KBS14-9 - Methyl esterification of ferrocenecarboxylic acid

Link to HIRAC and master page. Method developed from Julius Adamson.

Reaction Scheme

Outcome

333.4 mg (1.37 mmol), 34% (impure)

After columning: 166.1 mg (0.681 mmol), 17%

Poor outcome - likely had product remaining in aqueous layer.

Notes

Small amount of product volatilises and ended up in solvent trap after rotovapping to remove methanol (confirmed to be product by TLC and NMR).

("?" = red colour crystals from solvent trap, "Fc" = ferrocenecarboxylic acid SM, "14" = sample of KBS14 ferrocenyl methyl ester)

KBS14-9 bump_1.zip

KBS14-9 bump processed.pdf

KBS12-2 - Click coupling of azidoadamantane and bis-propargyl cyclam CONTINUED FROM HONOURS

Continuation from Honours work.

Link to HIRAC and original method.

Reaction scheme

Synthetic Chemistry Case Studies

Include embedded images e.g. of experimental results or reaction schemes

Link to past attempts #10 or master pages with overviews of your work
Link to external webpages like relevant papers - e.g. Spain et al., 2018
Include experimental data and safety documents - e.g. KBS16-4 Proton NMR.zip
Edit posts from your mobile device!

KBS20-1 - Boc protection of 1,8-diaminooctane

Link to HIRAC and master page.

KBS3 Generic boc protection of 1,n-diamine.docx

Reaction scheme

1.241 g (3.60 mmol), 100%

Breaking Good SSP compounds 2022 - 8A

Breaking Good SSP compounds - 8J

KBS11-5 - Azidation of 1-bromoadamantane

Link to HIRAC, original method and master page.

HIRAC doc file: KBS11 Azidation of 1-adamantane.docx

Reaction Scheme

Outcome

N/A - solids recovered appeared to be starting material rather than desired product

Notes

Altering solvent from THF to DMF (after repeated failure with THF). Remember to wash out DMF (5 x wash with water).

KBS15-4 - Reduction of ferrocenyl methyl ester

Link to HIRAC and master page.

Ferrocenylmethanol synthesis .docx

Reaction Scheme

Outcome

356.7 mg (1.65 mmol), 98%

KBS11-4 - Azidation of 1-bromoadamantane

Link to HIRAC, original method and master page.

KBS11 Azidation of 1-adamantane.docx

Reaction Scheme

Outcome

N/A

Notes

No evidence of product in NMR. Abandoned.

KBS16-5 - Azidation of ferrocenylmethanol

Link to HIRAC, original method and master page.

KBS16 Ferrocenylmethanol to azidomethylferrocene DPPA.docx

Previous attempt was #17.

Reaction Scheme

Outcome

KBS17-4 - Propargylation of 1,6-diaminohexane

Link to HIRAC, original method and master page.

Last attempt is #19.

Next attempt is #23

KBS17 Generic propargylation of 1,n-diamine.docx

Reaction Scheme

Using 1:5 mixture of DMF:THF as solvent.

Outcome

62% overall

Mono product: 164 mg (0.462 mmol), 36%
Bis product: 129 mg (0.330 mmol), 26%

KBS15-6 - Reduction of ferrocenyl methyl ester

Link to HIRAC and master page.

Last attempt was #15.

Ferrocenylmethanol synthesis .docx

Reaction Scheme

Outcome

354 mg (1.64 mmol), 104% - traces of ethyl acetate but ready to carry through.

Notes

N/A

KBS24-1 - Click coupling of bis-propargyl diaminohexane and azidomethylferrocene

Link to HIRAC, original method and [master page].

KBS24 Linear amine click coupling with azidomethylferrocene.docx

Reaction scheme

Outcome

62.1 mg (0.071 mmol), 70%

KBS16-3 - Azidation of ferrocenylmethanol

Link to HIRAC, original method and master page.

KBS16 Ferrocenylmethanol to azidomethylferrocene DPPA.docx

Reaction Scheme

Outcome

110 mg, 40%

Notes

TLC indicated reaction completion - is low yield due to loss during purification?

KBS11-6 - Azidation of 1-bromoadamantane

Link to HIRAC, original method and master page.

HIRAC doc file: KBS11 Azidation of 1-adamantane.docx

Reaction Scheme

Outcome

N/A - crude product appeared to be desired compound, but was lost in purification

Notes

Need to optimise purification techniques.

KBS17-7 - Propargylation of 1,6-diaminohexane

Link to HIRAC, original method and master page.

Last attempt is #28

Next attempt is #33

KBS17 Generic propargylation of 1,n-diamine.docx

Reaction Scheme

Using 1:5 mixture of DMF:THF as solvent.

Outcome

KBS10-3 - Bridge hydrolysis and boc protection of bis-propargyl cyclam

Link to HIRAC, original method and master page.

KBS10 Bridge hydrolysis + boc protection of bis-propargyl cyclam.docx

Reaction Scheme

Outcome

1.805 g (3.79 mmol), 128%

Notes

N/A

KBS17-3 - Propargylation of 1,6-diaminohexane

Link to HIRAC, original method and master page.

Next attempt is #22.

KBS17 Generic propargylation of 1,n-diamine.docx

Reaction scheme

Molecular weights
SM = 316.44
Product = 392.54
Predicted side product (mono-propargylated) = 354.49

Outcome

Only side product recovered (175 mg, 38%).

KBS14-8 - Methyl esterification of ferrocenecarboxylic acid

Link to HIRAC and master page. Method adapted from Shieh et al., 2002.

KBS14 ALTERNATIVE (DBU method) .docx

Reaction Scheme

Outcome

155.4 mg (0.637 mmol), 70% (still slightly wet)

Breaking Good SSP compounds - 8C

KBS14-6 - Methyl esterification of ferrocenecarboxylic acid

Link to HIRAC and master page. Method developed from Julius Adamson.

Ferrocenyl methyl ester synthesis .docx

Reaction Scheme

Outcome

715 mg (2.93 mmol), 67%

Notes

Further extractions would likely improve yield, but are time consuming. Consider alternative method here for next time.

KBS17-10 - Propargylation of 1,6-diaminohexane

Link to HIRAC, original method and master page.

Last attempt is #45.

KBS17 Generic propargylation of 1,n-diamine.docx

Reaction Scheme

Changes to make

Using DMF with 100 ppm water (i.e. properly dry - tested on Karl Fischer titrator)
propargyl bromide was passed through 2cm of neutral alumina)

KBS18-1 - Click coupling of azidomethylferrocene and bis-propargyl cyclam

Link to HIRAC, original method and master page

Reaction scheme

Outcome

217 mg (0.227 mmol), 91%

Breaking Good SSP compounds - 8G

Breaking Good SSP compounds 2022 - 8E

Breaking Good SSP compounds - 8H

Breaking Good SSP compounds 2022 - 8F

KBS25-1 - Propargylation of 1,6-diaminohexane

Link to HIRAC, original method and master page.

KBS25 Propargylation of unprotected 1,6-diaminohexane.docx

Reaction Scheme

Attempting to alkylate unprotected amine

KBS16-4 - Azidation of ferrocenylmethanol

Link to HIRAC, original method and master page.

KBS16 Ferrocenylmethanol to azidomethylferrocene DPPA.docx

Next attempt is #27.

Reaction Scheme

Outcome

236 mg (0.978 mmol), 64%

Notes

KBS16-2 - Azidation of ferrocenylmethanol

Link to HIRAC and original method.

KBS16 Ferrocenylmethanol to azidomethylferrocene DPPA.docx

Reaction Scheme

Outcome

49 mg (0.204 mmol), 45%

Notes

TLC indicated reaction completion - is low yield due to loss during purification?

KBS15-5 - Reduction of ferrocenyl methyl ester

Link to HIRAC and master page.

Next attempt is #18

Ferrocenylmethanol synthesis .docx

Reaction Scheme

Outcome

332 mg (1.54 mmol), 95%

Ready to carry through to azidation.

Notes

Breaking Good SSP compounds 2022 - 8B

NMR

BG_8B pure_1.zip

BG_8B pure processed.pdf

Looks good, minor solvent impurities between 1-3 ppm.

LRMS

BG_8B.d.zip
BG_8B.pdf

KBS17-5 - Propargylation of 1,6-diaminohexane

Link to HIRAC, original method and master page.

Last attempt is #22.

KBS17 Generic propargylation of 1,n-diamine.docx

Reaction scheme

Outcome

20 mg (0.0510 mmol), 10%

Overall, it does not seem to be worth attempting to "re-react" the mono product to obtain more of the bis product, as the yield was so poor. In future, the reaction will simply be uspcaled, though optimisation of solvents etc will still be attempted.

Breaking Good SSP compounds 2022 - 8I

KBS9-3 - Bis-propargylation of bridged cyclam

Link to HIRAC, original method and master page.

KBS9 Bis-propargylation of bridged cyclam.docx

Reaction Scheme

Outcome

1.9539 g (3.23 mmol), 72%

Notes

KBS11-3 - Azidation of 1-bromoadamantane

Link to HIRAC, original method and master page.

KBS11 Azidation of 1-adamantane.docx

Reaction Scheme

Outcome

54 mg (0.305 mmol), 7%

Notes

Not fully purified. Not pursued due to human error (spillage) resulting in low yield.

KBS22-1 - Linear click coupling of bis-propargyl diaminohexane and azidoadamantane

Link to HIRAC, original method and [master page].

KBS22 Linear amine click coupling with azidoadamantane.docx

Reaction scheme

Outcome

256 mg (0.343 mmol), 109%

KBS19-1 - Deprotection of bis-methylferrocenylcyclam

Link to HIRAC, original method and [master page.

KBS19 Deprotection of bis-methylferrocene cyclam.docx

Reaction scheme

Outcome

137 mg - impure

KBS17-8 - Propargylation of 1,6-diaminohexane

Link to HIRAC, original method and master page.

Last attempt is #32. Next attempt is #45.

KBS17 Generic propargylation of 1,n-diamine.docx

Reaction Scheme

Using DMF as solvent. Add NaH portionwise (and use only 3 equiv.), allow 1-2 hrs reaction time and cool reaction to 0 C before adding propargyl bromide.

Outcome

KBS17-11 - Propargylation of 1,6-diaminohexane

Link to HIRAC, original method and master page.

Last attempt is #45.

KBS17 Generic propargylation of 1,n-diamine.docx

Reaction Scheme

Changes to make

Using DMF with 100 ppm water (i.e. properly dry - tested on Karl Fischer titrator)
add 15-crown-ether

Breaking Good SSP compounds - 8G

KBS14-7 - Methyl esterification of ferrocenecarboxylic acid

Link to HIRAC and master page. Method adapted from Shieh et al., 2002.

KBS14 ALTERNATIVE (DBU method) .docx

Reaction Scheme

Outcome

Mass of 123.3 mg (unpurified, containing more SM than product). May be due to not allowing reaction to go to completion - next time, will add 1.2 equiv. of DBU at beginning and possibly allow longer reaction times.