RANEY NICKEL 1
Me
Raney Nickel1 N
Me
N
W-2 Raney Ni
(1)
Ni
N
EtOH, reflux
H S S
85%
N
H
[106-51-4] Ni (MW 58.69)
(1) (2)
InChI = 1/Ni
InChIKey = PXHVJJICTQNCMI-UHFFFAOYAH
Raney nickel is frequently used to remove the sulfur atom of
(useful as a reducing agent for hydrogenation of organic
thiols,3 sulfides, and disulfides from a carbon skeleton, regard-
compounds1)
less of whether the sulfur is attached to an alkyl carbon,4 an aryl
carbon,5 or a carbon atom in a heterocycle.6 Several examples are
Solubility: insol all organic solvents and water.
shown in eqs 2 5. A solvent effect was observed in the Raney
Form Supplied in: black solid.
nickel reduction of vinyl sulfide (11), which gave glycoside (12)
Preparative Methods: there are many types of Raney nickel; they
in methanol, whereas the double bond remained intact to produce
differ based on their methods of preparation. These methods
alkene (13) in THF (eq 6).7
essentially determine the hydrogen content as well as the re-
activities of various types of Raney nickel. The most popular SH
Raney Ni
(2)
W-type Raney nickels can be prepared as the seven different
OH
EtOH
OH
types listed in Table 1.
90%
(3) (4)
OH O OH O
Table 1 Types of Raney nickel
Raney Ni
(3)
NaOH MeOH, reflux
51%
NaOH/Al soln. conc. Temp. (ć%C)
S
Type (molar) (wt%) (time, h) Water wash method
(5) (6)
W-1 1.35 17 115 120 (4) Decant to neutral
W-2 1.71 20 75 80 (8 12) Decant to neutral
SR
W-3 1.73 20 50 (0.83) Continuous to
Raney Ni
neutral
(4)
acetone
W-4 1.73 20 50 (0.83) Continuous to
60%
neutral
SR
W-5 1.80 21 50 (0.83) Continuous to
neutral
(7) (8)
W-6 1.80 21 50 (0.83) Cont. to neut.
N N
under H2
Raney Ni
SR
W-7 1.80 21 50 (0.83) Directly washed
R1 R1 (5)
N N
EtOH
with EtOH1c
R2 Me R2 Me
OH OH
(9) (10)
Handling, Storage, and Precautions: Raney nickel is gener-
NPht NPht
ally stored in an alcoholic solvent, or occasionally in water,
Raney Ni
PhS
ether, methylcyclohexane, or dioxane. The activity of Raney
THF
nickel decreases due to loss of hydrogen over a period of about
85%
O O
OMe OMe
6 months. Raney nickel ignites on contact with air and should
(11) Pht = phthaloyl (13)
never be allowed to dry.
Raney Ni
MeOH (6)
87%
Original Commentary
NPht
Teng-Kuei Yang & Dong-Sheng Lee
National Chung-Hsing University, Taichung, Taiwan
O
OMe
(12)
Desulfurization. The most widespread application of Raney
nickel is the desulfurization of a wide range of compounds
The sulfur atom can be part of a heterocycle. Högberg8 and
including thioacetals, thiols, sulfides, disulfides, sulfoxides, sul-
Tashiro9 used Raney nickel to remove sulfur from thiophene
fones, thiones, thiol esters, and sulfur-containing heterocycles.
derivatives (14) and (16) to give compounds (15) and (17),
The well-known desulfurization of dithianes remains one of the
respectively (eqs 7 and 8).
most efficient methods for reductive deoxygenation of ketones.
Recently, Rubiralta demonstrated an example in his synthesis of
OH
H2, Raney Ni
OH
the aspidosperma alkaloid framework. Dithiane (1) was reduced to (7)
MeOH
S
indole derivative (2) in 85% yield without reduction of the alkene
85%
(14) (15)
(eq 1).2
Avoid Skin Contact with All Reagents
2 RANEY NICKEL
Br Br
S
OMe OMe
H2, W-7 Raney Ni
Raney Ni
(8)
(15)
EtOH
84%
t-Bu t-Bu
S
(16) (17)
(30) (31)
Raney nickel can remove the sulfinyl and sulfonyl groups
from sulfoxides and sulfones under neutral conditions (eqs 9 and Liu and Luo17 used Raney nickel to reduce glycidic thioester
10).10,11 Cox demonstrated the cleavage of both sulfur carbon (32) to the corresponding 1,3-diol (33) in good yield (eq 16).
bonds in sulfoxide (22) and noted that the stereogenic center With Sodium Borohydride at ambient temperature or Lithium
ć%
remained untouched (eq 11).12 Aluminum Hydride at -78 C, glycidic thioester (32) was re-
duced chemoselectively to furnish 2,3-epoxy alcohol (34) in82%
OH OH yield (eq 16).17
RO RO
O
O O
RO RO
Raney Ni
S
(9)
Ph THF
OH
83%
CO2Me
CO2Me
W-2 Raney Ni
(18) (19)
HO
95% EtOH, rt
O
87%
(33)
SPh (16)
S
1. Raney Ni
t-Bu
R R
NaBH4, rt
EtOH, reflux
O
O
(10)
2. NaOH, H2O
82%
N N (32)
SO2Ph
reflux
SO2Ph H
OH
71 91%
(20) R = alkyl, aryl (21) 3 examples
(34)
OTBDPS
OTBDPS
Raney Ni
(11)
EtOH, reflux Deoxygenation and Deamination. Besides the widely used
Ph
83% Ph
S
desulfurization process, Raney nickel can be used to reduce ben-
O
zylic nitrogen and oxygen atoms. Behren s report shows the partial
(22) (23)
deoxygenation of diol (35) to mono alcohol (36) in 75 96% yields
(eq 17).18 Ikeda used W-2 Raney nickel to remove the benzyl pro-
tecting group from compound (37) However, partial epimerization
Some thioamides are reduced by Raney nickel to the corre-
occurred in this reaction to produce a 3.7:1 mixture of the 6Ä…- and
sponding imines. Two typical examples are shown in eqs 12 and
6²-alcohols (38) (eq 18).19 Azetidine (39) was opened by Raney
13.13,14 Thiones have been reported to give alkanes, but only low
nickel in refluxing ethanol, to give acyclic amine (40) in 88% yield
or unstated yields are reported (eqs 14 and 15).15,16
(eq 19).20
H
S
N
N
Raney Ni
Ph
Ph
(12)
H2, Raney Ni
Ph
Ph N EtOH, reflux
2.5N NaOH, EtOH
HO OH HO
Me 71%
(17)
O
O
20 °C
(24) (25) 75 96%
R R
(35) (36)
S R = H, CN, NH2, CH2NH2
N
N
NH
Raney Ni N
(13)
OMe OMe
N N NH2 H2O, 50 °C N N NH2
73%
MeO MeO
Sugar
Sugar
(26) (27)
W-2 Raney Ni
(18)
EtOH, reflux
S
O O
N N
BnO HO
Raney Ni
(14) H H
Me Me
25%
(37) (38)
N N
H H
Ä…:² = 3.7:1
(28) (29)
A list of General Abbreviations appears on the front Endpapers
RANEY NICKEL 3
Me
Ac Ac
Raney Ni
Ph
(19)
R
HN N R HN HN R N
EtOH, reflux
1. H2, 40 atm
88%
Raney Ni
Ph Ph N
HN Boc
Ph
40 °C, MeOH
(39) (40)
Me
2. (Boc)2O
Me
(52) R = Me 73%
Ph
R
N
(53) R = t-Bu 0%
Me
(54) R = Ph 0%
N
HN N
Krafft reported that tertiary alcohols were also deoxygenated
Ph
(24)
Me Me
to alkanes by Raney nickel (eq 20). On the other hand, primary
Me
1. H2, 1 atm
Ph
(49) R = Me
alcohols were oxidized to aldehydes and then subsequently R
N
Raney Ni
(50) R = t-Bu
ultrasound
decarbonylated (eq 21), and secondary alcohols were oxidized
(51) R = Ph 20 °C, MeOH
N
NH2
Ph
to the corresponding ketones (eq 22).21
2. (Boc)2O
Me
(55) R = Me 72%
(56) R = t-Bu 66%
OH 70%
(57) R = Ph
Raney Ni
O
(20)
toluene, reflux
H2, Raney Ni
90%
CO2Et
2N HCl, EtOH, rt
TMSO N
(41) (42)
68%
O
(58)
O
O O
Raney Ni
(21)
CO2Et (25)
( )9 OH ( )9
MeO toluene, reflux MeO
O
73%
(43) (44) O
(59)
F
O
F
OH O
Raney Ni
Raney Ni
O
PhS PhS
(26)
(22)
N Me
acetone
N
benzene, reflux PhS PhS
Me
50%
95%
Ph
Ph
(45) (46)
(60) (61)
Recently, Ohta reported Raney nickel would deoxygenate Hydrogenation of Multiple Bonds. Applications in this area
N-oxide (47) to pyrazine (48), while Phosphorus(III) Bromide are not very popular for Raney nickel. Raney nickel in dilute base
gave many side products (eq 23).22 is, however, an effective reagent for reduction of pyridines to the
corresponding piperidines. The reaction is accelerated by sub-
stituents in the 2-position and by electron-withdrawing groups in
the 3- and 4-positions, while electron-donating groups in the 3-
N N
Raney Ni
and 4-positions retard the reaction (eq 27).27 Occasionally, Raney
(23)
+ nickel is used to reduce acyclic multiple bonds. An example for
EtOH
N N
62%
selective reduction of triple bonds to cis double bonds is shown in
O OH OH
eq 28.28
(47) (48)
1. Raney Ni
KOH, H2O
" HCl (27)
2. HCl, H2O
N N
77%
H
Cleavage of Heteroatom Heteroatom Bonds. Both N N
(62) (63)
and N O bonds can be cleaved by Raney nickel in the presence
18 other examples
of hydrogen. Alexakis reported that hydrazine (49) was easily
cleaved to the free amine by Raney nickel under hydrogen
Raney Ni
atmosphere, then protected to give carbamate (52) (eq 24).23 In +
PPh3 Cl
addition, he found even hindered hydrazines (50) and (51) were MeOH
80%
successfully deaminated to free amines (56) and (57),
respectively, without racemization if the reactions were assisted
by ultrasound.24 (64)
The N O bonds in 1,2-oxazine (58) and isooxazolidine (60)
(28)
+
were cleaved by Raney nickel via a radical mechanism to pro-
PPh3 Cl
duce 1,4-diketone (59) and ²-lactam (61), respectively (eqs 25
(65)
and 26).25,26
Avoid Skin Contact with All Reagents
4 RANEY NICKEL
Deselenation. Similar to the desulfurization process, Raney nickel under 200 psi pressure gave >98% of phenylalanine (eq 36).
nickel can be used to remove selenium from selenoketones, dise- Other Ä…-keto esters such as 4-hydroxyphenylpyruvic acid, pyruvic
lenides, selenides, and selenooxides. Typical examples are shown acid, and benzoyl acid also gave the corresponding amino acids in
in eqs 29 33.29-31 Moreover, Raney nickel has been used for excellent yield.36
a hydrodetelluration of chiral compound (76) without any race-
Raney Ni, H2 (100 atm), 70 °C
mization (eq 34).32
O
NH2
NH3, EtOH
61%
(35)
Raney Ni
(29)
Raney Ni, H2, 80 °C
PBr3
Se O
(78) (79)
15%
NH2OH" HCl, MeOH
80%
(66) (67)
O NH2
Raney Ni, H2 (200 psi)
Ph ONa Ph ONa (36)
NH3 (or NH4OH), MeOH
>98%
O O
(80) (81)
Se
Raney Ni
Se
benzene, EtOH
2 (30)
reflux
Asymmetric Reduction. Recently, asymmetric synthesis has
76%
become a center of attention for synthetic chemists. The use of
Raney nickel and tartaric acid was recently reported by Bartok.
(68) (69)
Reduction of ketone (82) gave alcohols (83) and (84) as a 92:8
mixture in 70% chemical yield.37 Takeshita et al.9 also reported
an asymmetric reduction of ²-keto ester (85) to give the corre-
Raney Ni
benzene, EtOH
sponding ²-hydroxy ester (86) in 80% ee (eq 38). In addition, it
(31)
reflux was found that enantioselectivities were improved by treatment
87%
Se
of the Raney nickel with ultrasound prior to use.38 Blacklock
(70) (71)
et al. reported an asymmetric reductive amination of Ä…-keto ester
(88) in which they used the chiral amine (87) instead of a chiral
catalyst. The result, shown in eq 39, indicates that the amino ester
Raney Ni
(89) was produced in 80% yield with 74% de.39
H2 (50 psi)
(32)
benzene, reflux
O OH OH
Se 63%
Raney Ni, NaBr
NH2
EtO2C EtO2C EtO2C
+ (37)
NO2
(R,R)-C4H6O6
(72) (73)
70%
(82) (83) 92:8 (84)
Raney Ni
benzene, EtOH
W-1 Raney Ni, NaBr
O O OH O
(33)
(38)
reflux
(R,R)-C4H6O6
OMe OMe
72%
Se
87%
(85)(86) 86% ee
O
(74) (75)
O
O
Raney Ni
N
PhCO2 PhCO2 +
CO2Et
Raney Ni
EtOH
+
(34)
H2 (200 psi) H3N CO2 70%
Cl3Te Cl Cl
58%
(87) (88)
(76) (77)
O O
N N
Reductive Amination of Carbonyl Groups. Reactions of this
NH + NH (39)
CO2 CO2
type can be accomplished by reduction of intermediate imines or
oximes.33-35 Recently, Chan and co-workers found that Raney
CO2Et CO2Et
nickel can be an efficient catalyst in the preparation of pheny-
lalanine. Treatment of sodium phenylpyruvate with either Am-
(89) 87:13 (90)
monia gas or aqueous ammonia solution in the presence of Raney
A list of General Abbreviations appears on the front Endpapers
RANEY NICKEL 5
First Update Catalytic Hydrogen Transfer Reactions. Mebane et al. have
reported the transfer hydrogenation of nitriles to amines using
Julia Haas
refluxing isopropanol as the stochiometric reducing agent.46
Array BioPharma, Boulder, CO, USA
After hydrolysis of the intermediate dimethyl imines, the corres-
ponding amines could be obtained in excellent yields (eq 43).
Selective Reduction of Functional Groups. New or impro-
Although excess Raney Ni was required, the catalyst could be
ved conditions for the selective reduction of various functional
recycled several times. The authors have also used the system
groups in the presence of others have recently been developed. To
Raney Ni/isopropanol for the reduction of alcohols47 and for the
discuss them in detail would be beyond the scope of this publi-
deiodination of iodolactones.48
cation, but representative examples will be discussed. Raney Ni
in THF at room temperature can reduce aldehydes in the pres- 1. Raney Ni, KOH, i-PrOH, reflux
CN
R NH2Å"HCl (43)
ence of ketones with high yields and selectivity.40 An exam-
2. HCl (aq), then NaOH, then HCl (ether)
R
88 97% overall
ple is shown in eq 40. While primary, aromatic, and secondary
aldehydes react under these conditions, tertiary aldehydes do not
react.
Phase transfer hydrogenations using hydrazinium monofor-
mate as the reducing agent together with Raney Ni are also
O
O
Raney Ni, THF
very interesting.49 The reactions proceed at room temperature in
OH (40)
rt, 92%
CHO methanol, and the yields are good for both the reduction of ni-
tro groups (75 94%) and the reduction of nitriles (72 80%). The
ć%
Raney Ni in THF, at room temperature or at 0 C, selectively
reduction of azo compounds to hydrazo compounds and ani-
reduces conjugated double bonds in the presence of isolated
lines using Raney Ni/hydrazinium monoformate has recently been
olefins.41 For example, the conjugated double bond in carvone
reported.50 Azo compounds can also be reduced using Raney
was selectively reduced under these conditions (eq 41). Under the
Ni/ammonium formate.51 Balicki et al. have reduced pyridine-
same conditions, acrylonitrile could be converted to propionitrile
N-oxides to the corresponding pyridines in good yields using
without significant reduction of the cyano group (93% yield).
ammonium formate as the catalytic hydrogen transfer agent
(eq 44).52 Various functional groups were tolerated in this
reaction including nitro groups, nitriles, halides, and ketones.
O
O
Raney Ni, THF
R
R
(41)
rt, 90%
HCO2NH4, Raney Ni
(44)
25 50 °C, 62 91%
N N
O
The selective reduction of aromatic nitro groups in the pres-
ence of halides is possible using Raney Ni poisoned with thiourea
Raney Ni/H2PO4 has been used to convert nitriles to to-
as the hydrogenation catalyst.42 These conditions were used to
sylhydrazines in one step.53 Both aromatic and aliphatic nitriles
convert halogenonitrobenzenes to the corresponding halogenoani-
were used, and with one exception the reported yields are good.
lines with high selectivity (>99%). The selective hydrogenation
of aromatic nitro groups in the presence of halides has also been
R
N
NaH2PO2, Raney Ni, NH2NHTs, AcOH
reported in ionic liquids.43
C
(45)
N
R H2O, pyridine, rt, 20 96%
Benzyl ethers can be cleaved efficiently under biphasic condi-
HN Ts
tions using Raney Ni in the presence of the phase transfer cat-
alyst Aliquat 336.44 An example of this reaction is shown in
eq 42. While under traditional conditions, for example in alcohol
Reduction of Aromatic Rings. Tsukinoki et al. have shown
solvents, high hydrogen pressures are often needed for Raney-
that activated aromatic groups can be reduced to the correspond-
Ni-promoted debenzylations, multiphase conditions allow for fast
ing saturated compounds using Raney Ni-Al alloy in aq KOH
reactions at atmospheric pressure. The hydrogenation of nitriles to
ć%
at 90 C.54 Using these conditions, phenol could be reduced to
the corresponding amines in the presence of Boc-protected amines
cyclohexanol in 93% yield. In a different publication, the authors
has been reported using a mixture of Raney Ni and Pd/C.45 Both
have reported that ring halogens [see eq 46 (X = Br or Cl)] can
catalysts were needed in the reaction mixture for clean conversion.
promote the reduction of phenols to the corresponding cyclohex-
anols under mild conditions.55 The halogens are removed during
Bn
O the reaction. Bromides and chlorides appear to promote this
Raney Ni, A 336, KOH (aq), H2 (1 atm)
O reaction equally well. Under the same conditions, phenol does
O isooctane, 50 °C, 100%
not react.
HO HN
O OH
HO
OH
O
Raney Ni, aq Ba(OH)2
O (42)
(46)
60 °C, 42 93%
HO HN
R
X
O R
Avoid Skin Contact with All Reagents
6 RANEY NICKEL
Improved Reaction Conditions for Raney Ni Reductions. Raney-Ni-promoted reductive alkylation reactions can show
Several groups have recently reported the positive effect of high diastereoselectivity when chiral amines are used. Chiral
ultrasonication on hydrogenation reactions with Raney Ni.56,57 benzylamine derivatives like 1-phenylethylamine74,75 and phenyl-
Ultrasound can afford faster reaction rates58 and prevent deacti- glycine amide76 have been used as chiral auxiliaries that were
vation of the catalyst.59 It can also promote higher yields and better subsequently removed to reveal chiral amines. For example,
recyclability of the catalyst. Both aqueous ammonium chloride60 Uiterweerd et al. have used this method to synthesize (S)-1-amino-
and sulfuric acid61 appear to improve certain Raney Ni-promoted indane with high enantiomeric excess (eq 50). Compared to other
reductions, for example, the reduction of nitro groups and benzyl transition metal catalysts like Pd/C, Raney Ni may show higher
halides. Isopropanol as the reaction solvent has been reported to diastereoselectivity in this type of reaction.76 A disadvantage of
have advantages over other solvents including ethanol or metha- using Raney Ni can be the high catalyst loading required to achieve
nol.62 A microwave-assisted reaction using Raney Ni/ammonium complete conversion in a reasonable timeframe.
vanadate as the reducing agent has been reported.63
1. p-TsOH·H2O
i-PrOAC, reflux, 90%
O
²
Enantiodifferentiating Hydrogenations of ² Esters.
²-Keto
2. Raney Ni, H2 (3.5 bars)
O
Enantiodifferentiating hydrogenation reaction of ²-keto esters
i-PrOAC, 40 °C
+
H2N
with tartaric acid-modified Raney Ni (TA-MRNi) have been
3. recrystallization of HCl salt
NH2
84%
known since the 1980s.64 For alkyl ketones, the conditions have
recently been optimized to achieve enantiomeric excess of up to
98% (eq 47).65 For aromatic ketones, the reaction is not as se-
O
lective with optical yields (OY) of 46 72%, depending on the
HN
electronic nature of the aromatic group.66
NH2 (50)
O OH
O O
TA-MRNi, H2, THF/AcOH
(47)
98% ee
O
60 100 °C R
O
R
(single diastereomer)
R = Alkyl: 82 98% ee
R = Aryl: 46 72% OY
3-Alkylation of Oxindole. The 3-alkylation of oxindole with
alcohols can be achieved in high yields using Raney Ni (eq 51).77
Reductive Amination Reactions. Raney Ni-promoted reduc-
This interesting reaction is believed to proceed via oxidation of
tive amination reactions are well known.64 Because Raney Ni can
the alcohol, condensation of the formed carbonyl compound with
reduce various functional groups to the corresponding amines, and
the oxindole, and reduction of the intermediate enone. The alcohol
it can also promote the oxidation of alcohols to aldehydes and
is also used as the reaction solvent. Both primary and secondary
ketones, functional precursors such as nitro groups67 and
alcohols form the corresponding products in good yields, and diols
nitriles68,69 can be utilized instead of the traditionally used amines,
can also be used in this reaction. Isatins (X = O) can be used as
and alcohols can be used in place of the carbonyl compound. For
oxindole precursors and reduced to the corresponding oxindoles
example, Zhou et al. have reported the reaction of nitroaromatics
in situ when the reaction is run under a hydrogen atmosphere.78
with primary alcohols to form the corresponding N-alkyl anilines
in good yields (eq 48).70
X
R
Y
Y
H
R-OH, Raney Ni (H2)
R
NO2
N
O
(51)
CH2 Raney Ni, H2, EtOH O
CH2 (48)
+
N
R OH 140 °C, 83 90% 150 220 °C, 69 98%
N
H
H
X = H2, O
The authors report that secondary alcohols and methanol gave
only low yields of the corresponding alkylation products under
these conditions. However, depending on the reaction conditions,
Cross-coupling Reactions. Raney Ni-Al alloy efficiently pro-
efficient methylation reactions or secondary alcohol alkylations71
motes Ullman-type cross-coupling reactions between phenols
of amines can be achieved. For example, Francois et al. have re-
and aryl halides (eq 52).79 These reaction conditions provide an
ported a one-pot benzyl group cleavage/methylation reaction us-
interesting alternative to the usually used procedures because they
ing Raney Ni/MeOH (eq 49).72 Raney Ni-promoted reductive am-
are fairly mild, the catalyst is not moisture- or air sensitive, and
inations of Ä…-ketocarboxylic acids have been used for the synthesis
the cheap base K2CO3 can be used instead of Cs2CO3. The yields
of amino acids in excellent yields.73
are generally good for aryl bromides and iodides, and even ortho-
substituents are tolerated on both the phenol and the aryl halide.
Raney Ni
Raney Ni-Al alloy
MeOH, reflux OH X O
(49)
OH
CuI, K2CO3, dioxane
O N
N 91% for R = SO2Tol (52)
+
100 °C, 32 99%
R
R1
R
X = I, Br, Cl
R1 R2 R2
O
A list of General Abbreviations appears on the front Endpapers
RANEY NICKEL 7
Hydrodehalogenation Reactions. Although Raney Ni- where an acid-catalyzed cleavage of the borane-amine complexes
mediated dehalogenation reactions are mostly used for the detoxi- is not viable. Good yields are generally obtained in this reac-
fication of environmental pollutants like PCBs, under certain tion, and various acid sensitive functional groups are tolerated, for
circumstances they can also be of value to synthetic chemists. example, tert-butyl esters and MOM ethers.
For example, a dechlorination reaction has been applied to the
total synthesis of gabapentin, an anti-epileptic drug.80 The most
R1 Raney Ni, MeOH, rt R1 (56)
commonly used procedures use a mixture of an organic solvent
N N
95 96%
R2
and aq KOH in the presence of the phase transfer catalyst Aliquat
H3B R2
336 (A 336). Mild reaction conditions such as catalytic Raney Ni,
ć%
50 C and 1 atm H2 are often sufficient. In the absence of A 336,
no reaction takes place for most substrates under these conditions.
Aromatic bromides can be reduced in the presence of chlorides
(eq 53),81 and the selective deiodination of 1-bromo-3-fluoro-4- 1. (a) Hauptmann, H.; Walter, W. F., Chem. Rev. 1962, 62, 347. (b) Caubere,
P.; Coutrot, P., Comprehensive Organic Synthesis 1991, 8, 835. (c)
iodobenzene has also been reported.81
Billica, H. R.; Adkins, H., Org. Synth., Coll. Vol. 1955, 3, 176.
Raney Ni, A 336, KOH (aq), H2 (1 atm)
2. Troin, Y.; Diez, A.; Bettiol, J. L.; Rubiralta, M. Grierson, D. S.; Husson,
Cl Br Cl (53)
H.-P., Heterocycles 1991, 32, 663.
isooctane, 50 °C, 80%
3. Graham, A. R.; Millidge, A. F.; Young, D. P., J. Chem. Soc. 1954, 2180.
4. Fujisawa, T.; Mobele, B. I.; Shimizu, M., Tetrahedron Lett. 1992, 33,
The outcome of Raney Ni-mediated dehalogenations can de-
5567.
pend strongly on the reaction conditions. Different products may
5. Lottaz, P. A.; Edward, T. R. G.; Mentha, Y. G.; Burger, U., Tetrahedron
be formed depending on the base,82 or the pH of the reaction
Lett. 1993, 34, 639.
mixture. For example, 4-bromobenzyl bromide can be reduced
6. Ohta, S.; Yamamoto, T.; Kawasaki, I.; Yamashita, M.; Katsuma, H.;
to 4-bromo toluene under acidic conditions, while under basic
Nasako, R.; Kobayashi, K. Ogawa, K., Chem. Pharm. Bull. 1992, 40,
conditions debromination on the aromatic ring competes with
2681.
benzylic debromination.83 When the Raney Ni is used in cat-
7. Tietze, L. F.; Hartfiel, U.; Hubsch, T.; Voss, E.; Bogdanowicz-Szwod,
alytic amounts, H2 is most commonly used as the stoichiometric
K.; Wichmann, J., Liebigs Ann. Chem. 1991, 275.
reducing agent but NaBH484 can also be used. Isopropanol has
8. Högberg, H. E.; Hedenström, E.; Fägerhag, J.; Servi, S., J. Org. Chem.
been reported as the stoichiometric reducing agent in the deio-
1992, 57, 2052.
dination of iodolactones.48 Excess Raney Ni in THF efficiently
9. Takeshita, M.; Tsuge, A.; Tashiro, M., Chem. Ber. 1991, 124, 411.
reduces aliphatic halides.85 Aromatic and vinylic halides do not
10. Kast, J.; Hoch, M.; Schmidt, R. R., Liebigs Ann. Chem. 1991, 481.
react under these conditions, and various other functionalities
11. Sadanandan, E. V.; Srinivasan, P. C., Synthesis 1992, 648.
are tolerated including esters, nitriles, and sulfones. Bromides
12. Cox, P. J.; Persad, A.; Simpkins, N. S., Synlett 1992, 197.
(but not chlorides) can be reduced in the presence of ketones,
13. Carrington, H. C.; Vasey, C. H.; Waring, W. S., J. Chem. Soc. 1953, 3105.
and double bonds may be conserved depending on the reaction
14. Kung, P. P.; Jones, R. A., Tetrahedron Lett. 1991, 32, 3919.
conditions (eq 54).
15. Coscia, A. T.; Dickerman, S. C., J. Am. Chem. Soc. 1959, 81, 3098.
O
16. Bourdon, R., Bull. Soc. Claim. Fr. 1958, 722.
Raney Ni, THF
17. Liu, H.-J.; Luo, W., Can. J. Chem. 1992, 70, 128.
rt, 60 min, 90% O
18. Behren, C.; Egholm, M.; Buchardt, O., Synthesis 1992, 1235.
O
19. Ishibashi, H; So, T. S.; Okochi, K.; Sato, T.; Nakamura, N.; Nakatani,
(54)
H.; Ikeda, M., J. Org. Chem. 1991, 56, 95.
O
Br
20. Ojima, I.; Zhao, M.; Yamato, T.; Nakahashi, K., J. Org. Chem. 1991, 56,
O
5263.
Raney Ni, THF
21. Krafft, M. E.; Crooks, W. J., III; Zorc, B.; Milczanowski, S. E., J. Org.
O
rt, 5 min, 80%
Chem. 1988, 53, 3158.
22. Aoyagi, Y.; Maeda, A.; Inoue, M.; Shiraishi, M.; Sakakibara, Y.; Fukui,
Y.; Ohta, A.; Kajii, K.; Kodama, Y., Heterocycles 1991, 32, 735.
Synthesis of Aldehydes and Ketones. Secondary alcohols
23. Alexakis, A.; Lensen, N.; Mangeney, P., Tetrahedron Lett. 1991, 32,
can be oxidized to the corresponding ketones using catalytic
1171.
Raney Ni, aluminum isopropoxide, and alumina (eq 55).86 The
24. Alexakis, A.; Lensen, N.; Mangeney, P., Synlett 1992, 3, 625.
reported yields are good, and the catalyst can be reused. The oxida-
25. Zimmer, R.; Collas, M.; Roth, M.; Reissig, H. U., Liebigs Ann. Chem.
tion of an allylic alcohol to the corresponding saturated aldehyde
1992, 709.
was also reported.
26. Purrington, S. T.; Sheu, K.-W., Tetrahedron Lett. 1992, 33, 3289.
27. Lunn, G.; Sansone, E. B., J. Org. Chem. 1986, 51, 513.
O
H OH Raney Ni, Al(Oi-Pr)3, Al2O3
(55) 28. Soukup, M.; Widmer, E., Tetrahedron Lett. 1991, 32, 4117.
R1 R2 120 170 °C, 52 98% R1 R2
29. Florey, K.; Restivo, A. R., J. Org. Chem. 1957, 22, 406.
30. Wiseman, G. E.; Gould, E. S., J. Am. Chem. Soc. 1954, 76, 1706.
31. Wiseman, G. E.; Gould, E. S., J. Am. Chem. Soc. 1955, 77, 1061.
Cleavage of Borane-amine Complexes. Raney Ni can
32. Backvall, J. E.; Bergman, J.; Engman, L., J. Org. Chem. 1983, 48, 3918.
catalyze the methanolysis of borane-amine complexes (eq 56).87
This reaction is especially of interest for acid-sensitive substrates 33. Freifelder, M.; Smart, W. D.; Stone, G. R., J. Org. Chem. 1962, 27, 2209.
Avoid Skin Contact with All Reagents
8 RANEY NICKEL
34. Botta, M.; De Angelis, F.; Gambacorta, A.; Labbiento, L.; Nicoletti, R., 62. Regla, I.; Reyes, A.; Korber, C.; Demare, P.; Estrada, O.; Juaristi, E.,
J. Org. Chem. 1985, 50, 1916. Synth. Commun. 1997, 27, 817.
35. Graham, S. H.; Williams, A. J. S., J. Chem. Soc. (C) 1966, 655. 63. Dave, M. A.; Prabhu, P. J., Asian Journal of Chemistry 2002, 540.
36. Chan, A. S. C.; Lin, Y.-C.; Chen, C.-C. Personal communication. 64. See also previous part of this article.
37. Wittmann, G.; Gondos, G.; Bartok, M., Helv. Chim. Acta 1990, 73, 635. 65. Sugimura, T., Catalysis Surveys from Japan 1999, 3, 37.
38. Tai, A.; Kikukawa, T.; Sugimura, T.; Inone, Y. D.; Osawa, T.; Fujii, S., 66. Nakagawa, S.; Tai, A.; Okuyama, T.; Sugimura, T., Topics in Catalysis
J. Chem. Soc. (C) 1991, 795. 2000, 13, 187.
39. Blacklock, T. J.; Shuman, R. F.; Butcher, J. W.; Shearin, W. E., Jr.; 67. Zhou, X.; Wu, Z.; Li, L.; Wang, G.; Li, J., Dyes and Pigments 1998, 36,
Budavari, J.; Grenda, V. J., J. Org. Chem. 1988, 53, 836. 365.
40. Barrero, A. F.; Alvarez-Manzaneda, E. J.; Chahboun, R.; Meneses, R., 68. Herkes, F. E., Chemical Industries (Dekker) 2003, 89, 429.
Synlett 2000, 197.
69. Dallons, J. L.; Van Gysel, A.; Jannes, G., Catalysis of Organic Reactions,
41. Barrero, A. F.; Alvarez-Manzaneda, E. J.; Chahboun, R.; Meneses, R., Chemical Industries (Dekker) 1992, 47, 93.
Synlett 1999, 1663.
70. Zhou, X.; Wu, Z.; Lin, L.; Wang, G., Dyes and Pigments 1998, 402,
42. Cordier, G.; Grosselin, J. M.; Bailliard, R. M., Catalysis of Organic 205.
Reactions, Chemical Industries (Dekker) 1994, 53, 103.
71. Botta, M.; De Angelis, F.; Gambacorta, A.; Labbiento, L.; Nicoletti, R.,
43. Xu, D.-Q.; Hu, Z.-Y.; Li, W.-W.; Luo, S.-P.; Xu, Z.-Y., Journal of J. Org. Chem. 1985, 50, 1916.
Molecular Catalysis A: Chemical 2005, 235, 137.
72. Francois, D.; Lallemand, M.-C.; Selkti, M.; Tomas, A.; Kunesch, N.;
44. Perosa, A.; Tundo, P.; Zinovyev, S., Green Chemistry 2002, 4, 492. Husson, H.-P., Angew. Chem., Int. Ed. 1998, 37, 104.
45. Klenke, B; Gilbert, I. H., J. Org. Chem. 2001, 66, 2480. 73. Chan, A. S. C.; Chen, C-C.; Lin, Y-C., Applied Catalysis, A: General
1994, 119, L1.
46. Mebane, R. C.; Jensen, D. R.; Rickerd, K. R.; Gross, B. H., Synth.
Commun. 2003, 33, 3373. 74. Lauktien, G.; Volk, F.-J.; Frahm, A. W., Tetrahedron: Asymmetry 1997,
8, 3457.
47. Gross, B. H.; Mebane, R. C.; Armstrong, D. L., Applied Catalysis, A:
General 2001, 219, 281. 75. Schlichter, W. H.; Frahm, A. W., Archiv der Pharmazie 1993, 326,
429.
48. Mebane, R. C.; Grimes, K. D.; Jenkins, S. R.; Deardorff, J. D.; Gross,
B. H., Synth. Commun. 2002, 32, 2049. 76. Uiterweerd, P. G. H.; van der Sluis, M.; Kaptein, B.; de Lange, B.;
Kellogg, R. M.; Broxterman, Q. B., Tetrahedron: Asymmetry 2003, 14,
49. Gowda, S.; Gowda, D. C., Tetrahedron 2002, 58, 2211.
3479.
50. Prasad, H. S.; Gowda, S.; Gowda, D. C., Synth. Commun. 2004, 34, 1.
77. Volk, B.; Mezei, T.; Simig, G., Synthesis 2002, 595.
51. Gowda, D. C.; Gowda, S.; Abiraj, K., Indian Journal of Chemistry,
78. Volk, B.; Simig, G., Eur. J. Org. Chem. 2003, 3991.
Section B 2003, 42B, 1774.
79. Xu, L.-W.; Xia, C.-G.; Li, J.-W. Hu, X.-X., Synlett 2003, 2071.
52. Balicki, R.; Maciejewski, G., Synth. Commun. 2002, 32, 1681.
80. Cagnoli, R. Ghelfi, F. Pagnoni, U. M.; Parsons, A. F.; Schenetti, L.,
53. Toth, M.; Somsak, L., Tetrahedron Lett. 2001, 42, 2723.
Tetrahedron 2003, 59, 9951.
54. Tsukinoki, T.; Kanda, T.; Liu, G.-B.; Tsuzuki, H.; Tashiro, M.,
81. Marques, C. A.; Rogozhnikova, O.; Selva, M.; Tundo, P., Journal of
Tetrahedron Lett. 2000, 41, 5865.
Molecular Catalysis A: Chemical 1995, 96, 301.
55. Tsukinoki, T.; Kakinami, T.; Iida, Y.; Ueno, M.; Ueno, Y.; Mashimo,
82. Liu, G.-B.; Tsukinoki, T.; Kanda, T.; Mitoma, Y.; Tashiro, M.,
T.; Tsuzuki, H.; Tashiro, M., J. Chem. Soc., Chem. Commun. 1995,
Tetrahedron Lett. 1998, 39, 5991.
209.
83. Evdokimova, G.; Zinovyev, S.; Perosa, A.; Tundo, P., Applied Catalysis,
56. Wang, H.; Lian, H.; Chen, J.; Pan, Y.; Shi, Y., Synth. Commun. 1999, 29,
A: General 2004, 271, 129.
129.
84. Roy, H. M.; Wai, C. M.; Yuan, T.; Kim, J.-K.; Marshall, W. D., Applied
57. Heropoulos, G. A.; Georgakopoulos, S.; Steele, B. R., Tetrahedron Lett.
Catalysis, A: General 2004, 271, 137.
2005, 46, 2469.
85. Barrero, A. F.; Alvarez-Manzaneda, E. J.; Chahboun, R.; Meneses, R.;
58. Disselkamp, R. S.; Hart, T. R.; Williams, A. M.; White, J. F.; Peden, C.
Romera, J. L., Synlett 2001, 485.
H. F., Ultrasonics Sonochemistry 2004, 12, 319.
86. Tarta, I. C.; Silberg, I. A.; Vlassa, M.; Oprean, I., Central European
59. Mikkola, J.-P.; Salmi, T., Chemical Engineering Science 1999, 54, 1583.
Journal of Chemistry 2004, 2, 214.
60. Bhaumik, K.; Akamanchi, K. G., Can. J. Chem. 2003, 81, 197.
87. Couturier, M.; Tucker, J. L.; Andresen, B. M.; Dube, P.; Negri, J. T., Org.
61. Okimoto, M.; Takahashi, Y.; Nagata, Y.; Satoh, M.; Sueda, S.;
Lett. 2001, 3, 465.
Yamashina, T., Bull. Chem. Soc. Jpn. 2004, 77, 1405.
A list of General Abbreviations appears on the front Endpapers