Science - USA (2022-05-06)

15. K. Newtonet al.,Science 343 , 1357–1360 (2014).


16. Q. Zhaoet al.,Cell Rep. 19 , 798–808 (2017).


17. Y. Liuet al.,Cell Death Differ. 24 , 1459–1469 (2017).


18. H. I. Muendleinet al.,Science 367 , 1379–1384 (2020).


19. K. Newtonet al.,Nature 540 , 129–133 (2016).


20. J. Linet al.,Nature 540 , 124–128 (2016).


21. T. Kuriakose, T. D. Kanneganti,Trends Immunol. 39 , 123– 134
    (2018).


22. R. Gomez-Pastor, E. T. Burchfiel, D. J. Thiele,Nat. Rev. Mol.
    Cell Biol. 19 ,4–19 (2018).


23. A. V. Jacobsenet al.,Cell Death Dis. 7 , e2051 (2016).


24. X. M. Zhaoet al.,Cell Death Dis. 7 , e2089 (2016).


25. M. Devoset al.,J. Exp. Med. 217 , e20191913 (2020).


26. J. W. Upton, W. J. Kaiser, E. S. Mocarski,Cell Host Microbe 11 ,
    290 – 297 (2012).


27. M. T. Lotzeet al.,Immunol. Rev. 220 , 60–81 (2007).


28. M. Zheng, R. Karki, P. Vogel, T. D. Kanneganti,Cell 181 ,
    674 – 687.e13 (2020).
    29. N. Kayagakiet al.,Nature 591 , 131–136 (2021).

ACKNOWLEDGMENTS

The authors thank J. Han, H. Zhou, and X. Xiao for sharing mouse

strains. We thank L. Li, X. Y. Wang, Z. Z. Yan, and Y. T. Liu for

managing mouse colonies and technical assistance. F.Y. was

supported by a Postdoctoral Research Station of the 3rd Xiangya

Hospital.Funding:This work was supported by the National

Outstanding Youth Science Fund Project of the National Natural

Science Foundation (no. 82025021 to B.L.), the National

Natural Science Foundation of China (no. 81930059 to B.L., no.

81801888 to F.Y., and no. 81971893 to Y.T.), a key scientific

project of Hunan Province (no. 2022SK2056 to B.L.), and the China

Postdoctoral Science Foundation (no. 2019M652811 to F.Y.).

Author contributions:B.L. conceived the project, supervised the

research, and wrote the manuscript; B.L. and F.Y. designed the

experiments; F.Y., J.C., J.W., K.Z., F.Li, F.Lia., and X.Y. performed

the experiments; T.R.B., H.W., Y.T., Z.H., and L.S. commented

on and edited the manuscript; and F.Y. and J.C. analyzed the

data and made the figures.Competing interests:The authors

declare that they have no competing interests.Data and

materials availability:All data are available in the main text or

the supplementary materials. Correspondence and requests for

materials should be addressed to B.L.

SUPPLEMENTARY MATERIALS

science.org/doi/10.1126/science.abg5251

Materials and Methods

Figs. S1 to S10

MDAR Reproducibility Checklist

Submitted 12 January 2021; resubmitted 6 August 2021

Accepted 1 April 2022

10.1126/science.abg5251

REPORTS

◥

CATALYSIS

Highly efficient catalytic production of oximes from

ketones using in situÐgenerated H 2 O 2

Richard J. Lewis^1 , Kenji Ueura^2 , Xi Liu3,4, Yukimasa Fukuta^2 , Thomas E. Davies^1 , David J. Morgan1,5,
Liwei Chen3,6, Jizhen Qi^7 , James Singleton^1 , Jennifer. K. Edwards^1 , Simon J. Freakley^8 ,
Christopher J. Kiely^9 , Yasushi Yamamoto^2 , Graham J. Hutchings^1 *

The ammoximation of cyclohexanone using preformed hydrogen peroxide (H 2 O 2 ) is currently applied
commercially to produce cyclohexanone oxime, an important feedstock in nylon-6 production. We
demonstrate that by using supported gold-palladium (AuPd) alloyed nanoparticles in conjunction
with a titanium silicate-1 (TS-1) catalyst, H 2 O 2 can be generated in situ as needed, producing
cyclohexanone oxime with >95% selectivity, comparable to the current industrial route. The
ammoximation of several additional simple ketones is also demonstrated. Our approach eliminates
the need to transport and store highly concentrated, stabilized H 2 O 2 , potentially achieving substantial
environmental and economic savings. This approach could form the basis of an alternative route to
numerous chemical transformations that are currently dependent on a combination of preformed H 2 O 2 and
TS-1, while allowing for considerable process intensification.

C

yclohexanone oxime is a key precursor

in the production of caprolactam, a com-

modity chemical used in the synthesis of

the polyamide nylon-6. With global pro-

duction of nylon-6 predicted to reach

8.9 million metric tons per annum by 2024

( 1 ), a concurrent increase in demand for cy-

clohexanone oxime is expected. The traditional

route to cyclohexanone oxime production in-

volves the reaction of cyclohexanone with hy-

droxylamine sulfate, producing ammonium

sulfate—a low-value fertilizer with limited

applications—as a major by-product ( 2 ). Alter-

native routes (fig. S1 and accompanying text)

arehamperedbytheneedtocontinuallymain-

tain a low reaction pH (by complex and energy-

intensive extraction steps) or by low selectivity

toward the desired product. A single-step am-

moximation process that overcomes these

challenges has been developed with titanium

silicate-1 (TS-1) as the catalyst and cyclohex-

anone, ammonia, and preformed H 2 O 2 as re-

actants ( 3 ). In this process, hydroxylamine

is formed catalytically in situ by TS-1 ( 4 ), with

this intermediate species subsequently react-

ing noncatalytically with cyclohexanone to

produce the oxime (fig. S1 and accompanying

text) ( 5 ). The catalytic activity of TS-1 with

H 2 O 2 , which has been crucial in the develop-

ment of numerous selective oxidation processes

(fig. S2), is often attributed to the ability of TiIV

sites to readily coordinate multiple species

which, in the case of cyclohexanone ammox-

imation, are crucial in the formation of hy-

droxylamine ( 6 ). Despite extensive advances

in catalyst design leading to the development

of a range of titanosilicates that are highly

selective toward cyclohexanone ammoxima-

tion and that offer greater catalytic stability

[including Ti-MOR ( 7 ), Ti-Beta ( 8 ), TS-2 ( 9 ),

and Ti-MWW ( 10 )], TS-1 is still widely con-

sidered the industrial standard for reactions

involving H 2 O 2 ( 11 ).

Although the industrial ammoximation pro-

cess based on H 2 O 2 /TS-1—which accounts for

~6 million metric tons per annum of global

oxime production ( 12 )—offers excellent cata-

lytic selectivity, an excess of H 2 O 2 is typically

required as a result of the low stability of the

oxidant under the associated reaction condi-

tions (elevated temperatures and high pH),

leading to elevated process costs ( 13 ). In ad-

dition, the preformed H 2 O 2 requires transpor-

tation from a centralized point of production,

where it is manufactured at concentrations

greatly exceeding those needed in the am-

moximation process; the requisite dilution

effectively wastes the energy previously used

in distillation and concentration steps. Fur-

thermore, the instability of H 2 O 2 necessitates

the addition of acid and halide stabilizing

agents to prevent its degradation during trans-

port and storage, which in turn can limit cat-

alyst stability, decrease reactor lifetime through

corrosion, and generate substantial costs as-

sociated with their removal from product

streams ( 14 ). Likewise, all chemical transform-

ations that use preformed H 2 O 2 suffer from

these drawbacks to a certain degree.

We have previously developed catalysts for

the direct synthesis of H 2 O 2 from the elements

that offer high synthesis rates and >99% H 2

utilization ( 15 , 16 ). However, to date, the direct

method has been unable to rival the current

SCIENCEscience.org 6 MAY 2022•VOL 376 ISSUE 6593 615

(^1) Max Planck–Cardiff Centre on the Fundamentals of
Heterogeneous Catalysis FUNCAT, Cardiff Catalysis Institute,
School of Chemistry, Cardiff University, Main Building, Park
Place, Cardiff CF10 3AT, UK.^2 UBE Corporation, 1978-5,
Kogushi, Ube, Yamaguchi 755-8633, Japan.^3 School of
Chemistry and Chemical, In-situ Centre for Physical
Sciences, Shanghai Jiao Tong University, Shanghai 200240,
P.R. China.^4 SynCat@Beijing, Synfuels China Technology Co.
Ltd., Beijing 101407, P.R. China.^5 Harwell XPS, Research
Complex at Harwell (RCaH), Didcot OX11 0FA, UK.^6 School of
Chemistry and Chemical Engineering, Frontiers Science
Centre for Transformative Molecules, Shanghai Jiao Tong
University, Shanghai 200240, P.R. China.^7 i-Lab, CAS Centre
for Excellence in Nanoscience, Suzhou Institute of Nano-Tech
and Nano-Bionics, Chinese Academy of Sciences, Suzhou
215123, P.R. China.^8 Department of Chemistry, University of
Bath, Claverton Down, Bath BA2 7AY, UK.^9 Department of
Materials Science and Engineering, Lehigh University,
Bethlehem, PA 18015, USA.
*Corresponding author. Email: [email protected] (R.J.L.);
[email protected] (X.L.); [email protected] (G.J.H.)
RESEARCH