenting.

Final Draft?

ScienceHideout - 28-3-2016 at 17:04

HeYBrO and BromicAcid,

I took your advice and made the following changes.

  1. I specified 'concentrated' acid in experimental section x.1
  2. I switched the sections so that results and discussion comes after experimental
  3. I removed many lab equipment refs from the experiment
  4. I verified my sigfigs
  5. I posted grams and mmol in parentheses


You also asked about drying the magnesium, I just left it under vacuum for a couple hours... that's what we do in the lab I work in for most wet reagents. Yes, water doesn't come off in the vacuum as easily as DCM or acetone, but it is sufficient for this procedure. Remember that the sonication allows us to have small quantities of water without ruining our Grignard.

Who would I talk to about maybe getting this in the member pub's? This certainly won't be my last tertiary alcohol, and I really would like to collaborate with someone who can replicate these procedures and test with sodium and potassium reduction.

Attachment: Green synthesis of tert alcohol 2.pdf (849kB)
This file has been downloaded 908 times

CuReUS - 29-3-2016 at 05:29

you might be able to increase the yield if you used 2-methyl THF instead of THF
http://pubs.acs.org/doi/abs/10.1021/op060155c (73% yield)

[Edited on 29-3-2016 by CuReUS]

blogfast25 - 29-3-2016 at 06:11

@ScienceHideout:

Nice synthesis but why do you call it 'green'?

ScienceHideout - 29-3-2016 at 08:35

CuReUs,

Thanks for the suggestion. At this time I don't have any methyl THF, but perhaps I could try that in the future.

Blogfast,

According to the American Chemical Society green synthesis utilizes careful approaches to limit exposure, hazardous byproducts, waste, and extreme conditions. I feel that I have made a careful effort to reduce these with my in situ bromination, lack of molecular sieves with THF, and regular air grignard formation.

Magpie - 29-3-2016 at 09:06

I think it is a good idea to synthesize as simply as possible, while still getting a decent yield. If the yield is poor then what is the point?

Your synthesis of n-butyl bromide looks standard to me. It is the same one that I use, which I took from Pavia, published in 1997. I performed this recently obtaining a 55% yield. So, I think your 31% yield here can be much improved.

I don't use an inert atmosphere with my Grignards but do use absolute ether. A smidgen of I2 gets it started OK. But If you can get a decent yield (>50%) with undried THF then this would be good. Right now your yield at 10% is poor. We'll have to see if this can be improved. Chemplayer... has a good YouTube out showing some good results in this effort.

You need to show some proof that you made the target compound. You could do this with a bp if you can get enough yield to do this.

If you want to publish this in Prepub I think the burden is on you to prove your claims instead of asking others to do this.

Please do not take these comments as anything other than constructive criticism. ;)

ScienceHideout - 29-3-2016 at 15:41

Magpie, thanks for your input!

I am going to try again this weekend with both parts... I think that for part 1 my problem was that I added to much sulfuric acid and I made an ether. This time I will try it with just a slight excess.

I am also going to do the grignard again, four times. Once with Et2O off the shelf, once with Et2O over MgSO4, one with off the shelf THF, and one with THF over MgSO4. If the yields of all four are similar, that would verify my hypothesis by showing that normal, not super dry THF is a cost effective, efficient, safe and overall GREEN :D way to go.

As far as characterization, I can certainly purify and work on a BP, and I can prove it is a tert alcohol with an SN1 reaction... I was thinking though, perhaps I could react it with something that could put the mass over 200 so I can run an LCMS to characterize?

DJF90 - 29-3-2016 at 16:28

Sorry I'm late to the party. I did actually see the original draft but was short on time and forgot to come back and comment.
Quote: Originally posted by HeYBrO  
I have only skimmed through it so far but you must actually post results and discussion after your experimental.


This is wrong. Results and discussion should always come first, and experimental details are usually tacked onto the end of the manuscript. Look at the articles in any reputable scientific journal and you'll see. Some journals don't even have an experimental section (eg. Tetrahedron Letters). Here's the general structure that I'd recommend:

Abstract/summary:
This should be a high level summary at the very start of the manuscript (after the title) detailing the key acheivements that will be detailed in the publication. You actually did a pretty good job of this! The bit I do have an issue with is this:
Quote:

The reaction produced few hazardous by-products, uses safe chemicals, and a very innovative approach to the Grignard reaction using ultrasounds to eliminate the need for argon-flushed glassware and anhydrous solvents.

Considering your overall yield was 10 %, you cannot tout this as "green" approach. It is far from it. More realistically, you can state that it uses relatively OTC chemicals and demonstrates the ultrasound assisted grignard reaction. Also note that the use of ultrasounic irradiation in the formation of grignard reagents is not innovative; there is plenty of existing literature on this and related chemistries, some of it relatively old (ca 1980's IIRC).

Introduction
This is where you set the scene to discuss your work. You should include what you aim to acheive, and others should be interested. Give a brief summary of relevant prior work, and use this to naturally lead onto your own work, commenting where appropriate as to the merits of your approach (eg. use of OTC precursors, specially dried solvents not required). You've done well with this section as well, although you need to add more references (and discuss why eg. t-BuOH is not satisfactory).

Results and discussion
This is where you detail and discuss your findings. Its probably best to to discuss each stage in sequence, stating what was tried and how it performed. You should be comparing and contrasting to existing work (if appropriate), and trying to rationalise your results. Again, you've made a good attempt at this, but it needs to be expanded upon; you're being too brief. One thing that baffles me is this statement:
Quote:

In an anhydrous, air-free Grignard reaction with similar reagents, it is reasonable to expect 67%.

Where did you pull that (arbitrary?) number from?

Experimental
This should be fairly straight forward. Remember to be consistent with significant figures.

Conclusion
This is where you summarise your acheivements, and tally them up against the objectives outlined in the introduction. If you did not acheive an intended aim, propose what could be done to improve chances of success on a subsequent attempt.
Quote: Originally posted by HeYBrO  

also, how would placing magnesium under vacuum dry it? surely you would need to heat it to dry it properly.

Given that the water content of the magnesium shreds will be significantly less than that of the THF, I wouldn't worry about this at all.
Quote: Originally posted by Magpie  
I think it is a good idea to synthesize as simply as possible, while still getting a decent yield. If the yield is poor then what is the point?

This is critical. A reaction cannot be considered "green" if you're losing the majority of your material at each stage.
Quote: Originally posted by Magpie  

Your synthesis of n-butyl bromide looks standard to me. It is the same one that I use, which I took from Pavia, published in 1997. I performed this recently obtaining a 55% yield. So, I think your 31% yield here can be much improved.

Digging through the ancient depths of OrgSyn, you shall find:
http://www.orgsyn.org/Content/pdfs/procedures/CV1P0025.pdf
The preparation of n-Butyl bromide is detailed using the NaBr/H2SO4 method, and a 90 %th yield is reported.
Quote: Originally posted by Magpie  

I don't use an inert atmosphere with my Grignards but do use absolute ether. A smidgen of I2 gets it started OK. But If you can get a decent yield (>50%) with undried THF then this would be good. Right now your yield at 10% is poor. We'll have to see if this can be improved.

Use of diethyl ether as solvent alleviates the need for inert atmosphere, due to the protective blanket of ether vapor. This was discussed recently elsewhere on the forum.
Quote: Originally posted by Magpie  

You need to show some proof that you made the target compound. You could do this with a bp if you can get enough yield to do this.

There are also crystalline derivatives you could prepare, and literature values for their melting points to compare to.

There are a few additional formatting issues to those mentioned above. The text of your publication should be "fully justified"; this will make it flush with both the left and right margins. Also try to get into the habit of using "non-breaking spaces" and "non-breaking hyphens" to ensure you don't get a line break between e.g. a value and its units. Putting them in as you go along is much easier than going through and adding them where needed.

Once again, this is meant to be constructive criticism.

[Edited on 30-3-2016 by DJF90]

ScienceHideout - 29-3-2016 at 16:52

DJF90, you outdid yourself! :D

Your criticism was very valuable, and you definitely clarified a lot of things as well as stressed things that I should've caught onto myself.

Once again, I am going to try this again and see if I can't get a higher yield, so when I am writing part III I will most certainly take everything into account.

DJF90 - 30-3-2016 at 06:52

Quote: Originally posted by ScienceHideout  

DJF90, you outdid yourself! :D
Your criticism was very valuable, and you definitely clarified a lot of things as well as stressed things that I should've caught onto myself.
Once again, I am going to try this again and see if I can't get a higher yield, so when I am writing part III I will most certainly take everything into account.


I'm glad my input was well received. There are a few other bits that I had failed to mention (it was late...):

> In the results and discussion section, I'd say that simple reaction schemes are sufficient, just as you have used in the introduction. Discuss each stage separately, and remember to include the RMM/MW under the starting/principal input material and the product. You do not need to provide mechanisms unless it is something that you believe to be worth discussing.

> You mention that the chemistry is suitable for preparing other tertiary alcohols. Perhaps you could take the time to exemplify this (once you've optimised the conditions at each step for the current substrates) as it would greatly improve your publication, especially if you're intending on doing so in future work anyway. You could vary either or both of the alkyl halide/ketone substrates, depending on how much time and effort you want to invest in this.

> You should perform a control experiment for the Grignard formation in the absence of ultrasonic irradiation. Maybe it would have worked satisfactory... did you test it? We'll come back to this in a bit...

>When describing wash procedures in the experimental, remember to include the volumes and (where appropriate) concentrations of each solution. I personally find the text to be more streamlined and readable with the following format (delete as appropriate):

"...was washed/extracted with [solvent/solution] ([conc.], [reps] x [volume] mL)". Note that the "x" should be a multiplication symbol and not the letter "x" as I have used. An applied example is shown below:

"The crude distillate was washed with water (10 mL) and sulfuric acid (80 %w/w, 0 to 5 *C, 10 mL). The organic phase was separated, dried over anhydrous magnesium sulfate and vacuum filtered. The filtrate was purified by distillation at atmospheric pressure, collecting the fraction boiling at 99 to 103 *C. The product was obtained as a colourless oil (4.67 g, 31 %th)."

> When giving concentrations as percentages, it is helpful to specify whether it is %w/w, %v/v or %w/v. Typically, percentage concentrations or purities are given as %w/w, but there are occasions where %v/v may be more appropriate (eg. chromatographic eluents). Being clear about what you're using saves any ambiguity.
Quote: Originally posted by ScienceHideout  

I think that for part 1 my problem was that I added to much sulfuric acid and I made an ether. This time I will try it with just a slight excess.

I'd really recommend using the OrgSyn procedure I linked to previously. I know you replied to Magpie before my post was made, so maybe this is your intention.
Quote: Originally posted by ScienceHideout  

I am also going to do the grignard again, four times. Once with Et2O off the shelf, once with Et2O over MgSO4, one with off the shelf THF, and one with THF over MgSO4. If the yields of all four are similar, that would verify my hypothesis by showing that normal, not super dry THF is a cost effective, efficient, safe and overall GREEN :D way to go.


Before embarking on this, perhaps it is worth considering the following... If your "off the shelf" solvents are already pretty dry (the bottles next to me specify <0.03% and <0.05% H2O for diethyl ether and THF respectively) then drying over MgSO4 is unlikely to remove any additional water and your "wet" and "dry" runs will be essentially identical. A more suitable approach may be to start with solvent as dry as you can get it, and spike it with a specified quantity of water (eg. 0.1 to 0.5 %w/w?) for the "wet" run. The problem with all of this work is that without access to a Karl Fisher titrator, its speculative and a bit meaningless.
Quote: Originally posted by ScienceHideout  

As far as characterization, I can certainly purify and work on a BP, and I can prove it is a tert alcohol with an SN1 reaction... I was thinking though, perhaps I could react it with something that could put the mass over 200 so I can run an LCMS to characterize?


Perhaps some qualitative analysis would be a nice addition to the characterisation. A test for 3* alcohol with Lucas' reagent should be easily performed. Formation of a crystalline derivative for melting point determination ought to be possible, but the required reagents may or may not be accessible.

[Edited on 30-3-2016 by DJF90]

ScienceHideout - 30-3-2016 at 18:32

Hi guys,

DJ, just want to thank you again for all of the criticism, it is appreciated and I will take it all into account while writing my next version. Today I tried the orgo syn procedure on making the butyl bromide. I got a 57% yield at 1/10 scale... not the 90 that was reported. I am wondering if I am making too much dibutyl ether?

I will try one more time to make BuBr with awesome yield. This time, I will mix COLD sulfuric acid with the bromide salt, stoiciometric amounts in respect to each other, and let warm to room temperature before dripping in the limiting reagent BuOH and refluxing.

HeYBrO - 30-3-2016 at 20:50

Quote: Originally posted by DJF90  


Quote: Originally posted by HeYBrO  
I have only skimmed through it so far but you must actually post results and discussion after your experimental.


This is wrong. Results and discussion should always come first, and experimental details are usually tacked onto the end of the manuscript. Look at the articles in any reputable scientific journal and you'll see. Some journals don't even have an experimental section (eg. Tetrahedron Letters).



[Edited on 30-3-2016 by DJF90]



Indeed you are correct that tetrahedron letters presents their papers in such a format, but they also have papers without any formal structures that you mentioned, can you explain why this the case.

Generally universities teach the layout i suggested for lab reports and seeing how sciencemadnesss pre-pub papers normally follow this form i thought i might suggest this correction. Either layout works anyway; the information is still transferred across to the experimenter.

CuReUS - 31-3-2016 at 03:59

Instead of using BuBr,why don't you try making BuCl, it can be easily made by the TCT/DMF method,and since you are using ultrasound to start the reaction,the slow reaction rate of RMgCl can be compensated
http://pubs.acs.org/doi/abs/10.1021/ol017168p

http://chemistry.mdma.ch/hiveboard/novel/000372508.html

BuBr can be obtained by adding NaBr to the TCT/DMF mixture
https://books.google.co.in/books?id=7oeQwEA_uVUC&pg=PA36...

DJF90 - 31-3-2016 at 05:09

Quote: Originally posted by ScienceHideout  

Today I tried the orgo syn procedure on making the butyl bromide. I got a 57% yield at 1/10 scale... not the 90 that was reported. I am wondering if I am making too much dibutyl ether?

You got a fairly decent yield for a first run through - Magpie stated upthread that he gets 55 %th using the method in Pavia (@Magpie - Any chance of providing a copy of the relevant pages?). There may be a couple of things that could get your yield up. I wonder if refluxing for 2 hrs is sufficient enough, considering the method using hydrobromic acid/sulfuric acid says:
Quote:

The flask is then attached to a reflux condenser and the mixture is refluxed during a period of five to six hours, during which time the formation of butyl bromide is carried practically to completion.

I'm not sure this is the right explanation though, as the procedure is checked independently (that's why OrgSyn preps are so great! You know they should work as described). It may be that the distillation is not driven to completion (how much does your crude distillate weigh?) although you say subsequent distillate is water miscible (almost certainly n-butanol-water azeotrope -which suggests the conversion is not complete and longer refluxing is required). I also cannot find any reference for the azeotrope of n-butyl bromide with water, except in a microscale organic chemistry textbook, which gives no data. I would not expect it to form an azeotrope, but that's just my gut feeling. If it does, then I would certainly be surprised if it wasn't heterogeneous, and you don't mention a biphasic distillate. Di-n-butyl ether boils too high for it to be a significant concern, and any that does pass over will be dealt with by the sulfuric acid wash (also note that the purpose of this wash dhould be discussed in the "results and discussion" section, not the experimental). I don't think a great amount will be formed in the first place, considering it results from butanol (which is likely protonated) acting as a nucleophile competitively with the bromide ions (which are present in excess). Another possible explanation for the moderate yield could be the use of excessive drying agent. OrgSyn has this to say on the matter:
Quote:

5. In many organic preparations too large a quantity of drying agent is usually employed, with the resulting loss of a considerable amount of material due to absorption by the drying agent. In the present experiments it is found that after a careful separation of the alkyl halide from the water layer as small a quantity as 15 g. of calcium chloride is sufficient for the drying of 1500 g. of alkyl halide.

Seeing how you're drying a neat liquid rather than an organic extract, the use of excessive drying agent should certainly be avoided as mechanical entrainment will destroy your yields (as you may well be experiencing).
Quote: Originally posted by ScienceHideout  

I will try one more time to make BuBr with awesome yield. This time, I will mix COLD sulfuric acid with the bromide salt, stoiciometric amounts in respect to each other, and let warm to room temperature before dripping in the limiting reagent BuOH and refluxing.

I'd follow the OrgSyn prep again using the pointers I've given above. I've not made n-butyl bromide before, although I've done similar preparations for ethyl bromide and isopropyl bromide, and both performed well.
Quote: Originally posted by HeYBrO  

Indeed you are correct that tetrahedron letters presents their papers in such a format, but they also have papers without any formal structures that you mentioned, can you explain why this the case.
Generally universities teach the layout i suggested for lab reports and seeing how sciencemadnesss pre-pub papers normally follow this form i thought i might suggest this correction. Either layout works anyway; the information is still transferred across to the experimenter.

I used Tet. Lett. as an example because it was the first one that came to mind that illustrated my point. The structure that I outlined was my personal preference based upon what I've seen in journals, and also seen/used for theses and project reports etc. Whilst articles may not explicitly have the headings that I mentioned, the text generally does follow that structure. A post-lab report is slightly different and many use that format when writing up experiments in the other sub-fora, but this is pre-publications and as such a higher standard should be required.
Quote: Originally posted by CuReUS  

Instead of using BuBr,why don't you try making BuCl, it can be easily made by the TCT/DMF method,and since you are using ultrasound to start the reaction,the slow reaction rate of RMgCl can be compensated...

...BuBr can be obtained by adding NaBr to the TCT/DMF mixture

This is simple case of economics and ease of acquisition. The yield of the Grignard stage is (currently) low enough with n-BuBr, so why make life even more difficult by using the chloride? n-Butanol is cheap, and its unlikely that TCT-DMF will afford any advantage over the currently employed method.

[Edited on 31-3-2016 by DJF90]

Magpie - 31-3-2016 at 09:16

Quote: Originally posted by DJF90  

You got a fairly decent yield for a first run through - Magpie stated upthread that he gets 55 %th using the method in Pavia (@Magpie - Any chance of providing a copy of the relevant pages?). There may be a couple of things that could get your yield up. I wonder if refluxing for 2 hrs is sufficient enough, considering the method using hydrobromic acid/sulfuric acid says:
Quote:

The flask is then attached to a reflux condenser and the mixture is refluxed during a period of five to six hours, during which time the formation of butyl bromide is carried practically to completion.



Yes, these school lab procedures often have to be rushed to meet a standard 3-hr lab period. Pavia specifies a reflux of 60-75 minutes.

I also think you are right about using too much CaCl2 for the drying step. Pavia specifies 1.0g CaCl2 for a charge of 10.0 ml of n-butyl alcohol.

I never worried too much about not meeting OrgSyn's %yields as their scale was usually 10X what I was doing. Therefore I expected my mechanical losses would be greater.

Here's the Pavia procedure:







[Edited on 31-3-2016 by Magpie]

[Edited on 31-3-2016 by Magpie]



Pavia n-butyl bromide procedure-1 (2).jpg - 109kB Pavia n-butyl bromide procedure-2.jpg - 103kB

[Edited on 31-3-2016 by Magpie]

ScienceHideout - 31-3-2016 at 10:14

Thanks for the literature, Magpie!

Unfortunately the TCT/DMF prep is not practical for me, because I have yet to acquire either of those reagents. I have a fairly well stocked lab, so If I don't have those reagents I don't expect others to have them. The biggest purpose of this experiment is to show that tertiary alcohols can be made with OTC chemicals.

Anyways, I will keep experimenting!

gdflp - 31-3-2016 at 11:56

I thought I would throw in my experience with this reaction here as well. I too followed the OrgSyn prep at 1/10th scale and got a yield of 63.8% according to my lab notes. I do vaguely remember that I estimated the crude yield(distillate from the initial reaction mixture) at around 75%, so this 10% was likely lost due to mechanical losses during the washings, drying, and distillation, as well as dibutyl ether and butanol which were removed during the sulfuric acid wash. Unfortunately, running the reaction at the OrgSyn scale is not possible for most of the members here, myself included, due to both the cost of the reagents, and the cost of the apparatus necessary to run a reaction on that scale; so seeing if the yield can be improved this way is difficult. In addition, I doubt that many of us have a use for over a kg of nBuBr.

Magpie - 31-3-2016 at 12:25

Quote: Originally posted by ScienceHideout  
Thanks for the literature, Magpie!


You're welcome.

I looked back in my notes and see that I performed this prep at 4X and used a reflux time of 75 minutes. Next time I will follow the OrgSyn procedure as you and gdflp got better yields. ;)

DJF90 - 31-3-2016 at 14:38

Quote: Originally posted by gdflp  
I thought I would throw in my experience with this reaction here as well. I too followed the OrgSyn prep at 1/10th scale and got a yield of 63.8% according to my lab notes. I do vaguely remember that I estimated the crude yield(distillate from the initial reaction mixture) at around 75%, so this 10% was likely lost due to mechanical losses during the washings, drying, and distillation, as well as dibutyl ether and butanol which were removed during the sulfuric acid wash. Unfortunately, running the reaction at the OrgSyn scale is not possible for most of the members here, myself included, due to both the cost of the reagents, and the cost of the apparatus necessary to run a reaction on that scale; so seeing if the yield can be improved this way is difficult. In addition, I doubt that many of us have a use for over a kg of nBuBr.


Thanks for sharing.

On 1/10th scale, I really wouldn't be so worried about mechanical losses. The theoretical yield is nearly 130 mL so its a non-issue (estimated losses = 5 mL, ca 4 %th). I suspect the drying step is where most of the material is lost, particularly if care is not taken to ensure a minimum of dessicant is used.

I do have the means to run the OrgSyn prep at the specified scale, but there is no reason to and I'd definately optimise the procedure on a smaller (eg. 0.5 mole) scale before commiting that that quantity of reagents (thats the process chemist in me talking...). If that were the case, I would seriously consider extending the reflux period prior to distillation if the losses are not accounted for by the use of excessive dessicant.

[Edited on 31-3-2016 by DJF90]

AvBaeyer - 31-3-2016 at 19:19

Here is a link to a paper which provides some useful information regarding the preparation of alkyl bromides, especially reaction time vs yield.

Ref: J Chem Educ 1949, 26, 329.

The paper is 1 page long so can be read in its entirety at the ACS web site without any charge:

http://pubs.acs.org/doi/abs/10.1021/ed026p329?journalCode=jc...

AvB

DJF90 - 1-4-2016 at 00:38

Thats a very insightful paper Av, thanks. Looks like the losses are associated with the isolation/workup and not the reaction itself.

ScienceHideout - 2-4-2016 at 09:52

Great news guys!!!

I was up until 12 last night in the lab refluxing and distilling, and I woke up at 6 today to do workup. I redistilled also.

Doing the reaction starting with 82.4 mL of BuOH, I finished with 64.8 mL of BuBr, corresponding to a 67% yield!

To accomplish this, I did it my own way which makes the most sense. First I mixed water, NaBr, and sulfuric acid, THEN added the BuOH dropwise whilst heating up. It refluxed for an hour before I started to do downward distillation, which took a few hours at this scale.

I will certainly write the whole procedure in my paper... it was labor intensive but well worth it.

According to Av's paper, I should expect to see 86% yield, therefore there is a 19% difference in the two procedures, however the following must be remembered:
a) Workup. Lionel Joseph et. al. does not specify HOW he made his BuBr for 86% yield. He could've done it like Pavia, who omits downward distillation, or he could've distilled and not did workup. Again, there is no 'standard procedure' for preparing this, so we don't know what he did or didn't do.
b) Purity. Did they dry it? Distill it? I did both of these multiple times, and it is possible that each time I may have lost a small amount of product. Purity is, however, necessary if I plan to use this for Grignard reactions.
c) Laboratory. As home chemists, we are limited by the quality of our equipment, materials, and our time. Working at home in and of itself often sacrifices a bit of our yield for some reason.

According to Macroscale and Microscale Organic Experiments, a typical yield is 10 g from 10 mL BuOH, corresponding to a 67% yield.

Considering these facts, I would say I did pretty damn good this time around!

gdflp - 2-4-2016 at 10:59

Nice job. I suspect that there is more going on here however which is responsible for the lowered yields. With 1,3-propanediol, I got an 83% yield on a scale using ~40ml of the alcohol. The dibrominated compound is significantly less volatile than butyl bromide, so it's possible that this is another source of loss as well. Even still, a 19% loss of yield solely due to product lost to vapor seems quite high to me, so there might be a difference in the reaction which is hurting the yield here, but not with the diol. One thing which stands out to me immediately is that BuBr has a lower boiling point than water, while 1,3-dibromopropane has a higher boiling point than water. Perhaps prefilling the receiver with a bit of ice water could help improve the yields. Regardless, a 67% yield is not a bad yield, especially considering that none of the reagents are particularly expensive. Also, just a note from my runs of this reaction, the distillation to remove the product from the reaction mixture can be pushed very quickly, and if you're source of heat is powerful enough it can be finished in under an hour.

Magpie - 2-4-2016 at 12:00

The best thing about this is that ScienceHideout has gone from a 31% yield to a 67% yield! A lot of learning has happened.

DJF90 - 2-4-2016 at 13:09

Quote: Originally posted by ScienceHideout  
I was up until 12 last night in the lab refluxing and distilling, and I woke up at 6 today to do workup. I redistilled also.

Doing the reaction starting with 82.4 mL of BuOH, I finished with 64.8 mL of BuBr, corresponding to a 67% yield!

Impressive commitment and a well deserved result. Congratulations. One point - Yields should be calculated and reported on a mass basis (its alot easier to weigh product (tared flask) than to measure the volume without losses/error). I'd personally also charge the principal input material by mass also, as its more accurate than doing so volumetrically, especially if you have a balance with 0.01 g resolution or better.
Quote: Originally posted by ScienceHideout  
To accomplish this, I did it my own way which makes the most sense. First I mixed water, NaBr, and sulfuric acid, THEN added the BuOH dropwise whilst heating up. It refluxed for an hour before I started to do downward distillation, which took a few hours at this scale.

I'm not sure how much of an issue the order of addition is in this case. Alkene and ether formation are really only an issue at elevated temperature with primary alcohols, so as long as the components are brought together at eg. room temperature it shouldn't make much difference.

When I prepared ethyl bromide, the ethanol and water were combined, cooled in a water-ice bath, and sulfuric acid added. This was followed by the addition of sodium bromide in one portion and sufficient heating to provide a slow rate of distillation. The crude yield for this reaction was ca 80 % th, not bad considering the additional problem of volatility encountered with ethyl bromide (b.p. 38 *C). The order of addition specified here was used to minimise formation of hydrogen bromide, something I have had issue with previously when attempting to preform the hydrobromic acid in situ before adding alcohol as you have done. Did you notice any evolution of fumes as you added the sulfuric acid?
Quote: Originally posted by ScienceHideout  
a) Workup. Lionel Joseph et. al. does not specify HOW he made his BuBr for 86% yield. He could've done it like Pavia, who omits downward distillation, or he could've distilled and not did workup. Again, there is no 'standard procedure' for preparing this, so we don't know what he did or didn't do.

A reference is given to the preparative method. The author of the paper appears to have varied only the reaction duration to determine the effect on the yield of this process. Unfortunately I do not have the referenced text - perhaps another member may have it in their own private collection?
Quote: Originally posted by ScienceHideout  
b) Purity. Did they dry it? Distill it? I did both of these multiple
times, and it is possible that each time I may have lost a small amount
of product. Purity is, however, necessary if I plan to use this for
Grignard reactions.

I'm not sure why you did both operations multiple times? You should have distilled to isolate the crude product, done your washes, dried, and re-distilled. That should have been sufficient.
Quote: Originally posted by ScienceHideout  
c) Laboratory. As home chemists, we are limited by the quality of our equipment, materials, and our time. Working at home in and of itself often sacrifices a bit of our yield for some reason.

I'm not sure I agree with you on that one. If you're concerned about the quality of your starting materials, you should purify them before use. Equipment usually falls down to having the right (sized) apparatus for the job, particularly when distillation is involved. The only real problem I've encountered is the lack of controlled "room temperature", particularly if your lab is located outside in a shed or garage.
Quote: Originally posted by gdflp  
Nice job. I suspect that there is more going on here however which is responsible for the lowered yields.

@ScienceHideout - Have you attempted to quantify losses during the workup? Mass before and after drying? That would help pinpoint the problem.
Quote: Originally posted by gdflp  
Perhaps prefilling the receiver with a bit of ice water could help improve the yields.

Good idea. Collecting volatile alkyl halides under water is an old trick to minimise cooling requirements and improve yields. I did this when I made isopropyl bromide, actually. A plain receiver bend reaching to the bottom of a measuring cylinder filled with a little cold water to submerge the end works nicely.
Quote: Originally posted by Magpie  
The best thing about this is that ScienceHideout has gone from a 31% yield to a 67% yield! A lot of learning has happened.

Agreed. Lets hope the success continues through the later stages of the synthesis also!

[Edited on 2-4-2016 by DJF90]

ScienceHideout - 2-4-2016 at 19:51

gdflp- Interesting facts with the diol, It probably is partially because of the volatility, but I would think that it is an easier reaction. If you add one bromine, you make an electron withdrawing group... wouldn't that let the next hydroxyl leave easier?

Magpie- Thanks, I agree!

DJ- I plan on reporting mass in the paper, however for this specific case I need to use density calculations. My balance reads milligrams, and therefore has a capacity of 120g. I couldn't have possibly weighed the sample in a plastic cup! :D

I believe that order of addition is everything. In the lab I work in, I have gone from 5% yields to 90% yields just from the order of addition (well, in extreme cases like Swern oxidation). My thinking is that if the acid and bromide are mixed FIRST, then it will form HBr which will dissolve in the water I added. When the alcohol is added dropwise, the few molecules of alcohol are literally 'swimming' in an ocean of HBr and given no choice but to SN2 instead of turn to ether. When I added the acid to the NaBr, I did it very slowly and the acid was very cold. I didn't notice too many fumes, but the solution turned orange.

After I received the crude product, I washed, dried, distilled and dried again. I have not taken mass before and after drying, again, I simply don't have the capacity.

AvBaeyer - 2-4-2016 at 19:51

I have a revised edition of the Robertson’s “Laboratory Practice of Organic Chemistry” (4th edition, 1962) which (more or less) corresponds to reference 1 in the Joseph, et al. J Chem Educ paper cited earlier. I had the actual edition cited but got rid of it during a recent clean out of my library. Following is a summary of the preparation of butyl bromide in the above mentioned text:

In a 500 ml flask fitted with a reflux condenser place 0.4 mole n-butyl alcohol and 0.5 mole of potassium bromide or sodium bromide. If sodium bromide is used, note any water of crystallization and account for this water in the amount of sodium bromide used as well as in the amount of water used in the following step.

Prepare a solution of sulfuric acid by adding 55 ml conc sulfuric acid to 30 ml cold water [This is where you account for water of crystallization in NaBr-AvB]. The acid solution is cooled and then added to the reaction flask with good mixing.

Reflux the reaction mixture for 30 minutes after which ABOUT 95% OF THE POSSIBLE PRODUCT WILL HAVE BEEN PRODUCED [my emphasis-AvB]. Further reaction for another 30 minutes only provides 1-2 grams of additional product.

Set the reaction for downward distillation and distill until no more oily product is observed. Separate the product from the aqueous layer. Wash the crude butyl bromide with 25 ml cold conc sulfuric acid, followed by 25 ml 1M NaOH then water. Dry the product over about 3 grams of CaCl2 or MgSO4 letting the product dry for 1 day or more. The dried product needs to be free of emulsified water. If during the following distillation any water is observed in the distillate, the product must be redried.

Finally, filter and distill collecting pure n-butyl bromide bp 99-103. Estimated yield, 45 grams or ca 88%.


Hope this helps - AvB

UC235 - 2-4-2016 at 21:02

The very first Orgsyn prep (Vol 1, 1921, pg 3 (http://www.orgsyn.org/Content/pdfs/procedures/CV1P0025.pdf)) is relevant here. A series of simple alkyl bromides are produced by various methods. BuBr is produced in 90-95% yield by three different methods. However, the scale is very large and mechanical/evaporative losses are thus minimized.

I have run several preps directly from or modified from this paper. 2 runs of ethyl bromide, 2 isopropyl bromide, 6-bromohexanoic acid and all have worked splendidly. I strongly suspect that chasing any string of references back ends with either this orgsyn paper or it's references.

DJF90 - 3-4-2016 at 03:35

Quote: Originally posted by ScienceHideout  
DJ- I plan on reporting mass in the paper, however for this specific case I need to use density calculations. My balance reads milligrams, and therefore has a capacity of 120g. I couldn't have possibly weighed the sample in a plastic cup! :D

I see. I've had similar issues with exceeding the balance capacity before, myself. My advice is to invest in a larger capacity balance with less resolution. Personally, I have a pair of Mettler balances, 160x0.001 g and 1600x0.01 g. I'm sure even 0.1 g resolution would be fine as a large scale balance, but I got a good deal. It should not be too expensive to find something suitable. The other alternative is to work within the limits of your equipment, but that doesn't sound very fun, does it?
Quote: Originally posted by ScienceHideout  

I believe that order of addition is everything. In the lab I work in, I have gone from 5% yields to 90% yields just from the order of addition (well, in extreme cases like Swern oxidation). My thinking is that if the acid and bromide are mixed FIRST, then it will form HBr which will dissolve in the water I added. When the alcohol is added dropwise, the few molecules of alcohol are literally 'swimming' in an ocean of HBr and given no choice but to SN2 instead of turn to ether. When I added the acid to the NaBr, I did it very slowly and the acid was very cold. I didn't notice too many fumes, but the solution turned orange.

I agree that order of addition can significantly affect the outcome of a reaction. However, to quote myself (with added emphasis):
Quote: Originally posted by DJF90  
I'm not sure how much of an issue the order of addition is in this case. Alkene and ether formation are really only an issue at elevated temperature with primary alcohols, so as long as the components are brought together at eg. room temperature it shouldn't make much difference.

To elaborate using ethanol as an example (because I'm familiar with the data), the formation of ether is only appreciable at temperatures exceeding 100 *C, and becomes preparatively useful at ca 140 *C. Ethylene formation occurs at a higher temperature (ca 180 *C) I'd be willing to bet that butanol behaves similarly, and your worries about ether formation are unfounded. I guess we'll never know without access to a GC.
Quote: Originally posted by AvBaeyer  
I have a revised edition of the Robertson’s “Laboratory Practice of Organic Chemistry” (4th edition, 1962) which (more or less) corresponds to reference 1 in the Joseph, et al. J Chem Educ paper cited earlier.

Thanks again for that Av. It looks to me as if the text was revised to incorporate the findings of the J. Chem. Ed. paper, because the portionwise addition of sulfuric acid and longer reflux period are no longer present.

[Edited on 3-4-2016 by DJF90]

ScienceHideout - 3-4-2016 at 09:02

So I was busy cleaning the lab this morning after all my hard work. I think that my BuBr yield is more than satisfactory, and I will go on to the next step. Maybe after I improve the grignard yield I will come back to the bromination.

But my next idea is to quantify the amount of water in my ether and THF. The idea is simple. First I will dry the solvent over sodium (scary, but whatever) and that will be my standard for a completely anhydrous solvent. Then, I will add a scoop of anhydrous CuSO4 and sonicate. I will pop it into my spectrometer and find the transmittance in the blue range. Then, I will take .95 mL of the anhydrous stuff and mix it with .05 mL of water. Again I will add a scoop of copper sulfate, but this time the transmittance will be higher. Lastly, I will take some from the bottle and then mix it with copper sulfate and sonicate. Then I can estimate the amount of water using Beers law.

Magpie - 3-4-2016 at 09:30

Quote: Originally posted by ScienceHideout  

But my next idea is to quantify the amount of water in my ether and THF. The idea is simple. First I will dry the solvent over sodium (scary, but whatever) and that will be my standard for a completely anhydrous solvent.


I have always dried my ether (recovered from starting fluid) over 3A mole sieves thinking that my sodium was too precious. However, use of sodium is a standard way for obtaining absolute ether. Brewster tells how to do it and so does Vogel. If the solvent only has a trace of water then use of sodium should not be scary. Others can advise you better than me.

[Edited on 3-4-2016 by Magpie]

Magpie - 5-4-2016 at 16:36

I thought the comparison of various procedures for making n-BuBr very interesting and the expected yields showed considerable variation. To provide further comparison I constructed an Excel spreadsheet comparing 3 student lab procedures from books that I have. Three observations jumped out at me:

1. The two older procedures have two distillations, one immediately following the reaction at reflux. The most recent one does not.

2. NaBr*2H20 may be a common form of NaBr, making me wonder about my pool chemical grade sodium bromide.

3. The amount of chemicals used has a half-life of 30 years.

My Excel spreadsheet is attached. Feel free to add to it the parameters of your procedure(s).

Attachment: Comparison of Some Methods for Making n-Butyl Bromide.xls (25kB)
This file has been downloaded 782 times

ScienceHideout - 5-4-2016 at 17:40

Thanks, I will take a look at this more during my free time.

As far as bromide, I suppose one thing that I can do is run a test. 1g pool-grade NaBr in excess AgNO3- how much precipitate does it produce?

Alice - 30-8-2016 at 14:19

Twelve principles of Green Chemistry:

1. It is better to prevent waste than to treat or clean up waste after it is formed.

2. Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.

3. Wherever practicable, synthetic methodologies should be designed to use and generate substances that possess little or no toxicity to human health and the environment.

4. Chemical products should be designed to preserve efficacy of function while reducing toxicity.

5. The use of auxiliary substances (e.g. solvents, separation agents, etc.) should be made unnecessary wherever possible and innocuous when used.

6. Energy requirements should be recognized for their environmental and economic impacts and should be minimized. Synthetic methods should be conducted at ambient temperature and pressure.

7. A raw material or feedstock should be renewable rather than depleting wherever technically and economically practicable.

8. Reduce derivatives – Unnecessary derivatization (blocking group, protection/deprotection, temporary modification) should be avoided whenever possible.

9. Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.

10. Chemical products should be designed so that at the end of their function they do not persist in the environment and break down into innocuous degradation products.

11. Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances.

12. Substances and the form of a substance used in a chemical process should be chosen to minimize potential for chemical accidents, including releases, explosions, and fires.

https://en.wikipedia.org/wiki/Green_chemistry#Principles


THF is a suspected cancerogen and forms peroxides. Greener alternatives are 2-MeTHF and cyclopentyl methyl ether with the latter having resistance to peroxide formation. The grignard reaction is not particularly a green reaction, it affords magnesium as stochiometric reagent instead of a catalyst for example. Of course a reaction can hardly suit all the criteria and there will be some trade-off between these criteria in most cases.

It's even more difficult to apply the green chemistry principles in an amateur scenario, so I would prefer the same reaction. Nevertheless, I would use diethyl ether, because it has a lower health impact.



[Edited on 30-8-2016 by Alice]

Protium-1 - 25-9-2016 at 22:03

I too was just about to reference the 12 principles of Green Chemistry, though I had sourced from the EPA website rather than Wiki...
https://www.epa.gov/greenchemistry/basics-green-chemistry#tw...

Please, for the love of all that is sacred, you've gotta stop calling this a "Green Synthesis."


[Edited on 9-26-2016 by Protium-1]

Calling out premise, asking for reference

Protium-1 - 25-9-2016 at 23:48

Chemists often praise the usefulness of their product by describing the context in which it solves or circumvents some other problem, or supersedes the prior art in some way. This you have done, it seems you describe tert-alcohols as a participant in a low-temp, non-hazardous-material-producing reaction to obtain Elemental Potassium and possibly Sodium in certain aliphatic solvents. Further, it seems that this remains your sole premise for calling this a "Green Reaction."

Aside from the argument that your actual reaction(s) involves very non-green solvents like THF, and aside from the fact that you've clearly put a lot of work into this, I find it very problematic your whole premise as stated in the Abstract and Intro and believe it possible you may have misunderstood something you had read in passing.

Please, correct me where I am wrong, and please DO provide at minimum one solid Reference.

I contend that there is no such reaction involving any tertiary-alcohol, nonetheless 3-methyl-heptan-3-ol, either as a reactant, co-solvent, catalyst, or otherwise participant in said reaction that produces elemental alkali metals such as Potassium or Sodium from their cationic form.

Assuming you can even get K+ ions to dissolve in aliphatic solution, by way of PTC or whatever, if a tert-alcohol itself were to be the reducing agent for producing elemental Potassium from K+ ions, the tert-alcohol would itself be oxidized. I pray you tell me what would the oxidized product of the tert-alcohol be?

If the tert-alcohol were acting merely as a cosolvent, catalyst, or otherwise spectator, any elemental alkali metal produced by unspecified reaction would simply deprotonate any remaining tert-alcohol, evolving hydrogen of course, and become ionized again.

I have tried to keep this short by not going into detail how tert-alcohols can for example be dehydrated and further oxidized into ketones and carboxylic acid by conc. aq. HNO3 because those products to would simply deprotonate in the presence of elemental alkali metals, once again to produce ions.

I hereby assert (at the risk of looking like a fool when the author of this paper provides any reputable reference otherwise) that tert-alcohols do not participate in any reaction that produces elemental alkali metals from their cations in any aliphatic (or any at all) solvent.

Unless shown otherwise, it should remain clear to see that the stated usefulness (and therefore the entire stated premise for this publication) of this 3-methyl-heptan-3-ol as a "Green" alternative to the electrolytic production of alkali metals is totally bogus.

[Edited on 9-26-2016 by Protium-1]

HeYBrO - 26-9-2016 at 00:54

Quote: Originally posted by Protium-1  
Chemists often praise the usefulness of their product by describing the context in which it solves or circumvents some other problem, or supersedes the prior art in some way. This you have done, it seems you describe tert-alcohols as a participant in a low-temp, non-hazardous-material-producing reaction to obtain Elemental Potassium and possibly Sodium in certain aliphatic solvents. Further, it seems that this remains your sole premise for calling this a "Green Reaction."

Aside from the argument that your actual reaction(s) involves very non-green solvents like THF, and aside from the fact that you've clearly put a lot of work into this, I find it very problematic your whole premise as stated in the Abstract and Intro and believe it possible you may have misunderstood something you had read in passing.

Please, correct me where I am wrong, and please DO provide at minimum one solid Reference.

I contend that there is no such reaction involving any tertiary-alcohol, nonetheless 3-methyl-heptan-3-ol, either as a reactant, co-solvent, catalyst, or otherwise participant in said reaction that produces elemental alkali metals such as Potassium or Sodium from their cationic form.

Assuming you can even get K+ ions to dissolve in aliphatic solution, by way of PTC or whatever, if a tert-alcohol itself were to be the reducing agent for producing elemental Potassium from K+ ions, the tert-alcohol would itself be oxidized. I pray you tell me what would the oxidized product of the tert-alcohol be?

If the tert-alcohol were acting merely as a cosolvent, catalyst, or otherwise spectator, any elemental alkali metal produced by unspecified reaction would simply deprotonate any remaining tert-alcohol, evolving hydrogen of course, and become ionized again.

I have tried to keep this short by not going into detail how tert-alcohols can for example be dehydrated and further oxidized into ketones and carboxylic acid by conc. aq. HNO3 because those products to would simply deprotonate in the presence of elemental alkali metals, once again to produce ions.

I hereby assert (at the risk of looking like a fool when the author of this paper provides any reputable reference otherwise) that tert-alcohols do not participate in any reaction that produces elemental alkali metals from their cations in any aliphatic (or any at all) solvent.

Unless shown otherwise, it should remain clear to see that the stated usefulness (and therefore the entire stated premise for this publication) of this 3-methyl-heptan-3-ol as a "Green" alternative to the electrolytic production of alkali metals is totally bogus.

[Edited on 9-26-2016 by Protium-1]

http://www.sciencemadness.org/talk/viewthread.php?tid=14970
Edit: just so its easier, here is the patent referring to the synthesis of potassium https://www.google.com/patents/US4725311

also, in the first page of the thread it was challenged whether this is a green synthesis.

[Edited on 26-9-2016 by HeYBrO]

[Edited on 26-9-2016 by HeYBrO]

[Edited on 26-9-2016 by HeYBrO]