Reactivity of M-C Bonds and Catalytic Formation of Heterocycles - Essay Example

?Reactivity of M-C bonds and catalytic formation of heterocycles of Background The key concepts that willbe considered in this project are CH activation, AMLA and CMD processes, and Heterocycle synthesis by oxidative catalysis. The processes of cyclometallation and catalytic cycles can be well established through the use of AMLA process. This process refers to Ambiphilic Metal Ligand Activation and it is helpful during cyclometallation and catalytic cycles (Song, Wang & Li, 2012). The second key element is the CH activation process and this process usually helps in electrophilic metal and acetate activation. The activation is achieved through combination of deprotonation as well as acetate which is an intramolecular base. Currently, close to 95% of all phenyl group activation relies on CH activation (Anastas & Warner, 1998). Current studies have showed the ease of activation of different types of CH bonds and some of these bonds are NH or NR types. This type of bond falls in type 1 of the heterocycles ligands and the second type is the vinyl group. This group is characterized by the formation of rings such as M ring which at times is an equivalent of p-cymene. The vinyl group which is type 2 of the heterocycles in ligands is able to react with alkynes after the process of CH activation. The ease of insertion of the various M-C bonds which comprises of the heterocycle, phenyl, and vinyl with alkynes are not yet known. This is because very limited research has been done on this area. The activation of these M-C bonds with the alkynes is expected to give type 3 of the heterocycles in ligands (Chen et al., 2009). Some of the end products of catalysis with heterocycles produce effects during the activation process and update such kind of effects have never been researched. Therefore, the effects that they are capable of producing are not well known. Basically, this project will tend to unveil the synthesis of complexes in group 2 like D, 1,2-Diphenylethane-1,2-diol (II) and their various reactions with the alkynes to form either group 3 or group 4 heterocycles ligands (Sanford & Lyons, 2010). The obtained experimental results will therefore, be compared to the various results that are obtained through computational chemistry. These computational chemistry results will be the ones that were obtained by the various collaborators who were present at the University of Heriott Watt. PREPARATION OF FUNCTIONALIZED HETEROCYCLES STARTING MATERIALS AND PRODUCTS The starting materials are 1-chloro-isoquinoline together with benzotriazole. The two are combined through nucleophilic substitution method. The combination of these two gives ligand 1. The use of deprotonation can also be used in the preparation of these functionalized heterocycles such as NH or NR. The deprotonation is carried out on imidazolium chloride salt together with a strong base as the solvent. The reaction time is at an interval of 10 to 15 minutes before the next step is undertaken. Reaction pass this time at times yield wrong results and therefore, keen observations of this reaction time is recommended for purposes of accurate results. The preferred chemical apparatus is Schlenk flask together with stir bar. Stir bar is used to prevent heat loss during the homogeneous mixing of the reactants. After the formation of ligand 1 the cyclometallated complexes 2 which is ligand 2 is formed from the reaction of 2-vinylpyridine and trithiazyl trichloride (Ng, Zhou & Yu, 2012). The ligand 3 is also formed from the reaction of rubeanic acid and double cyclocondesation of oxalamidoxime. These kinds of ligands are useful during the formation of multinuclear and mononuclear metal complexes. The other products formed are Diisopropoxytitanium (III) Tetrahydroborate, 1(2 mmol) and lithium bis (2,4,6-triisopropylphenyl)hydroboratylmethylpolystyrene (9) A reaction between tetrahydroborate 1 of heterocycles 1 equivalent took place with a-hydroxyketones also of 1 equivalent for a time ranging between 5 to 15 minutes. The reaction temperature was -20oC. From the reactions, syn-1,3-diols were formed and they had higher stereoselectivy degree. General procedure for the preparation of Diisopropoxytitanium (III) Tetrahydroborate, 1(2 mmol) A solution of (iPr0)2TiCl2(4ml, 2mmol) was added at a slow rate to benzyltriethylammoniumtetrahydroborate (0.828g, 4mmol). The mixture was then stirred. Benzyltriethylammoniumtetrahydroborate (0.828g, 4mmol) solution was in a dry CH2Cl2 (8mL) at a temperature of -20oC and it was under N2. The mixture was then stirred for close to 30 minutes and the resulting solution was then used for the various reductions reactions. General Procedure for the Reduction of r-Hydroxyketones A dry R-hydroxy ketone (0.392g, 2 mmol) together with dry CH2Cl2 of 2 mL were both added and stirred. The mixture gave solution 1 (2 mmol) and the reaction temperature was -20 oC. The same temperature was used to stir the mixture for about 5 minutes. K2CO3 solution of about 10 mLwas then added to the mixture and stirred for an extra 15 minutes at a temperature of 25 o C. The extraction of the reaction mixture was done through the use of ether(3, 20mL) and brine was used in the washing of the mixture (Na2SO4). After washing it was dried. Flash chromatography method was then used to remove the solvent and this was done in presence of silica gel (etherpetroleum ether 30:70). The use of silica gel managed to diastereometric (syn/anti) mixture of 1,2- diphenyl-1,2-ethandiol as a solid which was colorless. The solid was found to be identical with the sample that was used for authentication. H NMR analysis of 1,2- diphenyl-1,2-ethandiol (0.394g, 92%) indicated a ratio of 1:99 for the a syn/anti solid. HPLC analysis indicated a ratio of 3:97 (petroleum ether, 0.4mL/min flow rate, and 9.75 and 9.21 retention time respectively). H NMR (CDCl): ?4.68 (s, 1H), 4.84 (s, 1H) Preparation of lithium bis (2,4,6-triisopropylphenyl)hydroboratylmethylpolystyrene (9) and its use for selective reduction of ketones Round bottom flask which was oven-dried and of capacity equivalent to 50 cm3 and had nitrogen inlet together with glass-coating magnetic bar was charged with bis (2,4,6-triisopropylphenyl) borylmethylpolystyrene (8). The bis was 1.12g and it was present in THF of about 10cm3. The round bottom flask was flushed with nitrogen gas. A solution containing tert-butyllithium with 1.7 mol dm 3 , 1.7mmlo, and 1.0 cm3 mixed with Pentane was then added using syringe to the solution. The reaction was exothermic and the mixture was further stirred for close to 30 minutes at room temperature. A double-ended needle was used to remove the liquid phase of the mixture and drying was facilitated through the use dry THF (30 cm3) and it was finally suspended in the dry THF (10cm3). A ketone solution of 0.78mmol in THF 5 cm3 was added into the mixture and stirring was done overnight before it was filtered. The temperature was maintained at room temperature. The filtered solid was washed using 30 cm3 of THF and then dried. After drying it was ready for use for the reduction purposes. Combination of the filtrate and the washings was done using 5 cm3 of water together with diethyl ether of 5 cm3. drying of the organic layer was achieved through the use of MgSO4 and pressure was used to remove the solvent. CYCLOMETALLATED COMPLEXES How to prepare different cyclometallated complexes from different heterocycles D, 1,2-Diphenylethane-1,2-diol (II) Addition of silver acetate (56.8 g, 0.34 mol) was done to trans-stilbene (16.3g, 0.151 mol) in the presence of glacial acetic acid of 275 mL. The mixture was then combined with finely ground iodine 40.3g, 0.158 mol for a period of 30minutes. Stirring was vigorous for 45 minutes before wet acetic acid (164 mL of HOAc, 6.8 g of H2O) was finally added to the mixture (Philips, Carey, Jeffrey & Slayton, 1985). The temperature for the mixture was kept at 90-95 oC for a period of 3 hours. After this 60g of a solution of sodium chloride was added to the mixture and stirred for a period of 45 minutes. Filtering was done and the solid washed using 275mL warm toluene and concentration under pressure was done before the residue was dissolved into 180 mL methanol in the presence of N, Methanolic KOH (18.5g of KOH in 135 mL of methanol). Methanolic KOH was added to the resultant solution and stirring was done under ambient temperature in the presence of N for close to 36 hours (Philips, Carey, Jeffrey & Slayton, 1985). Concentration of the mixture was done after neutralization of the base using 10% aqueous HCl. Extraction was done using ether (5 * 250 mL) and dried in the presence of MgSO4 and concentrated through rotary evaporator. Substances identified as 77% d,l- and 23% meso-hydrobenzoin were collected and their mass was 16.21 g (75.6%). The other materials were two recrystallization (CHCl) of equivalence of 84% d,l- and 16% meso-hydrobenzoin and the usage of this material was without purification. H NMR (CDCl.) ?3.00 (brs, 2H, OH), 4.64(s,2H, CHOH), 6.98-7.30 (M, 10H, Ar CH) Meso-1,2-Diphenylethane-1,2-dio (10) 21.2 g, 0.15mol Benzoin in dry 200mL ether/ THF was dropwisely added to the LiAlH4 suspension of 5.0g, 0.13 mol present in ether 100mL. The temperature was maintained at 0oC and the addition was done for 6 hours under N2. Keeping of the mixture was done at 0oC for a period of 18 hours followed by ambient temperature for 5 hours (Philips, Carey, Jeffrey & Slayton, 1985). 5 mL water was added and this was followed by 25% aqueous , 15g of 85% H3PO4 IN 38mL of water. Extraction of the product was done and drying was done using MgSO4 and concentrated to give a white solid (19.3g, 90%). The resultant combination was 85:15 analysized by IH NMR meso; d, l-hydrobenzion. The analysis by IH NMR (CDCI) showed ?2.38 (s, 2H, OH), 4.76 (s, 2H, CHOH), 7.02-7.32(m,IO H, Ar CH). 4 (3-Chloropropoxy) benzaldehyde Dissolve 50mmol of sodium in 150ml EtOH. Add 50 mmol of 4-hydroxybenaldehyde to the mixture and heat the mixture under reflux for 3 hours. Add dropwise 0.2 mol 1,3-bromochloropropane, stir, and heat for extra 3 hours (Mathias, Johannes, Julia & BodoDobnerand, 2007). Evaporate the mixture in vacuo 150ml saturated sodium bicarbonate solution before the residue is poured twice at 100ml AcOEt. Drying of the organic layer was done through the use of Na2SO4 and evaporation was done in which oil was produced (Mathias, Johannes, Julia & BodoDobnerand, 2007). Heptane was used to extract the residue and recrystallization at -10oC was done. 7b were used as white needles to precipitate the filtrate. The oil yield was 62% and the melting point was 29oC (from heptane): The requirements of Anal C10H11ClO2 were C, 60.46; H, 5.58; Cl, 17.85. The found values were C, 60.53; H, 5.62; Cl, 17.98; MS (GC/MS)m/z 198 (Meso/trans)-2-[4-(3-Chloropropoxy)phenyl]-4,5-fiphenyl-1,3-dioxolane (8b/trans) and (meso/cis)-2-[4-(3-chloropropoxyl]-4,5-diphenyl-1,3-dixolane (8b/cis) Meso 0.1 mol6 and 0.1 mol7b were both dissolved in 200mlCHCl of and heating was done under reflux for 5 hours. Hydrogen-chloreide gas solution was poured into the solution. Washing of the organic was done using 150ml saturated sodium bicarbonate solution together with 100 ml water. Drying was done using Na2SO4 and evaporation was done in vacuo. Flash chromatography(heptane, Et2O, 9:1) was used to carry out separation of 8b/trans and 8b/cis (Mathias, Johannes, Julia & BodoDobnerand, 2007). Cyclometallated Analogues The formation of C, N-chelating systems in these analogues can be obtained through replacement of the N-donors of the various ligands present in the carbon atoms. The complete C, N-chelating of the various cyclopalladated compounds together with the various cyclopalladation reactions give rise to the formation of the different cyclometallated complexes (Boutadla et al., 2010). Chiral Ligands Add 50g of d,l methadone and dissolved it in petroleum ether. Concentration is then done and after concentration additional 2mg of sized d and l crystals are added and stirred for aound 125 hours at a temperature of 40 oC and the yield is two large d- and i-crystals and the percentage is 50%. These ligands are the products of the various asymmetric synthesis of the N, N- bidentate ligands. The applications of such ligands are numerous in the reactions between organic compounds. They are used as catalysts and they are capable of using conformationally side chains of amino acids (O’ Keefe, 1999). The side chains are free and the reason for this is to enable easy differentiation with the oxazoline rings. The natural camphor gives synthesized chiral ligands that have a combination of a rigid unit of bornane. The formation of chiral pyrazole cyclometallated complex is through the condensation of hydrazine together with 1, 3- dicarbonyl 11 compound (Watson, House & Steel, 1991). Polyheteroaryl-linked Arenes This group of cyclometallated complexes has a heterocycle number N-donor rings which is linked to the core through the use of a spacer. If changes are made to the arene core, the spacer number, and the heterocycle type then accessibility of the ligands library becomes easy. The use of the ligands library assist in the formation of the molecular multinuclear species and the extension of the polymers is possible. The composition of the arene core comprises of binaphthyls, benzenes, naphtalenes, and biphenyls (Boutadla et al., 2010). The spacer groups comprise of atom linkers and the linkers can be single, two, three, or many. When the atom linkers are many then the linkers are said to be longer. In the formation of these cyclometallated complexes, the preferred heterocycles include azoles (pyrazoles, tetrazoles and imidazoles) and azines (quinolines and pyridines). General reaction patterns and mechanisms of the oxidative coupling of arenes with alkenes and alkynes To further functionalize the active organorhodium, the coupling pattern must always be limited to alkenes and alkynes which are unsaturated. Chelation assistance is necessary for the formation of Rh-C bonds through C-H activation. In some cases chelation assistance is unnecessary more so during the reactions of palladium-catalyzed oxidation. This reaction forms the first step in the catalytic cycle together with the first coupling partner that always form and acts as functionalize Rh-C. The scope of coupling is always bigger during palladium catalysis. Two general reactions patterns can be observed during the Rh (III) - catalyzed reactions that occur between arenes in the presence of both unsaturated alkynes and alkenes (Aberico, Scott & Lautens, 2007). The first reaction pattern is the protic E-H bond reaction. In this reaction X= N or 0 and the E always acts as the directing group which is sufficient. The group ratio becomes 1:1 when E is used as the directing group. When the coupling is followed by alkynes then either five or six member of the heterocycle is formed. The formation of this heterocycle is due to the result of C-H and E-H. In the catalytic cycle of this protic reaction, the anionic directing group is always followed by the ortho activation of the C-H group. The C-H activation group is capable of affording metallacycle. Expansion of the Rh-C bond to form rhodacycle is possible through the use insertion and ligation (Boutadla et al., 2010). The product that results from the ligation and insertion can be coupled and generated at the same time with Rh (I) species. The Rh (I) is obtained from C-E elimination reduction of the various active species of Rh (I) itself and the Rh (III) catalyst. This catalyst is mostly generated obtained after the oxidation of Rh (I). 1:2 coupling ratio is undergone by the arenes functionalized in the absence of E-H directing group (Boutadla et al., 2009). The coupling ratio is able to yield naphthalenes which act as substitutes. During the formation of the naphthalenes substitutes, the two-fold cyclometallation process is always involved and the reversible chelator is the E donor. Oxidative C-H functionalization using external oxidants In the palladium catalyzed coupling oxidation of the arylboronic acids, the reactions involving Rh (III) are often rare. The oxidant in such kind of reactions is Cu (OAc) 2 and the catalyst is [RhCp*Cl2]2 and the use of two equivalents alkynes is used to couple the arylboronic acids. The yield of naphthalenes and anthracenes is greatly increased during such couplings. Most of the couplings products come from C-H activation and the site position is hindered. Isolation is done for most of the major products and this is so in order to aid the reactions of the boronic acid. The reaction at this stage is dominated by the fluoro group which doubles up as the directing effect (Boutadla et al., 2010). This oxidative C-H functionalization reaction is true for both 4-pyridylboronic acid as well as tetraphenylisoquinoline. Metallaindene is the result of cyclometallation and the orientation of the various ortho CH bonds are properly put in place. The formation of a seven-member rhodacycle can be achieved through the migratory insertion of the various Rh-C bonds into the alkynes equivalent bonds. C-H activation via chelation assistance (cyclometallation) Carboxylic acid as the directing group Couplings reactions involving metal catalysts are always aided through the use of arylcarboxylic acids. These acids are preferred because of their ability to undergo two types of reactions while used as catalyst. In the presence of decarboxylation these acids act as activated arenes forms and the result is the metal aryl species. This metal aryl species however, can further be manipulated in the reactions involving cross-coupling. When manipulated in this form then they can be conveniently used as surrogates (Satoh & Miura, 2010). They can be used as surrogates to the various organo-main conventional groups as well as transmetallating reagents. The directing effects to the ortho C-H activation are offered by the carboxyl group in the various carboxyl-retentive processes. The carboxyl group is used leading active intermediates for various cyclometalated groups (Wasa & Yu, 2008). These intermediates are the cross-coupling reactions and the achievement of the sequential combination of these various key elements will be possible. The group of carboxyl can also be used as the removal ortho and it can be used as the directing group. Carboxyl-retentive cross-coupling The RH (III) - aryl which is the incipient is capable of undergoing migratory insertion. The insertion is in the internal systems of the alkynes and after insertion the elimination of the O-C reduction then follows (Ackermann, 2011). O-C reductive elimination always results into formation of isocoumarin product. The coupling reactions between the internal alkynes and the benzoic acid was therefore, done with the help of catalytic amount of 0.5-1% mol of the [Cp*RhCl2]2. The oxidants in this reaction are catalytic amount of Cu (OAc) 2 and stoichiometric amount of Cu (OAc) 2 (Baudoin, 2011). With the oxidants and the catalysts, the yield of isocoumarin will definitely be high. Decarboxylative cross-coupling During all the reactions with alkynes, an observation of the decarboxylative as well as carboxyl-retentive coupling reactions is made irrespective of the reactions conditions (Mimoun, 1982). There is a corporation of the alkynes unit into the COOH ortho group and the process through which vinyl moiety is formed is said to be redox-neutral (Grohmann, Wang & Glorius, 2012). The oxidation of the decarboxylation process results into the formation of the C-C bond. The C-C bonds are formed in the various carbazole units. The directing group is the COOH group and it plays a dual role. The insertion of the alkyne into the ortho C-H bonds always takes place before the decarboxylation process. Hydroxyl as a directing group This unit of hydroxyl can be used as the directing group in either anionic or neutral form. The reactions that involve couplings can always be extended into other cresols which are used as substitutes (Colby, Bergman & Ellman, 2010). The prevention for the oxidation of alcohols can be achieved through the use of tertiary alcohols. Bibliography Anastas, P.T. & Warner, J.C. 1998. Green Chemistry Theory and Practice. 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