CHAPTER-II. Iron (III) chloride mediated Preparation of Achiral. bisimines

Transcription

1 CHAPTER-II Iron (III) chloride mediated Preparation of Achiral bisimines

2 60 Chapter Introduction Schiff bases have been playing an important part in the development of coordination chemistry. These types of complexes have been extensively explored in recent years and their applications as ligands, catalysts have been the subject of many papers and reviews. Many of them are focused on the catalytic activity of Schiff base complexes as a large number of homogeneous and heterogeneous reactions. It is difficult to cover in this chapter the literature on Schiff base metal complexes, which embraces very wide and diversified subjects comprising vast areas of organ metallic compounds and various aspects of bioinorganic chemistry. Therefore, the introduction part is limited to a brief discussion on the Schiff bases, their metal complexes and general applications of Schiff base complexes with an emphasis on catalytic applications. 2.2 Literature Review: Review of relevant Bis Imines Considerable efforts have been directed toward the synthesis of achiral bisimines via either protic acids route or by azeotropic distillation to remove water. General Scheme-2.1 NH 2 NH 2 + RCHO N N CHR CHR R= aryl, Heteroaryl & alkyl Thus bisimines have been prepared via condensation of ethyenediamine and requisite aldehyde or ketone in presence of formic acid, acetic acid, MgSO 4, Na 2 SO 4, azeotropic

3 61 Chapter-2 distillation, molecular Sieves, sulphuric acid on silica gel and also with organic acids leading to the achiral bismines Synthesis of achiral bismines from formic acid. Symmetrical bis-schiff bases have been prepared efficiently in the presence of formic acid catalyst in methanol from the reaction of symmetrical primary bis-amine 12 of 5, 5 -methylenebis (2-aminothiazole) and a series of aromatic aldehyde derivatives as mentioned in scheme-2. Scheme-2.2 Drawbacks: 1. Reaction time is more than 15hr. 2. Use of protic acid may lead to formation of mono imine Synthesis of achiral bismines from acetic acid. Symmetrical bis-schiff bases have been prepared efficiently in the presence of acetic acid catalyst in heptane at reflux to get the required compound with series of aromatic aldehyde 13 derivatives as mentioned in scheme-3. Scheme-2.3 NH 2 CHO N CH NH 2 + N CH

4 62 Chapter-2 Drawbacks: 1. Reaction time is more than 15hr. 2. Mono Schiff base as side product Synthesis of achiral bismines from dehydrating agents. Symmetrical bis-schiff bases have been prepared efficiently in the presence of dehydrating agents like sodium sulphate, magnesium sulphate and silica gel catalyst in heptane at reflux to get required compound with series of aromatic aldehyde 14 derivatives as mentioned in scheme-4 Scheme-2.4 NH 2 CHO N CH N Drawbacks: NH 2 + N N CH N 1. Reaction time is more than 15hr. 2. Heterogeneous reaction medium Synthesis of achiral bisimines from protic solvents. The journal mentions the conversion of ketone to thio ketone, then refluxing solution of above obtained thio ketone 15 and diamine in absolute ethanol was refluxed for 3 days as mentioned in scheme-5. NH 2 Scheme-2.5 N CHR NH 2 + RCHO N CHR R= aryl, Heteroaryl & alkyl

5 63 Chapter-2 Drawbacks: 1. Multi step synthesis. 2. Reaction time is more than 70hr Synthesis of achiral bisimines from molecular sieves. The synthesis of bis imines prepared from commercially available binaphthyl diamine that was reacted with different aromatic and heteroaromatic aldehyde 16 in toluene at reflux temperature to afford the corresponding bisimines as mentioned in scheme-6. Scheme-2.6 Drawbacks: 1. A costly molecular sieve has been used. 2. Reaction time is more than 70hr. 3. Heterogeneous reaction medium Synthesis of achiral bismines from Para-Toluene sulphonic acid. Symmetrical bis-schiff bases have been prepared efficiently in the presence of sulphuric acid on silica gel as catalyst in toluene at room temperature to get the required compound with series of aromatic aldehyde 17 derivatives as mentioned in scheme-7.

6 64 Chapter-2 Scheme-2.7 NH 2 NH 2 + RCHO Toluene p-tsoh N N CHR CHR R= aryl, Heteroaryl & alkyl Drawbacks: 1. Use of strong acid may lead to resinous material. 2. Reaction time is more than 70hr. 3. Tedious work up required getting pure compound. Conclusion: The following chapter describes the new approach for the preparation of achiral Bis-Imines

7 65 Chapter FeCl 3 mediated synthesis of achiral bisimines Introduction In this section, we have demonstrated that FeCl 3 can be used as an efficient environment friendly catalyst system for the preparation of achiral bismines with various substituents. The reactions proceed well to afford a variety of N 1,N 2 -bis(aryl)ethane-1,2- diamine and N 1,N 2 -bis(heteroaryl)ethane-1,2-diamine in good yields. This is a general and economical process and opens an easy way to access for the preparation of achiral bisimines in which a novel heteroaryl compound is also reported This is the first report on the FeCl 3 mediated synthesis of achiral bisimines of aryl aldehydes (3a-h) and heteroaryl aldehydes (3l-j) with ethylene diamine in the presence of iron chloride as a catalyst system in methanol, affording the corresponding achiral bisimines 3 in good yields as mentioned in scheme -1. Scheme 2.8 FeCl 3 NH 2 CH 2 CH 2 NH 2 + ArCHO ArHC NCH 2 CH 2 N CHAr rt, MeOH Although various methods are known for the synthesis of achiral bis imines, the present method would find a wide usage and the process is in itself novel with respect to literature as discussed above. Thus this is the first report, a very convenient and general method for the synthesis of bisimines with ethylene diamine through iron chloride catalysed reaction, for aryl and heteroaryl aldehydes 3 in good yields.

8 66 Chapter Reaction Mechanism: Condensation of carbonyl compounds with primary amines was discovered in 1864 by Hugo Schiff.1 This acid-catalyzed reaction is universal and makes it possible to obtain a broad variety of azomethines. The classical Schiff condensation using monocarbonyl compounds and amines as the starting compounds occurs with high yields. Its mechanism is well understood. All steps in this reaction sequence are reversible. Therefore, the Schiff condensation under thermodynamically controlled conditions can be used for generating dynamic combinatorial libraries if several different amines or carbonyl compounds are used as starting compounds simultaneously. General Mechanism Experimental Section: General methods Unless stated otherwise, reactions were monitored by thin layer chromatography (TLC) on silica gel plates (60 F 254 ), visualizing with ultraviolet light or iodine spray. Column chromatography was performed on silica gel ( mesh) using distilled petroleum ether and ethyl acetate. 1 H and 13 C NMR spectra were determined in CDCl 3 solution using 400 and 100 (or 125) MHz spectrometers, respectively. Proton chemical shifts (δ) are relative to tetramethylsilane (TMS, δ = 0.0) as internal standard and expressed in parts per million. Spin multiplicities are given as s (singlet), d (doublet), t

9 67 Chapter-2 (triplet), and m (multiplet) as well as b (broad). Coupling constants (J) are given in hertz. Infrared spectra were recorded on a FTIR spectrometer. Melting points were determined by using a Buchi melting point B-540 apparatus. MS spectra were obtained on a mass spectrometer. HRMS was determined using waters LCT premier XETOF ARE-047 apparatus. All the reagents used are commercially available. General procedure for the synthesis of bis-imines (3): A mixture of ethane-1, 2- diamine (1, 5.0 mmol), freshly distilled aldehyde (2, 11.0 mmol) and FeCl 3 (0.1 mmol) in methanol (40 ml) was stirred at room temperature for 30 min. The reaction mixture was then filtered through a celite bed and the filtrate was collected and concentrated under reduced pressure afforded the residue. The residue obtained was then treated with 10% ethyl acetate - n-hexane and filtered to give the required bis-imine. (N 1 E,N 2 E)-N 1,N 2 -bis(4-methoxybenzylidene)ethane-1,2-diamine (3a): off white solid, crystallized from EtOAc-petroleum ether (9:1), mp C; 1 HNMR (400 MHz, CDCl 3 ) δ 3.82 (s, 4H), 3.91 (s, 6H), 6.89 (d, J = 8.8 Hz, 4H), 7.63 (d, J = 8.8 Hz, 4H), 8.20 (s, 2H); 13 C NMR (CDCl 3, 100 MHz) (2C, C=N), (2C, 2H), (4C, C aryl ), (2C, C aryl ), (4C, C aryl ), 61.6 (2C, CH 2 ), 55.3 (2C, OCH 3 ); M/z ; IR (cm -1, KBr) 2843, 1605; HRMS (ESI): Calcd for C 18 H 21 N 2 O 2 (M+H) , found

10 68 Chapter-2 (N 1 E,N 2 E)-N 1,N 2 -bis(4-nitrobenzylidene)ethane-1,2-diamine (3b): pale yellow solid; mp C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 3.9 (s, 4H), 7.97 (d, J = 8.4 Hz, 4H), 8.28 (d, J = 8.4 Hz, 4H), 8.50 (s, 2H); 13 C NMR (DMSO-d 6, 100 MHz) (2C, C=N),148.5 (2C, CH), (2C, CH), (4C, C aryl ),123.9 (4C, C aryl ), 60.6 (2C, CH 2 ); M/z 394; IR (cm -1, KBr): 2855, 1603; HRMS (ESI): Calcd for C 16 H 15 N 4 O 4 (M+ H) , found ,5'-(1E,1'E)-(ethane-1,2-diylbis(azan-1-yl-1-ylidene))bis(methan-1-yl-1- ylidene)bis(2-methoxyphenol) (3c): pale yellow solid, crystallized from EtOAcpetroleum ether (90:10), mp C; 1 HNMR (400 MHz, DMSO-d 6 ) δ 3.7 (s, 4H), 3.91 (s, 6H), 6.92 (d, J = 4.0 Hz, 2H), 7.03 (d, J = 4.0 Hz, 2H), 7.20 (s, 2H), 8.14 (s, 2H), 9.14 (s, 2H); 13 C NMR (DMSO-d 6, 100 MHz) (2C, C=N), (2C, C aryl ), (2C, C-OH), (4C, C aryl ), (4C, C aryl ), 60.9 (2C, CH 2 ), 55.5 (2C, OMe); M/z 329; IR (cm -1, KBr) 3398, 2842, 1639; HRMS (ESI): Calcd for C 18 H 21 N 2 O 2 (M+H) , found

11 69 Chapter-2 (N 1 E,N 2 E)-N 1,N 2 -bis(2-fluorobenzylidene)ethane-1,2-diamine (3d): off white solid, crystallized from EtOAc: petroleum ether (90:10); mp C; 1 H NMR (400 MHz, CDCl 3 ) δ 4.00 (s, 4H), 7.15 (m, 2H), 7.36 (m, 2H), 7.53 (m, 2H), 7.95 (m, 2H), 8.6 (s, 2H); 13 C NMR (CDCl 3, 100 MHz) (2C, C=N), (2C, C aryl ), (2C,C aryl ), 132.2, (2C, C aryl ), 124.2, (2C, C aryl ), 115.8, (2C, C aryl ), 61.8 (2C, CH 2 ); M/z 272.1; IR (cm -1, KBr) 2857, 1640; HRMS (ESI): Calcd for C 16 H 15 N 2 F 2 (M+ H) , found ,4'-(1E,1'E)-(ethane-1,2-diylbis(azan-1-yl-1-ylidene))bis(methan-1-yl-1- ylidene)bis(2-methoxyphenol) (3e). white solid, crystallized from EtOAc: petroleum ether (90:10); mp C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 3.77 (s, 4H), 3.91 (s, 6H), 6.80 (d, J = 7.6 Hz, 2H), 7.09 (d, J = 9.6 Hz, 2H), 7.30 (s, 2H), 8.18 (s, 2H), 9.28 (s, 2H); 13 C NMR (DMSO-d 6, 100 MHz) (2C, C=N), (2C, C aryl ), (2C, CH-OH), (4C, C aryl ), (4C, C aryl ), 60.9 (2C, CH 2 ), 55.5 (2C, OMe); M/z 329; IR (cm -1, KBr) 3094, 2866, 1603; HRMS (ESI): Calcd for C 18 H 21 N 2 O 2 (M+H) , found

12 70 Chapter-2 3,3'-(1E,1'E)-(ethane-1,2-diylbis(azan-1-yl-1-ylidene))bis(methan-1-yl-1- ylidene)diphenol (3f). white solid, crystallized from EtOAc: petroleum ether (90:10); mp C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 3.83 (s, 4H), 6.81 (d, J = 6.0 Hz, 2H), (m, 2H), 7.21 (m, 4H), 8.2 (s, 2H), 9.5 (bs, 2H); 13 C NMR (DMSO-d 6, 100 MHz) (2C, C=N), (2C, CH-OH), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), 60.9 (2C, CH 2 ); M/z 269; IR (cm -1, KBr) 3053, 2868, 1632; HRMS (ESI): Calcd for C 16 H 17 N 2 O 2 (M+ H) , found (N 1 E,N 2 E)-N 1,N 2 -bis(naphthalen-2-ylmethylene)ethane-1,2-diamine (3g): pale yellow solid, crystallized from EtOAc: petroleum ether (90:10), mp C; 1 H NMR (400 MHz, CDCl 3 ) δ 4.1 (s, 4H), 6.9 (d, J = 3.6 Hz, 2H), 7.26 (d, J = 3.6 Hz, 4H), 7.82 (m, 6H), 7.92 (d, J = 3.6 Hz, 2H), 8.68 (s, 2H); 13 C NMR (CDCl 3, 100 MHz) (2C, C=N), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), (2C,

13 71 Chapter-2 C aryl ), 61.7 (2C, CH 2 ); M/z ; IR (cm -1, KBr) 2868, 1641; HRMS (ESI): Calcd for C 24 H 21 N 2 (M+ H) , found (N 1 E,N 2 E)-N 1,N 2 -bis(4-bromobenzylidene)ethane-1,2-diamine (3h): pale yellow solid, crystallized from EtOAc: petroleum ether (90:10), mp C; 1 H NMR (400 MHz, CDCl 3 ) δ 3.96 (s, 4H), 7.25 (d, J = 8.0 Hz, 2H), 7.52 (d, J = 8.0 Hz, 4H), 7.58 (d, J = 7.6 Hz, 2H), 8.2 (s, 2H); 13 C NMR (CDCl 3, 100 MHz) (2C, C=N), (2C, C aryl ),133.5 (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), (2C, C aryl ), 61.3 (2C, CH 2 ); M/z 392; IR (cm -1, KBr) 2841, 1642; HRMS (ESI): Calcd for C 16 H 15 N 2 Br 2 (M+ H) , found (N 1 E,N 2 E)-N 1,N 2 -bis((1h-imidazol-2-yl)methylene)ethane-1,2-diamine (3i). light brown solid, crystallized from EtOAc: petroleum ether (90:10), mp C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 4.1 (s, 4H), 7.81 (d, J = 3.2 Hz, 4H), 8.29 (s, 2H), (bs, 2H); 13 C NMR (DMSO-d 6, 100 MHz) (2C, C=N), (4C, C imidazolyl ), 132.0

14 72 Chapter-2 (2C, C imidazolyl ), 61.3 (2C, CH 2 ); M/z 217; IR (cm -1, KBr) 3122, 2836, 1648; HRMS (ESI): Calcd for C 10 H 13 N 6 (M+ H) , found (N 1 E,N 2 E)-N 1,N 2 -bis(pyridin-2-ylmethylene)ethane-1,2-diamine (3j): off white solid, crystallized from EtOAc: petroleum ether (90:10), mp C; 1 H NMR (400 MHz, CDCl 3 ) δ 4.01 (s, 4H), 7.33 (d, J = 9.6 Hz, 2H), 8.07 (d, J = 9.6 Hz, 2H), 8.32 (s, 2H), 8.63 (d. J = 6.4 Hz, 2H), 8.83 (s, 2H); 13 C NMR (CDCl 3, 100 MHz) (2C, C=N), (2C, C pyridyl ), (2C, C pyridyl ), (2C, C pyridyl ), (2C, C pyridyl ), (2C, C pyridyl ), 60.6 (2C, CH 2 ); M/z 239; IR (cm -1, KBr) 2848, 1644; HRMS (ESI): Calcd for C 14 H 15 N 4 (M+ H) , found

15 73 Chapter-2 (3a) Figure 2.2.3: 1 H NMR of (N 1 E,N 2 E)-N 1,N 2 -bis (4-methoxybenzylidene)ethane-1,2-diamine Figure 2.2.4: 13 C NMR of (N 1 E,N 2 E)-N 1,N 2 -bis(4-methoxybenzylidene)ethane-1,2-diamine (3a)

16 74 Chapter-2 Figure 2.2.5: 1 H NMR of (N 1 E,N 2 E)-N 1,N 2 -bis(4-nitrobenzylidene) ethane-1,2-diamine (3b) Figure 2.2.6: 13 C NMR of (N 1 E,N 2 E)-N 1,N 2 -bis(4-nitrobenzylidene) ethane-1,2-diamine (3b)

17 75 Chapter-2 Figure 2.2.7: 1 H NMR of 5,5'-(1E,1'E)-(ethane-1,2-diylbis(azan-1-yl-1-ylidene)) bis(methan-1-yl-1-ylidene)bis(2-methoxyphenol) (3c) Figure 2.2.8: 13 C NMR of 5,5'-(1E,1'E)-(ethane-1,2-diylbis(azan-1-yl-1-ylidene)) bis(methan-1-yl-1-ylidene)bis(2-methoxyphenol) (3c)

18 76 Chapter-2 Figure 2.2.9: 1 H NMR of (N 1 E,N 2 E)-N 1,N 2 -bis(2-fluorobenzylidene)ethane-1,2- diamine (3d) Figure : 13 C NMR of (N 1 E,N 2 E)-N 1,N 2 -bis(2-fluorobenzylidene)ethane-1,2-diamine (3d)

19 77 Chapter-2 Figure : 1 H NMR of 4,4'-(1E,1'E)-(ethane-1,2-diylbis(azan-1-yl-1- ylidene))bis(methan- 1-yl-1-ylidene)bis(2-methoxyphenol) (3e) Figure : 1 H NMR of 4,4'-(1E,1'E)-(ethane-1,2-diylbis(azan-1-yl-1- ylidene))bis(methan- 1-yl-1-ylidene)bis(2-methoxyphenol) (3e)

20 78 Chapter-2 Figure : 1 H NMR of 3,3'-(1E,1'E)-(ethane-1,2-diylbis(azan-1-yl-1- ylidene))bis(methan- 1-yl-1-ylidene)diphenol (3f) Figure : 13 C NMR of of 3,3'-(1E,1'E)-(ethane-1,2-diylbis(azan-1-yl- 1ylidene))bis(methan-1-yl-1-ylidene) diphenol (3f)

21 79 Chapter-2 Figure : 1 HNMR of of (N 1 E,N 2 E)-N 1,N 2 -bis(naphthalen-2-ylmethylene)ethane- 1,2-diamine (3g) Figure : 13 C NMR of (N 1 E,N 2 E)-N 1,N 2 -bis(naphthalen-2- ylmethylene)ethane- 1,2-diamine (3g)

22 80 Chapter-2 Figure : 1 H NMR of (N 1 E,N 2 E)-N 1,N 2 -bis(4-bromobenzylidene)ethane-1,2- diamine (3h) Figure : 13 C NMR of (N 1 E,N 2 E)-N 1,N 2 -bis(4-bromobenzylidene)ethane-1,2- diamine (3h)

23 81 Chapter-2 Figure : 1 H NMR of (N 1 E,N 2 E)-N 1,N 2 -bis((1h-imidazol-2- yl)methylene)ethane-1,2-diamine (3i) Figure : 13 C NMR (N 1 E,N 2 E)-N 1,N 2 -bis((1h-imidazol-2-yl)methylene)ethane- 1,2-diamine (3i)

24 82 Chapter-2 Figure : 1 H NMR of (N 1 E,N 2 E)-N 1,N 2 -bis(pyridin-2-ylmethylene)ethane-1,2- diamine (3j) Figure : 13 C NMR of (N 1 E,N 2 E)-N 1,N 2 -bis(pyridin-2-ylmethylene)ethane-1,2- diamine (3j)

25 83 Chapter Results and discussion A mixture of ethane-1, 2-diamine (1, 5.0 mmol), freshly distilled aldehyde (2, 11.0 mmol) and FeCl 3 (0.1 mmol) in methanol (40 ml) was stirred at room temperature the respective bis imines were obtained in good to excellent yields (> 85%) according to the following scheme-2.9 and scheme Scheme-2.9 FeCl 3 NH 2 CH 2 CH 2 NH 2 + ArCHO ArHC NCH 2 CH 2 N CHAr rt, MeOH Ar = 3a: 4-OCH 3 -C6H 4 3b:4-NO 2 - C 6 H 4 3c:3-OH-4- OCH 3 - C 6 H 3 3d:2-F- C 6 H 5 3e: 4-OH-3- OCH 3 - C 6 H 3 3f: 3-OH- C 6 H 5 3g: C 10 H 7 3h: 4-Br- C 6 H 4 Scheme-2.10 FeCl 3 NH 2 CH 2 CH 2 NH 2 + ArCHO ArHC NCH 2 CH 2 N CHAr rt, MeOH Ar = 3i: 2-C 3 H 2 NS, 3j:3-C 5 H 4 N

26 84 Chapter-2 Moreover, as per literature condition the reaction of 1, 2-amine with aromatic aldehyde under these reaction conditions afforded a mixture of mono and bis-schiff bases. Therefore the present research required an efficient and concise method to afford the required bis-imines. Accordingly, we have developed a new and milder method for this purpose by making use of the anhydrous Lewis acid as a catalyst. Thus a variety of achiral bis-imines 3 were prepared by condensation with ethane-1, 2-diamine (1) with a number of aromatic aldehydes (2) in the presence of anhydrous ferric chloride (Scheme 2). The experimental results of this study are summarized in Table 1. Thus both aryl and heteroaryl aldehydes reacted well with the diamine yielded the desired products in good to excellent yields. Aldehydes containing electron donating like (e.g. methoxy, hydroxyl, fluoro and bromo) or withdrawing groups (e.g. nitro) were found to be equally reactive in terms of product yields. The reactions were completed within 30 min in most of these cases. All bisimines were stable and characterized by the strong and sharp absorption band at cm-1 corresponding to the C=N bonds Reaction with different series of aliphatic aldehydes & Ketones The derivatives of the following aldehyde were found to produce oils or resinous substances: n-caproaldehyde, n-ethananthaldehyde, 2-ethyl-3-propylacrolein, n - ethyl - n - butyraldehyde, isobutyraldehyde, and acroleins. Whereas furfural aldehyde as resulted in gummy mass, in order to get pure compound performed column chromatography but afforded the starting material furfural. A series of ketones diethyl ketone, cyclohexanone, methyl propyl ketone, methyl isopropyl ketone, diisopropyl ketone, and diisobutyl ketone were treated with

27 85 Chapter-2 ethyenediamine under the same conditions used for aldehyde resulted in resinous substances. Initially it was assumed that hydroxyl groups located at the para position with respect to the imino groups were involved enol-keto tautomerisation process. Hydroxyl absorption bands for 3e were absorbed in the IR spectra because the hydroxyl groups located at the para position with respect to the imino groups were not involved in enol-keto tautomerisation process. Hydroxyl protons of 3e in 1H NMR spectrum observed broad signal at ppm clearly indicates the absence of enol-keto tautomerisation and remaining protons of the corresponding aromatic molecules showed in the aromatic regions. Mass spectra revealed the molecular ion peaks (M, M+2 and M+4) for compound 3h with intensities 1:2:1 due to have bromine atoms in these structures and other products exhibited the parent ions with medium intensity. The reactions were completed within 30 min in most of these cases. All bisimines were stable and characterized by the strong and sharp absorption band at cm-1 corresponding to the C=N bonds. The reaction of 1, 2-amine with aromatic aldehyde when subjected under these reaction conditions provided a mixture of mono and bis-schiff bases. Accordingly, we have developed a new and milder method for this purpose that involved the use of anhydrous Lewis acid as a catalyst.

28 86 Chapter-2 Table 2.1. Schiff base formation induced by iron chloride. a Entry Aldehyde Product b Yield c % Reaction Time(h)

29 87 Chapter a All the reactions were carried out using aryl aldehyde 2 (11.0 mmol), ethane-1,2- diamine (5.0 mmol) and FeCl 3 (0.1 mmol) in methanol (40 ml) at room temperature. b Identified by 1 H NMR, IR, MS. c Isolated yields. Methanol was used as solvent Nature of the products and product characterization The present method yielded ten compounds of achiral bisimines in good to excellent yields. All the products were stable at room temperature and could be handled and stored under ambient conditions. Whereas all the Compounds obtained as solids and the compounds were purified by using appropriate solvent. All the products were well characterized by spectroscopic data (IR, UV and 1 H NMR) and satisfactory elemental analyses Schiff base transition metal complexes Metal complexes of the Schiff bases are generally prepared by treating metal salts with Schiff base ligands under suitable experimental conditions. However, for some

30 88 Chapter-2 catalytic application the Schiff base metal complexes are prepared in situ in the reaction system. which involves the use of metal alkoxides (M(OR)n)? Alkoxides of early transition metals (M = Ti, Zr), are commercially available and easy to handle. The use of other alkoxide derivatives is not easy, particularly in the case of highly moisture-sensitive derivatives of lanthanides. Scheme 2.11 Metal amides M(NMe 2 ) 4 (M = Ti, Zr) are also employed as the precursors in the preparation of Schiff base metal complexes (Route 2). The reaction occurs via the elimination of the acidic phenolic proton of the Schiff bases through the formation of volatile NHMe 2. Other synthetic routes include treatment of metal alkyl complexes with Schiff bases (Route 3) or treatment of the Schiff base with the corresponding metal acetate under reflux conditions (Route 4). The synthetic scheme presented in route 5 which is quite effective in obtaining salen-type metal complexes consists of a two-step reaction involving the deprotonation of the Schiff bases followed by reaction with metal halides. Deprotonation of the acidic phenolic hydrogen can be effectively done by using NaH or KH in coordinating solvents and the excess sodium or potassium hydride can be

31 89 Chapter-2 eliminated by filtration. The deprotonation step is normally rapid at room temperature, but heating the reaction mixture to reflux does not cause decomposition. An elaborate discussion on synthesis of achiral bisimines has been attempted in the thesis Preparation of achiral bisimines transition metal complex. Generally Schiff base form a charge transfer complex between N atom and oxygen atoms of the Schiff bases with the aid of metals like Cu, Zn and Co. Transition metal complexes of such ligands are important enzyme models. The rapid development of these ligands resulted in an enhance research activity in the field of coordination chemistry leading to very interesting conclusions. Considerable efforts have been directed toward the synthesis of achiral bisimines metal complexes in this thesis. In order to achieve better enantioselectivity, we have attempted to prepare achiral bismines metal complexes with transition metals like cobalt & copper. Alkoxides of early transition metals (M = Ti, Zr), are commercially available and easy to handle. The use of other alkoxide derivatives is not easy, particularly in the case of achiral bisimines which are highly moisture-sensitive, instead the complex preparation are explored with metal chlorides. A suspension of bisimines (0.068 mg, 1 mol) in toluene was added anhydrous cobalt chloride (0.037 mg, 1 mol) and stirred for 1hr. To the light pink colored solution was added under nitrogen atmosphere, was turned out to be more effective process. The screening of achiral bisimines with different metal chorides is performed at C, which resulted in gummy mass. Generally the complexes are moisture

32 90 Chapter-2 sensitive, moreover not crystallized inspite of performing azeoeotropic dstillation. Though the reaction resulted in gummy mass, proceeded for screening as catalyst for resolution of benzyllic secondary alcohol. Among all the achiral bisimines the heteroaryl bisimines in combination with CoCl 2 was shown the best results as shown (entry-9, table 2, Chapter III). Table 2.2 Screening of different metal chorides S.No Bismines Solvent Time (h) Temp 0 C Metal Chloride Nature of complex 01 3a Toluene CoCl 2 CuCl 2 ZnCl b Toluene CoCl 2 CuCl 2 ZnCl c Toluene CoCl 2 CuCl 2 ZnCl d Toluene CoCl 2 CuCl 2 ZnCl e Toluene CoCl 2 CuCl 2 ZnCl f Toluene CoCl 2 CuCl 2 ZnCl g Toluene CoCl 2 CuCl 2 ZnCl h Toluene CoCl 2 CuCl 2 ZnCl i Toluene CoCl 2 CuCl 2 ZnCl j Toluene CoCl 2 CuCl 2 ZnCl 2 A suspension of bisimines (0.68 mg, 1 mol) in toluene was added anhydrous Metal chloride (0.37 mg, 1 mol) and stirred for 20hr. After initial screening of metal complexes, it has been observed that the heteroaryl bisimines cobalt metal complex has given good enantioselectivity. We have shifted complete focus on isolation of this heteroaryl bisimines metal complex as solid. Following Parameters has been studied to isolate as solid.

33 91 Chapter-2 Table 2.3: Screening of solvents S.No Bismines Solvent Time (h) Temp 0 C Metal Chloride Nature of complex 02 MTBE CoCl 2 03 THF CoCl 2 3i 04 VA CoCl 2 05 MIBK CoCl 2 07 MTBE CoCl 2 08 THF CoCl 2 3j 09 VA CoCl 2 10 MIBK CoCl 2 Solvents: VA= Vinyl acetate, THF = Tetrahydrofuran, MIBK = Methyl Iso Butyl Ketone MTBE= Methyl tert Butyl Ether. Table 2.3: Study of temperature with vinyl acetate as solvent. S.No Bismines Solvent Time (h) Temp 0 C Metal Chloride Nature of compex CoCl CoCl 2 3i VA CoCl CoCl CoCl CoCl 2 3j Va CoCl CoCl 2 Conclusion: We concluded that vinyl acetate in combination with cobalt choride afforded good color but resulted in gummy mass. The gummy mass was taken as such for ligand screening.

34 92 Chapter-2 Preparation of bis ((1H-imidazol-2-yl) methylene)ethane-1, 2-diamine transition metal complex. The aim was to introduce the vinyl acetate as solvent instead of toluene, so different set of experiments were performed with achiral bisimines, cobalt chloride and vinyl acetate as solvent. To our delight we observed that the reaction mass color not turned to dark brown even after 24 hr. In order to enhance the better selectivity, we screened the use of achiral bis-imines in combination with CoCl 2 a reaction performed in vinyl acetate The reactions were complete within 10 h when diarylidene-ethane-1,2- diamines cobalt complex resulted in 35% enantiomeric excess however, the best results were obtained with bis heteroaryl-1,2-diamines especially 3i. The heteroaryl bis-imine 3i facilitated enantioselective acetylation of the (R)-isomer over the (S)-isomer with high enantiomeric excess.(99% ee, 80% yield). Scheme-2.12 Brief process: A suspension of bisimines (0.068 mg, 1 mol) in vinyl acetate was added anhydrous cobalt chloride (0.037 mg, 1 mol) and stirred for 1hr, evaporated the

35 93 Chapter-2 solvent. The pink colored mass is used directly as catalyst without further purification. Conclusion: a) In conclusion, we have demonstrated that FeCl 3 which is an environmentally friendly catalyst can be used as an efficient catalyst system for preparation of achiral bisimines. b) The reactions proceeded well to afford a variety of aromatic and heteroaryl bisimines in good yields. The scope and limitations of the process along with mechanism of the reaction have been discussed. c) A detailed study related to the effect of reaction conditions on product formation was carried out with different aldehydes under FeCl 3 catalyst system. d) In contrast to the other methods of preparation this process exhibited greater selectivity and yield for achiral bisimines. An extensive work elaborated about the preparation of achiral bismines cobalt complex. e) This method is a general and economical process to access achiral bisimines, since the achiral bisimines has tremendous potential in chemical industry and used in medicinal chemistry, as ligands, as chiral activators and above all they are biologically active compounds.