House bulb light-induced photochemical acetalization of carbonyl compounds catalyzed by Eosin Y

Article abstract of DOI:10.1080/00397911.2018.1434545

We have systematically studied the reactions of acetalization and found that high reaction efficiency can be achieved using cheap and readily available organic Eosin Y as catalyst. The reaction proceeds smoothly under house bulbs and shows excellent functional group tolerance. The substrates of the reaction system are compatible with aromatic aldehydes, aliphatic aldehydes, aromatic ketones, and cyclic ketones with high yields.

Full text of DOI:10.1080/00397911.2018.1434545

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
House bulb light-induced photochemical
acetalization of carbonyl compounds catalyzed by
Eosin Y
Quan Zhou, Tao Jia, Xiao-Xuan Li, Lin Zhou, Chang-Jiang Li & Yi-Si Feng
To cite this article: Quan Zhou, Tao Jia, Xiao-Xuan Li, Lin Zhou, Chang-Jiang Li & Yi-Si Feng
(2018) House bulb light-induced photochemical acetalization of carbonyl compounds catalyzed by
Eosin Y, Synthetic Communications, 48:9, 1068-1075, DOI: 10.1080/00397911.2018.1434545
To link to this article: https://doi.org/10.1080/00397911.2018.1434545
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SYNTHETIC COMMUNICATIONS®
2018, VOL. 48, NO. 9, 1068–1075
https://doi.org/10.1080/00397911.2018.1434545
House bulb light-induced photochemical acetalization of
carbonyl compounds catalyzed by Eosin Y
Quan Zhoua, Tao Jiab, Xiao-Xuan Lib, Lin Zhouc, Chang-Jiang Lia, and Yi-Si Fengb,d
b
aSchool of Chemistry and Chemical Engineering, Huangshan College, Huangshan, P. R. China; Anhui Province
Key Laboratory of Advance Catalytic Materials and Reaction Engineering, School of Chemistry and Chemical
c
Engineering, Hefei University of Technology, Hefei, P. R. China; Tongcheng Teachers College, Tongcheng,
Anhui, P. R. China; dAnhui Provincial Laboratory of Heterocyclic Chemistry, Maanshan, Anhui, P. R. China
ABSTRACT
ARTICLE HISTORY
Received 4 November 2017
We have systematically studied the reactions of acetalization and
found that high reaction efficiency can be achieved using cheap and
readily available organic Eosin Y as catalyst. The reaction proceeds
smoothly under house bulbs and shows excellent functional group
tolerance. The substrates of the reaction system are compatible with
aromatic aldehydes, aliphatic aldehydes, aromatic ketones, and cyclic
ketones with high yields.
KEYWORDS
Acetalization; carbonyl
compounds; environment
friendly; Eosin Y
GRAPHICAL ABSTRACT
Introduction
Carbonyl compounds are essential building blocks of organic chemistry because of their
chemical versatility. Often this carbonyl functional groups must be protected while
performing a series of steps in organic synthesis, and acetalization is one of the preferred
methodologies.[1] This method provides an effective way to produce useful intermediates
and valuable chemicals that are specifically used as additives to extend lingering time of
perfume. The traditional way to synthesize the acetal and ketal compounds is to use
[3]
inorganic acids, for example, TsOH[2] and BF3 as catalysts. As the research progressed,
another methods for the acetalization reaction are catalyzed by solid acids,[4] metal salts,[5]
or ionic solvents.[6] These catalysts can partially solve the problems caused by inorganic
acids, but they do have their own drawbacks. Various useful organic reactions have
been well developed and the search for new and improved methods continues.[7]
Recently, organic molecules, including P-chloranil,[8] NBS,[9] tetra-t-butyl ammonium
bromide (TBATB),[10] and pyridine salts,[11] were extensively reported to be used as
CONTACT Yi-Si Feng
fengyisi@hfut.edu.cn
Anhui Province Key Laboratory of Advance Catalytic Materials and
Reaction Engineering, School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei 230009,
P. R. China.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data (full experimental detail, 1H and 13C NMR spectra) can be accessed on the publisher’s website.
© 2018 Taylor & Francis

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Scheme 1. Proposed reaction mechanism.[7,15]
catalysts in acetalization reactions. For example, Barbara reported that simple pyridinium
salt derivatives showed highly efficient catalytic activity at ambient temperature (Scheme
1a).[11] However, these methods have limitations such as being toxic and harmful to the
environment. Therefore, a general method for catalyzing efficient and environment-
friendly acetalization reactions is highly desirable.
In recent years, visible light-induced catalytic reactions have also been drawing
increasing attention.[13,14] Rangel found that P-chloranil could effectively catalyze the
acetalization reaction under 350 nm light bulbs and he inferred that the proton in
the phenolic hydroxyl group played a key role in the reaction (Scheme 1b).[8] But this
catalyst is relatively toxic and thus has limited industrial applications. Eosin Y[11] is a
very important organic photocatalyst and Lei’s group reported the Eosin Y-catalyzed
acetalization under green light. We found that a high yield could be achieved under
the irradiation from house bulbs. Based on this finding, in-depth and systematic studies
were performed to determine the adaptability of the catalytic reaction. The reaction
mechanism was then speculated and the same reaction was performed on the gram scale
(Scheme 1c).
Results and discussion
Initially, benzaldehyde (1a) and methanol were chosen as model compounds to optimize
the reaction conditions. As depicted in Table 1, the catalyst, time, and light affect the
efficiency of this reaction. In the control experiments, no reaction occurred without catalyst
(Table 1, entry 1). A series of catalysts were screened (Table 1, entries 2–6). The benzoic
acid and water-soluble Eosin Y were very inefficient in promoting this reaction
(Table 1, entries 2 and 3). When we used rhodamine B or fluorescein as catalysts

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Q. ZHOU ET AL.
Table 1. Optimization of the reaction conditions.a
Entry
Catalyst (mol%)
Time (h)
Yield (%)d
1
2
–
12
12
12
12
12
12
12
12
12
6
n.r.
n.r.
9
Eosin Yb (2)
Benzoic acid (2)
Rhodamine B (2)
Fluorescein (2)
Eosin Y (2)
3
4
74
5
63
6
90(92e)
87
7c
8
Eosin Y (2)
Eosin Y (0.5)
Eosin Y (1)
84
9
89
10
11
12f
Eosin Y (2)
82
Eosin Y (2)
24
12
85
Eosin Y (2)
n.r.
aYields determined by GC. Reaction conditions: 1a (0.5 mmol), solvent (2 mL), catalyst (2 mol%), room temperature, 15 W
house bulb under N2 atmosphere.
bWater-soluble Eosin Y.
cLight use of LED blue light.
dYields determined by GC.
eIsolated yield.
fIn the dark.
(Table 1, entries 4 and 5), we found that the yield was improved obviously. Specifically, a
promising result showed that alcohol-soluble Eosin Y could highly and efficiently play the
role of catalyst. The desired product (2a) in 90% yield was obtained when the acetalization
was performed at room temperature for 12 h (Table 1, entry 6). Then we did a control
experiment under the darkness, but the product was hardly observed without light. The
experimental results show that light is the key to this process. The yield under blue light
(16 W LED lamp, 465 nm) irradiation was similar to that under 16 W LED white lamp
(Table 1, entry 7). Finally, the reaction time was varied (Table 1, entries 6, 10, and 11)
and the results manifested that 12 h is the best reaction time.
At the same time, it was found that (Table 2) when the benzene ring had electron-
donating substituents such as methyl groups, the corresponding product decomposed
easily. We studied the adaptability of the reaction system to aliphatic aldehydes and
found that it took only 4 h to complete the reaction in the system (2q, 2r). Further
experiments showed that the reaction of aliphatic aldehydes containing benzene rings
in the chain only required 4 h (2n–2p). Ketones were much harder to react, even over
longer reaction time and under higher temperature. A series of reactions were per-
formed using different ketones as substrates, but only the cycloketones could get good
yields (2s) for being unaffected by steric hindrance. In general, the reaction system fol-
lows the rule of acetalization.
Usually, the acetalization of glycols is easier than methyl alcohol. We unsurprisingly
found that glycols also reacted under the same reaction conditions and favorable yields
were obtained with different carbonyl compounds (Table 3). This reaction was not limited
to methanol and diol derivatives also delivered the acetals in high yields. The results
showed that the yields when ethylene glycol and 1,3-propanediol were used as substrates
were better than if methyl alcohol was used and the target products were more stable

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Table 2. Scope of substrates.a
aReaction conditions: aldehydes or ketones (0.5 mmol), 2 mol% Eosin Y, methanol 2.0 mL, room temperature for 6 h, 16 W
house bulb; isolated yield under N2 atmosphere.
bReaction time for 4 h.
cReaction temperature is 90 °C.
(3a–3m, Table 3). When the aldehyde compounds had a substituents such as -CH3, -Cl on
the benzene ring, the reaction yield was low. Unexpectedly, it was found that if glycols
instead of methanol were reacted with ketones, the ketal carbonyl compounds also had
good yields (3l, 3m) in the reaction system.
The selectivity of the reaction system was further studied. The acetalization was
performed with methanol and a mixture of benzaldehyde and acetophenone as substrates.
(Table 4) The yields of the corresponding target products were found to be significantly
different. The yield of 2a was as high as 93% and no 5b was observed, indicating that
aromatic aldehydes in the reaction system were more likely to undergo acetalization. Then
methyl alcohol and ethylene glycol (volume ratio 1:1) mixture was used as the solvent for

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Table 3. Scope of substrates.a
aReaction conditions: 1a 1 equiv. (0.5 mmol), 2 mol% Eosin Y, 2 mL glycol, or 1,3- propanetriol as solvent at room
temperature for 6 h, 16 W house bulb under N2 atmosphere.
bReaction temperature is 90 °C.
Table 4. The experiments of the acetalization selectivity catalyzed by Eosin Y.

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Table 5. Gram-scale experiment.
acetalization of benzaldehyde and the yield of 3 h could reach 89% while the yield of 2a was
only 11%. The results further demonstrated that the diol was more likely to form a ring
carbonyl compound with benzaldehyde in the reaction system.
By analyzing the results above, we speculated the possible reaction mechanism of Eosin
Y-catalyzed acetalization. When CA is used as the catalyst, photolysis of CA (2,3,5,6-
tetrachloro-1,4-benzoquinone) in methanol results in the formation of 2,3,5,6-
tetrachloro-1,4-hydroquinone (TCHQ).[7] Excitation of this hydroquinone generates an
acidic species that protonates the carbonyl compound. Further reaction of this protonated
species with the solvent yields the acetal. Since both Eosin Y and TCHQ have a phenol
functional group, we hypothesize that the acetalization catalyzed by Eosin Y has a similar
mechanism in which the excitation of Eosin Y generates an acidic species that protonates
the carbonyl compound (directly or indirectly through a proton carrier such as MeOH).
Further reaction of this protonated species with the solvent yields the acetal (Scheme 1).
To further probe the application of Eosin Y-catalyzed protection of carbonyl in
preparative organic synthesis, a gram-scale reaction was performed. As depicted in
Table 5, the amount benzaldehyde (1a) was increased to 10 mmol and 1.3 g of 3a (88%)
was successfully obtained.
Conclusion
In summary, we have systematically achieved efficient acetalization reactions by selecting
cheap and readily available organic substance Eosin Y as the catalyst. This way is operation-
ally simple and can be conducted under mild conditions. A wide variety of synthetically
useful yet sensitive functional groups are well tolerated. In addition, the feasibility of this
method on the gram scale provides a possibility for the industrialization of carbonylation
reaction.
Experimental
General
All reactions were performed in Schlenk tubes filled with nitrogen. All solvents were
obtained from commercial suppliers and used without further purification. All light
reaction devices were obtained from the commercial suppliers. (16 W LED lamp and
16 W blue LED lamp 465 nm). Flash column chromatographic purification of products
1
was accomplished using forced-flow chromatography on Silica Gel (200–300 mesh). H
NMR and 13C NMR spectra were recorded on a Bruker Advance 400 or 600 spectrometer.
Data for 1H NMR are reported as follows: chemical shift (δ ppm), multiplicity, integration,
and coupling constant (Hz). Data for 13C NMR are reported in terms of chemical shift
(δ ppm). Gas chromatographic (GC) analyses were performed on a GC equipped with a

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Q. ZHOU ET AL.
flame ionization detector and an Rtx@-65 (30 m � 0.32 mm ID � 0.25 µm df) column. GC-
MS analyses were performed on a GC-MS with an EI mode. High-resolution mass spectra
were obtained by ESI on a TOF mass analyzer. All the products are known compounds and
were identified by comparing their physical and spectral data with those reported in the
literature.
Typical procedure for acetalization
A 25-mL oven-dried Schlenk tube was sequentially added a mixture of aldehyde derivatives
(0.5 mmol), dry CH3OH (2 mL), and Eosin Y (6.4 mg, 2 mol%). The tube was evacuated
and backfilled with nitrogen (three times). The reaction mixture was stirred under a
16 W LED white lamp irradiation at a distance of 10 cm at room temperature for 12 h.
The resulting mixture was diluted with EtOAc (8 mL). After completion of the reaction,
phenylhydrazine was added to react with the excess benzaldehyde. The resulting crude
product was washed with sodium hydroxide solution thrice. Subsequently, anhydrous
sodium sulfate was added to remove water and the resulting mixture was filtered to collect
the filtrate. The solvent in the filtrate was partially removed by rotary evaporation and the
remaining product was purified by column chromatography (ethyl acetate/petroleum
ether), followed by another round of rotary evaporation to afford the corresponding
compounds.
Spectral data for the selected compound
The product of 2a[12f] was purified by flash column chromatography on silica gel
(petroleum ether), obtained in 95% yield as a colorless liquid (69.9 mg). 1H NMR
(600 MHz, CDCl3) δ 7.45 (d, J ¼ 7.4 Hz, 2H), 7.40–7.31 (m, 3H), 5.40 (s, 1H), 3.33
(s, 6H). 13C NMR (151 MHz, CDCl3) δ 137.99, 128.41, 128.16, 126.64, 103.11, 52.67.
The product of 2b[12f] was purified by flash column chromatography on silica gel
1
(petroleum ether), obtained in 97% yield as a pale yellow liquid (122.1 mg). H NMR
(600 MHz, CDCl3) δ 7.43 (d, J ¼ 8.3 Hz, 2H), 7.25 (d, J ¼ 8.3 Hz, 2H), 5.29 (s, 1H), 3.24
(s, 6H). 13C NMR (151 MHz, CDCl3) δ 137.07, 131.30, 128.46, 122.46, 102.26, 52.54.
The product of 2j[12f] was purified by flash column chromatography on silica gel (pet-
roleum ether), obtained in 77% yield as a pale yellow liquid (63.5 mg). 1H NMR (600 MHz,
CDCl3) δ 7.36 (d, J ¼ 8.0 Hz, 2H), 7.20 (d, J ¼ 7.9 Hz, 2H), 5.39 (s, 1H), 3.34 (s, 6H), 2.37
(s, 3H). 13C NMR (151 MHz, CDCl3) δ 138.09, 135.08, 128.81, 126.54, 103.18, 52.58, 21.14.
Funding
We gratefully acknowledge the financial assistance from the National Natural Science Foundation of
China (Nos. 21371044, 21571047) and the Natural Science Foundation of Anhui Province
(No. KJ2016A701).
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