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Synlett 2019; 30(14): 1698-1702
DOI: 10.1055/s-0037-1612083
cluster
© Georg Thieme Verlag Stuttgart · New York

Sodium Selenosulfate from Sodium Sulfite and Selenium Powder: An Odorless Selenylating Reagent for Alkyl Halides to Produce Dialkyl Diselenide Catalysts

Yonghong Liu
b   School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, P. R. of China
,
Hai Ling
b   School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, P. R. of China
c   Department of Chemistry, East China Normal University, Shanghai, 200062, P. R. of China   Email: xfjiang@chem.ecnu.edu.cn
,
Chao Chen
b   School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, P. R. of China
,
Qing Xu
b   School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, P. R. of China
,
Lei Yu  *
a   Guangling College, Yangzhou University, Yangzhou, Jiangsu 225000, P. R. of China   Email: yulei@yzu.edu.cn
b   School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, P. R. of China
,
Xuefeng Jiang  *
c   Department of Chemistry, East China Normal University, Shanghai, 200062, P. R. of China   Email: xfjiang@chem.ecnu.edu.cn
› Author Affiliations

This work was supported by the Nature Science Foundation of Guangling College (ZKZZ18001).
Further Information

Publication History

Received: 12 November 2018

Accepted after revision: 26 December 2018

Publication Date:
07 February 2019 (online)

 
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Published as part of the Cluster Organosulfur and Organoselenium Compounds in Catalysis

Abstract

Na2SeSO3, which can be generated in situ by the reaction of Na2SO3 with Se power, was found to be an odorless reagent for the selenenylation of alkyl halides to produce dialkyl diselenides. These products have been recently shown to be good catalysts for the Baeyer–Villiger oxidation of carbonyl compounds, for the selective oxidation of alkenes, or for the oxidative deoximation of oximes. By using aqueous EtOH as the solvent and avoiding the generation of a malodourous selenol intermediate, the selenylation reaction with Na2SeSO3 is much more environmentally friendly than conventional methods. Owing to the cheap and abundant starting materials and selenium reagents, our novel synthetic method reduces the production costs of dialkyl diselenides as organoselenium catalysts, thereby advancing practical applications of organoselenium-catalysis technologies.


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Key words

dialkyl diselenides - alkyl halides - selenenylation - organoselenium catalysts - green synthesis

Owing to their unique biological and chemical activities, organoselenium compounds have a wide range of applications in biochemistry, medicinal chemistry, organic synthesis, and materials science.[1] [2] Researchers have recently paid a growing amount of attention to the ecofriendly side of organoselenium chemistry,[3] and among reported works, organoselenium catalysis[4] is considered to be one of the most significant and practical applications, because of its clean procedures, transition-metal-free conditions, and the metabolizable catalyst element,[5] thereby affording a potential alternative to transition-metal catalysis in the synthesis of medicines. A variety of organoselenium-catalyzed reactions have been reported,[6] [7] [8] [9] [10] and this field has recently shown rapid progress. In our researches, we have focused on organoselenium-catalyzed green reactions to produce useful industrial intermediates, for example, by the Baeyer–Villiger oxidation of carbonyl compounds,[8] by the selective oxidation of alkenes,[9] or by the dehydration or oxidative deoximation of oximes.[10] We were recently surprised to find that dialkyl diselenides can serve as unique catalysts in many reactions,[8b] [9b] [9d] [10a] despite their possible decomposition through selenoxide elimination, as previously believed.[11]

Classic methods for the synthesis of diselenides can be classified into three types. The first type involve selenol intermediates and proceed through selenylation of Grignard or organolithium reagents under oxidative conditions or through the reaction of ketones with pre-prepared H2Se [Scheme [1](a)]; however, this type of reaction involves selenium compounds that are toxic and malodorous. In the second type of synthesis, which eliminate laborious procedures involving selenols, inorganic salts serve as alternative sources of selenium for the formation of diselenides from halides, diazonium compounds, or carbonyl compounds [Scheme [1](b)]. In the third type of synthesis, special selenium-containing reagents, for example Se2 2– salts, are used to construct diselenides [Scheme [1](c)]; however, a series of safety problems has emerged in the laborious process of preparing the raw materials for this type of reaction.[12]

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Scheme 1 Methods for the synthesis of diselenides

In our studies on odorless sulfur-atom transfer, we found that SO3 2– attached to a sulfur atom is an appropriate candidate for use as a protecting group, because of its unique properties as an electron-withdrawing group, a sustained bulky group, and a conjugated group.[13] By using Na2S2O3/RS2O3Na as a sulfur source, we were able to avoid the generation of malodorous thiol intermediates through dissociation (Scheme [1], Previous Work). Inspired by these findings, we surmised that selenium atoms might also be introduced by using the similar Na2SeSO3 salt. Here, we will describe an odorless route to the formation of dialkyl di­selenides via Na2SeSO3 generated in situ from Na2SO3 and Se powder (Scheme [1], This Work).

We chose the selenenylation of BuBr (1a) to give dibutyl diselenide (2a) as a model reaction to optimize the conditions. Na2SO3 was initially heated for ten hours with one equivalent of Se powder in water at 100 °C in a sealed reaction tube[14] charged with N2. A solution of BuBr (1a) in ethanol was then added, and the mixture was heated in air for another ten hours. The desired product (BuSe)2 (2a) was then isolated in 44% yield (Table [1], entry 1). Further screenings demonstrated that extending the reaction times for both of the Na2SeSO3-formation step (t 1) and the selenylation step (t 2) enhanced the product yield (entries 2 and 3). Next, the effect of the molar ratio of Se to BuBr (1a) was investigated, and it was found that an excess of Se was necessary to ensure full conversion of 1a (entries 3–7). In terms of the product yield and the atom economy of the reaction, a 50 mol% excess of Se is favorable (entry 5). By elevating the temperature of the Na2SeSO3-formation step (T 1), the product yield was obviously enhanced to a maximum of 74% (Table [1], entry 9). Moreover, EtOH was found to be a necessary solvent for the selenenylation of 1a, and the yield decreased in its absence (entry 10).

Table 1 Optimization of the Synthesis of Dibutyl Diselenide (2a)a

Entry

Se/BuBrb

T 1 c (°C)

t 1 d (h)

t 2 e (h)

Yieldf (%)

1

2.0

100

10

10

44

2

2.0

100

24

24

48

3

2.0

100

48

48

56

4

3.0

100

48

48

58

5

1.5

100

48

48

56

6

1.2

100

48

48

49

7

1.0

100

48

48

22

8

1.5

120

48

48

62

9

1.5

140

48

48

74

10g

1.5

140

48

48

63

a Reaction conditions: 1a (1 mmol), H2O (2 mL), EtOH (1 mL); Na2SO3 and Se were used in equimolar amounts.

b Molar ratio of Se to 1a.

c Temperature for the first step reaction step.

d Time for the first reaction step.

e Time for the second reaction step.

f Isolated yield.

g No EtOH was added in the second step reaction.

The scope of this method was then examined under the optimized conditions.[15] Selenenylation reactions of primary alkyl chlorides or bromides afforded the corresponding dialkyl diselenides 2 smoothly in moderate to good yields (Table [2], entries 1–9), and in these cases, cheap alkyl chlorides were the preferred substrates (entries 3, 5, 7, and 9). Notable, the reaction could be performed in a ten-times scaled-up reaction without a decrease in the yield (entry 2). In comparison, reactions of secondary alkyl halides produced the related diselenides 2 in decreased yields due to the increased steric hindrances of the substrates (entries 10–15). Almost no reaction occurred with bulky tertiary alkyl halides, such as t-BuCl or t-BuBr (entry 16). Benzyl halides were also favorable substrates, giving the related dibenzyl diselenides 2i–m in moderate yields (entries 17–21). In these reactions, the corresponding dialkyl selenides 3 were also generated as minor byproducts, as observed in 1H NMR spectra.

Table 2 Synthesis of dialkyl diselenides 2 a

Entry

RX

Product 2 [yieldb (%)]

Product 3 [yieldc (%)]

1

BuBr

2a (74)

3a (12)

2d

2a (77)

3a (13)

3

BuCl

2a (78)

3a (9)

4

Me(CH2)4Br

2b (70)

3b (17)

5

Me(CH2)4Cl

2b (72)

3b (16)

6

Me(CH2)7Br

2c (66)

3c (10)

7

Me(CH2)4Cl

2c (72)

3c (7)

8

i-BuBr

2d (55)

3d (28)

9

i-BuCl

2d (56)

3d (26)

10

i-PrBr

2e (42)

3e (4)

11

i-PrCl

2e (35)

3e (7)

12

c-C5H9Br

2f (40)

3f (16)

13

c-C5H9Cl

2f (38)

3f (19)

14

CyBr

2g (45)

3g (5)

15

CyCl

2g (18)

3g (12)

16

t-BuX (X = Cl, Br)

2h (trace)e

–

17

BnCl

2i (66)

3i (26)

18

3-FC6H4CH2Cl

2j (73)

3j (26)

19

4-ClC6H4CH2Cl

2k (70)

3k (15)

20

3-ClC6H4CH2Cl

2l (62)

3l (20)

21

2-TolCH2Cl

2m (70)

3m (11)

a The reactions were performed on a 1 mmol scale; Na2SeSO3 was prepared in situ as described in Table [1], entry 9.

b Isolated yields based on 1.

c NMR yields.

d The reaction was performed on a 10 mmol scale.

e Yield < 3%.

The mechanism of this interesting reaction was our next concern. To gain information on the mechanism, we performed a series of control experiments (Scheme [2]). First, Se powder was heated in water at 140 °C for 48 hours in the absence of Na2SO3, and then the mixture was heated with an EtOH solution of BuBr at 100 °C. However, no reaction occurred after 48 hours (Scheme [2], eq. 1). Next, the reaction of BuBr with Se in the presence of Na2SO4 was tested, but this still gave none of the desired diselenide product (Scheme [2], eq. 2). Moreover, although Se can disproportionate into Se2–and Se4+ under alkaline conditions, no reaction occurred when Na2SO3 was replaced with NaOH (Scheme [2], eq. 3). These results clearly demonstrate that Na2SO3 is a crucial carrier in the selenenylation reaction.

Zoom Image
Scheme 2 Control experiments

On the basis of the experimental results as well as reports in the literature,[13] [16] a plausible mechanism shown, in Scheme [3], is proposed. The reaction of Na2SO3 with Se powder (A) initially generates the selenium reagent Na2SeSO3 (B),[16] which rearranges to the highly nucleophilic intermediate species D.[13] Nucleophilic attack by D on alkyl halides leads to the organoselenium intermediate F, which is an efficient alkylselenium reagent that can be oxidized by air to produce the diselenide 2 through a homocoupling reaction.[13] The reaction of F with RX might also produce the selenide 3, which was the observed byproduct of the reaction, and could be detected by NMR spectroscopy.

Zoom Image
Scheme 3 Possible mechanism

In conclusion, we have developed a novel method for the synthesis of dialkyl diselenides. The method uses Na2SO3 and Se powder as starting materials to generate the selenylation reagent Na2SeSO3 in situ; this is odorless and can convert alkyl halides into the corresponding dialkyl diselenides in moderate to good yields. The low cost of the starting materials, as well as the green features of the procedures, should permit the application of this synthetic method in large-scale production. Because dialkyl diselenides have been found to be efficient catalysts for many reactions, this work might promote practical applications of organoselenium catalysis technologies.


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Acknowledgment

We thank the analysis center of Yangzhou University for assistances.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/s-0037-1612083.
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Zoom Image
Scheme 1 Methods for the synthesis of diselenides
Zoom Image
Scheme 2 Control experiments
Zoom Image
Scheme 3 Possible mechanism