Reimer-Tiemann Reaction

Description: The Reimer-Tiemann reaction is a method for installing a formyl group (CHO) onto an electron-rich aromatic such as phenol using CHCl3 and strong base. Yields are generally not great.

Notes:  The reaction proceeds through formation of a dichlorocarbene from CHCl₃ through deprotonation with a concentrated aqueous solution of NaOH followed by alpha-elimination.

In the reaction above, both ortho- and para– products are formed, although ortho– dominates.

See Also:  Dichlorocyclopropanation

Examples:

Notes: Note that this reaction only really works with very electron-rich aromatics (e.g. phenols) and yields are typically quite poor. A mixture of ortho– and para– products are obtained.

When the ortho and/or para positions are blocked (example 4) then dichloromethyl products are obtained.

Mechanism: 

The first step is formation of a dichlorocarbene from chloroform. In the first step, hydroxide ion deprotonates chloroform to form its conjugate base, (Step 1, arrows A and B) which can then lose chloride to form the neutral dichlorocarbene.

Part 1: Formation of Dichlorocarbene

At the same time, phenol is deprotonated by strong base to give the phenoxide ion (Step 3, arrows D and E) which is a more reactive nucleophile than phenol itself.

Attack of the dichlorocarbene by the phenoxide ion (Step 4, arrows F and G) forms a new C-C bond and gives a carbanion. Protonation of the carbanion (Step 5, arrows H and I) followed by deprotonation adjacent to the ketone (Step 6, arrows J and K) gives another phenoxide. (These two steps are often just combined and described as “proton transfer”. ) Note that the phenoxide formed after step 6 has two prominent resonance forms. For simplicity, we’ve chosen to draw the final elimination step (Step 7, arrows L and M) as elimination from the carbanion resonance form, although you could certainly draw it coming from the phenoxide resonance form as well.

Part 2: Addition of Dichlorocarbene To The Aromatic Ring

The final sequence involves a conjugate addition/elimination reaction to give a product that tautomerizes to the final product.

In the first step, hydroxide ion performs a conjugate addition to the alpha, beta unsaturated ketone (Step 1, arrows A, B, and C). This results in an anion; we can draw resonance forms for both the phenoxide ion (O^– ) and carbanion. In the next step, elimination of chloride ion occurs (Step 2, arrows D, E, F, and G) to give what is essentially a substitution product.

Deprotonation of the hydroxyl group (Step 3, arrows H and I) gives its conjugate base, which can then tautomerize to restore aromaticity to the phenol (Step 4, arrows J, K, and L). Protonation of the phenoxide (Step 5, arrows M and N) gives the final product.

That’s a lot of work for a 20% yield.

Notes:  As noted, you can draw the elimination step as arising from several different resonance forms; the carbanion was chosen here because it’s the simplest.

• No selectivity for double bond geometry (E/Z) is implied.
• The driving force for tautomerization is formation of the aromatic ring.
• Although the ortho product is shown here, the para product will be formed as well (not shown).

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(Advanced) References and Further Reading

1. The Reimer-Tiemann Reaction.
   Hans Wynberg
   Chemical Reviews 1960 60 (2) 169-184
   DOI: 10.1021/cr60204a003
   Early review on the RT, with discussion and mechanism.
2. The Reimer-Tiemann Reaction.
   Dauben, W. G.
   Organic Reactions, Volume 28. Hoboken, NJ: Wiley-Interscience. pp. 1–36
   DOI: 10.1002/0471264180
   Comprehensive treatment of this reaction, with every example up to this point.
3. The Mechanism of the Reimer-Tiemann Reaction
   Jack Hine and James M. Van Der Veen
   Journal of the American Chemical Society 1959 81 (24) 6446-6449
   DOI: 10.1021/ja01533a028
   First major study on the mechanism of the Reimer-Tiemann, and our view of the mechanism is essentially unchanged today.
4. Ueber die Einwirkung von Chloroform auf Phenole und besonders aromatische Oxysäuren in alkalischer Lösung
   K. Reimer and Ferd. Tiemann
   Berichte der deutschen chemischen Gesellschaft 1876 9 (2) 1268-1278
   DOI: 10.1002/cber.18760090270
   Original report on the Reimer-Tiemann.