NMR assay for 1-isopropyl-6,7-dimethoxyisochroman not optimised

[katb]

OPS reaction carried out twice: ~100 mg scale, 60 C, 1 h (http://bit.ly/15C7KLy, http://bit.ly/1dsV0rC).

Calculated vs isolated yields: KAB68-2: 80.7 mg (51%) vs 62.8 mg (40%) KAB68-3: 83.4 mg (58%) vs 72.2 mg (51%)

[mattodd]

Calcd yield depends on signal used? On Jul 13, 2013 12:37 PM, "Katrina Badiola" notifications@github.com wrote:

OPS reaction carried out twice: ~100 mg scale, 60 C, 1 h ( http://bit.ly/15C7KLy, http://bit.ly/1dsV0rC).

Calculated vs isolated yields: KAB68-2: 80.7 mg (51%) vs 62.8 mg (40%) KAB68-3: 83.4 mg (58%) vs 72.2 mg (51%)

— Reply to this email directly or view it on GitHubhttps://github.com/opensourcecatalysis/KatOPS/issues/10 .

[katb]

The 1-position has the most resolved signal. The only other signals that are sort of clear are the two aromatic signals, one of the methyl doublets and one of the CH2 protons. Calculated yields using those signals are slightly higher; perhaps slight baseline overlap.

[mattodd]

Meaning that it's likely that the problem lies in the isolation? Perhaps a difficult column? There's an explanation here - what is it? If we can't find it we're going to have to see if the discrepancy is reliable - i.e. similar order of magnitude in the same direction - and then qualify the results we find with a statement to that effect but that's sub-optimal from a cosmic knowledge perspective.

On 13 July 2013 12:58, Katrina Badiola notifications@github.com wrote:

The 1-position has the most resolved signal. The only other signals that are sort of clear are the two aromatic signals, one of the methyl doublets and one of the CH2 protons. Calculated yields using those signals are slightly higher; perhaps slight baseline overlap.

— Reply to this email directly or view it on GitHubhttps://github.com/opensourcecatalysis/KatOPS/issues/10#issuecomment-20913653 .

MATTHEW TODD | Senior Lecturer and Honours Coordinator School of Chemistry | Faculty of Science

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[katb]

The columns are easier than purifying 6,7-dimethoxy-1-(4-nitrophenyl)isochroman. The KAB68-2 column wasn't my best, but I was uber careful with the KAB68-3 column. Not sure. Could be isolation issues, or maybe something to do with the standard curve? Shouldn't make a difference if the product I used to construct the curve was a solid? It takes a couple of days in the fridge to solidify. Although, if anything, I would have thought that might give the reverse result i.e. higher isolated yield, lower calculated yield. I'm going to have to do this reaction, assay vs isolated again, aren't I? Not sure if I should do a triplicate reaction, or maybe increase the scale or something. To work out the discrepancy, won't I need a cluster of results to try and fit a curve? Sounds a little bit time consuming.

[mattodd]

First thing to try, because it's quickest, is to check whether changing the relaxation time during the NMR experiment makes any difference. Talk to Ian. We've previously seen that make a lot of difference in some cases. So run the NMR spectra for yield calculations with variation in that parameter and see if it makes a difference to the numbers. This method has to be pretty good if it's to be something we are going to recommend to others. Aside from this assay, though, the protocol pages are both done? Shall I examine one last time, then send an email?

On 13 July 2013 22:43, Katrina Badiola notifications@github.com wrote:

The columns are easier than purifying 6,7-dimethoxy-1-(4-nitrophenyl)isochroman. The KAB68-2 column wasn't my best, but I was uber careful with the KAB68-3 column. Not sure. Could be isolation issues, or maybe something to do with the standard curve? Shouldn't make a difference if the product I used to construct the curve was a solid? It takes a couple of days in the fridge to solidify. Although, if anything, I would have thought that might give the reverse result i.e. higher isolated yield, lower calculated yield. I'm going to have to do this reaction, assay vs isolated again, aren't I? Not sure if I should do a triplicate reaction, or maybe increase the scale or something. To work out the discrepancy, won't I need a cluster of results to try and fit a curve? Sounds a little bit time consuming.

— Reply to this email directly or view it on GitHubhttps://github.com/opensourcecatalysis/KatOPS/issues/10#issuecomment-20919354 .

MATTHEW TODD | Senior Lecturer and Honours Coordinator School of Chemistry | Faculty of Science

THE UNIVERSITY OF SYDNEY Rm 519, F11 | The University of Sydney | NSW | 2006 T +61 2 9351 2180 | F +61 2 9351 3329 | M +61 415 274104 E matthew.todd@sydney.edu.au | W http://sydney.edu.au/science/chemistry/research/todd.html

CRICOS 00026A This email plus any attachments to it are confidential. Any unauthorised use is strictly prohibited. If you receive this email in error, please delete it and any attachments.

[katb]

The standard curve won't be applicable with an altered D1 (relaxation time). The assay D1 parameter is set at 2 sec. It's not quantitative, but the standard curve was linear (analogous to the other NMR assays). If I change that parameter, I'm pretty sure I need to construct another standard curve with the increased D1. Unless I can get the TCE standard and the isochroman to completely relax (probably more than 10 seconds) but I can do an inversion experiment to work out parameters for getting the integrals quantitative, in which case, I shouldn't need a standard curve. I'll check with Ian on Monday. It's great when it works. I've been able to get some really quick results, but it's annoying if it doesn't. The other downside is it is product specific. Wouldn't be ideal to have to construct a standard curve for every product for assay. I'll see if I can get a solid quantitative NMR experiment to correlate amount of TCE to product. RE protocol pages: Yep. Have a look one last time (http://bit.ly/12CTfBD). Just the NMR assay and I don't have the chiral HPLC trace for 1-isopropyl-6,7-dimethoxyisochroman. Waiting on results from UQ, but I forgot to ask them if I can post the results. Otherwise, I've got the chiral HPLC booked on Wednesday.