[1112]

I am attempting to brominate 2,5-dihydroxybenzaldehyde at C6, with no success. I have been attempting the reaction the following way:

reagents: 2,5-dihydroxybenzaldehyde, Br₂
solvent: chloroform

procedure:

pipet Br₂ into chloroform. stir.

Over the course of 45 minutes to an hour add 2,5-dihydroxybenzaldehyde. Room temp. stir for 2.5-3 hrs.

wash with sat. sodium bicarbonate. isolate solid from chloroform layer. (I do not know the name of the product: 2,5-dihydroxybenzaldehyde brominated at C6)

I have not been able to get a good proton NMR of the product. It seems to be a mixture. My glassware was very clean.

I have found an article in which a similar method was used to brominate 2,5-dihydroxybenzaldehyde at C6:

Tetrahedron Letters
Volume 47, Issue 6, 6 February 2006, Pages 909-911   

Total synthesis of bioactive frustulosin and frustulosinol

Mary-Lorène Goddarda and Raffaele Tabacchi

doi:10.1016/j.tetlet.2005.11.150

[macman104]

That is not the quite exact procedure being used.  If you follow the references in the paper, you eventually get to another paper that provides a full experimental reference.  I've copied just the experimental procedure below, and provided the doi reference:

2-Bromo-3,5-dihydroxybenzaldehyde:

To a solution of 2,5-dihydroxybenzaldehyde (5.0 g, 36.2 mmol, 1.0 equiv.) in 170 mL CHCl3 was added Br2 (1.94 mL, 37.7 mmol, 1.04 equiv.) in 120 mL CHCl3 dropwise over 1.5 h.
After addition, the reaction was stirred for another 1.5 h. The CHCl3 solution was then washed with 8 × 100 mL sat. Na2S2O3 to thoroughly remove excess Br2. The organic phase was dried over MgSO4, filtered, and the solvent removed in vacuo to afford 7.4 g (34.3 mmol, 94%) of 2-Bromo-3,5-dihydroxybenzaldehyde as yellow solid, which was adequately pure for characterization and used directly in the next step.

1H NMR (400 MHz, CDCl3) δ 11.63 (s, 1H), 10.24 (s, 1H), 7.21 (d, 1H, J = 9.2 Hz), 6.89 (d, 1H, J = 9.2 Hz), 5.39 (s, 1H); 13C NMR (75.0 MHz, CDCl3) δ 197.1, 158.5, 145.8, 125.7, 118.8, 116.7, 112.1; IR (thin film) νmax 3281, 1634, 1457, 1286, 1170 cm-1; CIHRMS M+ calculated for C7H5BrO3: 215.9438, found: 215.9422.

http://dx.doi.org/10.1021/ol0159367

[1112]

Thanks for your help. I am very new to organic synthesis, so I have to learn to follow references etc.

Did you see any problems with the procedure I was using? My research adviser okayed it. However, it has not been working, so I assume it is flawed. I don't know what is wrong with it. (I forgot to include that I dried the chloroform layer with magnesium sulfate when I wrote the procedure I was following).

[macman104]

I don't know if they will make much difference, and I claim to have no practical experience with this reaction, but your procedures are slightly different.  And reaction conditions may play a role, because I see two spots that you could brominate, and I actually think the 3 position should be more favored (meta to the aldehyde, meta-directing and ortho to the hydroxyl, o/p directing). 

First, you are dripping your benzaldehyde into a solution of bromine (possibly allowing for dibromination?), instead of them dripping their solution of bromine into the benzaldehyde (this keeps concentrations of free bromine low compared to the concentrations of benzaldehyde).  Also, how concentrated is your solution of bromine, do you see how little bromine is in the chloroform solution (a lower concentration will help control how much/fast the bromine enters the reaction flask).