Hydrotalcite-supported palladium for reductive coupling of haloaryls to biaryls

Zhuo Guanglan 1, Jiang Xuanzhen 2, Zhang Bo 3, Ge Zhonghua 3
(1Department of Chemistry, Zhejiang Sci. & Tech. University, Hangzhou, Zhejiang, 310018; 2Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, 310027; 3Department of Chemical Engineering , Zhejiang University of Technology, Hangzhou, Zhejiang, 310014)

Abstract A new and efficient heterogeneous catalyst based on palladium particles supported on hydrotalcite was developed for reductive coupling of chloro- and bromo-aryls to biaryls. The catalyst was reusable without obvious loss in catalytic activity.

    Reductive coupling of aromatic halides is a well-known synthesis tool for C-C bond formation. The coupling products are found numerous applications in the preparation of agrochemicals, pharmaceuticals and natural products. It offers a mild alternative to the classical Ullmann coupling, which required a stoichiometric amount of copper and very high temperature. The reductive coupling reaction is often catalyzed by palladium, based on the Pd2+¡úPd0 redox cycle.[1] Although alternative coupling reactions such as Suzuki, Still, Grignard etc. are effective, reductive coupling is considered to be a more convenient and straightforward method for the synthesis of symmetrical biaryls, especially on industrial standpoint.
    Various palladium-catalyzed biaryls synthesis are described in the literature [2-7]. In order to in situ regenerating the active palladium catalyst, different reductive reagents, e.g. 2-propanol, hydrogen gas, zinc, or aqueous alkali formate salts, have been attempted. Despite of its feasibility, however, the homogeneous palladium catalyst suffer from the difficulty of reusing. Therefore, heterogeneous catalyst systems are highly desirable. Recently, Sasson and co-workers investigated Pd/C catalyzed homocouplings of aryl chlorides in detail [8-12]. They demonstrated that Pd/C is a very effective catalyst for this coupling reaction. Furthermore, they found that supported PTC ( phase transfer catalyst) is a selective agent for biphenyl synthesis, meanwhile it can suppress the side reaction.
    On the other hand, hydrotalcite like anionic clays (HTLC) have received much attention in recent years because it is regarded as an environment-friendly solid base catalyst. Hydrotalcite -supported palladium catalyst has been used in many important reactions such as the oxidation of  alcohols[13,14]. Recently palladium modified hydrotalcite was found to be an effective catalyst for Heck, Suzuki, Sonogashira and Stille type coupling reactions[15,16]. This encourages us to apply Pd-hydrotalcite catalyst (Pd/HT) on the reductive coupling reaction. To our knowledge, this is the first report of Pd-HT used as a heterogeneous catalyst for reductive coupling reaction.
    The diffraction peaks of sample which was prepared in this study can be indexed by the JCPDS X-ray powder diffraction file of No.22-700 as shown in Figure 1. It indicated that the sample was a typical hydrotalcite-supported palladium.
    Various supported catalysts, such as Pd/C, Pd/g-Al2O3, Pd/KF/g-Al2O3 and Pd/HT etc. were examined in reductive coupling reaction of chlorobenzene. The experimental results were given in Table 1. It can be seen therein that, surprisingly, 10wt%Pd/HT exhibits the highest catalytic activity among them with 85% yield of biphenyl product and 95% selectivity (Entry 5). However the commercial available 10%Pd/C catalyst shows moderate reactivity (Entry 3) which is quite consistent with the results in literature[8,9]. The rest catalysts demonstrate relatively low catalytic activities(Entries1 and 2) compared with Pd-HT and Pd/C catalysts. However when unreduced Pd2+/HT catalyst was used as the catalyst for reductive coupling, even for longer reaction time (12 h), no reaction takes place at all (Entry 6). It maybe attributed to its heterogeneous nature because homogeneous Pd(OAc)2 and PdCl2(PhCN)2 catalysts are able to catalyze the reductive coupling of aryl and heteroaryl halides as reported by Hassan and Tanaka [2,6].

    Figure 1. X-ray diffraction pattern of samples with 10%Pd/HT

Table 1 Reaction performances of reductive coupling of chlorobenzene catalyzed by different catalysts

Entry Catalyst Yield (%) Selectivity (%)
1 Pd/g-Al2O3 43 75
2 Pd/KF/g-Al2O3 55 78
3 Pd/C 70 80
4 Pd/C a 25 48
5 Pd/HT 65 82
6 Pd2+/HT none none

Reaction conditions: 0.03 mol of aromatic halides, 0.03 mol of sodium formate, 0.03 mol of NaOH, 0.05 mol of TBAB, 0.2 g Pd0-HT, T=65ºC, t=2hr.
a. In the absence of TBAB

The influence of phase transfer catalyst (PTC, e.g. TBAB) on the reaction performence was also examined as presented in Entries 3 and 4 of Table 1. The yield of biaryl product sharply reduced when TBAB was absent (see Entry 4), it is well-known that supported palladium catalysts are very active for hydrodehalogenation, which results in the formation of benzyl derivatives. Therefore there exists a competitive reaction between hydrodehalogenation and coupling reaction. The role of PTC has been previously investigated [10,11], it prevents the hydrodehalogenation reaction and promotes the selectivity towards the aryl-aryl coupling direction.
Various aromatic halogenide substrates were performed in reductive coupling reactions (Scheme1), and the results were listed in Table 2. It can be seen from Table 2 that chlorobenzene and its derivatives could be converted to the corresponding biaryl products with moderate to good yields and high selectivities. It is worthwhile to note KOH seems to be a more suitable base in this reaction. But the m-amino chlorobenzene yields no coupling product. We also try to enlarge the application scope. But the results are disappointed. When o-chloro or o-bromo pyridine were selected as the substrate, the reaction seemed to turn to the hydrodehalogenation and the main product was pyridine, only small amount of bipyridine (<20%) were obtained. When chlorobenzene and phenol were selected as the substrates, no cross coupling products were formed but biphenyl with 35% yield.

X= Br, Cl
R= H, Me, OH, NH2
                                                           Scheme 1

Table 2. Reductive coupling of aromatic halides over Pd0-HT heterogeneous catalyst

Entry Substrate Product Yield
1 Br H biphenyl 70 80
2 Cl H biphenyl 65 82
3 Cl H(a) biphenyl 85 95
4 Cl o-Me 2,2-dimethyl biphenyl 25 64
5 Cl p-Me 4,4-dimethyl biphenyl 63 80
6 Cl m-NH2 0
7 Br o-Me 2,2-dimethyl biphenyl 45 75
8 Br p-Me 4,4-dimethyl biphenyl 72 85
9 Cl p-OH 4,4-dihydroxy biphenyl 60 70

Reaction conditions: 0.03 mol of aromatic halides, 0.03 mol of sodium formate, 0.03 mol of NaOH, 0.05 mol of TBAB, 0.2 g Pd0-HT, T=65ºC, t=2hr.
a: KOH was used instead of NaOH as the base.

As regards catalyst recycling , after simple filtration and washing with methanol, the recovered Pd/HT catalyst could be reused at least three times, no obvious deactivation was observed as presented in Table 3.

Table 3. The recycling performance of Pd/HT in reductive coupling of chlorobenzene

No. 1st run 2nd run 3rd run 4th run
Yield (%) 85 82 77 80
Selectivity (%) 95 95 92 92

Reaction conditions: 0.03 mol of chlorobenzene, 0.03 mol of sodium formate, 0.03 mol of KOH, 0.05 mol of TBAB, 0.2 g Pd0-HT, T=65ºC, t=2hr.
In conclusion, Pd0-hydrotalcite is the efficient heterogeneous catalyst for reductive coupling reaction. Unlike the homogeneous catalysts, it could be reusable without obviously losing catalytic activity. This makes it to be a suitable candidate for C-C bond formation reactions.

    3.1 Preparation of Pd0-hydrotalcite ( Pd/HT) catalyst
    A solution of 0.49 mol of NaOH and 0.1 mol of Na2CO3 in 200 ml of water was added dropwise to a solution of 0.15 mol of Mg(NO3)2·6H2O and 0.05 mol of Al(NO3)3·9H2O in 75 ml of water over a period of 1 h with vigorous stirring at room temperature. After that, an aqueous solution of H2PdCl4 (0.01188g Pd/ml) was slowly added with stirring. The final pH was kept above 10. The solution was then heated at 80ºC for 18 h with stirring. The yielded dark brown precipitate was filtered and washed repeatedly till the filtrate was neutral. Then the precipitate was dried at 110ºC for 24 h. The Pd loading was kept about 10 wt% and the ratio of Mg/Al was 3. XRD spectra indicated that the sample was a typical structure of hydrotalcite. The sample thus obtained was then reduced with hydrazine hydrate in ethanol for 10 h at room temperature, filtered and washed with ethanol to give gray to blackish powder(Pd0-HT).
    3.2 General procedure for reductive coupling of aromatic halides
    A 100 ml flask reactor was charged with 0.03 mol of aromatic halides, 0.03 mol of sodium formate, 0.03 mol of NaOH 0.05 mol of TBAB, 0.2 g Pd0-HT, 5 ml water and 15 ml of methanol. The mixture was stirred and heated to reflux (ca. 65ºC) for 2 h, cooled to room temperature and diluted with water. The catalyst was filtered. The organic compounds were extracted with CH2Cl2 (2¡Á20 ml). The combined filtrates were evaporated to give the products. The products were analyzed by GC and identified by GC-MS and FT-IR.