New issue

Have a question about this project? Sign up for a free GitHub account to open an issue and contact its maintainers and the community.

By clicking “Sign up for GitHub”, you agree to our terms of service and privacy statement. We’ll occasionally send you account related emails.

Already on GitHub? Sign in to your account

Taking Over Synthesis of "The Ketone" - Haverford College Superlab Q2 #460

Open
doravont opened this Issue Nov 4, 2016 · 4 comments

Comments

Projects
None yet
3 participants
@doravont

doravont commented Nov 4, 2016

Liana Alves ( @lianaboo3 ) and I will be taking over Steph Terrell and John Halifax's work on "The Ketone", and below is their most recent proposed scheme:
screen shot 2016-11-04 at 10 11 39 am

We have begun the first step based off of this paper: Collot, A.-G.; Courtney, M.; Coyne, D.; Eustace, S. E.; O’Ferrall, R. A. M. The Journal of Organic Chemistry J. Org. Chem. 2009, 74 (9), 3356–3369.

The experimental section we are following reads:
Phenylethylacetate
(5.49 g, 0.033 mol) and methyl pyrazinoate (4.0 g 0.027
mol) in dry THF (30 mL) were added dropwise with stirring to a
freshly prepared solution of sodium ethoxide (0.75 g sodium, 0.033
mol) in 12 mL of ethanol. The solution turned orange and then
dark red during the course of the addition. It was heated to reflux
for 3 h and after cooling poured into water (200 mL). Unreacted
starting material was extracted with chloroform and the solution
acidified with concentrated sulfuric acid
to give a brown semisolid
which was extracted with chloroform (3 × 100 mL). The
product was dried (Na2SO4) and evaporated to give a brown oil
which solidified on standing (4.05 g, 60%). A portion of the product
(2.5 g) was purified by flash chromatography on silica. Elution with
10:2 hexane/ethyl acetate gave 1.1 g of white solid.

We were hoping for some clarification regarding the italicized part, since it is a bit unclear as to which solution they are referring to. When we attempted these steps, we accidentally added both water and chloroform to an extraction funnel, followed by concentrated sulfuric acid. However, Rob Broadrup read it as doing the extraction of chloroform first to remove starting material in the organic layer, and then adding sulfuric acid to the remaining aqueous layer with product. Since we already had water, chloroform and acid in the extraction funnel, we went ahead and did the extraction and collected the organic layer, dried it with Na2SO4, and concentrated it under reduced pressure, yielding a dark brown liquid.

Our lab notebook can be found here: http://malaria.ourexperiment.org/ketone_q2

@mattodd

This comment has been minimized.

Show comment
Hide comment
@mattodd

mattodd Nov 8, 2016

Member

Hi @doravont - welcome aboard! Could you take a quick look at some previous comments I wrote about this "hand-over" phase and see if there's anything we (as onlookers) could benefit from. I like the way that you're framing this Issue, i.e. as a question that can be closed. But remember not to orphan this issue if you can help it, e.g. by installing a link to this page in your lab notebook.

I would read this procedure as: chloroform is added to the aqueous layer that has previously been separated from the organic layer. But it's not a well-written procedure, since "extraction" normally implies something you want. Here I'd take this as meaning that unreacted S/M is removed from the aqueous phase, and the aqueous phase is then acidified.

Member

mattodd commented Nov 8, 2016

Hi @doravont - welcome aboard! Could you take a quick look at some previous comments I wrote about this "hand-over" phase and see if there's anything we (as onlookers) could benefit from. I like the way that you're framing this Issue, i.e. as a question that can be closed. But remember not to orphan this issue if you can help it, e.g. by installing a link to this page in your lab notebook.

I would read this procedure as: chloroform is added to the aqueous layer that has previously been separated from the organic layer. But it's not a well-written procedure, since "extraction" normally implies something you want. Here I'd take this as meaning that unreacted S/M is removed from the aqueous phase, and the aqueous phase is then acidified.

@mattodd

This comment has been minimized.

Show comment
Hide comment
@mattodd

mattodd Nov 21, 2016

Member

Hi - great that you're recording data in the ELN. Just a plea: can you add schemes to each ELN entry so we can see what reaction you're talking about? And rather than saying "Step 1" etc, could you give reactions unique identifiers, so that we can track which reaction/product is which? So something like DvT-1-2 for Dora's second attempt at her first reaction, etc?

Let us all know how you're getting on and whether there's anything people can help you with.

Member

mattodd commented Nov 21, 2016

Hi - great that you're recording data in the ELN. Just a plea: can you add schemes to each ELN entry so we can see what reaction you're talking about? And rather than saying "Step 1" etc, could you give reactions unique identifiers, so that we can track which reaction/product is which? So something like DvT-1-2 for Dora's second attempt at her first reaction, etc?

Let us all know how you're getting on and whether there's anything people can help you with.

@mattodd

This comment has been minimized.

Show comment
Hide comment
@mattodd

mattodd Nov 21, 2016

Member

Also, I do worry that this synthetic route is quite steppy - it'll take you a while to execute all the steps. What about the umpolung addition of an acyl anion equivalent to the chloro-intermediate that people have been able to make reasonably easily at Haverford. Could be much faster, though the coupling is non-trivial.

Member

mattodd commented Nov 21, 2016

Also, I do worry that this synthetic route is quite steppy - it'll take you a while to execute all the steps. What about the umpolung addition of an acyl anion equivalent to the chloro-intermediate that people have been able to make reasonably easily at Haverford. Could be much faster, though the coupling is non-trivial.

@MFernflower

This comment has been minimized.

Show comment
Hide comment
@MFernflower

MFernflower Dec 6, 2016

Contributor

The chlorinated pyrazine ester can be grabbed from alfa (USA only) for ~90 USD a gram (provided the chlorine is not too reactive)

https://www.alfa.com/en/catalog/H66682/

@mattodd @doravont @rbroadrup-HC

Contributor

MFernflower commented Dec 6, 2016

The chlorinated pyrazine ester can be grabbed from alfa (USA only) for ~90 USD a gram (provided the chlorine is not too reactive)

https://www.alfa.com/en/catalog/H66682/

@mattodd @doravont @rbroadrup-HC

Sign up for free to join this conversation on GitHub. Already have an account? Sign in to comment