Determination of hydride affinities of various aldehydes and ketones in acetonitrile

Article abstract of DOI:10.1021/ol2006488

Chemical equations presented. The hydride affinities of 21 typical aldehydes and ketones in acetonitrile were determined by using an experimental method, which is valuable for chemists choosing suitable reducing agents to reduce them. The focus of this paper is to introduce a very facile experimental method, which can be used to determine the hydride affinities of various carbonyl compounds in solution.

Full text of DOI:10.1021/ol2006488

ORGANIC
LETTERS
2011
Vol. 13, No. 9
2456–2459
Determination of Hydride Affinities of
Various Aldehydes and Ketones in
Acetonitrile
Xiao-Qing Zhu,* Xi Chen, and Lian-Rui Mei
The State Key Laboratory of Elemento-Organic Chemistry, Department of Chemistry,
Nankai University, Tianjin 300071, P. R. China
xqzhu@nankai.edu.cn
Received March 16, 2011
ABSTRACT
The hydride affinities of 21 typical aldehydes and ketones in acetonitrile were determined by using an experimental method, which is valuable for
chemists choosing suitable reducing agents to reduce them. The focus of this paper is to introduce a very facile experimental method, which can
be used to determine the hydride affinities of various carbonyl compounds in solution.
The reduction of aldehydes and ketones by the addition
of a hydride ion is an issue of fundamental importance in
chemistry and biochemistry. Consequently, there have
been many studies of the reductions of various aldehydes
and ketones with a wide variety of reagents.1,2 Since the
hydride affinity of aldehydes and ketones is one crucial
thermodynamic parameter to scale the chemical activity of
aldehydes and ketones for their reductions, there are many
chemists who have contributed much time to examine the
hydride affinities of aldehydes and ketones.3,4 However,
the available data related to the hydride affinities of
aldehydes and ketones are all limited to the gas phase
and most of them come from theory estimation using a
computer.3,4 No experimental method can be available to
directly determine the hydride affinities of aldehydes and
ketones in solution. The main reason is that the hydride ion
solution is not available. Moreover, some side reactions, in
general, appear during the reduction processes of alde-
hydes and ketones, which strictly hinder the development
of an efficient experimental method. Since the theoretical
results require further identification of experimental results
and most reductions of aldehydes and ketones in research
laboratories and industries all take place in solution, experi-
mental data for hydride affinities of aldehydes and ketones
in solution should be very important and urgently required.
In our previous paper,5 we reported an efficient experi-
mental method to determine the hydride affinity of various
polarized olefins in acetonitrile by using N-methylacridinium
perchloride as a hydride acceptor. But when we subse-
quently extended this method to determine the hydride
affinity of aldehydes and ketones in dry acetonitrile, the
extensions were all in failure. The reason is that N-methyl-
acridinium perchloride is not an efficient hydride acceptor
tothe hydridesof aldehydesandketones(alkoxideanions),
but a good electrophilic agent to combine with the alkoxides
(Scheme 1). The reason could be that the formed ether
(1) (a) Patai, S., Ed. The Chemistry of Carbonyl Group; Interscience;
New York, 1966, 1970; Vols. 1 and 2. (b) Jencks, W. P. Acc. Chem. Res.
1980, 13, 161. (c) Hajos, A. Comlex Hydrides; Elsevier: New York, 1979.
(d) March, J. Advanced Organic Chemistry; John Wiley and Sons, Inc.: New
York, 1985; p 809.
(2) (a) Malkov, A. V. Angew. Chem., Int. Ed. 2010, 49, 9814. (b)
Inagaki, T.; Ito, A.; Ito, J.; Nishiyama, H. Angew. Chem., Int. Ed. 2010,
49, 9384. (c) Tajuddin, H.; Shukla, L.; Maxwell, A. C.; Marder, T. B.;
Steel, P. G. Org. Lett. 2010, 12, 5700. (d) Shalbaf, H. Asian J. Chem.
201022, 6761. (e) Eagon, S.; DeLieto, C.; McDonald, W. J.; Haddenham,
D.; Saavedra, J.; Kim, J.; Singaram, B. J. Org. Chem. 2010, 75, 7717.
(3) (a) Rosenberg, R. E. J. Am. Chem. Soc. 1995, 117, 10358. (b)
Rosenberg, R. E. J. Org. Chem. 2008, 73, 6636. (c) Gronert, S.; Keeffe,
J. R. J. Am. Chem. Soc. 2005, 127, 2324. (d) Goebbert, D. J.; Wenthold,
P. G. Int. J. Mass Spectrom. 2006, 257, 1.
(4) (a) Madura, J. D.; Jorgensen, W. L. J. Am. Chem. Soc. 1986, 108,
2517. (b) Blake, J. F.; Jorgensen, W. L. J. Am. Chem. Soc. 1987, 109,
3856. (c) Yamabe, S.; Minato, T. J. Org. Chem. 1983, 48, 2972. (d) Lee,
I.; Lee, D.; Kim, C. K. J. Phys. Chem. A 1997, 101, 879. (e) Lee, I.; Kim,
C. K.; Li, H. G.; Sohn, C. K.; Kim, C. K.; Lee, H. W.; Lee, B.-S. J. Am.
Chem. Soc. 2000, 122, 11162.
(5) Zhu, X.-Q.; Zhang, M.; Liu, Q.-Y.; Wang, X.-X.; Zhang, J.-Y.;
Cheng, J.-P. Angew. Chem., Int. Ed. 2006, 45, 3954.
r
10.1021/ol2006488
Published on Web 04/01/2011
2011 American Chemical Society

Scheme 1. Reaction Selectivities of the Hydrides of Aldehydes
and Ketones with Oxoammonium and Acridinium in Acetoni-
trile
Figure 1. Isothermal titration calorimetry (ITC) for the reaction
heat of alkoxide anion 6Hꢀ with 4-acetylamino-2,2,6,6-tetra-
methylpiperidine-1-oxoammonium perchlorate (TEMPOþ) in
acetonitrile at 298 K. Titration was conducted by adding 10 μL
of TEMPOþ (1.75 mM) every 500 s into the acetonitrile con-
taining the 6Hꢀ (ca. 20.0 mM), which was obtained in situ from
the reactions of the corresponding saturated neutral compounds
(6H2) with KH.
(X) in acetonitrile can be derived from the hydride affinity
of TEMPOþ and the reaction heat of TEMPOþ with the
hydrides of aldehydes and ketones (XHꢀ) in acetonitrile
(eq 4). In eq 4, Qrxn is the reaction heat of eq 3 in
acetonitrile, which can be determined by titration calori-
bond, RꢀOꢀR0, is a strongchemical bond [BDE(CꢀO) =
85.6 kcal/mol],6 which indicates that carbenium ions can-
not be used to determine the hydride affinity of aldehydes
and ketones in solution according to the strategy applied in
the previous paper.5 Although we were frustrated in the
determination of the hydride affinity of aldehydes and
ketones in solution, we believe that organic oxygen cations
should be a suitable agent for abstracting hydride anions
from the hydrides of aldehydes and ketones in solution,
because the peroxide bond (ROꢀOR0) is a weak chemical
bond [BDE(OꢀO) = 39.1 kcal/mol],6 which is unfavor-
able to the formation of peroxide products when the
hydrides of aldehydes and ketones are treated with organic
oxygen cations in solution. According to this idea, we finally
found that 4-acetylamino-2,2,6,6-tetramethyl-piperidine-1-
oxoammonium perchlorate (TEMPOþ) is quite a suitable
hydride acceptor for abstracting hydride anions from the
hydrides of aldehydes and ketones in acetonitrile without
any side products, which can be used to determine the
hydride affinity of various aldehydes and ketones in
acetonitrile.7 Herein we wish to report the detailed experi-
mental results.
metry (Figure 1); ΔHH A(TEMPOþ) is the hydride affinity
ꢀ
of TEMPOþ in acetonitrile (ꢀ105.6 kcal molꢀ1), which is
available from the reaction heat of TEMPOþ with BNAH.
The hydride affinities of 21 typical aldehydes and ketones
in acetonitrile and the corresponding Qrxn in acetonitrile
are summarized in Table 1.
The hydride affinity of aldehydes and ketones (X) in
acetonitrile inthisworkwas defined as the enthalpychange
of the aldehydes and ketones [ΔHH-A(X)] to capture a
hydride ion in acetonitrile (eqs 1 and 2). According to eq 3,
it is clear that the hydride affinity of aldehydes and ketones
Table 1 shows that the hydride affinities of the 6 alde-
hydes (1ꢀ6) in acetonitrile range from ꢀ31.6 kcal/mol (4)
to ꢀ47.1 kcal/mol (5) and the hydride affinities of the 15
ketones (7ꢀ21) in acetonitrile range from ꢀ28.9 kcal/mol
for ketone 7 or 8 to ꢀ61.8 kcal/mol for ketone 17. Since the
hydride affinities of the aldehydes and ketones are all much
smaller than those of the general carbocations, such as the
benzyl cation [ΔHH-A(PhCH2þ) = ꢀ122.9 kcal/mol]9 in
acetonitrile, these aldehydes and ketones should be all
due to very weak hydride acceptors, which indicates that
these aldehydes and ketones are quite difficult to reduce
with mild organic reducing agents, such as BNAH
(1-benzyl-1,4-dihydronicotinamide), HEH (Hantzsch
(6) Luo, Y.-R. Handbook of Bond Dissociation Energies in Organic
Compounds, 3rd ed.; Science Press: China, 2002.
(7) Wþhen the hydrides of aldehydes or ketones (XHꢀ) were treated by
TEMPO in acetonitrile, it is found that the reactions took place by
hydride transfer to yield the corresponding aldehydes or ketones (X) and
TEMPOH quantitatively (eq 3), no side product ether was formed,
which were identified by MS and 1H NMR spectroscopy, and the rate of
the hydriþde transfer is very fast. These experimental results indicate that
TEMPO as an efficient hydride acceptor completely met the criteria of
calorimetric titration measurement to determine the hydride affinity of
aldehydes and ketones in acetonitrile.
Org. Lett., Vol. 13, No. 9, 2011
2457

pyridine), and AcrH2 (9,10-dihydroacridine), as well as
with H2, an extensively applied inorganic reducing agent in
research laboratories and industry, without the aid of
catalysts. Onlyquite stronginorganic hydridedonors, such
as NaBH4 or LiAlH4, can be chosen to reduce them
efficiently. From eq 1, it is found that different from the
reduction of benzyl cation by hydride anion, the reduction
of aldehydes and ketones not only involves the formation
of a new CꢀH σ-bond to release energy but also involves
the dissociation of one CdO π-bond to consume energy.
Hence, the hydride affinity magnitude of aldehydes and
ketones in solution should be equal to the heterolytic
dissociation energy of the newly formed CꢀH σ-bond
minus the heterolytic dissociation energy of the broken
CdO π-bond. Thus it is not difficult to understand why the
hydride affinities of aldehydes and ketones are much
smaller than that of the benzyl cation, since the hydride
affinityof the benzyl cation does not involve the heterolytic
dissociation of the CdO π-bond. From the three hydride
affinities of benzaldehyde (ꢀ42.8 kcal/mol), acetophenone
(ꢀ35.0 kcal/mol), and the benzyl cation (ꢀ122.9 kcal/
mol),8 it is clear that if the three CꢀH σ-bonds energies
in the three compounds were postulated to be equal, the
CdO π-bond heterolytic dissociation in benzaldehyde and
acetophenone should be 80.1 and 87.9 kcal/mol, respec-
tively. And the π-bond heterolytic dissociation energy of
benzaldehyde is smaller than that of the corresponding
acetophenone by 7.8 kcal/mol. The reason could be that
the polarity of the aldehyde CdO double bond is larger
than that of the ketone CdO double bond. In order to
moreaccuratelyestimatethe differenceinhydride affinities
between the aldehyde CdO double bond and ketone CdO
double bond, the hydride affinities of aldehyde 5 and
ketone 10 were compared, the result being that the hydride
affinity of aldehyde 5 is more negative than that of ketone
10 by ꢀ7.0 kcal/mol. Since aldehyde 5 and ketone 10 are of
the same structure, the ꢀ7.0 kcal/mol should be the
intrinsic difference in hydride affinities between the alde-
hyde CdO double bond and ketone CdO double bond in
acetonitrile.
Table 1. Hydride Affinities of Carbonyl Compounds (X) and
Reaction Heats (Qrxn) of XHꢀ with TEMPOþ in Acetonitrile
(kcal/mol)
If the data in Table 1 were examined in detail, the
following findings can be obtained: (1) By comparing the
hydride affinities of aromatic aldehyde 6 (ꢀ42.8 kcal/mol)
and aliphatic aldehyde 2 (ꢀ33.8 kcal/mol), it is found that
the hydride affinity of the aromatic aldehyde is larger than
that of the aliphatic aldehyde by ca. 9 kcal/mol. Mean-
while, when the hydride affinities of aromatic ketone 12
(ꢀ35.0 kcal/mol) and aliphatic ketone 7 (ꢀ28.9 kcal/mol)
were compared, it is found that the hydride affinity of the
aromatic ketone is larger than that of the aliphatic ketone
a Uncertainties were smaller than 1 kcal/mol in each case. b ΔHH-A
values were estimated from eq 4, taking ΔHH-A(TEMPOþ) = ꢀ105.6
kcal/mol, which was derived from the reaction heat (41.4 kcal/mol, which
was determined in this work) of TEMPOþ with BNAH in acetonitrile.9
(8) ΔHH-A(PhCH2þ) = ΔGH-A(PhCH2þ) ꢀ 4.9 in acetonitrile10 and
ΔGHꢀA(PhCH2þ) = ꢀ118.0 kcal/mol, which is derived from Parker’s
work: Cheng, J.-P.; Handoo, K. L.; Parker, V. D. J. Am. Chem. Soc.
1993, 115, 2655.
by ca. 6 kcal/mol. The two findings indicate that the
π-bond heterolytic dissocialer than those of the correspond-
ing aliphatic carbonyl compounds by 6ꢀ9 kcal/mol. The
reason could be that π-electrons have a larger space to
delocalize in aromatic carbonyl compounds. (2) When the
hydride affinities of the 2-oxopropanal 5 (ꢀ47.1 kcal/mol)
and the general propionaldehyde 3 (ꢀ34.4 kcal/mol) were
(9) The hydride affinity of BNAþ in acetonitrile was determined
(ꢀ64.2 kcal/mol),11 which has been supported by DuBois and co-work-
ers’ work (ꢀ63.9 kcal/mol);12 the difference iþs smaller than the experi-
mental error. It is worth noting that ΔHH-A(BNA ) =ΔGH-A(BNAþ) ꢀ 4.9
in acetonitrile, which has been identified.10 In this work, the value of ꢀ64.2
kcal/mol was chosen as the hydride affinity of BNAþ in acetonitrile.
2458
Org. Lett., Vol. 13, No. 9, 2011

compared, it is found that the hydride affinity of 2-oxopro-
panal 5is greater than that of the general propionaldehyde 3
by 12.7 kcal/mol. Meanwhile, when 1-oxo-propan-2-one 10
and the general acetone 7 were compared, it is found that
the hydride affinity of 1-oxo-propan-2-one 10 (ꢀ40.1 kcal/
mol) is greater than that of the general acetone 7 (ꢀ28.9 kcal/
mol) by 11.2 kcal/mol. The two findings suggest that the
contribution of the adjacent carbonyl substituent to the
hydride affinity of aldehydes and ketones is more than 10
kcal/mol. The main reason could be that π-electrons can
delocalize in an OdCꢀCdO system, and in addition, the
oxygen atom at the end position can increase the polariza-
tion of vicinal carbonyl CdO double bond. But if ketone
11and7 can be compared, the resultshows thatthehydride
affinity difference between ketone 11 (ꢀ50.7 kcal/mol) and
ketone 7 (ꢀ28.9 kcal/mol) is 21.8 kcal/mol, which is much
larger than 10 kcal/mol.10 This result indicates that the
contribution of the ester carboxyl group at the adjacent
position to the hydride affinity of ketone is much greater
than that of the general carbonyl group at the adjacent
position to the hydride affinity of ketone. The main reason
should be that the carboxyl group has a larger resonance
orbit to accommodate the π-electrons from the vicinal
carbonyl CdO double bond than the general carbonyl
group. (3) When ketones 18 and 19 were examined, it is
found that the hydride affinity of cyclohexanone 18 (ꢀ34.9
kcal/mol) is smaller than that of the corresponding cyclo-
pentanone 19 (ꢀ36.5 kcal/mol) by ca. 2 kcal/mol. The
reason is that the stretching force of cyclopentanone is
larger than that of cyclohexanone, which makes the over-
lap of 2pz orbitals for CdO π-bond formation in cyclo-
pentanone become smaller than that in cyclohexanone. A
similar result can be also found for the ketones 20 (ꢀ44.8
kcal/mol) and 21 (ꢀ46.7 kcal/mol). (4) When ketones 8
and 9 werecompared, itisfound thatthe hydrideaffinity of
butan-2-one (ꢀ28.9 kcal/mol) is smaller than that of the
corresponding but-3-en-2-one (ꢀ35.5 kcal/mol) by 6.6
kcal/mol, which suggests that the heterolytic CdO π-bond
dissociation energy in 9 is smaller than that in 8 by 6.6 kcal/
mol. It is evident that those important findings are all very
valuable in the understanding of the nature of the CdO π-
bond in various carbonyl compounds.
In summary, the hydride affinities of 21 aldehydes and
ketones in acetonitrile were determined by an experimental
method for the first time. The determined thermodynamic
data should be not only very valuable for choosing suitable
reducing agents to reduce aldehydes and ketones in re-
search laboratories and industry but also useful for devel-
oping the structure theory of carbonyl compounds. After
examining the data in Table 1, the following suggestions
can be made: (1) Aldehydes and ketone are quite weak
hydride acceptors; in general, the reductions need strong
hydride donorsand/orneedtheaid ofsuitablecatalysts. (2)
The hydride-accepting abilities of aldehydes are generally
larger than those of the corresponding ketones by about 7
kcal/mol. (3) The hydride-accepting ability of the aromatic
carbonyl compounds is greater than that of the corre-
sponding aliphatic compounds by about 9 kcal/mol.
(4) The hydride-accepting ability of the cyclic carbonyl
compounds is larger than that of the corresponding open-
chain carbonyl compounds by about 1ꢀ3 kcal/mol.
(5) The hydride-accepting ability of the vicinal double
carbonyl compounds is larger than that of the corre-
sponding single carbonyl compounds by more than 10
kcal/mol. The most salient contribution of this paper is
introducing an efficient experimental method, which
can be used to determine the hydride affinities of
various carbonyl and carboxyl compounds in solution.
Acknowledgment. We would like to acknowledge the
financial support from the National Natural Science
Foundation of China (Grant Nos. 20921120403, 20832004,
20721062, and 20672060), the Ministry of Science and
Technology of China (Grant No. 2004CB719905), and the
111 Project (Grant No. B06005).
Supporting Information Available. Experimental de-
tails and some representative ITC spectra. This material is
available free of charge via the Internet at http://pubs.
acs.org.
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J.-P. Chem.;Eur. J. 2003, 9, 871.
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