PLANNED MAINTENANCE

There will be scheduled maintenance work beginning on Wednesday 26th February 2020 from 11:00 AM through to 12.00 PM (GMT).

During this time, you may not be able to log into ChemSpider Synthetic Pages. We apologise for any inconvenience this might cause and thank you for your patience.

Print version Print setup

Coupling of 2-bromobenzoic acid with 4-methoxythiophenol under Ullmann conditions; 2-((4-Methoxyphenyl)thio)benzoic acid

SyntheticPage 846
DOI: 10.1039/SP846
Submitted Aug 23, 2018, published Oct 15, 2018
Robert Smith (rbsmith@uclan.ac.uk), Mariyah Sajjad (), Mark Wainwright (M.Wainwright@ljmu.ac.uk), Joshua Gettins ()
A contribution from Smith Group


			Reaction Scheme: <IMG src="/images/empty.gif"><IMG alt="" src="/images/empty.gif">Coupling of <SPAN id=csm1547225500421 title="2-bromobenzoic acid" class=csm-chemical-name grpid="1">2-bromobenzoic acid</SPAN> with <SPAN id=csm1547225506699 title=4-methoxythiophenol class=csm-chemical-name grpid="2">4-methoxythiophenol</SPAN> under Ullmann conditions<IMG alt="" src="/images/empty.gif"><IMG src="/images/empty.gif">

Chemicals Used

2-Bromobenzoic Acid (Sigma Aldrich)

4-Methoxythiophenol (Sigma Aldrich)

Anhydrous potassium carbonate (Sigma Aldrich)

100 mesh copper bronze (Alfa Aesar)

Procedure

A mixture of 2-bromobenzoic acid (10.63 g, 52.9 mmol), 4-methoxythiophenol (6.57 g, 52.9 mmol), K2CO3 (14.60 g, 105.8 mmol) and powdered Cu bronze (1.71 g, 26.44 mmol) in DMF (100 mL) was stirred at reflux for 6 hours. Upon cooling, the reaction mixture was poured into ice (500 g) and acidified with concentrated HCl to pH=4 giving a white solid.  The solid was isolated and dried at the vacuum pump** to yield 2-((4-methoxyphenyl)thio)benzoic acid (6.10 g, 44%) as a white solid.

Author's Comments

*** Round bottom flask fitted with a reflux condenser was used which fitted snuggly into a metal heating block.  A thermocouple was used to control the temperature and reaction was open to the air (no inert gasses were required).  Stirring was accomplished using a stirring bar which was controlled from the hot plate.  The whole reaction was accomplished in the open air without the need of dry/inert conditions.
** pH determined using universal indicator paper.
***No purification required, but the authors suggest holding the compound at the vacuum pump for at least an hour until dry.

Data

1H NMR (400 MHz, DMSO-d6) δ 13.27 (s, 1H), 7.93 (dd, J = 7.7, 1.5 Hz, 1H), 7.47 (d, J = 8.5 Hz, 2H), 7.36 – 7.29 (m, 1H), 7.15 (td, J = 7.5, 1.2 Hz, 1H), 7.06 (d, J = 8.6 Hz, 2H), 6.65 (dd, J = 8.3, 1.2 Hz, 1H), 3.81 (s, 3H). 13C NMR (101 MHz, DMSO) δ 167.80, 160.80, 143.95, 137.89, 132.81, 131.42, 127.13, 126.37, 124.57, 122.41, 116.15, 55.77. MS m/z: 261.02 [M+].


Lead Reference

Wang, C., Jiang, H., Jin, J., Xie, Y., Chen, Z., Zhang, H., Lian, F., Liu, Y.-C., Zhang, C., Ding, H., Chen, S., Zhang, N., Zhang, Y., Jiang, H., Chen, K., Ye, F., Yao, Z., Luo, C. 
Development of Potent Type i Protein Arginine Methyltransferase (PRMT) Inhibitors of Leukemia Cell Proliferation 
Journal of Medicinal Chemistry, (2017): 60 (21), pp. 8888-8905.

Supplementary Information

1H - 19862-91-0.pdf
13C - 19862-91-0.pdf
135DEPT - 19862-91-0.pdf
135DEPT vs 13C - 19862-91-0.pdf
1H1H COSY- 19862-91-0.pdf
MS - 19862-91-0.pdf

This page has been viewed approximately 2133 times since records began.

Get structure file (.cdx, .sk2, .mol)

Keywords: aromatics/arenes, carboxylic acids, nucleophilic, thiol, Ullmann

Post new comment
  • Registered user Susan Elizabeth RichardsonJan 11 2019 2:43PM

    Just marking up the compounds here, and I've noticed that the reaction scheme depicts 4-methoxythiophenol, the product is a thioether, but the text repeatedly mentions 4-methoxyphenol. Should the text be amended to 4-methoxythiophenol?

    • Guest Robert B SmithJan 11 2019 3:11PMCorrection

      Please if this could be changed. Thanks for sorry for the typo. Rob

      • Registered user Susan Elizabeth RichardsonJan 11 2019 4:47PM

        Now changed!

Loading ...