2.1 Synthesis of the benzothiazole-based Pd(II) complexes 4a,b
Treatment of benzothiazole-2-amine derivatives (1a,b) with N,N-dimethylformamide dimethylacetal (DMF DMA) (2) afforded the corresponding benzothiazole-based formamidine ligands (3a,b) as depicted in Scheme 1. The structural proof of ligands 3a,b was established based on their spectroscopic data. For example, the proton NMR spectrum of the 3a showed the resonance of protons of the two methyl groups of N(Me)2 group as two singlet signals at δ 3.00 and 3.14ppm and two sets of triplets at δ 7.13 and 7.28 ppm with coupling constant J = 8.5 Hz due to the two-aromatic ring (CH) protons. Also, two sets of doublets at δ 7.55 and 7.75 ppm with coupling constant J = 8.5 Hz due to the other two aromatic ring (CH) protons. The proton of -N=CH- of the formamidinyl group resonates as a singlet at δ 8.46 ppm (Fig.1). 13C NMR spectra of the same ligand 3a showed the characteristic 9 carbon atoms resonance at their expected chemical shifts as shown in Fig 2. The other derivatives 3b reveled both 1H and 13C NMR spectra and the interpretation is showed in Fig. 3 and Fig. 4, respectively. Considering the IR spectrum of ligands 3a,b, the C=N group frequency showed the expected absorption band near 1636 cm-1 (see experimental part).
The targeted palladium complexes could be easily accessed by addition of sodium tetrachloropalladate in methanol as a solvent to equimolar amount of methanolic solution of benzothiazole-based formamidine ligands 3a,b at room with constant continuous stirring at temperature. After complete addition of the palladate salt, the corresponding 1:2 benzothiazole-based palladium(II) complex 4a,b in a moderate yield (Scheme 2). The structural elucidation of synthesized Pd complexes 4a,b has been achieved by their spectroscopic analysis and physical characteristics. 1H NMR investigation of recorded spectrum of the coordination products revealed the formation of mainly 1:2 complexes and traces of 1:1 complex which was also confirmed by analytical investigation and thermogravimetric analysis that will be discussed latter. The 1H NMR spectrum (Fig. 5) for complex 4a (taken as example) showed a sets of singlet signals at δ 3.03, 3.17, 3.18 ppm due to the protons of N(Me)2 group. In addition to four triplets’ signals at δ 7.16, 7.32, 7.33 and 7.50 ppm with J = 8.5 Hz assigned to the two aromatic rings (CH) protons at position 5 and 6 in each benzothiazole moiety and three doublet signals at δ 7.57, 7.78 and 7.83 ppm due the other aromatic positions at position 4 and 7 in each benzothiazole moiety. The last aromatic proton in position 7 in the benzothiazole moiety which is directly coordinated to the palladium atom showed a unique splitting pattern because of palladium field, where it appears as a doublet of doublet at δ 8.29 and 8.35 ppm with large value of coupling constant J = 59.5 Hz. The protons of (CH) group in formamidine moieties in 3a was found to resonates a singlet at δ 8.49 ppm for the formamidine group that is far from the coordination center and a doublet at δ 8.44 and 8.51 ppm for the formamidine group that is involved in the coordination center. The latter splitting of the formamidine proton signal is due to influence of the nitrogen atom coordination of the formamidinyl moiety with the Pd metal with coupling constant J = 59.5 Hz (Fig. 5a). Moreover, the 13C NMR spectrum of complex 4a showed the characteristic carbon atoms resonance at the expected chemical shifts as shown in Fig.6. 1H NMR spectral elucidation of the structure of complex 4b could be accounted in similar manner and was shown in Fig. 7. The recorded IR spectrum of complex 4a,b revealed the expected absorption band at 1627-1632 cm-1 assigned to the C=N bond vibration.
2.2. The Job’s of continuous variation method
The stochiometric ratio and the molecular structure of the complex formed between Pd(II) and benzothiazole-based ligand was determined spectrophotometrically using a continuous variation method [27]. Within this method, 1.0x10-3 M solutions from both Pd(II) and ligand were prepared, then nine complex mixtures were prepared using various concentrations of both Pd(II) and ligand keeping the total concentration at constant value. The obtained results were represented by drawing the relation between the obtained absorbance at λmax = 330 nm and the mole fraction for each mixture Fig. 8. As seen from the Fig. 8, two clear intersections at about 0.3 and 0.7 giving an evidence for a formation two stable complexes between the reaction species of stoichiometric ratios mainly (1:2) and traces of (1:1) (Pd(II):ligand). However the 1:1 complexes was not detected by NMR analysis which may atributed to their unstability in the NMR solvent DMSO-d6. Based on these obtained results, two solid complexes with the previous stoichiometries were prepared and a thermogravimetric analysis (TGA) was performed to confirm the structure. Figs. 9 and10 illustrated TGA for (1:2) and (1:1) complexes. From these figures, the calculated and the found weight losses for each thermo degradation step were determined and were listed in Table 1. Based on this date the proposed structures for the prepared complexes are constructed in Scheme 2,
2.3 Thermogravimetric analysis
TG (thermogravimetric) and DTA (differential thermal analysis) were performed for the palladium complexes of ligands 3a and 3b to investigate their thermal stability. TG and DTA analysis were investigated in range of temperature varies from ambient temperature up to 800 °C with a heating rate of 10 °C/min and under N2 flow. The obtained TG/DTA thermograms for the complexes 4a and 4b are shown in Figures 9 and 10, respectively. Both complexes showed similar thermal decomposition, with a high thermal stability up to 278 °C. The weight loss observed below ⁓ 250 °C in TGA curve of sample 4a is attributed to the physically adsorbed water and solvent, as shown in differential thermal analysis by an exothermic the peak with a maximum at around ⁓ 180 °C. However, this loss of weight was not noticed for 4b because this sample was dry and crystalized. The degradation of the ligand started at around 279 °C for both complexes and was presented in the TGA curve by an obvious endothermic peak with a minimum at around 307 °C and 313 °C for samples 4a and 4b, respectively. This degradation corresponded to the weight loss of .66% (calculated 68%) for sample 4a and 70% (calculated 69%) for sample 4b.
Table 1: Results for thermogravimetric analysis (TGA) of selected two complexes formed between benzothiazole-based ligand and Pd(II).
Complex
|
Complex (M.Wt)
Chemical formula
|
Temperature range (0C)
|
Process
|
Weight loss %
|
Calcd.
|
found
|
4a
|
[RPd2Cl2]
585
|
70-250
|
Loss of 2Cl
|
12
|
10.5
|
[RPd2Cl2]
|
250-800
|
Loss of organic part and PdCO3 formation
|
71.5
|
69.7
|
4b
|
[RPdCl2]
399
|
300-800
|
Loss of 2Cl and organic part then PdO formation
|
69.3
|
71.2
|
2.3 The scanning electron microscopy (SEM)
The morphology of ligands 3a and 3b, and their palladium complexes 4a and ab, respectively, was studied by scanning electron microscopy. The resulted micrographs of SEM are shown in Figures 11 and 12. The SEM images of ligand 3a (Fig. 11a-c) depicted highly agglomerated particles with irregular shape, and with sizes in the micrometer range. After the complexation reaction of ligand 3a with palladium, the SEM images of the obtained complex 4a (Fig. 11d-f) revealed the formation of thin micro platelets with irregular shape and low aggregation compared to ligand 3a.
SEM micrographs of ligand 3b (Fig. 12a-c) showed creme-like surface morphology with high degree of agglomeration compared to ligand 3a. However, after the complexation reaction of ligand 3b with palladium, the SEM micrographs of the obtained complex 4b (Fig. 12d-f) revealed the formation of rectangular microcrystals 3a, with sharp edges, and a size ranging from few µm to 20 µm.
2.5 X-ray diffraction Analysis
The XRD pattern of complex 4a recorded eight principal reflections observed at 2Ɵ = 11.2, 16.0, 19.4, 24.9, 28.6, 35.1, 41.2 and 43.6, assigned to the (001), (111), (1-11), (022), (-122) (0-22) (114) and (0-32) planes, respectively, (Fig. 13). The calculations were performed for the crystal system Anorthic from all important peaks. For the complex 4b the XRD pattern recorded twelve main reflections at 2Ɵ = 10.5, 13.1, 16.0, 19.3, 21.9, 23.6, 24.5, 25.9, 31.4, 39.3 and 44.6, attributed to the (200), (11-1), (020), (220), (221) (202) (130), (022), (13-2), (62-1) , (133) and (730) planes, respectively, (Fig. 14). The crystal system for this sample, which was determined from all important peaks, was Monoclinic. The particle size for both complexes was calculated via Deby–Scherrer equation [28]. It was found that the obtained size present outstandingly in the nanometer range, which is around 10 nm, and 16 nm for complex 4a and 4b, respectively.
2.6. Catalytic Study
2.6.1. The catalytic efficiency of complex 4a,b in Suzuki –Miyaura Cross-Couplings
2.6.1.1. Effect of concentration of the complex 4a,b in catalysis of Suzuki –Miyaura Cross-Couplings
To investigate the catalytic performance of the synthesized palladium complexes for the Suzuki Miyaura C-C cross coupling we have intially studied of the effect of concentration of the palladium complexes 4a,b on the formation of 4-acetyl-1,1´-biphenyl (7a) by the cross-coupling of phenylboronic acid (5a) and 4´-bromoacetophenone (6) in water as a solvent and using K2CO3 as a base. The latter reaction was considered as the model reaction of the investigation of the catalytic efficiency using the developed catalysts. Also, a co-catalyst tetrabutylammonium bromide (TBAB) was used a phase transfere reagent in such aqueous reaction. Thus, refluxing the reaction mixture in the presence of the complex 4a with different concentrations furnshed the desired cross couplined product, 4-acetyl-1,1´-biphenyl (7a) after thermal heating for three hours as iullstrated in Scheme 3 and Table 2. When the cross coupling was carried out in the presence of 1 mol% of the complex 4a and the other molar ratio of 6: 5a: K2CO3: TBAB was .01:1.2:1.0:0.6, it resulted in 100% conversion (mesured by GC-analysis) and the cross coupling product 7a was obtained with complete disappearence of the starting materials (entry 1, Table 2). By gradual increase of the complex 4a concentration from 0.75 to 0.125 mol%, we also obtained a full GC-conversion under the same reaction conditions (entries 2-5, Table 2). Thus, from the data in Table 2, it can be decided that the palladium complex 4 exhibited outstanding catalytic efficiency in the Suzuki Miyaura C-C cross coupling even when using very low mol%. On the other hand, the starting 4´-bromoacetophenone (6) was completely recovered when the cross coupling was carried out without addition of the palladium complex 4a as expected (entry 6, Table 2). The obtained product, 4-acetyl-1,1´-biphenyl (7a) was analysed and its structure was confirmed by spectroscopic tools.
Table 2: Effect of concentration of complex 4a,b on the coupling of 4´-bromoacetophenone (6) with phenylboronic acid (5a) in water.
GC Conversion%
|
Pd, mol%%
|
Entry
|
Cat 4b
|
Cat 4a
|
100
|
100
|
1.5
|
1
|
100
|
100
|
1
|
2
|
100
|
100
|
0.75
|
3
|
100
|
100
|
0.5
|
4
|
100
|
100
|
0.25
|
5
|
0
|
0
|
0.00
|
6
|
a Conditions: 4´-bromoacetophenone (6) / phenylboronic acid (5a)/ K2CO3/ TBAB / water: 1.0/1.2/1.0 / 0.6/ 10 mL, under thermal heating at 100°C for 3 h. b Conversions were based on GC-analysis: the conversion was monitored by Shimadzu GC-17A gas chromatography (GC), equipped with flam ionization detector and RTX-5 column, 30 m x 0.25 mm, 1 µm film thickness. Helium was used as carrier gas at flow rate 0.6 mL/min. Samples were withdrawn from the reaction mixture periodically. Injection volume was 1 µl, and total flow was 100 ml/min. Oven temperature was initiated at 100 °C for 2 min up to 130 °C at a rate of 15 °C/ min held for 2 min, then increased to 150 °C at a rate of 2 °C/ min held for 2 min. The Injector temperature was 160 °C and the detector temperature was 200 °C.
|
In order to explain how does the palladium complex 4 take part in the catalytic process of the reaction, it was suggested that the complex acts as “dormant species” and does not participate in the reaction catalytic cycle in an actual manner. the palladium complex 4 is considered as the main precursor for the palladium catalytically active species, thus it is considered as a precatalyst in the cross coupling reaction. Generally, the palladium(0) species was considered to be the true active catalysts as reported previouusly [29.30]. Therefore, the precatalyst 4 may serve as a reservoir that is indirectly involved in the catalytic cycle of the cross coupling and it is the main source of release of nano-sized palladium(0) which can afford catalytic role even when used with very low concentrations [31].
2.6.1.2. Effect of solvent and base on Suzuki –Miyaura Cross-Couplings using complex 4a as a catalyst
Optimization of the cross coupling conditions have been achieved by studying the effect of different parameters that may affect the cross-coupling reaction. Firstlty, solvent/base pair is one of the important factors that controls the efficiency of the catalyst in the cross coupling reactions and in consequence affects the yield optimization. However, there is no general rule for choosing the solvent/base pair for a given cross coupling, the selection of the solvent/base pair is still empirical. In the present work, we have invetigated some bases and a variety of solvents to perform the cross coupling reaction between 4´-bromoacetophenone (6) and phenylboronic acid (5a) as iullistrated in Scheme 4. Also, the heating mode for Suzuki-Miyaura cross-coupling reaction is one of the most important parameters in combination with base/solvent parameter specially in case of using the microwaves irradiation conditions. In this work we have used a solvothermal like technique under microwave irradiation in which the reaction was carried out in a special reaction vessel made from teflon and capped well to isolate it tightly which insure no leakage of the reaction solvent (see experimental part). As Shown in Scheme 4 and Table 3, cross couplings were carried out using different solvents e.g. H2O, DMF, toluene, 2-PrOH, dioxane and THF. In all entries, the catalyst concentration was 0.75 mol% of complex 4a. Three appropriate bases were used in the cross coupling namely, KOH, K2CO3 and TEA under conventional heating (thermal condirions) and microwaves irradiation conditions. In case of using water as a solvent (Hydrothermal conditions) a co-catalyst tetrabutylammonium bromide (TBAB), have been used in the cross coupling reaction. From results obtained in Table 3, when H2O was used as a solvent in the presence of K2CO3 as a base we got a full conversion after either 3h reflux (estimated by GC) or 7 min of microwaves irradiation and (entries 1 and 3, Table 3). Replacement of water by nonpolar solvent, toluene, we achieved less conversions and lower isolated yield of the product regardless the mode of heating as shown in Table 3 (entries 6 and 7). When less polar solvents: DMF, dioxane, or THF were used instead of water as a solvent using the same base, we obtained excellant conversions under conventional heating (entries 4,8 and 12, Table 3). When K2CO3 was replaced by KOH as a base we obtained the same conversions (entries 15 and 16, Table 3) however the isolated yield decreased in such case. Also, 2-propanol was found to be a suitable solvent for the reaction using either conventional heating or under microwave irradiation (entries 10, and 11, Table 3). Finally, when we used triethylamine (TEA) as an organic base using water as a solvent the cross coupling afforded 80% conversion and good isolated yield (entry 14, Table 3).
Table 3: Effect of base and solvent Suzuki cross coupling of 4´-bromoacetophenone (6) with phenylboronic acid (5a)
Entry
|
Base
|
Solvent
|
Heating mode
|
Time
|
Yield %a
|
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
|
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
TEA
KOH
KOH
|
H2O
H2O
H2O
DMF
DMF
Toluene
Toluene
Dioxane
Dioxane
2-PrOH
2-PrOH
THF
THF
H2O
H2O
DMF
|
D
mW
mW
D
mW
D
mW
D
mW
D
mW
D
mW
D
D
|
3h
5 min
7 min
3h
7 min
4h
7 min
3h
7 min
4h
7 min
4h
7 min
4h
4h
4h
|
100(95)
75(64)
100(100)
100(90)
80(77)
77(74)
84(83)
100(73)
100(92)
100(98)
100(98)
100(83)
100(87)
80(71)
100(91)
100(81)
|
a Conversion by GC-analysis and the value between parenthesis indicates the product isolated yield%. Conditions: 4´-Bromoacetophenone/ phenylboronic acid/co-catalyst (if used)/ base/ solvents: 1/1.2/ 0.6/ 1/ 10 mL, under thermal heating at 100°C for 3 h. mW power was 300 W
|
H2O as a green solvent is usually prefered in organic transformations due to the environmental advantages and K2CO3 is considered as a common base since it is a cheap. Thus, we recomand H2O/ K2CO3 pair is the best solvent/Base combination for carrying out all the cross coupling reaction of aryl bromides in the presence of TBAB as a co catalyst. In general microwaves irradiation conditions and pressurized conditions affforded the cross coupled product in good yield and with high purity with a shorter time than the thermal conditions.
2.6.2. Suzuki–Miyaura cross-coupling reaction with arylboronic acid derivatives under conventional heating and microwaves irradiation using complex 4a
Under the optimized conditions, Suzuki–Miyaura cross-coupling of 4’-bromoacetophenone 6 with a variety of boronic acid derivatives 5b-g were performed under thermal and microvave assisted hydrothermal heating as iullistrated in scheme 4. Expectedly, complex 4a was found to be an efficient catalyst for the cross-coupling reaction of boronic acid derivatives 5b-g in excellent yield using water/K2CO3 as a solvent/base pair (Table 4) regardless the nature of the substituent pendant on the aromatic ring in the boronic acid.
Table 4: Conventional and microwaves assisted SMC reaction of 4´-bromoacetophenone (6) with arylboronic acid derivatives 5b-g using complex 4
Compd. No.
|
Ar
|
D heating
|
mW heating
|
Timea (h)
|
Yield%b
|
Timea (min)
|
Yield %b
|
7b
|
4-F-C6H4-
|
4
|
100
|
7
|
100 (99)
|
7c
|
4-CN-C6H4-
|
4
|
100
|
7
|
100 (98)
|
7d
|
4-Me-C6H4-
|
5
|
100
|
9
|
100 (93)
|
7e
|
4-MeO-C6H4-
|
4
|
100
|
7
|
100 (95)
|
7f
|
4-MeCO-C6H4-
|
4
|
99
|
8
|
100 (92)
|
7g
|
3,5-Me2-C6H3-
|
5
|
98
|
9
|
100 (94)
|
Molar ratio of 4´-Bromoacetophenone/ arylboronic acid derivative/ TBAB /K2CO3 is 1:1.2:0.6/1and 0.75 mol% of the precatalsyt 4a in 10 mL of a given solvent. Thermal reaction was carried out at 100°C with stirring and microwave heating have been done using 300 W power at 100 °C. a TLC or GC were used to determine the time of reaction. b Determined by GC and isolated yield was indicated between paranthesis.
|