Gas-Phase UV Spectroscopy of Chemical Intermediates Produced in Solution: Oxidation Reactions of Phenylhydrazines by DDQ

Solution: Oxidation Reactions of Phenylhydrazines by DDQ

Article

Gas-Phase UV Spectroscopy of Chemical Intermediates Produced in

Shiori Machida, Motoki Kida, Satoru Muramatsu, Takehiro Hirao, Takeharu Haino,

and Yoshiya Inokuchi*

Cite This: https://doi.org/10.1021/acs.jpca.1c04669

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sı Supporting Information

ABSTRACT: In this study, we demonstrated cold gas-phase spectroscopy of chemical

intermediates produced in solution. Herein, we combined an electrospray ion source with a T-

shaped solution mixer for introducing chemical intermediates in solution into the gas phase.

Speciﬁcally, the oxidation reaction of 2-(4-nitrophenyl)hydrazinecarboxaldehyde (NHCA) by 2,3-

dichloro-5,6-dicyano-p-benzoquinone (DDQ) was initiated by mixing the methanol solutions of

NHCA and DDQ in the T-shaped mixer, and the chemical species were injected into the vacuum

apparatus for ultraviolet photodissociation (UVPD) spectroscopy. A cationic intermediate was

strongly observed at m/z 150 in the mass spectrum, and the UVPD spectrum was observed under

cold (∼10 K) gas-phase conditions. The UVPD spectrum showed a strong, broad absorption at

−

−1

∼

38,000 cm , accompanied by a relatively weak component at ∼34,000 cm . These spectral

patterns can be ascribed to a diazonium cation intermediate, whose existence has been predicted in

a previous study. This report indicates that cold gas-phase UV spectroscopy can be a useful method for identifying the structure of

chemical intermediates produced in solution.

. INTRODUCTION

spectroscopy using an electrospray ionization (ESI) source.

Oonishi et al. reported an MS study based on the oxidation of

Chemical intermediates play a crucial role in examining the

reaction mechanism. If the intermediates present in a chemical

reaction are identiﬁed, the mechanism can be revealed at the

molecular level. The reactant solution contains chemical

intermediates and residual reactants and products. Chemical

intermediates are generally not very abundant in solution due

to their short lifetimes, which prevents their selective detection

in the solution. In the last three decades, several mass

spectrometric (MS) techniques have been extensively applied

phenylhydrazine derivatives by DDQ. Scheme 1, which is

expected on the basis of a previous study, shows a plausible

reaction route for the oxidation of NHCA by DDQ. The ﬁnal

product was 4-nitroresorcinol (5). Several intermediates were

expected to exist in the reaction, some of which were detected

in the mass spectra using a fast atom bombardment (FAB) ion

source. Because these intermediates have diﬀerent time

−15

proﬁles from each other, it would be possible to obtain

information on the time scale of chemical intermediate that

can be probed by our gas-phase spectroscopic techniques. With

the oxidation reaction of NHCA by DDQ, this study aims to:

(1) examine whether chemical intermediates can be detected

using an ESI ion source; (2) observe their UV spectra under

cold gas-phase conditions; and (3) determine the electronic

and geometric structures of the intermediates on the basis of

the UV spectra. We believe that these results would provide

valuable information for a microscopic understanding of the

chemical reaction mechanism.

to the chemical intermediates produced in solutions.

These studies could determine the molecular weight or the

atomic constituents of the species; however, spectroscopic

investigations are required to predict the structure of the

intermediates. Recently, Mayer and Asmis reported the gas-

phase IR spectroscopy of chemical intermediates produced

using a microﬂuidic chip-reactor.

In the present study, the structures of the chemical

intermediates produced in solution were investigated via gas-

phase UV spectroscopy. UV−Vis spectroscopy can provide

information on the electronic structure (such as the oxidation

state and charge distribution) in a molecule. UV spectroscopy

under cold gas-phase conditions has potentially high ability to

discriminate conformers and determine their geometric

structure (conformations) based on the narrow bandwidths

Received: May 27, 2021

Revised: July 15, 2021

17−19

of vibronic transitions.

In this study, we examined the

chemical intermediates for the oxidation of 2-(4-nitrophenyl)-

hydrazinecarboxaldehyde (NHCA) by 2,3-dichloro-5,6-dicya-

no-p-benzoquinone (DDQ) in methanol by cold gas-phase

XXXX American Chemical Society

J. Phys. Chem. A XXXX, XXX, XXX−XXX

The Journal of Physical Chemistry A

Article

Scheme 1. Plausible Reaction Route for the Oxidation of

NHCA by DDQ

The details of our experimental approach for ultraviolet

photodissociation (UVPD) spectroscopy have been reported

21,22

elsewhere.

brieﬂy introduced into a cold, Paul-type quadrupole ion trap

QIT) through a vaporization tube and two octopole ion

The ions produced in the ESI source were

(

guides. The QIT was cooled to ∼4 K using a He cryostat, and

He buﬀer gas was continuously introduced into the QIT. The

ions were stored in the QIT for ∼90 ms and were cooled

translationally and internally by collisions with the cold He

buﬀer gas. Ions other than the parent ions of interest can be

removed from the QIT by applying an RF potential to the

entrance end cap. The cold ions in QIT were irradiated using

a tunable UV laser (EKSPLA NT342B), and the resulting

fragment ions were mass-analyzed and detected using a

homemade time-of-ﬂight mass spectrometer. The UVPD

spectra of the parent ions were obtained by plotting the yield

of the fragment ions against the wavenumber of the UV laser.

We also performed density functional theory (DFT)

calculations to predict the stable forms and electronic

transitions of the chemical intermediates. Geometrical

optimization of the intermediates was performed using the

GAUSSIAN 16 program at the ωB97XD/6-311++G(d,p)

The numbers in parentheses represent the molecular weight of each

species.

. EXPERIMENTAL AND COMPUTATIONAL

METHODS

level. Vibrational analysis was performed for the optimized

structures at the same computational level. We carried out

time-dependent DFT (TD-DFT) calculations at the ωB97XD/

We used an ESI source with a T-shaped solution mixer to

produce the chemical intermediates in the solution. Figure 1

-311++G(d,p) level to obtain the electronic transition energy

and the oscillator strength. We determined the structure of the

chemical intermediates by comparing the experimental UVPD

spectra to the theoretical ones.

3. RESULTS AND DISCUSSION

Figure 2a,b shows the mass spectra of the NHCA solution and

mixed solution of NHCA and DDQ that was prepared using

the T-shaped mixer, respectively. The ion intensity in Figure

a,b was normalized as the signal at m/z 150 in Figure 2b

became unity; it is possible to compare the ion intensity in

Figure 2a,b to each other. In Figure 2a, the Na (NHCA),

H (NHCA), and H O (NHCA) ions were observed. Because

we did not add any Na or H source in the solutions, these

ions were weakly detected in the mass spectrum. In the mass

spectrum of the mixed solution [Figure 2b], the signals

Figure 1. ESI ion source with the T-shaped solution mixer.

shows the ESI source used in this study; it consisted of a 1/16

in. stainless steel union tee (GL Science 3006-43310), a

stainless steel needle with a length of 25.4 mm and an inner

diameter of 0.108 mm (Hamilton Stainless Steel Tubing

corresponding to the Na (NHCA) and H O (NHCA)

complexes disappeared, while intense and very weak signals

were observed at m/z 150 and 140, respectively. The molecular

weight of the expected ﬁnal product (5 in Scheme 1) in this

reaction was 155. Hence, the signals at m/z 150 and 140 are

related to the chemical intermediates in this reaction. Based on

the plausible reaction mechanism shown in Scheme 1, the

signals at m/z 150 and 140 can be attributed to the diazonium

1033A), and a 1/16 in. plastic sleeve to connect the thin

needle to the union tee. In this study, NHCA and DDQ were

independently dissolved in methanol at concentrations of 0.1

and 5 M, respectively. The reactant solutions were delivered

using syringes (Hamilton 1010TLL) to the T-shaped mixer

through 1/16 in. Teﬂon tubes by syringe pumps (KD Scientiﬁc

cation intermediate [3, C H N O ] and the protonated

species of the phenol derivative intermediate [H (4),

C H NO ], respectively. This result demonstrates the

80-100E). These solutions were mixed in the T-shaped mixer

to initiate the oxidation of NHCA by DDQ. The typical ﬂow

rate was 0.1 mL h⁻for both the reactant solutions. After

mixing the solution with the ESI tip, the dead volume was

estimated as ∼0.01 mL from the size of the union tee. Thus, it

took ∼3 min to inject the mixed solution into the vacuum

chamber after mixing the reactant solutions at a ﬂow rate of 0.1

mL h for each solution (0.2 mL h in total). NHCA was

synthesized from 4-nitrophenylhydrazine. The details for this

procedure are described in the Supporting Information. DDQ

was purchased from Aldrich and used without further

puriﬁcation.

usefulness of the T-shaped mixer for MS observations of the

chemical intermediates produced in solutions. However, it

should be noted that the ion intensity in the mass spectra does

not necessarily represent the abundance of the chemical

intermediates in solution because the ionization process is

diﬀerent for each intermediate; the chemical intermediate 3 is

cationic species and can be detected directly with the ESI

source, but the intermediate 4 is neutral and the protonation is

required to be detected in the MS measurements. Quantitative

analysis for the abundance of chemical intermediates in

solution by the MS measurements will be our future work.

−

−1

The Journal of Physical Chemistry A

J. Phys. Chem. A XXXX, XXX, XXX−XXX

intermediate at m /z 150 to examine the structure. Figure 3

Article

corresponding to intermediate 3 would be the strongest.

Hence, there was a trade-oﬀ relationship between the residence

time and the intensity of chemical intermediate in the

experiment performed using a 1/16 in. union tee. It would

be eﬀective to use microreactors for detecting the chemical

intermediates with shorter lifetimes and intensities suﬃcient

for spectroscopic measurements, as performed in a recent

study. In contrast, the marked advantages of the T-shaped

mixer with a simple union tee are as follows: (1) it is easy to

handle and (2) absence of any block in the ﬂow path and

contamination as it can be cleaned easily. Hence, it would be

better to choose the appropriate solution mixer on the basis of

the lifetime of chemical intermediates.

We performed UVPD spectroscopy of the chemical

Figure 2. (a) Mass spectrum of the NHCA solution. (b) Mass

spectrum of the mixture of NHCA and DDQ with the T-shaped

solution mixer. The mass spectra in panels (a,b) were normalized with

the intensity of the chemical intermediate observed at m/z 150 in

panel (b). Hence, the ion intensity of the mass spectra in panels (a,b)

can be compared to each other.

Figure 3. UVPD mass spectrum of the mixture of NHCA and DDQ

at 260 nm. The diﬀerence mass spectrum was obtained by subtracting

the mass spectrum without UV irradiation from the one with

irradiation at 260 nm.

In the previous study, the oxidation of the phenylhydrazine

derivative by DDQ was investigated via MS measurements.

The diﬀerences between the previous and present study are the

substituent group on phenylhydrazine and the ion source. N′-

formyl-N-(4-asylaminophenyl)hydrazine (AFH) was used in

the previous study. FAB and ESI were the ion sources used in

the previous and present studies, respectively. In the MS study

of AFH, the intermediates corresponding to 1, 2, and 4 in

Scheme 1 were detected as protonated species in addition to

shows the UVPD mass spectrum of the mixed solution of

−

NHCA and DDQ observed at 260 nm (38,462 cm ). We

obtained the spectrum by subtracting the mass spectrum

without irradiation from that with irradiation. The ion intensity

of the chemical intermediate at m/z 150 decreased

signiﬁcantly. Fragment ions were detected at m/z 74 and 91,

the diazonium cation (3 in Scheme 1). Oonishi et al.

observed the time proﬁles of ion intensities in the mass spectra

after mixing the reactant solutions to verify the longest lifetime

and they were ascribed to N O and C H N , respectively.

(

>80 s) of the intermediate corresponding to 3 (>80 s).

This result indicates that the chemical intermediate at m/z 150

has a strong absorption at 260 nm.

Because the residence time of the mixed solution in the T-

shaped mixer was calculated as ∼3 min, it would be reasonable

to detect only intermediate 3 in this study. The ESI source

used herein could continuously inject the intermediate solution

into the vacuum chamber, making it suitable for the

spectroscopic measurements, whereas the FAB-MS used in

the previous study was devoted only to the MS measurements

Figure 4a shows the UVPD spectrum of chemical

intermediate at m/z 150, which was obtained by monitoring

the intensity of the fragment ion at m/z 91. The UVPD

spectrum showed a very broad and strong band at ∼38,000

−

cm , and it was accompanied by a relatively weak component

−

at ∼34,000 cm . The theoretical electronic spectrum of

intermediate 3 (Scheme 1) is shown in Figure 4b. Table 1 lists

the calculation results for the following: transition energy,

oscillator strength, molecular orbitals (MOs) contributing to

the electronic transitions, CI coeﬃcients, and percentage

contribution. In the calculated spectrum, the S −S and S −S

for a short period of time. In the mass spectrum of the mixed

solution, shown in Figure 2b, the signal of protonated NHCA

[

H (NHCA)] was also observed, suggesting that the oxidation

of the protonated NHCA by DDQ did not proceed.

Increasing the ﬂow rate of the ESI source reduces the

residence time in the T-shaped mixer, thereby enabling the

detection of chemical intermediates with shorter lifetimes. In

this study, the ﬂow rate was optimized such that the signal

−

transitions are located at ∼33,100 and ∼38,100 cm ,

respectively, with smaller oscillator strengths (<0.04). The

S −S transition located at ∼38,400 cm results in a strong

−

The Journal of Physical Chemistry A

J. Phys. Chem. A XXXX, XXX, XXX−XXX

as an intramolecular charge transfer (CT) band. Figure 5

Article

spectroscopy. Intermediate 3 will not have multiple con-

formations because of its simple chemical structure. Hence, it

should be noted that this study does not necessarily

demonstrate the ability of gas-phase spectroscopy to

distinguish diﬀerent conformers with intermediate 3. Because

UV spectroscopy under cold gas-phase conditions has high

ability to examine the conformation because of sharp vibronic

features, it will reveal the geometric structure of chemical

intermediates that have a high degree of conformational

freedom.

UV−Vis spectroscopy of benzene diazonium salts and

26−31

nitrobenzene in solution has been reported previously.

Weak and strong bands were observed at ∼33,900 and

−

∼

38,600 cm , respectively, for the benzene diazonium cation

in solution. Nitrobenzene showed absorption at ∼35,300 and

−

∼

41,600 cm in hexane, wherein the latter band was assigned

Figure 4. (a) UVPD spectrum of the chemical intermediate at m/z

50 observed with the mixture of the NHCA and DDQ solutions with

the T-shaped solution mixer. (b) Calculated electronic transitions of

the diazonium cation intermediate (3 in Scheme 1). The calculation

was carried out at the ωB97XD/6-311++G(d, p) level and a scaling

factor of 0.95 was employed for the calculated transition energy for

comparing the theoretical spectrum to the UVPD one.

Figure 5. MOs contributing largely to the S −S , S −S , and S −S

band. The oscillator strength of the S −S transition (∼0.41) is

transitions of the diazonium cation intermediate. The numeric

characters in the ﬁgure represent the number of the MOs. Color

code of atoms: gray (carbon), white (hydrogen), blue (nitrogen).

order of magnitude stronger than that of the S −S and S −

S₀transitions. Comparing the UVPD spectrum to the

theoretical spectrum, we assigned the weak and strong

−

components at ∼34,000 and ∼38,000 cm in the UVPD

spectrum to the S −S and S −S /S −S transitions,

shows MOs that contribute largely to the S −S , S −S , and

respectively. Thus, it was experimentally conﬁrmed that the

chemical intermediate detected at m/z 150 in this study had

the form of intermediate 3 in Scheme 1. The UV spectrum of

intermediate 3 was broad even though it was observed under

cold gas-phase conditions, which prevented the detection of

multiple conformers, if any. Theoretical calculations provided

only one conformation for intermediate 3. This study

identiﬁed the species of intermediate 3 on the basis of UV

S −S transitions of intermediate 3. The electron promotions

involved in these transitions are listed in Table 1. As seen in

Figure 5, MOs numbered 34 and 35 were recognized mainly as

the π orbitals in the benzene moiety, but the MO numbered 37

has a large contribution from the nitro group (NO ). The

lowest unoccupied MO (LUMO, number 39) is formed with

the π* orbitals of the diazonium (N ) and benzene moieties.

As seen from Table 1, the S −S and S −S transitions were

Table 1. Transition Energy, Oscillator Strength, MOs Contributing to the Electronic Transitions, CI Coeﬃcients, and

Percentage Contribution Calculated for the S −S , S −S , and S −S Transitions of the Diazonium Cation Intermediate (3 in

Scheme 1)

transition

transition energy (cm⁻¹)^a

33,100

oscillator strength

0.0398

MOs

CI coeﬃcients

contribution (%)

S₃−S₀

35 → 39

0.58389

0.36807

−0.36024

0.57941

0.68215

7 → 39

35 → 39

7 → 39

34 → 39

S₅−S₀

38,100

38,400

0.0242

0.4065

S₆−S₀

A scaling factor of 0.95 was employed for the calculated transition energy.

J. Phys. Chem. A XXXX, XXX, XXX−XXX

The Journal of Physical Chemistry A

https://pubs.acs.org/doi/10.1021/acs.jpca.1c04669.

Article

mainly due to the electron promotions of 35 → 39 and 37 →

ASSOCIATED CONTENT

Supporting Information

The Supporting Information is available free of charge at

■

9, respectively. Hence, the S −S and S −S transitions have

sı

the CT characteristics from the benzene to the diazonium parts

35 → 39) and from the nitro to the benzene parts (37 → 39),

respectively. In contrast, the S −S transition is predominantly

(

Detailed procedure for synthesis of NHCA; H and ¹³C

NMR spectra, 2D NMR spectra, and X-ray data;

transition energy and oscillator strength calculated for

the cationic intermediate at the ωB97XD/6-311+

assigned to the CT from the benzene to the diazonium parts

(

34 → 39).

As mentioned above, the ion intensity in the mass spectra

does not necessarily represent the abundance of the chemical

intermediates in solution. In addition, Cooks, Zare, and their

co-workers reported the acceleration of chemical reactions in

G(d,p) level; and full list of the authors in ref 25

(PDF )

2,33

charged droplets.

Hence, the MS measurements may not

Crystallographic data (CIF )

necessarily probe the kinetics of chemical reactions quantita-

tively in solution. On the other hand, our gas-phase

spectroscopy can provide insights into the structure of

chemical intermediates. It will be needed to conﬁrm the

mechanism of chemical reactions in solution by theoretical

methods based on the experimental results of the structure of

chemical intermediates in the gas phase.

AUTHOR INFORMATION

Corresponding Author

■

Yoshiya Inokuchi − Department of Chemistry, Graduate

School of Advanced Science and Engineering, Hiroshima

University, Higashi-Hiroshima 739-8526, Japan;

orcid.org/0000-0001-7959-5315; Email: y-inokuchi@

hiroshima-u.ac.jp

In this study, we used a simple union tee to mix the reactant

−

solutions with slow ﬂow rates (∼0.2 mL h ), providing a

relatively long sampling time (3 min). Given this situation,

stopped-ﬂow techniques would be competitive with our gas-

phase spectroscopic techniques for the identiﬁcation of

Authors

Shiori Machida − Department of Chemistry, Graduate School

of Advanced Science and Engineering, Hiroshima University,

Higashi-Hiroshima 739-8526, Japan

Motoki Kida − Department of Chemistry, Graduate School of

Advanced Science and Engineering, Hiroshima University,

Higashi-Hiroshima 739-8526, Japan

transient species in solution. In the stopped-ﬂow techniques,

the dead time could be shortened to less than 1 ms,

substantially shorter than that in this study. On the other

hand, they used conventional detectors for solution such as

spectrophotometers and spectroﬂuorimeters. As seen in

Scheme 1, plausible chemical intermediates in a chemical

reaction tend to have similar chromophores to the reactants

and products. Hence, it would be challenging to identify

chemical intermediates in solution on the basis of their

spectroscopic results. Our gas-phase spectroscopic technique

uses the mass spectrometer, which enables us to determine the

m/z ratio of chemical intermediates. Because the mass

selection is performed before UVPD spectroscopy, there is

no ambiguity for chemical intermediates responsible for the

UVPD spectra. In addition, our UVPD spectroscopy is free

from solvent and thermal eﬀects, which would result in broad

spectral features. The UVPD spectra can show sharp vibronic

bands, making it possible to determine the number of

Satoru Muramatsu − Department of Chemistry, Graduate

School of Advanced Science and Engineering, Hiroshima

University, Higashi-Hiroshima 739-8526, Japan;

orcid.org/0000-0002-1575-7570

Takehiro Hirao − Department of Chemistry, Graduate School

of Advanced Science and Engineering, Hiroshima University,

Higashi-Hiroshima 739-8526, Japan; orcid.org/0000-

0003-4377-7541

Takeharu Haino − Department of Chemistry, Graduate

School of Advanced Science and Engineering, Hiroshima

University, Higashi-Hiroshima 739-8526, Japan;

orcid.org/0000-0002-0945-2893

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.jpca.1c04669

conformers and their conformations. According to the

advantages described above, cold gas-phase UV spectroscopy

will become a prospectively powerful tool for investigation of

chemical intermediates produced in solution.

Notes

The authors declare no competing ﬁnancial interest.

X-ray crystallographic coordinates for a structure reported in

this study have been deposited at the Cambridge Crystallo-

graphic Data Centre (CCDC), under a deposition number of

. CONCLUSIONS

084370. The data can be obtained free of charge from the

This study aimed to demonstrate the cold gas-phase

spectroscopy of chemical intermediates produced in solution.

An ESI source with a T-shaped solution mixer could produce

chemical intermediates in the oxidation of NHCA by DDQ in

methanol. The mixed solution was injected into the vacuum

apparatus for UVPD spectroscopy. The cationic intermediate

was strongly observed at m/z 150 and the UVPD spectrum

observed under cold (∼10 K) gas-phase conditions showed a

CCDC via www.ccdc.cam.ac.uk/data_request/cif.

ACKNOWLEDGMENTS

■

This work was partly supported by JSPS KAKENHI (grant

numbers JP16H04098 and JP20H00374). Part of the

calculations were performed at the Research Center for

Computational Science, Okazaki, Japan.

−

very broad and strong band at ∼38,000 cm accompanied by

−

a relatively weak component at ∼34,000 cm . These spectral

patterns can ascertain the existence of the diazonium cation

intermediate (3 in Scheme 1). This report infers that cold gas-

phase UV spectroscopy is a useful method to identify the

structure of the chemical intermediates produced in solution.

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