Sciencemadness Discussion Board

Preparation of Salicylaldehyde

Magpie - 30-3-2015 at 14:18

a lab report


A. Introduction
Salicylaldehyde (SA) can be prepared using a Reimer-Tiemann reaction, ie:


Attachment: Reimer-Tiemann.doc (26kB)
This file has been downloaded 542 times
reaction

This reaction proceeds through formation of a :CCl2 carbene as shown in reference 1.

I followed the procedure found in Vogel’s 3rd ed, page 703 (ref 2). The expected yield is 12g. My crude flowsheet for this preparation is shown below:


salicylaldehyde flowsheet.jpg - 95kB
SA preparation flowsheet

B. Apparatus
3-neck 1000 ml RBF (24/40)
overhead stirrer
west condenser (24/40)
west condenser (19/22)
60 ml p-e addition funnel
hotplate
thermocouple w/readout
2-quart waterbath (steel bowl)
distillation head (24/40)
distillation head (19/22)
vacuum adapter (19/22)
adapter (24/40 to 19/22)
100 ml RBF (19/22)
25 ml RBF (19/22)
cooling water (iced) supply
1000 ml heating mantle
100 ml heating mantle
aluminum foil
fiberglass insulation blanket
thermometer good to 200°C
steam distillation apparatus:
1. 500 ml separation funnel (steam trap)
2. 5mm x 30cm glass tube
3. 2-hole rubber stopper
4. ¼” latex rubber tubing, ~2’
5. hot plate
6. pressure cooker
7. thermometer adapter (19/22)
8. adapter (24/40 to 19/22)
9. 2ea glass plugs (24/40)

125 ml separatory funnel
250 ml separatory funnel
miscelaneous beakers

C. Reagents
28.4g phenol (aqueous, 88%)
40.5 ml chloroform
80g NaOH
water
1M H2SO4 (~500 ml)
dichloromethane (~ 85 ml)
anhydrous MgSO4
sodium bisulfite (or sodium metabisulfite)

D. Procedure

1. Reaction
The reaction apparatus was set up as shown below. The 2nd picture shows the utilities outside the hood that were required for support.

salicylaldehyde reaction vessel.jpg - 85kB
SA reaction setup


salicylaldehyde - utilities.jpg - 114kB
SA utilities – outside the hood

To the 1000ml RBF was added a warm solution of 80g NaOH dissolved in 80 ml of water. To that was added a solution of 28.4g of 88% phenol dissolved in 21.6 ml of water. The water bath was kept at about 65°C. 40.5 ml of chloroform was added to the 60ml p-e funnel attached to the outlet of the condenser using a notched rubber stopper.

40.5 ml of chloroform was added to the p-e funnel. With the overhead stirrer running at 222 rpm the chloroform was added slowly over a period of ½ hour. I attempted to keep the temperature of the reactants at 65-70°C per procedure by adding boiling water to the water bath. However, the temperature ranged from 59°C to 64°C. I didn’t turn on the hotplate as I was afraid of a possible runaway. This never happened and I never did have to cool the bath. The mix was then heated with the water bath boiling for another hour.

During the addition of the chloroform the reactant mix turned red and eventually turned to a dark brown, looking very much like beef gravy. Chloroform refluxed all the while. There was foaming for a time but it was not a problem due to the generous freeboard of the 1000ml RBF. At cleanout of the RBF a disc of tar about the size of a 50 cent piece was found at the bottom of the flask. It was soluble in alcohol and a tiny bit gave a strong yellow coloration - dare I say à la Perkin. Pictures of the reactants at various stages are shown below:

salicylaldehyde reaction later.jpg - 109kB
SA reactants – later – after all chloroform added

salicylaldehyde reaction - final hold.jpg - 94kB
SA reaction – during final 1 hour hold

2. Workup
The workup for this synthesis is very long, nearly discouraging me from even starting this synthesis. Garage chemist described it succintly as “a pain.” See the flowsheet above.

a. Steam distillation to remove unused chloroform
This was performed in the 1000ml pot as shown below. I recovered no chloroform. I believe that any unused chloroform escaped from the 24/40 West condenser (on ice-water). Vogel calls for “an efficient (double wall) reflux condenser.” I don’t have one of those. The picture below shows the steam distillation.


salicylaldehyde - steam dist - chloroform removal.jpg - 92kB
Steam distillation to remove excess chloroform

b. Acidification
The pot mix was then acidified with ~250 ml of 1M H2SO4. The color of the mix lightens considerably during the acid addition.


c. Steam distillation to remove the SA/unreacted phenol

A second steam distillation was now done to remove the SA and any unreacted phenol as shown below:


salicylaldehyde steam dist for oil.jpg - 96kB
2nd steam distillation to remove SA/phenol

d. Extraction
The distillate from the 2nd steam distillation was now extracted with 25ml x 25ml dichloromethane (DCM) to remove the SA/phenol from water. This is shown below. The yellow liquid in the beaker is the first extraction, the clear liquid in the bottom of the funnel is the second extraction.


salicylaldehyde extraction with DCM.jpg - 82kB
SA/phenol extraction with DCM

e. Distillation
The combined extracts are distilled to remove DCM. 45ml of good quality DCM was obtained for recycle. This is done using a water bath as shown below:


Removal of DCM from SA + phenol.jpg - 82kB
Removal of DCM by distillation

This report is continued on the next post due to the excessive number of images.


[Edited on 30-3-2015 by Magpie]

[Edited on 30-3-2015 by Magpie]

[Edited on 31-3-2015 by Magpie]

morganbw - 30-3-2015 at 14:46

Looking forward for the workup.

Magpie - 30-3-2015 at 14:58

Continuation

f. Sulfite adduct formation
The sulfite adduct is now formed to separate the salicylaldehyde from the excess phenol. This is done by adding 2X its volume of saturated aqueous sodium bisulfite (I used Na metabisulfirte). Since the mix is biphasic Vogel called for this to be shaken vigorously for 1/2hr, then allowed to sit for 1 hour. The resting product is shown below:

salicylaldehyde bisulfite adduct - post shaking.jpg - 70kB
SA bisulfite adduct – post shaking

g. Separation of the adduct by filtration
The adduct, a pure white solid, was then separated from the water and phenol by filtration using a 7cm Buchner filter. It is shown in the picture below:

salicylaldehyde bisulfite adduct flitered.jpg - 66kB
SA adduct filtered

At one point during the filtration I did not get the filter paper properly sucked down (sealed) against the ceramic base. Consequently I lost some product here – possibly as much as a gram. The dried adduct was weighed (17g), indicating the presence of 9.2g of SA.

h. Recovery of the salicylaldehyde
The SA is recovered by decomposition of the adduct. This is done by adding 1M H2SO4 then gently warming in a water bath. I added 75ml of the acid. During the warming I got too aggressive with the heating in an effort to fully decompose the adduct to SA and SO2, forgetting to follow the direction of “warming.” As a consequence I believe I lost 2-3g of product via steam distillation up the hood vent. I could visibly see that the volume of yellow oil on the bottom of the flask had decreased. Warming the adduct in the water bath is shown below:

salicylaldehyde bisulfite adduct decomposition.jpg - 71kB
SA bisulfite adduct decomposition

i. Extraction
The SA/water product was then extracted with 25ml x 15ml of DCM. The extract is shown drying overnight over anhydrous MgSO4 in the picture below:


salicylaldehyde in DCM being dryed.jpg - 77kB
SA in DCM being dryed

i. Distillation
The next day the DCM was removed by distillation. Following this with the pot heavily insulated with a fiberglass blanket shrouded in aluminum foil, the SA was distilled. The product was captured that boiled in the range of 193-196°C. Literature value (Vogel) is 195-197°C. Pictures of the distillation apparatus, the thermometer at product take-off, and the salicyaldehyde product are shown below:

salicylaldehyde distillation.jpg - 84kB
SA distillation

salicylaldehyde distillation temperature.jpg - 49kB
SA distillation temperature

salicylaldehyde.jpg - 60kB
SA product

E. Results
My yield was a disappointing 6g. The yield would have been better if not for the losses described above. The expected yield (Vogel) is 12g. Even this is only a 37% yield.

F. Conclusions
1. Salicylaldehyde can be successfully made using the Riemer-Tiemann reaction and Vogel’s procedure. My poor yield can certainly be much improved.
2. DCM can be successfully substituted for diethyl ether as the extractant in this synthesis. Other than its obvious advantages I think DCM gives cleaner separations, and is quite recoverable by distillation.
3. My homemade overhead stirrer performed satisfactorily.

G. Discussion
My reasons for doing this synthesis are many: (1) I wanted to perform a complex synthesis involving relatively benign chemicals as I have been out of the lab for ~3 months due to a health issue which has since been satisfactorily resolved, (2) I had 500ml of reagent grade phenol that I’ve had for over 5 years without use, (3) I wanted to find out how well DCM could be substituted for diethyl ether for extraction, (4) I wanted to test out my new stepper motor overhead mixer, and (5) JimmyMajesty’s work with aldehydes piqued my interest in isolating an aldehyde by sulfite adduct. Also I wanted to perform a name reaction new to me. I found the Riemer-Tiemann mechanism to be fascinating; and carbenes are always fascinating.

Salicylaldehyde has a smell very similar to benzaldehyde, but with a little bite and is not as sweet or strong. One source said it smells of bitter almond.

H. References
1. http://en.wikipedia.org/wiki/Reimer%E2%80%93Tiemann_reaction
2. Practical Organic Chemistry, 3rd edition, by Arthur I. Vogel, 1956 (see forum library)

Questions, comments, and suggestions are welcomed.


[Edited on 30-3-2015 by Magpie]

[Edited on 30-3-2015 by Magpie]

[Edited on 31-3-2015 by Magpie]

blogfast25 - 30-3-2015 at 15:09

That looks very interesting, Magpie, but I think I'll pass on trying it myself. ;)

morganbw - 30-3-2015 at 15:24

Good job, it would take many of us more than one try, to get any product.


Loptr - 30-3-2015 at 16:23

You are on of my inspirations in this hobby!

Magpie - 30-3-2015 at 17:38

Thank you blogfast, morganbw and Loptr. ;)

I hope JimmyMajesty tries isolating his acetaldehyde by sulfite adduct.

[Edited on 31-3-2015 by Magpie]

Crowfjord - 30-3-2015 at 18:29

Did you only decompose the solid adduct? A fair amount tends to remain dissolved in the aqueous filtrate (see Len1's Illustrated Practical Guide for benzyl chloride, benzal chloride, benzaldehyde, etc in prepublications). Could have been another contributor to your low yield. I'm away from my notes, but in isolating 2,5-dimethoxy benzaldehyde from reaction solvent and starting compound (Beauveault aldehyde synthesis) via bisulfite adduct, I think I actually got more aldehyde from the aqueous solution than the filtered solid.

Magpie - 30-3-2015 at 19:00

No, I did not. The adduct that slipped under the filter paper would have been in there too, along with the phenol, and a little alcohol/DCM wash. I should have reviewed Len1's benzaldehyde synthesis.

Waffles SS - 30-3-2015 at 22:27

That is Great,

Magpie,i want to suggest another method

As you know Riemer-Tiemann is low yield method but o-formylation of phenols by mg has better yield.

Have you ever tried Mg-mediated o-formylation of phenols method?

also there is another interesting method according to Mg-mediated o-formylation of phenols.

I want to try it and will share the result:

Quote:

The One Pot Synthesis Salicylaldehyde Prepared by Reactive Grinding with Derivative Phenol and Paraformaldehyde in Absence Magnesium Methoxide

A aromatic Phenol (0.1 mol), magnesium methoxide (5 gr ), and the mixture was grinding to 1 minute at room temperature. A slurry of paraformaldehyde powder (4 gr) in under grinding was added in small portions over 2 min to the reaction mixture. Stirring was continued at r.t for 8 min, after which added slowly to 10% sulfuric acid (20 ml g). The resulting mixture was stirred for 10 min, after which the aqueous layer was separated and extracted with ethyl acetate (2 x 100 ml). The combined organic layers and extracts were washed with 10% sulfuric acid (20 ml) and water (20 ml) and evaporated under reduced pressure to give the salicyaldehyde (Yield 85%)

http://dx.doi.org/10.13005/ojc/290445




and also below:




Quote:

Magnesium-mediated ortho-Specific Formylation and Formaldoximation of Phenols


2-Hydroxybenzaldehyde -Phenol (37.6 g, 0.4 mol) was
added to magnesium methoxide (259 g of 8 wt.% solution in
methanol; 20.7 g, 0.24 mol) and the mixture was heated to
reflux. Approximately half the methanol was distilled off and
toluene (300 g) was added to the residue. The azeotropic
mixture of toluene and methanol was removed by fractional
distillation, until the temperature of the reaction mixture rose to
95 "C. A slurry of paraformaldehyde powder (43.2 g, 1.44 mol)
in toluene (75 g) was added in small portions over 1 h to the
reaction mixture at 95 "C with concurrent removal of volatile
materials by distillation. Stirring was continued at 95 "C for 1 h,
after which mixture was cooled to 25 "C and added slowly to
10% sulfuric acid (450 g). The resulting mixture was stirred at
30-40 "C for 2 h, after which the aqueous layer was separated
and extracted with toluene (2 x 100 g). The combined organic
layers and extracts were washed with 10% sulfuric acid (50 g)
and water (50 g) and evaporated under reduced pressure to give the aldehyde 2a as a pale yllow oil (48.35 g, 84%)

Aldred, Robert; Johnston, Robert; Levin, Daniel; Neilan, James; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); nb. 13; (1994); p.1823 - 1832
DOI: 10.1039/P19940001823




[Edited on 31-3-2015 by Waffles SS]

Loptr - 31-3-2015 at 03:53

How sensitive are aldehydes to air oxidation? Any particular measures that must be taken during the procedure, or doing its storage? I know you previously synthesized benzaldehyde using persulfate, and am curious if the oxidation potential is the same for both salicylaldehyde and benzaldehyde.

lullu - 31-3-2015 at 08:26

Very nice Magpie!

Is there any specific reason you liberated the aldehyde in acidic conditions, thereby forming SO2?
Or just because you can as you have one of the nicest fume hoods I've seen on here :D?

I would also recommend the Mg formylation as an alternative it is a breeze.

Magpie - 31-3-2015 at 08:42

Thank you waffles and lullu. I used the Reimer-Tiemann for the reasons stated in the "Discussion" section of my report. But thanks for the information on o-formylation. ;)

lullu, that is an interesting question about using acid for liberation of the aldehyde from the adduct. I've seen for other syntheses, and expected, that this would be done with a base. I just followed the direction in Vogel in using the acid, 1M H2SO4.

Loptr, I can't say for sure for salicylaldehyde (yet) but for benzaldehyde it is surprisingly stable. I would expect SA to be similar. But for butyraldehyde and propionaldehyde my experience is that they oxidize easily.


Waffles SS - 31-3-2015 at 10:05

Are you sure Benzaldehyde is stable in oxidation?

According to my experience it will oxidized almost fast with air oxygen .

Also it is suggested by different resource to distill it before use or wash it with Carbonate solution for get rid of Benzoic acid

Oxidation of Salicyldehyde depend on oxidation substance.
Usually Electron donating group(activating groups) make Benzaldehyde more stable in radical oxidation but for OH group i think we should test it.


[Edited on 31-3-2015 by Waffles SS]

Magpie - 31-3-2015 at 11:23

Quote: Originally posted by Waffles SS  
Are you sure Benzaldehyde is stable in oxidation?


I made my benzaldehyde some time ago and have used it at least 2 times since for successful syntheses. That's all I have to go on.

NexusDNA - 31-3-2015 at 16:22

Excellent, Magpie! Thank you!

I'm interested in doing this preparation. I'll post here if everything goes ok.

Magpie - 31-3-2015 at 18:45

Thank you Nexus.

After recovering the 2nd batch of DCM (40 mls) I gave it a sniff test (not recommended) for quality control before placing it in the mother supply bottle. It had a sharp, nasty sting so I set it aside for later cleanup w/activated charcoal. After running it through the charcoal I checked again with a sniff (not recommended) and - ouch - it had not changed. But this time I realized what it was: SO2!

Of course - it had been dissolved during the extraction following the adduct decomposition. So, I treated it with an aqueous CaCO3 slurry. This was a mistake as the CaCO3 seemed to react with the DCM forming a gummy mess. It did get rid of the SO2 however, so I did recover about 20 mls. Na2CO3, NaOH, or KOH, would probably have been a good choice.

Jimmymajesty - 1-4-2015 at 08:59

Hey Magpie,

Well done!

I tried to isolate the acetaldehyde as the bisulhite adduct.
It needs time for the formation and for the decomp also, also you can precipitate the bisulphite without the adduct if there is an ethanol carry over and there is always some with the catalytic method. So I do not isolate the acetaldehyde rather use it as a gas, but if you need some more info on the acetaldehyde adduct I surely can do some experiments for you:)

Magpie - 1-4-2015 at 10:08

Thanks Jimmy. No, I have no plans to make acetaldehyde at this time. But I might in the future, as like I said before, for some reason I want to make crotonaldehyde. I just wanted you to see how the adduct is used in case you wanted to use it to isolate your acetaldehyde or store it in powder form.

learningChem - 3-9-2015 at 12:43

Would the reaction work with cresol ? (yielding some kind of methyl aldehyde?)

CaptainPike - 4-9-2015 at 16:52

Magpie,

We love you – you make the absolute best OC Porn, ever!

Magpie - 4-9-2015 at 20:08

Thanks, Captain. ;)

ronstark - 9-2-2017 at 14:41

Did try the adduct for the first time to improve my chemistry. It was made according to Vogel's: 50g Sodium Bisulfite in 100mL water and 70mL EtOH. Some chunks remained undissolved, but filtered to a clear solution. 50g Salicylaldehyde added to the solution and stirred 1h. The crystals were filtered and the filtrate had a blue purplish colour. Is this normal? After the filtrate was dried, 90g SA adduct. 100mL 10% NaOH was added and crystals begin to form on the bottom. The solutiom is reddish and on top oily drops, more like chicken fat. Can I saturate this with NaCl? Think I will try with H2SO4 next time. Looks more clean on your photos. I did extract a portion with DCM and upon evaporation it was a red purple oil. It seems very hard to extract that oily drops from the solution. Xylene is a better solvent?

[Edited on 9-2-2017 by ronstark]

Magpie - 10-2-2017 at 08:30

I saw no colors after the formation of the adduct other than a slight yellowing of the final product.

I have no special insight into where your blue and red colors came from. My only guess would be impure product/reagents somewhere along the line.

There could be a reason for Vogel's specification of 1M H2SO4 instead of using NaOH for regeneration of the aldehyde.

I don't know if xylene would be a suitable solvent as it is completely non-polar. DCM and ether have some polarity, however, which would seem more appropriate.

[Edited on 10-2-2017 by Magpie]

[Edited on 10-2-2017 by Magpie]

UC235 - 11-2-2017 at 06:18

Purplish color sounds like iron contamination to me with salicylic acid around.

I looked into the Reimer-Tiemann reaction a while ago for salicylaldehyde since I lack paraformaldehyde, but except for certain substrates, the yield is quite terrible. The magnesium mediated approach is vastly superior.

Attachment: ReimerTiemannreview.pdf (1.4MB)
This file has been downloaded 780 times


ronstark - 11-2-2017 at 12:40

It was extracted with 50mL 50% DCM and 50% CHCl3 (1:1) ratio, washed with a NaCl saturated solution, washed again with water, dried and the solvents stripped off. The colour is bright yellow, very beautiful. Final yield: 67%. I really don't know why that red / purplish colour was there. I am satisfied with this result.

[Edited on 11-2-2017 by ronstark]

Magpie - 11-2-2017 at 13:13

I am glad this synthesis worked out so well for you. That's an amazing yield compared to what Vogel claimed, which was 37%.

I did find a note in an internet dictionary that said salicylaldehyde was soluble in benzene. So xylene would probably be good also.

cubalibre - 12-2-2017 at 03:42

If you liberate phenolic aldehyde adducts with NaOH, you must neutralize it afterwards otherwise you will loose product with your aqueous washes.
Very likely the reason they do it using H2SO4 in Vogel in the first place.

[Edited on 12-2-2017 by cubalibre]

ronstark - 12-2-2017 at 03:56

It was neutralized with HCl 36.5% until pH was neutral. Forgot to mention that.

[Edited on 12-2-2017 by ronstark]

RustyShackleford - 19-1-2021 at 10:08

I attempted this preparation, with the differences being using Kmetabisulfite , crashing more adduct with acetone and ofcourse a huge experience and knowledge gap between me and magpie (bless his soul).
IMG_20210117_171844.jpg - 1.6MB
IMG_20210117_173940.jpg - 1.5MB
The reaction mixture formed a thick slurry of goop, i think a flatbottom 3neck with a large stirbar would have been much preferable.
IMG_20210117_191152.jpg - 1.4MB
The steam distillation seemingly went quite well, i stopped after the drips reached clarity.
IMG_20210118_104342.jpg - 1.4MB
This is where it started to get wierd, the DCM extracted organics from the steam distillation were VERY red, but sufite reduced this to a dirty yellow.
After stirring the organics with metabisulfite solution for 4h, nothing had precipiated (but it had become homogenous), so i decided to evaporate it. and chill. After filtering i added 3x the filtrates volume of acetone to crash out more of the adduct while hopefully keeping the phenol dissolved. This made it very yellow but seemingly worked well.
IMG_20210118_151527.jpg - 1.2MB

Sadly i dont have an image of the acid degradation or distillation of the salicylaldehyde, but notably after extracting the acidic solution with DCM it again turned red. Distilling didnt separate this color.
IMG_20210119_182455.jpg - 1.4MB
Final yield was 15% assuming the distillate is mostly pure.
Dont do this preparation yourself, make/get formaldehyde and do the Mg mediated formylation, this sucked

Small thing of note: a solution of oxone was used to rid the recovered DCM of SO2, worked great.

[Edited on 19-1-2021 by RustyShackleford]

Fery - 19-1-2021 at 23:03

Hi RustyShackleford, very well done! My old commercial salicylaldehyde is pale yellow, as magpie. I did not try to redistill it, maybe it would be colorless then. Strange that the distillation did not separate the red color in your case. Did you distill it at atmospheric pressure, or vacuum? Vacuum would significantly reduce oxidation to salicylic acid, but small contamination with this acid (if distilling at atm pressure) should not be the case of the red color. Phenolic compounds are able to produce very colored complexes with metals, e.g. with Fe3+, like here:
https://sci-hub.st/10.1021/ja01124a041
But this should not be your case as you certainly used glass distillation apparatus.

RustyShackleford - 20-1-2021 at 03:00

Fery, i distilled at atmospheric pressure and ofcourse did use an all glass distillation vessel, but if the color complex is very potent i guess its possible there was some contamination in my glassware that re-formed the red compound after it condensed.

Pumukli - 20-1-2021 at 23:17

Maybe the red color means there is unreacted phenol that is oxidized. Phenol distills with steam as far as I know.
On the other hand I read somewhere that hydroxy aldehydes resist oxidation pretty well. Salicylaldehyde was explicitely mentioned. Maybe it is only true at room temp, I 'm not sure.

RustyShackleford - 21-1-2021 at 11:31

Quote: Originally posted by Pumukli  
Maybe the red color means there is unreacted phenol that is oxidized. Phenol distills with steam as far as I know.
On the other hand I read somewhere that hydroxy aldehydes resist oxidation pretty well. Salicylaldehyde was explicitely mentioned. Maybe it is only true at room temp, I 'm not sure.

I think this is the case, it has turned a little bit more red over time so its more likely to be oxidation than a complex

Fery - 22-1-2021 at 02:27

Just an idea, but couldn't it be purified by partial crystallization, its melting point is -7 C so putting into a freezer with -18 C for some short time so not the whole content solidifies?

zed - 24-2-2021 at 15:33

The way I remember it, Benzaldehyde loves to be oxidized. Moreover, it loves to oxidize/reduce itself into two more stable conformations... Benzyl Alcohol and Benzoic Acid. I can remember Ancient Bottles of Benzaldehyde in the Chem Storeroom.... where I used to work; Packed with crystals of Benzoic Acid they were.

The Cannizarro used to be a favorite College Organic Chemistry Experiment. Back, before the federal government, in the USA, became totally paranoid about Benzaldehyde.

This Oxidation, or base catalyzed re/dox tendency, is not automatic for all Benzaldehydes. Seems I've read that Vanillin is less likely to do it than Benzaldehyde.

Perhaps that Phenolic "Acidity", produces some stability.

As for the "Red" Salicaldehyde. Benzaldehyde itself, is supposed to be distilled under reduced pressure.

In general, aldehydes are very reactive. I'm thinking steam distill from an acetic solution, or distill under reduced pressure.

[Edited on 24-2-2021 by zed]

[Edited on 24-2-2021 by zed]

clearly_not_atara - 25-2-2021 at 08:27

Arenes with a formyl group that is ortho or para to a hydroxyl group show a resonance isomerization when the phenol is deprotonated, which inhibits both A: the Cannizzarro reaction and also B: the alkylation of the phenol. This is why the bromination of vanillin works, and also why the methylation of salicylaldehyde or syringaldehyde usually requires high temperatures.