A Complete and Sustained Clemmensen Reduction Mechanism

Abstract

The mechanism for the Clemmensen reduction is not yet fully understood and there are two principal proposals: the 'Carbanionic Mechanism' and the 'Carbenoid Mechanism'. After a critical review, we present a complete and coherent reaction mechanism that involves the formation of a free carbene as well as a zinc carbene and two different carbanionic species as intermediates. This point of view is based on well known reactivities and eliminates all the wrong, dubious or hindered intermediates suggested in previous proposals.

Full text

American Journal of Chemistry 2018, 8(1): 8-12
DOI: 10.5923/j.chemistry.20180801.02
A Complete and Sustained Clemmensen Reduction
Mechanism
Francisco Sánchez-Viesca*, Martha Berros, Reina Gómez
Department of Organic Chemistry, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City (CDMX), México
Abstract The mechanism for the Clemmensen reduction is not yet fully understood and there are two principal
proposals: the ‘Carbanionic Mechanism’ and the ‘Carbenoid Mechanism’. After a critical review, we present a complete
and coherent reaction mechanism that involves the formation of a free carbene as well as a zinc carbene and two different
carbanionic species as intermediates. This point of view is based on well known reactivities and eliminates all the wrong,
dubious or hindered intermediates suggested in previous proposals.
Keywords Carbanions, Carbenes, Carbonyl deoxygenation, Ionic sequence, Organometallic intermediates
1. Introduction
The Clemmensen reduction of carbonyl compounds to
alkane analogs by means of amalgamated zinc and
hydrochloric has been studied with many substrates.
Aliphatic and aromatic compounds have been employed
and have shown different chemical deportments. Thus, the
original reaction giving methylene analogs is not strictly
followed by the aryl derivatives since other products are
also formed.
Other point of interest has been the reaction mechanism
because with the aliphatic compounds the reduction does
not go through the alcohol. There is not a detailed
presentation on this subject. We present a complete and
clear reaction mechanism, with the respective comment in
each step.
Our sequence is a unified theory of the carbanionic
mechanism and the carbenoid proposal. There must not be
two very different mechanisms in order to explain the same
reaction, but a complete and coherent one. This way the two
theories are conciliated.
This will also fill a gap in Chemical Education.
2. Early Approaches and Modern
Theories
The Clemmensen reaction consists in the reduction of a
carbonyl compound to a methyl or methylene group by
means of zinc amalgam and hydrochloric acid. There are two
reviews [1, 2] and general information [3-8].
* Corresponding author:
franviesca@yahoo.com (Francisco Sánchez-Viesca)
Published online at http://journal.sapub.org/chemistry
Copyright © 2018 Scientific & Academic Publishing. All Rights Reserved
We will comment only pertinent studies that are
subsequent to the 1942 review.
Brewster [9] studied the Clemmensen reduction. He
considers the solid metal as an “electron pump”, this
mechanical simile can be misleading since zinc has been
interpreted by other authors as a source of free electrons in
the reaction medium. He represents the metal as - (:M)x+.
This is inadmissible because there is no reason to polarize the
reagent. There is no such dipole in Zn0.
In other communication [10], Brewster studied the
reduction of some sterically hindered ketones and proposes
as intermediary the structure in Figure 1. This is in
contradiction with his previous paper in which he considers
there is no carbonium ion. If so, how the proposed
intermediate can be formed?
(:M)x
R
C
C
HO
Figure 1. Brewster’s outmoded representation of a reaction intermediate
Staschewski [11] repeated Brewster’s wrong
representation of zinc, but he included the needed
carbocation previous to the interaction with the metal. The
next two steps are confusing due to the unusual distribution
of the electrons and electrical charges which is totally
inadequate today.
Nakabayashi [12] gave evidence for the formation of an
intermediate carbonium ion in the Clemmensen reduction.
He studied the initial stages with acetophenone and
t-butylphenyl ketone. A scheme related to the mechanism
was provided in his previous paper [13].
After the formation of a cationic intermediate he proposes
further reaction with another zinc atom giving a dipole with
negative zinc, Figure 2.

American Journal of Chemistry 2018, 8(1): 8-12 9
C
Zn
R'
R
Cl
Zn:
C
Zn
R'R
:
Zn-Cl
+
Figure 2. Unfeasible electrophilic reaction
This is completely unlikely, in the chloro-zinc bond
chlorine has a δ‒ and thus it is not electrophilic. So, there is
not either negative zinc. Moreover, in the zincate anions the
negative charge arises from the ligands, i.e., oxygen,
chlorine, etc., not from the zinc.
The reduction of certain 2-benzoylbenzoic acids and esters
was discussed by Risinger and Thomson [14]. This study
revealed neighboring group participation and the formation
of bimolecular reduction products. However, this theme is
far away from the original Clemmensen reaction.
Reusch [15], in Augustine’s book ‘Reduction’, comments
the Clemmensen reduction in the section on ‘Deoxygenation
of Carbonyl Compounds’. He presents a modified version of
the Brewster’s mechanism. A proposed intermediate is in
Figure 3, which is unacceptable because active metals form
positive ions, not negative ones. Also, there are missing steps
in order to have an understandable and coherent reaction
mechanism, as we will see in the Discussion.
R C (Zn)
R
(+)
(-1)
X-1
Figure 3. A variant of the previously rejected intermediate
Ten years later, Horner and Schmitt [16] proposed a
reaction mechanism for the Clemmensen reduction. Two
zinc atoms were differentiated as Zn’ and Zn’’. The step after
the carbocation formation is in Figure 4. In this
representation the electric charges are missing, the halogen
and the zinc must be negative and positive, respectively, as
indicated below. Then the zinc atom must leave the metal
surface and form a covalent bond with a chloride ion.
O-H
C
Hg
Zn'
Zn"
+
X
O-H
C
Zn'
Zn"
Hg
X
;
Zn C
OH
X
OH
CZnCl
Figure 4. Incorrect and corrected structure after reaction with zinc
The proposed next step is in Figure 5, a double 1,2
migration. This is very improbable since there is no reason
for the rupture of two sigma bonds.
OH
C
Zn
X
C H
O-Zn-X
Figure 5. Arbitrary twofold atom tranfer
Other paper is that of Crump and Davis [17], from New
Zealand. They studied the Clemmensen reduction of some
1,4-diketones and obtained alcohols which are not normally
produced in this reaction. For instance, hexane-2,5-dione
gave hexane-2-ol, as well as cis- and trans-hex-4-en-2-ol,
Figure 6. Obviously, neighboring group participation
deviates completely the normal reactivity.
The Clemmensen reduction of 2-acetylflourene [18] is
abnormal since it yields not only 2-ethylflourene but also the
carbinol, 2-(α-hydroxyethyl)fluorene, and eight derivatives
of this alcohol. What is interesting from the mechanistic
point of view is the ease of the proposed metallic
intermediate to form the alcohol, Figure 7.
O
O
OH
OH
+
OH
+
Figure 6. An example of I,4 diketone reduction by Clemmensen reaction
OH
C
Zn-Cl
Fl CH
3
OH
C
Fl CH
3
..
Zn Cl
OH
C
H
Fl CH3
HCl ZnCl2
+
CCH
3
OH
..
CCH
3
OH
..
Figure 7. Formation of methyl-2-fluorylcarbinol and carbanion
stabilization
The stability of this carbanion can be explained by the
extended cross conjugated double bond system that results
from electron delocalization by resonance. This is not the
case in ordinary Clemmensen reductions and results in a
different chemical deportment.
Burdon and Price [19] evidenced the presence of carbene
intermediates since they were captured by an alkene to give a
cyclopropane. The authors studied the reaction of substituted
acetophenones with amalgamated zinc in homogeneous
(50% aq. EtOH) solution at 20°C and HCl. They propose
direct formation of a zinc-carbene from the ketone, Figure 8.

10 Francisco Sánchez-Viesca et al.: A Complete and Sustained Clemmensen Reduction Mechanism
Ar C CH
3
O
+
2 Zn
Ar C CH
3
Zn
+
ZnO
Figure 8. Main reaction of the so-called ‘Carbenoid mechanism’
The viability or not of this proposal is discussed later in
‘The Carbenoid mechanism’. We consider that the carbene is
formed through previous intermediates as we will see in the
Discussion.
The free carbene was captured by reaction with added
styrene as indicated in Figure 9.
Ar C
CH3
H2CCAr
H
:
C C
Ar
H
3
C
Ar
H
Figure 9. Formation of a cyclopropane derivative with capturing styrene
Actual information online on the Clemmensen Reduction
[20] states ‘the mechanism is not yet fully understood’ and
there are two principal proposals: the ‘Carbanionic
mechanism’ and the ‘Carbenoid mechanism’.
In one presentation of the ‘Carbanionic mechanism’ [21]
every carbocation reacts with two free electrons, supposedly
emitted by the zinc, forming a carbanion that afterwards is
protonated. The resulting short sequence is apparently
flawless but it omits the formation of a carbene, a key
intermediate that has been detected experimentally. But if a
neutral organometallic intermediate is formed in the
sequence, as we will see later, there is possibility to form a
carbene, otherwise no. The misconception of free electrons
in the reaction medium derives from considering literally the
zinc as an ‘electron pump’. Besides, this would increase
hydrogen formation in the acidic medium.
In the other mechanism presented, the ‘Carbenoid’ [20],
the first formed intermediate is a zinc-carbenoid, without
hydrogen chloride participation, Figure 10.
OR"
R'
Zn Zn
OR"
R'
.
.
.. ..
Zn Zn
OR"
R'
.
.
R'
R"
Zn
Zn
O
Figure 10. Supposed formation of zinc oxide and a zinc-carbene
The simultaneous interaction of the carbonyl compound
with two vicinal zinc atoms in the zinc surface is not
probable because the Zn-Zn distance is 2.3 times longer
(2.84 Å) than the C=O bond length (1.21 Å). Besides, it is
very dubious that would be reaction between a carbonyl
compound and zinc alone, i.e., without the intervention of
hydrochloric acid.
In the next section we present the formation of a free
carbene and a zinc-carbene after other stages and by reaction
with a second zinc atom.
In this review, dedicated exclusively to the mechanistic
theme, we have pointed out the errors, the false reactivities
and the missing links that we have encountered in the
communications on the Clemmensen reduction mechanism.
We present our theory in the next section.
3. Discussion
Instead of two different reaction mechanisms, the
‘Carbanionic’ and the ‘Carbenoid’, we present a complete
mechanism that includes the formation of both species. This
has been possible considering the formation of sigma bonded
organometallic intermediates, Figure 11.
R
1
CR
2
O
-
[H
3
O (3 H
2
O)]
+
Cl
-
HCl / H
2
O
H
9
O
4+
Cl
R
1
CR
2
OH
Cl
-
+
R
1
CR
2
OH
+
Zn
..
Cl
-
O
C
Zn
R
1
R
2
H
Cl
-
+
O
C
Zn
R
1
R
2
Cl
H
HCl
O
C
Zn
R1R2
Cl
H
H+Cl
-
C R
2
R
1
.. ZnCl
2
H
2
O
+
C R
2
R
1
.. H
2
O
+
C R
2
R
1
..
Zn
..
+
-
C
Zn
R
2
R
1..
HCl
H
C
Zn-Cl
R
2
R
1
-
H
CR
2
R
1
..
ZnCl
+
H
C
Zn-Cl
R2
R1
Cl
-
-
H
CR
2
R
1
..
ZnCl
2
HCl
H
C
H
R
2
R
1
+
ZnCl
2
Figure 11. Complete reaction mechanism of the Clemmensen reduction

American Journal of Chemistry 2018, 8(1): 8-12 11
The first step is interaction of the ketone or aldehyde with
a solvated hydroxonium ion [22, 23] coming from the
aqueous hydrochloric acid. The resulting oxonium chloride
is in resonance with a carbonium ion electromer. This
carbocation, in a chemisorption step, reacts with elemental
zinc, an electrodoting reagent [24], leading to a two-electron
reduction. The obtained organometallic intermediate reacts
with hydrochloric acid: a carbene is formed with
concomitant water and zinc chloride elimination. The
electron deficient species reacts with another zinc atom and a
dipolar ion is formed. This metal carbene complex is of
Schrock type [25], a carbanion and an electron deficient
metal. It can be represented double bonded to zinc, but ab
initio quantum mechanical methods display a zinc- carbon
single bond for ZnCH2 [26].
Reaction of the above zwitter ion with hydrochloric acid
yields a deoxy organometallic derivative. Finally, ionization
gives a carbanion which by protonation affords the reduction
product, i.e., with a methylene instead of the original
carbonyl group. The ionization can be assisted by direct
formation of zinc chloride due to interaction with a chloride
ion. This is supported by the fact that zinc chloride in the
presence of hydrochloric acid forms the tetrachlorozincate
anion, ZnCl4= [27], showing the zinc receptivity to chloride
ions.
The Clemmensen reduction can be summarized in the
following equation:
R1-CO-R2 + 2 Zn + 4 HCl ―> R1-CH2-R2 + H2O
+ 2 ZnCl2
In the mechanism presented by Vedejs [2], the hydroxy
organometallic intermediate, after protonation and water
elimination yields a bis-chlorozinc structure, Figure 12a, and
no carbene is formed. However, carbenes are known
intermediates whose formation has been confirmed
experimentally.
OH
C
ZnCl
R'
R
+
H
H
2
O
_
C
ZnCl
R'R +Zn
Cl :
-
ZnCl
C
ZnCl
R'
R
+
H
RCH2R'
Figure 12a. Improbable protolysis to the hydrocarbon
Moreover, the bis-chlorozinc structure is not prone to the
required ionization in order to be protonated and yield the
reduction product because a chlorozinc ligand causes a δ‒ at
the carbon atom and thus a carbanion from the second
chlorozinc group would be at the seminegative carbon atom,
which is highly unlikely. On the other hand, the carbanions
in our reaction sequence are far likely.
Figure 12b shows our alternative to the previous reactions.
The protonated hydroxy organometallic intermediate goes
ahead with an almost synchronic water elimination, carbene
formation and +ZnCl displacement.
O
C
Zn
RR'
Cl
H
H
+
C R'
R
+
..
H
2
O
+
H
2
O
+
ZnCl
Figure 12b. The required carbene formation via a concerted reaction
mechanism
4. Conclusions
• We present a complete and coherent reaction
mechanism for the Clemmensen reduction in order to
explain the deoxygenation of a carbonyl group to a
methylene.
• The sequence is fully commented and is based on facts
and well known reactivities.
• This reaction mechanism includes the intermediates
proposed by the two actual theories: the ‘Carbanionic
Mechanism’ and the ‘Carbenoid Mechanism’.
• The unification of both theories has been possible
postulating certain organometallic links instead of free
electrons reduction or direct formation of a
zinc-carbene.
• The finding that both carbenes and carbanions are
formed in the same reaction sequence eliminates
the disagreement on the Clemmensen reduction
mechanism.
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