Stephen aldehyde synthesis
{{Distinguish|Stevens rearrangement}}
{{Reactionbox
| Name = Stephen aldehyde synthesis
| Type = Organic redox reaction
| NamedAfter = Henry Stephen
}}
Stephen aldehyde synthesis, a named reaction in chemistry, was invented by Henry Stephen (OBE/MBE). This reaction involves the preparation of aldehydes (R-CHO) from nitriles (R-CN) using tin(II) chloride (SnCl2), hydrochloric acid (HCl) and quenching the resulting iminium salt ([R-CH=NH2]+Cl−) with water (H2O).{{cite journal|last1=Williams|first1=Jonathan W.|title=β-Naphthaldehyde|journal=Organic Syntheses |date=1943|volume=23|page=63|doi=10.15227/orgsyn.023.0063}}{{cite journal | author = Stephen, Henry. | title = A new synthesis of aldehydes | journal = J. Chem. Soc., Trans. | year = 1925 | volume = 127 | pages = 1874–1877 | doi = 10.1039/CT9252701874| author-link = Henry Stephen (chemist) }} During the synthesis, ammonium chloride is also produced. It is a type of nucleophilic addition reaction.
Mechanism
The following scheme shows the reaction mechanism:
File:Stephen-Aldehyd-Synthese MV5.svg
By addition of hydrogen chloride the used nitrile (1) reacts to its corresponding salt (2). It is believed that this salt is reduced by a single electron transfer by the tin(II) chloride (3a and 3b).{{cite book | first1=Zerong |last1=Wang | title=Comprehensive Organic Name Reactions and Reagents, 3 Volume Set | publisher=John Wiley & Sons, Hoboken, New Jersey | year=2009 | isbn=978-0-471-70450-8 | pages=2659–2660}} The resulting salt (4) precipitates after some time as aldimine tin chloride (5). Hydrolysis of 5 produces a hemiaminal (6) from which an aldehyde (7) is formed.
Substitutes that increase the electron density promote the formation of the aldimine-tin chloride adduct. With electron withdrawing substituents, the formation of an amide chloride is facilitated.{{cite book | first1=Mordecai | last1=Rabinovitz | title= The Cyano group (1970) | chapter=Chapter 7. Reduction of the cyano group | series=PATAI'S Chemistry of Functional Groups | editor-first=Zvi | editor-last=Rappoport | publisher=John Wiley & Sons, Ltd., Chichester, UK | year=1970 | isbn=978-0-470-77124-2 | page=308 | doi=10.1002/9780470771242.ch7}} In the past, the reaction was carried out by precipitating the aldimine-tin chloride, washing it with ether and then hydrolyzing it. However, it has been found that this step is unnecessary and the aldimine tin chloride can be hydrolysed directly in the solution.{{cite book | first1=Zerong | last1=Wang | title=Comprehensive Organic Name Reactions and Reagents, 3 Volume Set | publisher=John Wiley & Sons, Hoboken, New Jersey | year=2009 | isbn=978-0-471-70450-8 | pages=2659–2660}}
This reaction is more efficient when aromatic nitriles are used instead of aliphatic ones. However, even for some aromatic nitriles (e. g. 2-cyanobenzoic acid ethyl ester) the yield can be low.
Sonn-Müller method
In the Sonn-Müller method{{cite journal|last1=Adolf|first1=Sonn|last2=Müller|first2=Ernst|title=Über eine neue Methode zur Umwandlung von Carbonsäuren in Aldehyde|trans-title=About a new method for converting carboxylic acids into aldehydes|journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series)|date=1919|volume=52|issue=10|pages=1927–1934|doi=10.1002/cber.19190521002|url=https://zenodo.org/record/1426667}}{{cite journal|last1=Williams|first1=Jonathan W.|last2=Witten|first2=Charles H.|last3=Krynitsky|first3=John A.|title=o-Tolualdehyde|journal=Organic Syntheses |date=1946|volume=26|page=97|doi=10.15227/orgsyn.026.0097}} the intermediate iminium salt is obtained from reaction of an amide PhCONHPh with phosphorus pentachloride.
See also
- Amide reduction
- Nitrile reduction
- Pinner reaction – a similar reaction using alcohols or amines as the nucleophile and without the reduction; generated esters, carboximidates or orthoesters.