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DDQ
= 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone

 CAS: [84-58-2]

 Formula: C8Cl2N2O2

 Molecular weight:
227,01 g/mol
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About DDQ

 Physical properties
• Melting point: 213-216 °C
• Form: Bright yellow solid
• E0 ≈ 1000mV

 Handling, Storage and Precautions:

Indefinitely stable in a dry atmosphere, but
decomposes in the presence of water with the
evolution of HCN. Storage under an inert atmosphere
at low temperature.
Encyclopedia of Reagents for Organic Synthesis, 2nd ed., vol. 5, 3418.
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Benzoquinones

 DDQ is a member of large family of benzoquinones.

Walker, D.; Hiebert, J.D. Chem. Rev. 1967, 67, 153-195.

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How was it made?

 Thiele and Günther reported the synthesis of DDQ in

1906

Thiele, J.; Günther, F. 1906, 349, 45-66.

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Later developments

 Walker and Waugh improved the method for making

DDQ in 1965

Walker, D.; Waugh, T.D. J. Org. Chem. 1965, 30, 3240.

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How do we get it today?

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Usage

 DDQ can be used as an oxidant and a

dehydrogenation agent.

 During the reaction 2,3-Dichloro-5,6-

dicyanohydroquinone (=DDQH) is formed.

Encyclopedia of Reagents for Organic Synthesis, 2nd ed., vol. 5, 3418-3429.

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Suggested reaction mechanisms

 A simplified 2-step reaction mechanism containing an

initial rate-determing transfer of hydride ion followed
by a rapid proton transfer leading to hydroquinone
formation.

a) Encyclopedia of Reagents for Organic Synthesis, 2nd ed., vol. 5, 3418. b) Fu, P.P.; Harvey, R.G. Chem. Rev. 1978, 78, 317-361.
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Suggested reaction mechanisms

 An example of a single electron transfer mechanism.

Cheng, D.; Bao, W. Adv. Synth. Catal. 2008, 350, 1263-1266.

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DDQ and the other benzoquinones

 Quinones have the property to oxidize compounds.

 DDQ is one of the most versatile reagent because it

has high oxidant ability and relative stability compared
to others.

a) Walker, D.; Hiebert, J.D. Chem. Rev. 1967, 67, 153-195. b) Encyclopedia of Reagents for Organic Synthesis, 2nd ed., vol. 5,
3418.
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Applications of DDQ

1. Dehydrogenation of Hydrocarbons
2. Dehydrogenation of Carbonyl Compounds
3. Benzylic Oxidation
4. Oxidation of Alcohols
5. Phenolic Cyclizations and Coupling Reactions
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1. Dehydrogenation of Hydrocarbons

 DDQ can be used to make double bonds, aromatic

rings and stable aromatic cations.

 Functionality that is capable of stabilizing the formed

cation in the transition state and initiate hydrogen
transfer is needed, typically an aromatic moiety.

 Hydrocarbons lacking these functionalities are stable

to the action of DDQ.

Encyclopedia of Reagents for Organic Synthesis, 2nd ed., vol. 5, 3418-3429.

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1. Dehydrogenation of Hydrocarbons

 An example of dehydrogenation reaction of chromene

derivative made by Chauncey et al.

Chauncey, M.A.; Grundon, M.F. Synthesis 1990, 11, 1005-1007.

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1. Dehydrogenation of Hydrocarbons

 One of the early examples for the use of DDQ for this
type of dehydrogenations was by Braude et al. in
1954.

Braude, E.A.; Brook, A.G.; Linstead, R.P. J. Chem. Soc. 1954, 3569.
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1. Dehydrogenation of Hydrocarbons

 An example of aromatization reaction for a more

complex heteroatomic structure.

Kämpfen, U.; Eschenmoser, A. Tetrahedron Lett. 1985, 26, 5899-5902.

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1. Dehydrogenation of Hydrocarbons

 DDQ can be used also in natural product synthesis.

Movassaghi, M.; Tjandra, M.; Qi, J. J. Am. Chem. Soc. 2009, 131, 9648-9650.
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1. Dehydrogenation of Hydrocarbons

 An example of the formation of tropylium salt made by

Reid et al. in 1961

Reid, D.H; Fraser, M.; molloy, B.B.; Payne, H.A.S. Tetrahedron Lett. 1961, 530.
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2. Dehydrogenation of Carbonyl
Compounds
 DDQ is a versatile reagent for the synthesis of α,β-
unsaturated carbonyl compounds.

 A wide amount of examples in 3-keto steroid chemistry

from the 60’s.

Encyclopedia of Reagents for Organic Synthesis, 2nd ed., vol. 5, 3418.

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2. Dehydrogenation of Carbonyl
Compounds
 An interesting example of 3-keto steroids where
dehydrogenation is highly dependent on the initial
steroidal geometry.

a) Walker, D.; Hiebert, J.D. Chem. Rev. 1967, 67, 153-195. b) House, H.O.; Trost, B.M. J. Org. Chem. 1965, 30, 1341-1348.
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2. Dehydrogenation of Carbonyl
Compounds
 Dehydrogenation has been made also for lactones
and lactams. Here is an example of preparation of
steroid lactone.

Syntex Corp., Netherlands Patent Appl. 6,503,543 (1965); Chem. Abstr., 64, 5177, (1966).
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3. Benzylic Oxidation

 DDQ can be used in reactions to attach carbonyl or

acetal groups to benzylic or aromatic alkyl groups.

 DDQ can be used for selective deprotection of

alkoxybenzyl ethers.

 The stabilization of carbonium ion with e.g. an

aromatic moiety is important.

Encyclopedia of Reagents for Organic Synthesis, 2nd ed., vol. 5, 3418-3429.

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3. Benzylic Oxidation

 Takase et al. made a DDQ oxidation, which leads to a

ketone compound.

Amemiya, T.; Yasunami, M.; Takase, K. Chem. Lett. 1988, 587-590.

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3. Benzylic Oxidation

 An example of oxidation of an aromatic compound

made by Corey and Xiang.

Corey, E.J.; Xiang, Y.B. Tetrahedron Lett. 1987, 28, 5403-5406.

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3. Benzylic Oxidation

 In dry conditions DDQ can be used for intramolecular

oxidative formation of a methoxybenzylidine acetal

 In aqueous conditions the dimethoxybenzyl group is

cleaved.

Oikawa, Y.; Yoshioka, T.;Yonemitsu, O. Tetrahedron Lett. 1982, 23, 889-892.

Oikawa, Y.; Tanaka, T.; Horita, K.; Yoshioka, T.; Yonemitsu, O. Tetrahedron Lett. 1984, 25, 5393-5396.
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4. Oxidation of Alcohols

 Quinones have long been known to dehydrogenate

alcohols to aldehydes and ketones in the presence of
light.

 Example of oxidation for hindered secondary alcohol.

Walker, D.; Hiebert, J.D. Chem. Rev. 1967, 67, 153-195.

Iwamura, J.; Hirao, N. Tetrahedron Lett. 1973, 2447.
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5. Phenolic Cyclizations and Coupling

Reactions
 Phenolic compounds treated with DDQ can be used to
make oxygen containing heterocycles i.e. coumarins,
chromenes and benzofurans.

 DDQ can be used to make C-C or C-O couplings.

Encyclopedia of Reagents for Organic Synthesis, 2nd ed., vol. 5, 3418-3429.

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5. Phenolic Cyclizations and Coupling

Reactions
 An example of cyclization reaction, where the product
ratio is temperature dependent.

Ameer, F.; Giles, R.G.F.; Green, I.R.; Nagabhushana, K.S. Synth. Commun. 2002, 32, 369.
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5. Phenolic Cyclizations and Coupling

Reactions
 DDQ can be used in cross-coupling reactions. Here is
an example made by Cheng et. al.

Cheng, D.; Bao, W. Adv. Synth. Catal. 2008, 350, 1263-1266.

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Conclusion

 DDQ has been discovered about 100 years ago.

 It has been used in versatile reactions during that time.

 The field of usage of DDQ is expanding all the time

with new applications still being discovered.
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