Charles E. Miller' Columbia University
Hydrogenation with Diimide
N e w York City
T h e azo compound diirnide (HN=NH) is a short-lived species recently recognized for its ability t,o hydrogenate nlultiple bonds. Its selectivity (both fuiictional and stereo-) malies diimide reduction a useful alternative to catalytic hydrogenation. Diimide exists as a transient intermediate and cannot be isolated under normal condit,ions. I t is more stable a t low temperatures, however, and was first detected in the solid state in 1955 by Dows, Pimentel, and Whittle (I) and in 1958 by Foner and Hudson (Z) as one of the products in the electrical decomposition of hydrazine and hydrazoic acid. The latter authors found that by condensing the gaseous deconlposition products on a surface cooled by liquid nitrogen (77'R), a yellow solid formcd consisting of ammonia and a new substance whose infrared and mass spectra indicated that it possessed the diimide structure (8, 3). When this yellow material was allowed to warm up above 120°K, it decoinposed into ammonia, nitrogen, and hydrazine; the last two products presunlably arose from disproportionation of the diimide (see below). Dows, Pimentel, and Whittle (1) considered the following possible struct,ures for diimide: H-N=N-H
/
N=N
H
H \
N=N'
Diinlide reduces nonpolar carbon-carbon and nitrogen-nitrogen n~ultiplebonds such as olefins, acetylenes, and azo compounds:
Acetylenes
/H Azo Compounds
H
+/ N=N
non-planar (as in HaOs)
\H (4
Analysis of the infrared spectrum of the substance in question tended to eliminate (c) and ( d ) as possible structures, although no basis could be found for choosiug between (a) and ( b ) . Since the instability of diimide precludes its isolation, procedures for these reductions necessarily involve generation of the reagent iu sik. Such methods include: oxidation of hydrazine acid decomposition of aaodioarboxylate salts action of alkali on certain sulfonyl and acyl hydrazides thermal decomposition of the diimide-anthracene adduet, anthraeene-9,lO-biimhe (.5 .) alkaline decom~osition of hydroxylamhe-Oaulfonic acid ( 6 ) alkaline decomposition of chloramine (1) (2) (3) (4)
'Acknowledgment is made to the National Institutes of Health for support of this work.
/
Selectivity
-
(c)
254
This variety of methods permits choice of a wide range of reaction conditions t o suit the stability requirements of the substrate. Since the fate of the diimide molecule arid its behavior toward reducible systems are independent of the mode of preparation, the reducing properties of diimide will be treated first, after which methods for carrying out these reductions will be discussed.
Journal o f Chemical Education
The yield of product decreases with increasing subst,itution and crowding about the multiple bond (4, 5). Thus, acetylenes and mono- and disubstituted olefins are ordinarily reduced in yields of 70-90%, whereas trisubstituted olefins are reduced in yields of 20-40%. Although diimide reduces acetylenes to alkenes as in equat,ion (2), the method is not generally useful for preparing alkenes since the olefin is reduced t o the saturated compound a t a comparable rate (6). A special case of the reduction of azo compounds shown in equation (3) is that in which diimide, acting as both a hydrogen donor and an acceptor, undergoes disproportionation, which is the main side reaction in diimide reductions: H
H
On the other hand, polar functional groups, many of
which undergo catalytic hydrogenation, are usually inert toward diimide under those conditions in which nonpolar multiple bonds are reduced (7,s) : -C=O -C=N
-NO. -N=C
-C-S-0-O-
/
\ Thus, the vinyl groups on chlorins and porphyrins have been reduced to ethyl groups by diimide (generated from hydrazine) without disturbing the other multiple bonds of these systems (9). The presence of sulfur in a molecule does not seem to affect the ability of diimide as a reducing agent as is the case in metal catalyzed hydrogenation. For example, ally1 disulfide is reduced to n-propyl disulfide. This reduction cannot be performed in any other way (7) :
catalytic processes (8). Also, deutero-diimide is an excellent way of introducing deuterium across a multiple bond, since there is no danger of deuterium-hydrogen exchange in other parts of the molecule which often occurs in metal catalyzed reactions (11). Stereochemistry
It has been well established through isotopic labeling experiments that diimide reduction proceeds with cisaddition across the multiple bond (6): R R
\
-
/
C=C
H
HN=NH
\
(5)
/
1:
I
-
/
or
\st
C . . .D
(9)
R H
1 1 -+ D...CC...D I I DN=ND
(10)
H R dl (97% yield)
Also, symmetrical cis-tetrasubstituted olefins are hydrogenated to the meso derivatives, indicating cis-addit,ion of hydrogen: Me
HOOd
C-C-C-
H
\R
/
c=c
\+
g7
-COOH
iI 4
trans
\
C=C-Ctt
-CH*OH;
meso (97% yield)
C=C
H
=
..
.
H '
R
If the stability of polar multiple bonds toward diimide is in fact due to their polarity, then it would be expected that a,B-unsaturated carbonyl compounds, for example, would be somewhat less reactive toward diimide due to the polarity of the double bond:
DN=ND
D
cis
CHFCH-CH2-SS-CH1-CH=CHp CHaCHsCH-CTS-CH,CH,CH,
Although conjugated systems have not been studied in detail, it is known that aromatic nuclei are stable to diimide, whereas conjugated dienes are reduced, since attempts to trap diimide by Diels-Alder interception with cyclopentadiene resulted in the formatiou of cyclopentene and cyclopentane (4,lO) :
R
Me Me
lle HN=NH
-AH...LL...H
\COOH
(11)
I
HOOd COO" mew
Acetylenic linkages are converted to cis-olefin and saturated compound, without any trans-olefin being produced (6,10, 13):
s-
C=C-C
/
On the ot,her hand, multiple bonds which are flanked on both sides by the same polar groups should themselves be nonpolar and hence easily reduced by diimide, as wac; shown by Corey (6) and van Tamelen (11) : -&LC-c-
I
HN=NH
-GAL!-c-
-A
I1
X
(7)
T O-r C
X H H
Recent studies indicate that diimide attacks trans double bonds more rapidly than cis double bonds. Thus, fumaric acid is more rapidly reduced than maleic acid (5), although there appears to be little difference in the rate of reaction with isomers such as oleic (cis) and elaidic (trans) acids (8). Trans double bonds are also rcduced faster than cis double bonds when both are present on the same molecule (13):
= + C~ @
H
.
C
H
,
.
,
~
Product studies show that during diimide reduction, Stereochemicol Results of Diimide Reduction
Olefin reduced
Product ( % cis: lmns)
Zmkthylrnethylenecyclohexane 61 :39 bGh~>t,vlrnet,hvlene" ~~~~~~~, -.~~. cyclohenane 49:51 camphene 92(endo):X(exo) 2-norhorneneendo-cis (by isoh2,3-dicsrhoxylic acid tian of a. single product in 40% vield)
Catalytic redn. (Pt.) product iOio em:trans)
68:32
~
In addition to high functional specificity, diimide possesses other advantages over metal catalyzed hydrogenation. For example, diimide reduction gives no migration or cis-trans isomerization of double bonds when reduct,ioo is done in stages as is characteristic of
83: 17 75(endo):25(exo) endo-cis
Volume 42, Number 5, May 1965
/
255
hydrogen insertion occurs from the less hindered side of the molecule (11). Where bulk effects are large, reduction is highly subject to steric approach control. However, when steric effects are moderate, there is less stereochemical discrimination, although the stability of the product still does not govern the course of the reaction. I n the following examples from the table ( l l ) , the olefins chosen were those in which approach from the less hindered side resulted in the less stable product:
would be expected to proceed similarly. The following points support the above mechanism: (1) A four-center mechanism is in agreement with the observed &-addition of hydrogen across multiple bonds. Since the addition of deutero-diimide across cis and trans olefins results almost exclusively in meso and dl products, respectively (see above), there is little likelihood of a step-wise addition of hydrogen. In such a mechanism, the trigonal carbon atom generated could \
hZ
C=C
/
-
\
/ + \ / (14)
i &OOH COOH endo-cis (40%yield)
2-norbornene2,s-dicarboxylic acid
HN=NH
-
- / \
/
+ ' / +N=N
\
CH-C
CH-CH
(18)
H-NeN
result in an epimeric center, giving both meso and dl products from both eis and trans olefins (6,lO). (2) Corey (4) has shown (from thermodynamic values obtained from mass spectral data) that the reduction step is highly exothermic (AH- -70 to -80 kcal/mole). This, together with the fact that such reactions are fast, permits application of the Hammond Postulate (5, 18, Id), which states that if a one-step reaction is fast and highly exothermic, the structure of the transition state should resemble that of the reactants more closely than it does that of the products. Moreover, if the rate of the over-all reaction is comparable to that of the formation of intermediate complex shown in equation (17), then the complex and the transition state should closely resemble each other. (3) The mechanism agrees with the observation that the rate of reduction (as measured by the yield of product) decreases with increasing substitution about the multiple bond due to steric crowding in the transition state. Furthermore, the transition state complex should be more cluttered for cis than for trans olefins, since in the former case the substituents are crowded more closely together when going from the olefin to the tetrahedral bond angle of log", thereby raising the activation energy (5). This theory is supported by the observed faster rate of hydrogenation of trans olefins over that of cis olefins.
I n the first two examples approach from the underside of the molecule is hindered by the two hydrogen atoms projecting downward from the fifth and sixth carbon atoms. The last example is interesting since it demonstrates that, although the approach is equally hindered from either direction, the more and less stable products are formed in approximately equal amounts.
cis
Mechanism
The mechanism of diirnide reduction of a multiple bond is believed to involve what has been described as a "synchronous transport" of hydrogen through a cyclic transition state (6, 7, 10):
+
111
N
+
I I H-CI
H-C-
(17)
The reaction of acetylenes and azo compounds 256
/
Journul of Chemical Education
(4) Under ordinary conditions, hydrogenation of multiple bonds using substituted hydrazines such as phenyl or hydroxyethyl hydrazine have been unsuccessful (8). The substituted diimides thus formed as intermediates could not be expected to react with multiple bonds according to the above mechanism. (5) Condnctometric studies show that the reduction step is nonionic (8). Moreover, para-substituents on
cinnamic acid have almost no effect on the rate of hydrogenation of the triple bond. This means that electronic interaction between the aromatic moiety and the reaction center is weak, which is understandable if the transition state is weakly polar (6). (6) The stability of polar multiple bonds (see above) toward diimide may be due in part to the higher activa tion energy required to form the correspondingly more polar transition state complex (7).
less polar
more polar
A point of interest concerning the four-center mechanism is that the diimide must have the syn-conformation in the six-membered cyclic transition state. There are three ways of satisfying this requirement, assuming that syn- and anti-diimide are more stable than the linear form: (1) anti-diimide is converted to the synform when forming the transition state complex, such a process requiring a certain expenditure of energy which contributes to the energy of activation; (2) the synand anti-forms may be in rapid equilibrium with each other as in equation (21);
anti
N /H
N /H
N
N
I]
11
S W
(21)
(3) syn- and anti-diimide are formed independently and are non-interconvertible, the syn-form being the only one which reacts with the multiple bond. This possibility was proffered by Aylward and Sawistowska (8) to explain the fact that the kinetics of the reduction (with hydrazine as the source of diimide) showed that exactly two molecules of hydrazine were required to reduce one double bond. They postulated the following mechanism for the format,ion of diimide from hydra zine:
As shown in equation (22), the syn- and anti-diimide are formed in equal amounts.
early as 1914 that hydrazine reduces oleic to stearic acid (16). Gibberellic acid is smoothly converted, stereospecifically, to tetrahydrogibberellic acid in hydrazineethanol (16) :
HsC
HaC
COOH H
(23)
These reductions were performed in open vessels, since oxygen was found necessary for the reactions to take place (17, 18). Other oxidizing agents were later employed, such as potassium periodate (lQ), ferricyanide ion (5, 20), and hydrogen peroxide (4). I t became apparent that the function of the oxidant was to convert the hydrazine to something capable of reducing multiple bonds, and, in 1961, Corey (4) postulated the intermediacy of diimide, based on thermodynamic data and on the fact that diimide had recently been detected by infrared and mass spectrometry as a product in the electrical decomposition of hydrazine a t low temperatures (see above). Diimide is also believed to be responsible for the hydrogenation of double bonds during WolffIcishner reduction of certain unsaturated keto acids with hydrazine (10). A recent study of hydrazine reductions by Aylward and Sawistowska (8) has brought to light a number of interesting facts: (1) in aqueous and alcoholic solutions of hydrazine, the results are poor or negative unless the pH is between 8.5 and 9.0; (2) reduction of an olefin does not occur unless a carboxylic acid function is present, either on the substrate molecule or else added externally. This, together with the fact that conductometric measurements showed the transient existence of a cationic species, indicates acid catalysis; (3) kinetic measurements showed that two molecules of hydrazine are required for the hydrogenation of one double bond (see above); (4) it was found that only those oxidizing agents which act as L'didelectronators"toward hydrazine are effective in reducing multiple bonds. Such oxidations were postulated by Audrieth and Ogg (17) as proceeding via the following acid-catalyzed scheme:
(2) From azodicarboxylate salts. Attempts to prepare diimide per se were first made by Thiele in 1892, who made potassium azodicarboxylate and found that it decomposed in warm water (21):
Methods of Generating Diimide
(1) From hydrazine. Although only recently discovered, diimide has been used as a hydrogenating agent for over 50 years, with aqueous and alcoholic solutions of hydrazine as reaction media. Thus, it was known as
COOH
CHs
COO-KC
1
2
ff + 2H20 -N. + N A+ 2C02 + 2KsCOs
(25)
/
257
I
Volume 42, Number 5, May 1965
He reasoned correctly that the nitrogen and hydrazine arose from disproportionation of diimide, whose instability precluded its isolation.
-
H O H H
I I I I
I
H-5-&-N-a-HT-oH
HSO
+
cI-
COO-K'
I n the absence of olefin, the diimide undergoes disproportionation to nitrogen and hydrazine as in equation (4). The hydrazine thus formed is acetylated by the ketene to give acetylhydrazide, which can be isolated: 2HN-NH
Further studies on the decomposition of azodicarboxylate salts were made by King (22), who found the reaction to he subject to general acid catalysis. When the above reaction is performed in the presence of an olefin, reduction of the latter occurs, and the method has found some use in preparative work (4,6, 7, 10, 25, 24). For example, "Dewar benzene," recently synthesized by van Tamelen (M), is hydrogenated by diimide generated from potassium azodicarboxylate in pyridine-water-acetic acid solution:
-
Nz
+ HnN-NHI
.1
HsC=C=O
0
(31)
cHa-LH-N&
(4) Thermal decomposition of the diimide-anthracene adduct, anthracene-9J0-biimine. I n order t,o avoid use of acid or basic media when generating diimide, Corey and Mock (28) devised a method whereby the reagent could he formed by heating anthraceue-9,lO-biimline together with the olefin in refluxing ethanol. The scheme for the procedure is as follows:
+* COOEt
bicyclo [2. 2.01 hexane
a
+;
I COOEt
(3) Action of alkali on certain sulfonyl and a y l hydrazides. Other attempts a t preparing diimide were made by Raschig (85), who decomposed benzenesulfonyl hydrazide with sodium hydroxide, hoping to form diimide by beta-elimination:
However, in addition to sodium benzenesulfinate, he obtained only hydrogen and nitrogen. It was later found by Hiinig and co-workers (10) that when this reaction is carried out in the presence of olefins (with boiling glycol monomethyl ether as the solvent), reduction of the latt,er occurs in high yield. At about the same time, Dewey and van Tamelen (26) found that paratoluenesulfonylhydrazide in boiling diglyn~ebehaved sin~ilarlytoward olefins:
COOEt I
N'
N 'COOE~
The yields of reduced olefin are comparable to those obtained by the other methods. (5) Alkaline decomposition of hyd~ozylamine-0-su1fonic acid. Appel and Biichner (IS) found that simple olefins such as ethylene, cyclohexene, and fumaric acid are hydrogenated by hydroxylamine-0-sulfonic acid in aqueous or methanolic alkali. Yields were of the order of 40%. The reaction is believed to proceed through the formation of "nitrene" which dinlerizes to diimide:
OH-
1
[HN=NHI
I\
,c=c'
More recently, a procedure was found whereby the redurtion eould be accomplished rapidly a t O°C ($7). 258
/
Journal o f Chemical Educdion
(33)
a
( 6 ) Allcaline decomposition of chloramine. According to Raschig ($9),the above mechanism applies also to the alkaline decomposition of rhloramine: NH&I
+ NaOH
-
NaCl
+ Ha0 + [NH]
(34)
Recently, Schmitz and Ohne (SO) applied the reaction to the reduction of olefins. Thus, undecylenic acid is reduced to undecanoic acid in 80% yield in the presence of four moles of chloramine and alkali. Cinnamic acid is reduced to hydrocinnamic acid and maleic acid to succinic acid in 50% yield. All the above methods for hydrogenating multiple bonds, although versatile, have the common disadvantage of requiring large excesses of reagent with respect to the amount of substrate because of the compet,ing reaction whereby diimide undergoes disproportionation as in equation (4). Nevertheless, hydrogenation with diimide illustrates the growing trend in organic chemistry in which highly unstable species, such as diimide, carhenes, and nitrenes have become synthetically useful reagents.
( 8 ) AYLWARD, F., A N D SAWISTOWSKA, M., Chem. Ind. (London), 484, (1962). ( 9 ) FISCHER,H., A N D GIBIAN, H., Ann., 548, 183 (1941); 550, 208 (1942). (101 H i i ~ l o . 5.. MWLLER. H.. A N D THIER. W.. Tetraherlrn
. ,
,
,
(11) TAN TAMELEN, E. E., AND TIMMONS, R. J., J. Am. Chem. Soc., 84, 1067 (1962). (12) OHNO,M., h N D OKAMOTO,M., Telrahed~on Lellers, 35, 2423 (1964). W., Angm. Chem., 73, 807 (13) APPEL, R., AND BWCHNER, ,,Of,\ \'""',. ( 1 4 ) HAMMOND, G. S., J . Am. Chem. Soe., 77, 334 (1955). P., A N D MANNINO, A,, Ann. Chim. Appl., 2, 351 ( 1 5 ) FALCIOLA, 119141. (16) C&S, k. E., J . Chem. Soe., 3022 (1960). (17) AUDRIETH,L. F., A N D OGG, B. A,, "The Chemistry of Hydrazine," John Wiley and Sons, Ine., New York, 1951, Chapter VI. (18) AYLWARD, F., A N D SAWISTOWSKA, M., Chem. Ind., 404, 433 (1961). J. S., J . Am. Chem. Sot., 85, (19) GRIM, n. J., A N D BRADSHAW, 1108 119631. ~, HANUSJ., AND VORISEK,J., Collection Czech. Chem. Commun., 1, 223, (1929). THIELE,J., Ann. 271, 127 (1892). KING,C. V., J . Am. Chem. Soc., 62, 379 (1940). VAN TAMELEN, E. E., AND PAPPAS,S. P., J . Am. Chem. Soc., 85, 3297 (1963). VAN TAMELEN, E. E., DEWEY,R. S., AND TIMMONE., K. J., J. Am. Chem. Soe.. 83. 3725 (1961). RASCHIG, F., Z. ~ n g k w ~hem.,'23,9'72 . (1910). DEWEY,R. S., AND VAN TAMELEN, E. E., J. Am. Chem. Soe., 83, 3729 (1961). BUYLE,R., V A N OVERBTRAETEN, A,, A N D ELOY,F., Ghem. Ind. (London),839 (1964). COREY,E. J., AND MOCK,W. L., J. Am. Chem. Soc., 84, 685 (1962). ( 2 9 ) Rascnm, F., "Sehwefel- und Stickstoffstudien," Berlsg Chernie, Leipig-Berlin, 1924, p. 74. E., AND OHNE,R., Angm. Chem., 73, 807 (1961). (30) SCHMITZ,
.
Literature Cited ( 1 ) Ilows, D. A., PIMENTEL, G. C., AND WHITTLE,E. J. Chem. Phys., 23, 1606 (1955). R. C., J. Chem. Phys., 28, 719 ( 2 ) FONER,S. F., AND HUDSON, ,lo**\ ,."w,.p
( 3 ) BLAU,E. J., HOCHHEIMER, B.F., AND UNGER, H. J., J. Chem. Phys., 34, 1060 (1961). ( 4 ) COREY,E. J., MOCK,W. L., AND PASTO,D. J., Tetrahedron Letters, 11,347 (1961). ( 5 ) HBNIG,S., A N D MWLLER,H. R., Angm. Chem., 74, 215
-.
11Qfi2) \ * ,
( 6 ) COREY, E. J., PASTO,D. J., A N D MOCK,W. L., J . Am. Chem. Soe., 83, 2957 (1961). E . E., ET AL., J. Am. C h a . Soc., 83, 4302 ( 7 ) VAN TAMELEN, (1961).
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