SODIUM HYDRIDE 1
Sodium Hydride1
HO MeO
1. 2 equiv NaH
DMF
H H
NaH (3)
2. MeI (excess)
H H H H
3 5
HO HO
[7646-69-7] HNa (MW 24.00)
H H
InChI = 1/Na.H/rHNa/h1H
C-5² (C-3 axial): 91%
InChIKey = MPMYQQHEHYDOCL-RVEWWXDUAC
C-5Ä… (C-3 equatorial): 93%
(used as a base for the deprotonation of alcohols, phenols, amides
Sodium hydride in DMF is also used to deprotonate carbohy-
(NH), ketones, esters, and stannanes; used as a reducing agent for
drate derivatives, for methylation or benzylation (eq 4).6
disulfides, disilanes, azides, and isoquinolines)
ć% Ph O Ph O
1. NaH, DMF
Physical Data: mp 800 C (dec); d 1.396 g cm-3. O O
O O
(4)
HO MeO
Solubility: decomposes in water; insol all organic solvents; insol
2. MeI
HO MeO
OMe 79% OMe
liq NH3; sol molten sodium.
Form Supplied in: free-flowing gray powder (95% dry hydride);
gray powder dispersed in mineral oil. Unstable benzyl tosylates may be made by deprotonation of
Handling, Storage, and Precautions: the dispersion is a solid benzyl alcohols and acylation with p-Toluenesulfonyl Chloride
and may be handled in the air. The mineral oil may be removed (eq 5).7
from the dispersion by stirring with pentane, then allowing the
1. NaH, ether
hydride to settle. The pentane/mineral oil supernatant may be
reflux, 15 h
pipetted off, but care should be exercised to quench carefully
(5)
PhCH2OH PhCH2OTs
2. p-TsCl
any hydride in the supernatant with a small amount of an alcohol
 70 to 25 °C
before disposal. The dry powder should only be handled in an
80%
inert atmosphere.
Sodium hydride dust is a severe irritant and all operations
An interesting conformational effect is seen when p-t-butylcalix
should be done in a fume hood, under a dry atmosphere. Sodium
[4]arene is tetraethylated. When Potassium Hydride is used as the
ć%
hydride is stable in dry air at temperatures of up to 230 C
base, the partial cone conformation predominates (i.e. one of the
before ignition occurs; in moist air, however, the hydride rapidly
aryl groups is inverted), whereas with sodium hydride, the cone
decomposes, and if the material is a very fine powder, sponta-
is produced exclusively (eq 6).8
neous ignition can occur as a result of the heat evolved from the
hydrolysis reaction. Sodium hydride reacts more violently with
t-Bu t-Bu
t-Bu t-Bu
t-Bu t-Bu t-Bu t-Bu
EtI
water than sodium metal (eq 1); the heat of reaction usually
NaH
causes hydrogen ignition.
(6)
DMF or MeCN
NaH + H2O NaOH + H2 (1)
OH OH OEt OEt
OH OH OEt OEt
cone
Deprotonation of vinylsilane-allylic alcohols using sodium hy-
Original Commentary
dride in HMPA is followed by an  essentially quantitative C O
silicon migration (eq 7).9
Robert E. Gawley
University of Miami, Coral Gables, FL, USA
TMS H
NaH (catalytic)
OH OTMS (7)
HMPA
Introduction. The following is arranged by reaction type:
>95%
NaH acting as a base on oxygen, nitrogen, germanium/silicon,
and carbon acids, and as a reducing agent.
Nitrogen Acids. Sodium hydride in DMSO, HMPA, NMP, or
Oxygen Acids (Alcohol Deprotonation). Sodium hydride
DMA assists the transamination of esters (eq 8).10
may be used as a base in the Williamson ether synthesis in neat
benzyl chloride,2 in DMSO,3 or in THF (eq 2).4 Phenols may also
O
be deprotonated and alkylated in THF.4b
CO2Et NH2 NaH
NH
+ (8)
THF
DMSO
N N
Ph3COH + NaH + MeI (2)
Ph3COMe 85%
85%
Curiously, tertiary propargylic alcohols may be alkylated in
Acyl amino acids and peptides may be alkylated on nitrogen us-
preference to either axial or equatorial secondary alcohols, using
ing sodium hydride, with no racemization (eq 9).11 A slight change
sodium hydride in DMF (eq 3).5
of reaction conditions allows simultaneous esterification.12
Avoid Skin Contact with All Reagents
2 SODIUM HYDRIDE
also doubly deprotonate ²-diketones, allowing acylation at the
1. 3 equiv NaH
2. 8 equiv MeI
less acidic site (eq 17).22
O O
(9)
THF DMF (10:1)
BnO N CO2H BnO N CO2H
OO
H H
H
NaH, HCO2Et
Me
(16)
OH
70 74%
A similar intramolecular alkylation has been used to make ²-
lactams (eq 10).13
O O O O O
1. 4 equiv NaH
(17)
O O
Ph 2. PhCO2Et Ph Ph
N S N S 87%
NaH, CH2Cl2
Ph Ph
(10) An undergraduate experiment using sodium hydride involves
Cl
DMF
N N the crossed condensation of ethyl acetate and dimethyl phthalate
82%
O O
H (eq 18).23 Sodium hydride is also effective as a base in the Stobbe
CO2Me
MeO2C
condensation24 and the Darzens condensation.25 It is also effective
in a stereoselective intramolecular Michael reaction (eq 19).26
Germanium/Silicon Acids. Germanium hydrogen and
ONa
silicon hydrogen bonds are quantitatively cleaved with sodium
CO2Me
hydride in ethereal solvents (eq 11).14
NaH
+ MeCO2Et (18)
CO2Me
54 83%
DME
CO2Me
R3XH + NaH (11)
R3XNa O
>95%
O O
R = Bu, Ph; X = Si, Ge
MeO2C MeO2C
NaH (catalytic)
O O
(19)
benzene
90%
Carbon Acids. Active methylene compounds, such as mal-
H
onates and ²-keto esters, can be deprotonated with sodium
hydride and alkylated on carbon (eqs 12 and 13).15 Alkylation
The Dieckmann condensation of esters27 and thioesters28 is
of Reissert anions is also facile with sodium hydride (eq 14).16
mediated by sodium hydride (eq 20). Conditions for the latter are
significantly more mild than for the former, and the yields are
O O O O
1. NaH, DMF
higher.
(12)
OEt OEt
2. EtBr
O
74%
Et
X = O, NaH, toluene, 45 °C, 65 80%
COXEt
(20)
COXEt
COXEt
X = S, NaH, DME, EtSH, 20 °C, 90%
O O O O
1. NaH, DMF
EtO OEt EtO OEt (13)
Sodium hydride may be used to cleave formate esters and for-
2. BuBr
Bu Ph
75%
Ph Ph
manilides (eqs 21 and 22).29 The mechanism apparently involves
Ph
removal of the formyl proton and loss of carbon monoxide.
1. NaH, DMF
2. PhCH2Cl
DME
(14)
N N BuOCHO + NaH BuONa + CO + H2 (21)
COPh COPh
3. H2O 68%
CN 84%
Ph
DME
Ph(Me)NNa + CO + H2 (22)
Ph(Me)NCHO + NaH
70%
Normally, sodium enolates of ketones alkylate on oxygen. A
 superactive form of sodium hydride is formed when butylsodium
Dehydrohalogenation with sodium hydride is a means of mak-
is reduced with hydrogen; superactive sodium hydride is an
ing methylenecyclopropanes (eq 23).30
excellent base for essentially quantitative deprotonation of
ketones, trapped as their silyl ethers.17 For example, cyclodode- Br
NaH
(23)
canone is converted to its enol ether (containing a  hyperstable
CO2Et CO2Et
EtOH
double bond) in 92% yield (eq 15).
60%
O OTMS
NaH, TMSCl Enolate formation apparently accelerates the Diels Alder cy-
(15)
cloaddition/cycloreversion, shown in eq 24, which occurs at room
hexane, 0 °C
92%
temperature.31
O O OH O
More commonly, sodium hydride is used as a base for carbonyl
condensation reactions. For example, Claisen condensations of
NaH
O
+ (24)
ethyl acetate18 and ethyl isovalerate19 are effected by sodium
THF
O
hydride. Condensations of cyclohexanone with methyl benzoate19
88%
O O
and ethyl formate (eq 16)20 are also facile.21 Sodium hydride can
A list of General Abbreviations appears on the front Endpapers
SODIUM HYDRIDE 3
An unusual cyclization of N-allyl-Ä…,²-unsaturated amides is sodium hydride and trichloroacetonitrile without cleavage of the
mediated by sodium hydride in refluxing xylene (eq 25).32 The base-labile Fmoc group (eq 30).38
reaction is thought to proceed by intramolecular 1,4-addition of
OBn
the dianion shown.
1. 0.1 equiv NaH
FmocO O
O O O
OH 2. CCl3CN
NaH
BnO
Na
NPhth 97%
HN N HN (25)
xylene 70%

OBn
FmocO O (30)
O CCl3
BnO
NPhth
Reductions. The sodium salt of trimethylsilane is produced
NH
quantitatively by reduction of hexamethyldisilane with sodium
hydride (eq 26).33
Conversion of optically active 1-(benzothiazol-2-ylsulfanyl)-
TMS TMS + NaH TMSNa + TMSH (26) alkanols to thiiranes can be achieved without racemization by
>95%
treatment with sodium hydride in THF at ambient temperature
(eq 31).39
Sodium hydride in DMSO is an effective medium for the
reduction of disulfide bonds in proteins under aprotic conditions.34
OH
When the molar ratio of hydride to 1/2 cystine residues exceeds
S
NaH
S S
2:1, essentially complete reduction of the disulfide bonds of bovine
n-Bu
n-Bu
(31)
THF, rt
serum albumin is achieved. N
64% yield
Azides are reduced to amines by sodium hydride, although
99% ee
99% ee
the yields are moderate (eq 27).35 Sodium hydride also reduces
isoquinoline to 1,2-dihydroisoquinoline in good yield (eq 28).36
Addition of alkoxides generated from sodium hydride to imin-
BuN3 + NaH (27)
BuNH2
odithiazoles give 4-alkoxyquinazoline-2-carbonitriles (eq 32).40
39%
This reaction generally requires 40 h in refluxing alcoholic sol-
1. 3 5 equiv NaH, HMPA vents. The reaction times can be reduced to a couple of hours using
(28)
microwaves, giving similar yields of the desired products.
N N
2. Ac2O, benzene
Ac
77%
Cl
MeO N NaH
N
EtOH
S
S
MeO CN microwave/reflux
First Update
80%
MeO N CN
(32)
D. David Hennings
N
Array BioPharma, Boulder, CO, USA
MeO
OEt
Introduction. This update is arranged by reaction type: NaH
acting as a base on oxygen, nitrogen, sulfur/selenium, and carbon
acids, followed by reductions, deprotection, and debromination.
Several examples of SNAr reactions using sodium hydride to
generate the necessary alkoxide have been reported. An interest-
Oxygen Acids. Alkylations using sodium hydride can be
ing example of an intramolecular variation was reported using
attenuated depending upon the conditions used. Diaryloxy- ²-lactams to give the 4-oxa-7-azabicyclo[4.2.0]octane skeleton
methanes have been prepared using dichloromethane as the
(eq 33).41
ć%
methylenation agent under harsh conditions (>120 C). These
Selectivity can be achieved using sodium hydride to gener-
same substrates can be conveniently prepared in very good yields
ate various alkoxides. In the case of myo-inositol orthoesters,
ć%
using sodium hydride with NMP as the solvent at 40 C (eq 29).37
sulfonylation using sodium hydride as the base led to 4,6-di-
O-sulfonylated products whereas the use of pyridine or triethyl-
OH O O
amine gave 2,4-di-O-sulfonylated products.42 Coordination of an
NaH, CH2Cl2
(29)
alkoxide to metals can also be used to direct facial selectivity
NMP, 40 °C
in various types of organometallic processes. In the preparation
R R
R
of the C(29 40) fragment of pectenotoxin-2, the key step was
R = Cl, Me, OMe 92-99% yield
alkoxide-directed hydrogenation using a cationic rhodium cata-
(m- and p-)
lyst (eq 34).43 The use of sodium hydride not only promoted the
selective hydrogenation, it also prevented dehydration of the sub-
The formation of trichloroacetimidates in the presence of an
strate to the corresponding furan.
Fmoc-protected hydroxyl group was achieved using catalytic
Avoid Skin Contact with All Reagents
4 SODIUM HYDRIDE
F
OH Nitrogen Acids. Sodium hydride can be used to achieve
H H
selective N-alkylation of 2-hydroxycarbazole (eq 36).47
NaH
Ph
DME, rt
N
O2N O PMP
NaH, BuBr
OH
O2N O THF/DMF
H
N
rt, 91%
(33)
Ph
H
H H
N
O PMP (36)
OH
N
78% yield
Bu
PMP =
OMe
SNAr reactions have been performed using sodium hydride to
deprotonate various aromatic primary amines and diamines.48 In
OH
Rh catalyst
the case of 2-aminobezenethiol, the SNAr pathway can be mini-
MOMO H2 (800 psi)
mized giving good yields of fluorinated 2-substituted phenylben-
MOMO
O
NaH, THF
O
zothiazoles (eq 37).49 The choice of solvent is critical to achieving
H 68%
Me OSEM
addition of the aniline anion to the benzonitrile.
O
OH
MOMO
H
F
SH
(34)
MOMO
O
NaH
O
+
H
THF, 60 °C
Me OSEM
O NC
NH2
(o-, m-, and p-F)
An interesting selectivity between sodium hydride and potas-
sium hydride was observed in the preparation of the macrocyclic
S F
dilactone core of Macroviracin A.44 In both cases, the carboxylic
(37)
acid was activated using 2-chloro-1,3-dimethylimidazolinium
N
chloride followed by addition of the base. Using potassium
80-88%
hydride as the base led exclusively to monomer cyclization,
whereas sodium hydride gave a 44% yield of the desired dilactone.
Sodium hydride has also been useful in manipulating the paclitaxel
The synthesis of Ä…-lactams from Ä…-haloamides can be accom-
core. Epimerization and subsequent conversion of the C-7
plished using t-BuOK or KOH/18-crown-6. Alternatively,
hydroxyl group to the corresponding xanthate using NaH/
using sodium hydride with 15-crown-5 ether provided the
CS2/MeI ultimately provided a route to prepare 7-deoxygenated
products in superior yields while reducing the necessary reaction
taxolanalogs.45 Deoxygenation of the C-2 hydroxyl group was
time (eq 38).50
also achieved using similar chemistry (eq 35).46 In this example,
a novel NaH-promoted benzoyl group migration occurs followed
by formation of the C-2 xanthate, which was ultimately deoxy-
Br
H NaH R
genated under standard conditions.
N
15-crown-5
N
(38)
R
CH2Cl2, rt
O
O
AcO O
Ph NH O O
R = adamantyl (2 h)
OTES 1. NaH
R = trityl (1 h)
Ph O
2. CS2, MeI
91%
OTES
HO
BzO Aziridines can readily be prepared by intramolecular cycli-
O
AcO
zation of protected amines with the appropriate electrophilic
functionality. The method of cyclization, the nature of the elec-
O
AcO trophilic component, and the configuration of the substrate can
Ph NH O O
lead to different stereochemical outcomes. Using allylic mesy-
OTES
lates it is possible to prepare 2,3-trans-2-alkenyl-3-alkylaziridines
Ph O
(eq 39).51 The cyclization of sulfonyl-protected amino-bromoal-
(35)
OTES
lenes using sodium hydride gives 2,3-cis-2-ethynylazidiridnes
BzO
with good selectivity (eq 40).52 It is interesting to note that the cis
O
O
S OAc
selectivity is only observed with sulfonyl-protected amines. The
SMe use of Boc-protected amines gives little to no selectivity.
A list of General Abbreviations appears on the front Endpapers
SODIUM HYDRIDE 5
Me
MeO2C CO2Me
NaH
PdCl2(PPh3)2
NaH
OMs
(39)
+ + PhI
DMF, 0 °C Me THF/DMSO
H
H N
NH
N 75%
Ms
Ms H N
93% yield
CO2Me
100:0 trans selectivity
Ph
CO2Me
(43)
N
Ph
N
Ph " Me
NaH
Br
(40)
H
H N
NH DMF, 0 °C
Ts H
Ms
88% yield
Bn Bn
NaH
89:11 cis selectivity
NbzONH2 H2N
PhCHO
HN N
dioxane, 60 °C
O O
Aziridination of unsaturated ketones can be achieved directly O
O
Bn
using sodium hydride in conjunction with N,N -diamino-1,4-
diazoniabicyclo[2.2.2]octane dinitrate (eq 41).53 This reaction
N
Ph
N
(44)
proceeds through a nitrogen-nitrogen ylide. The ylide undergoes
O
Michael addition followed by cyclization of the resulting enolate
O
and expulsion of the tertiary amine.
80%
O
NbzONH2 =
NO2
NH2
NaH
N H2N O
Ph Ph
+
2NO2 i-PrOH, PhH
N
O
H2N
Selenium/Sulfur Acids. A strong base such as sodium hy-
Ph Ph
(41)
dride is not normally needed to facilitate alkylation of thiols. How-
NH
O ever, it was necessary to use sodium hydride for the alkylation of
5-bromo-D-pentano-1,4-lactones (eq 45).58 The base typically
95%
employed for this transformation (NaOMe) is not compatible with
the lactone functionality.
Urethanes can be deprotonated with sodium hydride, and with
the assistance of silver triflate, can perform intramolecular allylic
Br RS
O O
displacements to give bicyclic structures (eq 42). This method was O O
NaH
RSH (45)
+
employed in the stereoselective formal synthesis of palustrine.54
THF/DMSO, rt
HO OH HO OH
OH OH
82-95%
NaH
R = hexyl, octyl, decyl, and dodecyl
H
AgOCOCF3
H H
(42)
THF, rt
Cl HN N
72%
The method used to prepare phenyl selenide can have a pro-
O O
O O nounced effect on the selectivity of the reagent. It was observed
that Michael addition or acetate displacement could be selec-
tively achieved by changing the method of preparation of phenyl
Conjugate addition of amines can be useful in cascade sequ-
selenide.59 In the illustrated case, the reagent prepared using
ences. The addition of secondary propargylic amines have been
sodium hydride gave the conjugate addition product (eq 46).
used in conjunction with palladium catalysis to generate highly
functionalized pyrrolidines (eq 43).55 The sequence involves con-
O
jugate addition followed by carbopalladation using an aryl halide. OAc
NaH
PhSeH
This method has also been used with proargylic alcohols to gen-
OC
H
CH2Cl2, rt
erate 2,3-disubstituted furans.56
AcO
98%
O
Electrophilic amination can be achieved using hydroxylamine- H
CO2Me
Me
based ammonia equivalents. The preferred conditions for this
transformation utilize sodium hydride in dioxane. Addition of the
O
OAc
anion to O-(p-nitrobenzoyl)hydroxylamine (NbzONH2) gener-
OC
ates the N-amino-2-oxazolidinone (eq 44).57 Although the amino H (46)
compound can be isolated, typically the product is converted to AcO
O SePh
H
CO2Me
the more stable hydrazone.
Me
Avoid Skin Contact with All Reagents
6 SODIUM HYDRIDE
O
Carbon Acids. One of the more common uses of sodium
O
O
hydride is the deprotonation of activated methylene compounds S
NaH
X
+
to generate highly reactive carbanions. A shuttle-deprotonation
DMSO/Et2O
N
system has been described in which sodium hydride is the
C
stoichiometric base and is used in conjunction with a crown ether
TBSO
(TosMIC)
cocatalyst to generate ketenes used in asymmetric catalysis.60
O
Enaminones can be converted to naphthyridinones using sodium
hydride in THF (eq 47).61
HN X
(50)
R1 N Cl
NaH
R5 TBSO
X = O (87%)
N R3 THF, reflux
R2
X = NBoc (97%)
O O
R4 O R3
A novel approach to aziridines employs the use of sodium
R1 N
R4
hydride in DMSO with dichloroazetidines (eq 51).67 The choice
(47)
N
of DMSO is critical in obtaining the desired product. This trans-
R2 R5
formation is proposed to go through a highly strained 2-azetine.
O
R1 = H; R2 = Cl, F; R3 = Me, Ph
30-80%
R4 = H, Ph; R5 = H, alkyl, Ph
R1
O
NaH
Cl
(51)
Lactams62 and ketones63 have been enolized using sodium
DMSO, 80 °C
N
hydride and have subsequently undergone intramolecular alky- Cl
R1
N R2
lation and acylation on the oxygen atom (eqs 48 and 49).
R2
46-59%
R1 = H, Me, OMe, F
MeO N
R2 = i-Pr, Cy
NaH
O
DMF, 0 °C
N
75%
Br
It is possible to oxidize the carbon center of enolates generated
MeO N
using sodium hydride. This transformation is assumed to occur
O
by addition of the enolate to traces of O2 present in the solvent.68
(48)
N
The oxidation of a carboxylated tetrahydroisoquinoline can be
achieved in quantitative yield using NaH in DMF (eq 52).69 This
transformation is presumed to occur by addition of the enolate to
O
oxygen, followed by oxidative decarboxylation.
Me
Ph
S O O
NaH
MeO MeO
NaH
THF, rt
(52)
N Me
DMF, rt
85% NBn NBn
MeO quant. MeO
Me
MeO
CO2Me O
MeO
Me Sodium hydride can also be used to deprotonate certain sp2
S
(49)
carbon atoms. Deprotonation of acyldiazomethanes using sodium
Ph hydride followed by treatment with N-sulfonylamines gave N-
O
tosyl diazoketamines in good yields (eq 53).70
O
Ts
O
A general route to pyrroles has been developed using iso-
Ts
NH O
NaH
N
cyanides with sodium hydride in the presence of Michael accep- H + (53)
THF, 50 °C
OEt
Ph OEt
tors. The reagents tosylbenzyl isocyanide (TosBIC)64 and tosyl-
74%
Ph H
N2
N2
methyl isocyanide (TosMIC)65 have been the preferred reagents
in these transformations (eq 50). Pyrroles have also been pre-
pared using sodium hydride in conjuction with ²-carbonyl-O-
methyloximes via alkylation followed by intramolecular Michael The carbene of 1,3-dimethylimidazolium iodide can be gen-
addition.66 erated using sodium hydride. In the presence of a benzaldehyde
A list of General Abbreviations appears on the front Endpapers
SODIUM HYDRIDE 7
and an electron deficient aryl fluoride, this carbene can promote with sodium hydride effected reductive dehalogentaion of aryl
acylation of the aryl fluoride with the aldehyde (eq 54).71 chlorides and fluorides.78 The reduction of aldehydes and ketones
has been demonstrated using sodium hydride with dialkylzincs.
Dialkylzinc hydride  ate complexes are useful in the reduction of
F
Me
aliphatic aldehydes without promoting aldol reactions.79 Sodium
I
N
NaH
hydride is also useful in converting aryl halides into the corre-
+ PhCHO +
H
DMF, 0 °C
sponding biaryls when used with other metal cocatalysts. It is
N
57%
proposed that sodium hydride reduces Ni(OAc)2 and Al(acac)3 to
Me
NO2
produce subnanometrical Ni-Al clusters that are responsible for
(catalytic)
the coupling reaction (eq 58).80 A similar system using nickel and
zinc with sodium hydride to promote homocoupling of aryl and
Ph
(54)
vinyl halides has also been reported.81
O2N
O
Ni-Al (10 mol %)
R R
R
2.22 -bipyridine
X (58)
NaH
Lastly, sodium hydride can be used with allenyl ketones and
THF, 65 °C
dialkyl phosphites to give ²-alkynyl-enol phosphates (eq 55).72
X = Cl or Br 34-99%
The use of sodium hydride made the process highly stereoselctive
and nearly pure Z-isomer was isolated.
Deprotection. Deprotection of 2-(trimethylsilyl)ethyl esters
using sodium hydride in DMF occurred cleanly in the presence of
O OEt
O other silyl ethers (eq 59).82 The reactive intermediate is presumed
P OEt
NaH, (EtO)2POH
O
(55)
to be traces of  anhydrous sodium hydroxide generated from
"
CCl4/THF
R
adventitious water in the solvent.
R
O
61-74% yields
R = various aryl groups
TMS
>95:5 Z selective
NaH
O
DMF, rt
RO
O
Reductions. Elemental selenium can be reduced using sodium
hydride. The resulting sodium diselenide (Na2Se2) can be used to
(59)
OH
prepare dialkyl selenides (eq 55).73 Similarly, elemental sulfur can
RO
be reduced to diatomic sulfur by sodium hydride in the presence
R = TIPS (82%)
of a phase transfer catalyst.74
R = SEM (82%)
1. NaH, DMF, 70 °C
(56)
Se R Se R
2. R-Br, DMF, 20 °C
Debromination. Treatment of 1,1,2-tribromocyclopropanes
60 88%
R = alkyl with sodium hydride and dialkyl phosphates provides an efficient
route to 1-bromo-2-alkylcyclopropenes (eq 60).83
Sodium hydride has been used in combination with tellurium to
R Br
NaH, (EtO)2P(O)H
reduce carbon-selenium bonds in Ä…-phenylseleno carbonyl com-
(60)
R Br
neat, 0 °C
Br Br
pounds using DMF as the solvent without reducing the carbonyl
R = pentyl (64%)
functionality.75 Changing the solvent NMP enhances the red-
R = octyl (96%)
ucing ability of the telluride anion.76 Sodium telluride (Na2Te)
is generated by heating tellurium and sodium hydride in NMP
ć%
at 100 C. Aromatic aldehydes can be reduced by Na2Te at 80
Related Reagents. Calcium Hydride; Iron(III) Chloride
ć%
C. Surprisingly, 7-deazapurines can be obtained by treatment of
Sodium Hydride; Lithium Aluminum Hydride; Potassium
benzonitriles with sodium hydride/tellurium in NMP (eq 57).
Hydride; Potassium Hydride s-Butyllithium N,N,N ,N -Tetra-
methylethylenediamine; Potassium Hydride Hexamethylphos-
Ar
phoric Triamide; Sodium Borohydride; Sodium Hydride
copper(II) Acetate Sodium t-Pentoxide; Sodium Hydride
N
NaH, Te
nickel(II) Acetate Sodium t-Pentoxide; Sodium Hydride
(57)
ArCN
NMP, 100 °C
N
palladium(II) Acetate Sodium t-Pentoxide; Tris(cyclopenta-
N Ar
Me
dienyl)lanthanum Sodium Hydride; Lithium Hydride; Sodium
Ar = Ph, p-tolyl, m-tolyl
15-28%
Telluride.
Reduction of Ä…-chloro boronic esters using sodium hydride and
DMSO has been reported to give clean conversion to the dechlori-
1. (a) Mackay, K. M. Hydrogen Compounds of the Metallic Elements; Spon:
nated product.77 The combination of lanthanide chloride catalysts London, 1966. (b) Hurd, D. T. An Introduction to the Chemistry of
Avoid Skin Contact with All Reagents
8 SODIUM HYDRIDE
the Hydrides; Wiley: New York, 1952. (c) Wiberg, E.; Amberger, E. 38. Roussel, F.; Knerr, L.; Grathwohl, M.; Schmidt, R. R., Org. Lett. 2000,
Hydrides of the Elements of Main Groups I IV; Elsevier: New York, 2, 3043.
1971.
39. Di Nunno, L.; Franchini, C.; Nacci, A.; Scilimati, A.; Sinicropi, M. S.,
2. Tate, M. E.; Bishop, C. T., Can. J. Chem. 1963, 41, 1801. Tetrahedron: Asymmetry 1999, 10, 1913.
3. Doornbos, T.; Strating, J., Synth. Commun. 1971, 1, 175.
40. Besson, T.; Rees, C. W., J. Chem. Soc., Perkin Trans. 1 1996, 2857.
4. (a) Stoochnoff, B. A.; Benoiton, N. L., Tetrahedron Lett. 1973, 21.
41. Buttero, P. D.; Molteni, G.; Papagni, A.; Pilati, T., Tetrahedron 2003, 59,
(b) Brown, C. A.; Barton, D.; Sivaram, S., Synthesis 1974, 434.
5259.
5. Hajos, Z. G.; Duncan, G. R., Can. J. Chem. 1975, 53, 2971.
42. Sureshan, K. M.; Shashidhar, M. S.; Praveen, T.; Gonnade, R. G.;
Bhadbhade, M. M., Carbohydr. Res. 2002, 337, 2399.
6. (a) Brimacombe, J. S.; Jones, B. D.; Stacey, M.; Willard, J. J., Carbohydr.
Res. 1966, 2, 167. (b) Brimacombe, J. S.; Ching, O. A.; Stacey, M., J.
43. Peng, X.; Bondar, D.; Paquette, L. A., Tetrahedron 2004, 60, 9589.
Chem. Soc. (C) 1969, 197.
44. Takahashi, S.; Souma, K.; Hashimoto, R.; Koshino, H.; Nakata, T., J.
7. Kochi, J. K.; Hammond, G. S., J. Am. Chem. Soc. 1953, 75, 3443.
Org. Chem. 2004, 69, 4509.
8. Groenen, L. C.; Ruël, B. H. M.; Casnati, A.; Timmerman, P.; Verboom,
45. Chaudhary, A. G.; Chordia, M. D.; Kingston, D. G., I., J. Org. Chem.
W.; Harkema, S.; Pochini, A.; Ungaro, R.; Reinhoudt, D. N., Tetrahedron
1995, 60, 3260.
Lett. 1991, 32, 2675.
46. Chaudhary, A. G.; Rimoldi, J. M.; Kingston, D. G., I., J. Org. Chem.
9. Sato, F.; Tanaka, Y.; Sato, M., J. Chem. Soc., Chem. Commun. 1983, 165.
1993, 58, 3798.
10. Singh, B., Tetrahedron Lett. 1971, 321.
47. Albanese, D.; Landini, D.; Penso, M.; Spano, G.; Trebicka, A.,
11. Coggins, J. R.; Benoiton, N. L., Can. J. Chem. 1971, 49, 1968.
Tetrahedron 1995, 51, 5691.
12. McDermott, J. R.; Benoiton, N. L., Can. J. Chem. 1973, 51, 1915.
48. Subrayan, R. P.; Rasmussen, P. G., Tetrahedron 1995, 51, 6167.
13. (a) Baldwin, J. E.; Christie, M. A.; Haber, S. B.; Kruse, L. I., J. Am. Chem.
49. Mettery, Y.; Michaud, S.; Vierfond, J. M., Heterocycles 1994, 38, 1001.
Soc. 1976, 98, 3045. (b) Wasserman, H. H.; Hlasta, D. J.; Tremper, A.
50. Cesare, V.; Lyons, T. M.; Lengyel, I., Synthesis 2002, 1716.
W.; Wu, J. S., Tetrahedron Lett. 1979, 549. (c) Wasserman, H. H.; Hlasta,
51. Ohno, H.; Toda, A.; Fujii, N.; Miwa, Y.; Taga, T.; Yamaoka, Y.; Osawa,
D. J., J. Am. Chem. Soc. 1978, 100, 6780.
E.; Ibuka, T., Tetrahedron Lett. 1999, 40, 1331.
14. Corriu, R. J. P.; Guerin, C., J. Organomet. Chem. 1980, 197, C19.
52. Ohno, H.; Hamaguchi, H.; Tanaka, T., Org. Lett. 2001, 3, 2269.
15. Zaugg, H. E.; Dunnigan, D. A.; Michaels, R. J.; Swett, L. R.; Wang, T.
53. Xu, J.; Jiao, P., J. Chem. Soc., Perkin Trans. 1 2002, 1491.
S.; Sommers, A. H.; DeNet, R. W., J. Org. Chem. 1961, 26, 644.
54. Hirai, Y.; Watanabe, J.; Nozaki, T.; Yokoyama, H.; Yamaguchi, S., J.
16. (a) Kershaw, J. R.; Uff, B. C., J. Chem. Soc., Chem. Commun. 1966, 331.
Org. Chem. 1997, 62, 776.
(b) Uff, B. C.; Kershaw, J. R., J. Chem. Soc. (C) 1969, 666.
55. Azoulay, S.; Monteiro, N.; Balme, G., Tetrahedron Lett. 2002, 43, 9311.
17. Pi, R.; Friedl, T.; Schleyer, P. v. R.; Klusener, P.; Brandsma, L., J. Org.
56. Garcon, S.; Vassiliou, S.; Cavicchioli, M.; Hartmann, B.; Monteiro, N.;
Chem. 1987, 52, 4299.
Balme, G., J. Org. Chem. 2001, 66, 4069.
18. Hinckley, A. A. Sodium Hydride Dispersions; Metal Hydrides, Inc., 1964
57. Shen, Y.; Friestad, G. K., J. Org. Chem. 2002, 67, 6236.
(quoted in: Fieser & Fieser 1967, 1, 1075) .
58. Lalot, J.; Manier, G.; Stasik, I.; Demailly, G.; Bequpere, D., Carbohydr.
19. Swamer, F. W.; Hauser, C. R., J. Am. Chem. Soc. 1946, 68, 2647.
Res. 2001, 335, 55.
20. Ainsworth, C., Org. Synth., Coll. Vol. 1963, 4, 536.
59. Harrison, P. A.; Murtagh, L.; Willis, C. L., J. Chem. Soc., Perkin Trans.
21. (a) Bloomfield, J. J., J. Org. Chem. 1961, 26, 4112. (b) Bloomfield, J. J.,
1 1993, 3047.
J. Org. Chem. 1962, 27, 2742. (c) Anselme, J. P., J. Org. Chem. 1967,
32, 3716. 60. Taggi, A. E.; Wack, H.; Hafez, A. M.; France, S.; Lectka, T., Org. Lett.
2002, 4, 627.
22. Miles, M. L.; Harris, T. M.; Hauser, C. R., J. Org. Chem. 1965, 30, 1007.
61. Vales, M.; Lokshin, V.; Pepe, G.; Guglielmetti, R.; Samat, A.,
23. Gruen, H.; Norcross, B. E., J. Chem. Educ. 1965, 42, 268.
Tetrahedron 2002, 58, 8543.
24. (a) Ref. 18. (b) Daub, G. H.; Johnson, W. S., J. Am. Chem. Soc. 1948,
62. Van de Poel, H.; Guillaumet, F.; Viaud-Massuard, M. C., Tetrahedron
70, 418. (c) Daub, G. H.; Johnson, W. S., J. Am. Chem. Soc. 1950, 72,
Lett. 2002, 43, 1205.
501.
63. Kim, B. S.; Kim, K., Tetrahedron Lett. 2001, 42, 4637.
25. (a) Ref. 18. (b) Della Pergola, R.; DiBattista, P., Synth. Commun. 1984,
14, 121.
64. Di Santo, R.; Costi, R.; Massa, S.; Artico, M., Synth. Commun. 1995,
25, 795.
26. Stork, G.; Winkler, J. D.; Saccomano, N. A., Tetrahedron Lett. 1983, 24,
465.
65. Frieman, B. A.; Bock, C. W.; Bhat, K. L., Heterocycles 2001, 55,
2099.
27. Pinkney, P. S., Org. Synth., Coll. Vol. 1943, 2, 116.
28. Liu, H.-J.; Lai, H. K., Tetrahedron Lett. 1979, 1193. 66. Song, Z.; Reiner, J.; Zhao, K., Tetrahedron Lett. 2004, 45, 3959.
29. Powers, J. C.; Seidner, R.; Parsons, T. G., Tetrahedron Lett. 1965, 1713. 67. Dejaegher, Y.; Mangelinckx, S.; De Kimpe, N., J. Org. Chem. 2002, 67,
2075.
30. Carbon, J. A.; Martin, W. B.; Swett, L. R., J. Am. Chem. Soc. 1958, 80,
1002. 68. Stefanic, P.; Breznik, M.; Lah, N.; Leban, I.; Plavec, J.; Kikelj, D.,
Tetrahedron Lett. 2001, 42, 5295.
31. Tamura, Y.; Sasho, M.; Nakagawa, K.; Tsugoshi, T.; Kita, Y., J. Org.
Chem. 1984, 49, 473. 69. Bois-Choussy, M.; De Palois, M.; Zhu, J., Tetrahedron Lett. 2001, 42,
3427.
32. Bortolussi, M.; Bloch, R.; Conia, J. M., Tetrahedron Lett. 1977, 2289.
70. Jiang, N.; Ma, Z.; Qu, Z.; Xing, X.; Xie, L.; Wang, J., J. Org. Chem.
33. Corriu, R. J. P.; Guérin, C., J. Chem. Soc., Chem. Commun. 1980, 168.
2003, 68, 893.
34. Krull, L. H.; Friedman, M., Biochem. Biophys. Res. Commun. 1967, 29,
71. Suzuki, Y.; Toyota, T.; Imada, F.; Sato, M.; Miyashita, A., Chem.
373.
Commun. 2003, 1314.
35. Lee, Y.-J.; Closson, W. D., Tetrahedron Lett. 1974, 381.
72. Ding, Y.; Huang, X., Synth. Commun. 2001, 31, 449.
36. Natsume, M.; Kumadaki, S.; Kanda, Y.; Kiuchi, K., Tetrahedron Lett.
1973, 2335. 73. Krief, A.; Derock, M., Tetrahedron Lett. 2002, 43, 3083.
37. Liu, W.; Szewczyk, J.; Waykole, L.; Repic, O.; Blacklock, T. J., Synth. 74. Okuma, K.; Kuge, S.; Koga, Y.; Shioji, K.; Wakita, H.; Machiguchi, T.,
Commun. 2003, 33, 2719. Heterocycles 1998, 48, 1519.
A list of General Abbreviations appears on the front Endpapers
SODIUM HYDRIDE 9
75. Silveira, C. C.; Lenardao, E. J.; Comasseto, J. V., Synth. Commun. 1994, 80. Massicot, F.; Schneider, R.; Fort, Y.; Illy-Cherry, S.; Tillement, O.,
24, 575. Tetrahedron 2001, 57, 531.
76. Suzuki, H.; Nakamura, T., J. Org. Chem. 1993, 58, 241. 81. Lin, G.; Hong, R., J. Org. Chem. 2001, 66, 2877.
77. Matteson, D. S.; Soundararajan, R.; Ho, O. C.; Gatzweiler, W., 82. Serrano-Wu, M. H.; Regueiro-Ren, A.; St. Laurent, D. R.; Carroll, T.
Organometallics 1996, 15, 152. M.; Balasubramanian, B. N., Tetrahedron Lett. 2001, 42, 8593.
78. Zhang, Y.; Liao, S.; Xu, Y.; Yu, D., Synth. Commun. 1997, 27, 4327. 83. Al Dulayymi, A. R.; Baird, M. S., J. Chem. Soc., Perkin Trans. 1 1994,
1547 and 3047.
79. Uchiyama, M.; Furumoto, S.; Saito, M.; Kondo, Y.; Sakamoto, T., J. Am.
Chem. Soc. 1997, 119, 11425.
Avoid Skin Contact with All Reagents