PHOSPHINE FREE COBALT BASED CATALYST, PROCESS FOR PREPARATION AND USE THEREOF

Abstract

The present invention discloses a phosphine free cobalt based catalyst of formula (I) and a process for preparation thereof. The present invention further discloses a process for the synthesis of aromatic heterocyclic compounds of formula (II) and pyrazine derivative using the phosphine free cobalt based catalyst of formula (I).

Claims

1-15. (canceled)

16. A phosphine free cobalt based catalyst of formula (I) ##STR00023## wherein: R is selected from the group consisting of hydrogen, linear or branched alkyl, substituted or unsubstituted aryl and heteroaryl containing O, N atoms; and X is selected from the group consisting of F, Cl, Br and I.

17. The phosphine free cobalt based catalyst of formula (I) as claimed in claim 16, wherein said cobalt based catalyst of formula (I) is selected from cobalt based dimer complex of bis(2-(diethyl-3-sulfanyl)ethyl)amine, bis(2-(isopropylthio)ethyl)amine, bis(2-(phenylthio)ethyl)amine or bis(2-((substituted)phenylthio)ethyl)amine.

18. A process for the preparation of cobalt based catalyst of formula (I) as claimed in claim 16, comprising the steps of: i. preparing a solution of CoX.sub.2 in solvent ii. preparing a solution of SNS ligand in solvent iii. mixing the solution of step (i) and (ii) iv. stirring the reaction mixture of step (iii) at a temperature ranging from 25 C. to 30 C. for a time period ranging from 3 to 4 hours to yield cobalt based catalyst of formula (I).

19. The process as claimed in claim 18, wherein said CoX.sub.2 is selected from the group consisting of Cobalt (II) chloride (CoCl.sub.2), Cobalt (II) bromide (CoBr.sub.2) or Cobalt (II) Iodide (CoI.sub.2).

20. The process as claimed in claim 18, wherein said SNS ligand is selected from bis(2-(diethyl-3-sulfanyl)ethyl)amine (.sup.EtSNS; L1) or bis(2-(isopropylthio)ethyl)amine (.sup.isoPrSNS; L2).

21. The process as claimed in claim 18, wherein said solvent is selected from the group consisting of methanol, ethanol, tetrahydrofuran, acetonitrile or diethylether.

22. A process for the synthesis of aromatic heterocyclic compound of formula (II) ##STR00024## wherein: n is selected from 0 or 1, R is selected from the group consisting of hydrogen, linear or branched alkyl, substituted or unsubstituted aryl and heteroaryl containing 0, N atoms, R.sup.1, R.sup.2, and R.sup.3 are same or different and independently selected from the group consisting of hydrogen, substituted or unsubstituted linear or branched alkyl, substituted or unsubstituted aryl, R.sup.1 and R.sup.2 may form a substituted or unsubstituted cyclic or heterocyclic ring, and the process comprises heating a reaction mixture of amino alcohol, alcohol, phosphine free cobalt based catalyst of formula (I) and base in a ratio ranging between 1:2:0.2:1 to 1:0.5:0.25:1.5 and solvent at a temperature ranging from 150 to 180 C. for a time period ranging from 24 to 30 hours followed by cooling the reaction mixture to afford aromatic heterocyclic compound of formula (II).

23. The process as claimed in claim 22, wherein said alcohol is selected from the group consisting of aliphatic short- and long-range primary alcohols, secondary alcohols, aromatic substituted or unsubstituted primary and secondary alcohols, heteroaromatic alcohols or cyclic alcohols.

24. The process as claimed in claim 22, wherein said alcohol is selected from the group consisting of 1-phenylethanol, 1-p-tolylethanol, 1-(4-chlorophenyl)ethanol, 1-(4-methoxyphenyl)ethanol, 1-(4-aminophenyl)ethanol, 1-(naphthalen-2-yl)ethanol, 1-(naphthalen-1-yl)ethanol, 2-decanol, 1-m-tolylethanol, 2-dodecanol, 1-(4-(trifluoromethyl)phenyl)ethanol and 1-(3-methoxyphenyl)ethanol.

25. The process as claimed in claim 22, wherein said amino alcohol is selected from aliphatic and aromatic and amino alcohols.

26. The process as claimed in claim 22, wherein said amino alcohol is selected from the group consisting of 2-aminobutan-1-ol, 2-amino-3-methylbutan-1-ol, 2-amino-4-methylpentan-1-ol, 2-amino-3-methylpentan-1-ol, 2-amino-3-phenylpropan-1-ol, 2-amino-2-phenylethanol, 3-aminopropan-1-ol and (2-aminophenyl)methanol.

27. The process as claimed in claim 22, wherein said base is selected from the group consisting of potasium tert-butoxide (t-BuOK), sodium tert-butoxide (t-BuONa), lithium tert-butoxide (t-BuOLi), potassium hydride (KH), sodium hydride (NaH), potassium Bis (trimethylsilyl) amide [KHMDS], lithium bis (trimethylsilyl) amide [LiHMDS], sodium isopropoxide (NaOiPr), sodium ethoxide (NaOEt) or sodium methoxide (NaOMe).

28. The process as claimed in claim 22, wherein said solvent is selected from the group consisting of m-xylene, toluene, octane, mesitylene or decane.

29. The process as claimed in claim 22, wherein said aromatic heterocyclic compound of formula (II) is selected from the group consisting of i. 2-methyl-5-phenyl-1H-pyrrole (5a), ii. 2-ethyl-5-phenyl-1H-pyrrole (5b), iii. 2-isopropyl-5-phenyl-1H-pyrrole (5c), iv. 2-isobutyl-5-phenyl-1H-pyrrole (5d), v. 2-sec-butyl-5-phenyl-1H-pyrrole (5e), vi. 2,5-diphenyl-1H-pyrrole (5f), vii. 2-benzyl-5-phenyl-1H-pyrrole (5g), viii. 2-isopropyl-5-p-tolyl-1H-pyrrole (5h), ix. 2-(4-chlorophenyl)-5-isopropyl-1H-pyrrole (5i), x. 2-isopropyl-5-(4-methoxyphenyl)-1H-pyrrole (5j), xi. 4-(5-isopropyl-1H-pyrrol-2-yl)aniline (5k), xii. 2-isopropyl-5-m-tolyl-1H-pyrrole (5l), xiii. 2-isopropyl-5-(naphthalen-1-yl)-1H-pyrrole (5m), xiv. 2-isopropyl-5-octyl-1H-pyrrole (5n), xv. 2-isobutyl-5-(naphthalen-2-yl)-1H-pyrrole (5o), xvi. 2-phenyl pyridine (7a), xvii. 2-p-tolylpyridine (7b), xviii. 2-(4-methoxyphenyl) pyridine (7c), xix. 2-m-tolylpyridine (7d), xx. 2-octyl pyridine (7e), xxi. 2-decyl pyridine (7f), xxii. 2-phenyl quinoline (7g), xxiii. 2-(3-methoxyphenyl) quinoline (7h), xxiv. 2-(4-fluorophenyl)quinoline (7i), xxv. 2-(4-(trifluoromethyl)phenyl)quinoline (7j) or xxvi. 2-(naphthalen-2-yl)quinoline (7k).

30. A process for the synthesis of 2.5 di phenyl pyrazine comprising refluxing the reaction mixture of 2-amino-2-phenylethan-1-ol and cobalt based catalyst of formula (I) as claimed in claim 16 in solvent at temperature in the range of 130 to 135 C. for the period in the range of 22 to 24 hrs under argon atmosphere to afford the 2.5 di phenyl pyrazine.

Description

BRIEF DESCRIPTION OF THE DRAWING

[0065] FIG. 1 represents X-ray crystal-structure analysis of phosphine free cobalt based catalyst of formula I with 50% probability of thermal ellipsoids.

[0066] FIG. 2 presents the process for the preparation of phosphine free cobalt based catalyst of formula (I).

[0067] FIG. 3 represents direct synthesis of 1H-pyrroles via dehydrogenative annulation reaction, wherein Reaction conditions are as follow: 0.25 mmol of 3, 0.5 mmol of 4, 2.5 mol % of catalyst 1, KOtBu (0.26 mmol), and 2 mL of m-xylene heated at reflux (150-180 C.) under argon atmosphere for 24 h.

[0068] FIG. 4 represents direct synthesis of pyridines and quinolines via dehydrogenative annulation reaction, wherein Reaction conditions are as follow: 0.25 mmol of 6, 0.5 mmol of 4, 2.5 mol % of catalyst 1, KOtBu (0.26 mmol), and 2 mL of m-xylene heated at reflux under argon atmosphere for 24 h.

[0069] FIG. 5 represents Synthesis of pyrazine (8) from -aminoalcohol.

DETAILED DESCRIPTION OF THE INVENTION

[0070] The present invention provides a phosphine free cobalt based catalyst of formula (I) and a process for the preparation thereof. The present invention further provides the base-metal (non-precious) catalyzed dehydrogenative annulation of -aminoalcohols and secondary alcohols into C2-substituted pyridine and quinoline derivatives via the acceptorless dehydrogenative coupling (ADC) strategy. The alcohols and -aminoalcohols are efficiently coupled via a sequence of acceptorless dehydrogenation and condensation to lead to the selective formation of CN and CC bonds. The acceptorless dehydrogenation leads to aromatization and the condensation step deoxygenates the alcohol component. Three equivalents of dihydrogen and water are liberated in the present reaction.

[0071] The present invention provides phosphine free cobalt based catalyst of formula (I)

##STR00003##

[0072] wherein

[0073] R is selected from the group consisting of hydrogen, alkyl (linear or branched), substituted or unsubstituted aryl and heteroaryl containing O, N atoms.

[0074] X is selected from group consisting of F, Cl, Br and I.

[0075] The phosphine free cobalt based catalyst of formula (I) is selected from the group consisting of cobalt based dimer complex of bis(2-(diethyl-3-sulfanyl)ethyl)amine, bis(2-(isopropylthio)ethyl)amine, bis(2-(phenylthio)ethyl)amine or bis(2-((substituted)phenylthio)ethyl)amine.

[0076] The phosphine free cobalt based catalyst of formula (I) is used for dehydrogenative annulation of unprotected amino alcohols with secondary alcohols for the direct synthesis of aromatic heterocyclic compound of formula (II) in presence of Transition-metal-catalyzed acceptorless dehydrogenation (AD) and hydrogen autotransfer (HA) reactions.

[0077] The present invention provides a process for the preparation of phosphine free cobalt based catalyst of formula (I) comprising [0078] i. preparing a solution of CoX.sub.2 in solvent [0079] ii. preparing a solution of SNS ligand in solvent [0080] iii. mixing the solution of step (i) and (ii) [0081] iv. stirring the reaction mixture of step (iii) at a temperature ranging from 25 C. to 30 C. for a time period ranging from 3 to 4 hours to yield cobalt based catalyst of formula (I).

[0082] The SNS ligand is selected from bis(2-(diethyl-3-sulfanyl)ethyl)amine (.sup.EtSNS; L1), and bis(2-(isopropylthio)ethyl)amine (.sup.iosPrSNS; L2). The CoX.sub.2 is selected from the group consisting of Cobalt (II) chloride (CoCl.sub.2), Cobalt (II) bromide (CoBr.sub.2) or Cobalt (II) Iodide (CoI.sub.2). The solvent is selected from the group consisting of methanol, ethanol, tetrahydrofuran, acetonitrile or diethylether.

[0083] The process for the preparation of cobalt based catalyst of formula (I) is as depicted in FIG. 2.

[0084] The cobalt based catalyst 1 and 2 can be handled under an ordinary atmosphere (in air) as it is not sensitive towards moisture and oxygen over a considerable period of time (2 weeks). Complexes 1 and 2 catalyze the dehydrogenative coupling of unprotected 1,2- and 1,3-amino alcohols with secondary alcohols in an efficient manner that enables the direct and sustainable synthesis of 1H-pyrroles, and pyridines (or quinolines), respectively. This reaction involves the consecutive CN and CC bond formation with the liberation of hydrogen gas and water.

[0085] FIG. 1 depicts X-ray crystal-structure analysis of 1 with 50% probability of thermal ellipsoids. Hydrogen atoms (except NH) are omitted for clarity. Selected bond length [Ao] and angle [o]: Co(1)-N(1) 2.124(7), Co(1)-S(1) 2.544(2), Co(1)-S(2) 2.555(2), Co(1)-Cl(1) 2.351(2), Co(1)-Cl(2) 2.548(2), Co(1)-Cl(3) 2.441(2), S(1)-Co(1)-S(2) 161.29(9), Cl(1)-Co(1)-Cl(2) 178.32(8), Cl(1)-Co(1)-N(1) 94.82(19), Co(1)-Cl(2)-Co(2) 95.74(8), S(1)-Co(1)-N(1) 81.58(18), S(2)-Co(1)-N(1) 82.39 (18).

[0086] The present invention also provides a process for the preparation of aromatic heterocyclic compound of formula (II) by using phosphine free cobalt based catalyst of formula (I) comprises heating the reaction mixture of amino alcohol, alcohol, catalyst of formula (I), base and solvent at the temperature ranging from 150180 C. for the time period ranging from 24 to 30 hours followed by cooling the reaction mixture to afford aromatic heterocyclic compound of formula (II).

[0087] The aromatic heterocyclic compound of formula (II) is represented as follows:

##STR00004##

[0088] wherein;

[0089] n is selected from 0 or 1,

[0090] R is selected from the group consisting of hydrogen, alkyl (linear or branched), substituted or unsubstituted or aryl and heteroaryl contains 0, N atoms;

[0091] R.sup.1, R.sup.2, and R.sup.3 are same or different and independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl (linear or branched), substituted or unsubstituted aryl;

[0092] R.sup.1 and R.sup.2 may form a substituted or unsubstituted cyclic or heterocyclic ring.

[0093] The aromatic heterocyclic compounds of formula (II) is selected from the group consisting of 2-methyl-5-phenyl-1H-pyrrole (5a), 2-ethyl-5-phenyl-1H-pyrrole (5b), 2-isopropyl-5-phenyl-1H-pyrrole (5c), 2-isobutyl-5-phenyl-1H-pyrrole (5d), 2-sec-butyl-5-phenyl-1H-pyrrole (5e), 2,5-diphenyl-1H-pyrrole (5f), 2-benzyl-5-phenyl-1H-pyrrole (5g), 2-isopropyl-5-p-tolyl-1H-pyrrole (5h), 2-(4-chlorophenyl)-5-isopropyl-1H-pyrrole (5i), 2-isopropyl-5-(4-methoxyphenyl)-1H-pyrrole (5j), 4-(5-isopropyl-1H-pyrrol-2-yl)aniline (5k), 2-isopropyl-5-m-tolyl-1H-pyrrole (5l), 2-isopropyl-5-(naphthalen-1-yl)-1H-pyrrole (5m), 2-isopropyl-5-octyl-1H-pyrrole (5n), 2-isobutyl-5-(naphthalen-2-yl)-1H-pyrrole (5o), 2-phenyl pyridine (7a), 2-p-tolyl pyridine (7b), 2-(4-methoxyphenyl) pyridine (7c), 2-m-tolylpyridine (7d), 2-octyl pyridine (7e), 2-decyl pyridine (7f), 2-phenyl quinoline (7g), 2-(3-methoxyphenyl) quinoline (7h), 2-(4-fluorophenyl)quinoline (7i), 2-(4-(trifluoromethyl)phenyl)quinoline (7j) or 2-(naphthalen-2-yl)quinoline (7k).

[0094] The alcohol is selected from the group consisting of aliphatic short and long range primary alcohols, secondary alcohols, substituted or unsubstituted aromatic primary alcohols, aromatic secondary alcohols, heteroaromatic alcohols or cyclic alcohols. Preferably, the alcohol is selected from the group consisting of 1-phenylethanol, 1-p-tolylethanol, 1-(4-chlorophenyl)ethanol, 1-(4-methoxyphenyl)ethanol, 1-(4-aminophenyl)ethanol, 1-(naphthalen-2-yl)ethanol, 1-(naphthalen-1-yl)ethanol, 2-decanol, 1-m-tolylethanol, 2-dodecanol, 1-(4-(trifluoromethyl)phenyl)ethanol and 1-(3-methoxyphenyl)ethanol.

[0095] The amino alcohol is selected from aliphatic and aromatic ( and ) amino alcohols. Preferably, the amino alcohol is selected from the group consisting of 2-aminobutan-1-ol, 2-amino-3-methylbutan-1-ol, 2-amino-4-methylpentan-1-ol, 2-amino-3-methylpentan-1-ol, 2-amino-3-phenylpropan-1-ol, 2-amino-2-phenylethanol, 3-aminopropan-1-ol and (2-aminophenyl)methanol.

[0096] The solvent is selected from the group consisting of m-xylene, Toluene, Octane, mesitylene or Decane.

[0097] The base is selected from the group consisting of potasium tert-butoxide (t-BuOK), sodium tert-butoxide (t-BuONa), lithium tert-butoxide (t-BuOLi), potassium hydride (KH), sodium hydride (NaH), potassium Bis (trimethylsilyl) amide [KHMDS], Lithium bis (trimethylsilyl) amide [LiHMDS], Sodium isopropoxide (NaOiPr), Sodium ethoxide (NaOEt) or Sodium methoxide (NaOMe).

[0098] The phosphine free cobalt based catalyst of formula (I) is selected from the group consisting of cobalt based dimer complex of bis(2-(diethyl-3-sulfanyl)ethyl)amine, bis(2-(isopropylthio)ethyl)amine, bis(2-(phenylthio)ethyl)amine, and bis(2-((substituted)phenylthio)ethyl)amine.

[0099] The present invention further provides direct synthesis of 1H-pyrroles via dehydrogenative annulation reaction as depicted in FIG. 3.

[0100] In the dehydrogenative condensation steps, two equivalents of H.sub.2 are liberated per pyrrole motif, thus making the protocol completely environmentally benign. The reaction proceeded successfully with both aliphatic and aromatic unprotected -aminoalcohols and gave the de-sired 1H-pyrroles in moderate to good yields (58%-86%).

[0101] The present invention also provides direct synthesis of pyridines and quinolines via dehydrogenative annulation reaction as shown in FIG. 4.

[0102] All of the pyridine derivatives (7a-f) are isolated in moderate to good yields (60-83%). C-2 substituted quinolines (7g-k) are also prepared involving dehydrogenative cyclization of 2-aminobenzyl alcohol with various secondary alcohols using our established protocol in very good yields (up to 87%). Thus, the phosphine-free cobalt (II) catalyst as disclosed in the present invention displayed remarkable activity in the sustainable synthesis of various 2-substituted pyridines and quinolines.

[0103] The present invention provides a process for the synthesis of pyrazine derivative comprises refluxing the reaction mixture of 1,2 amino alcohol and cobalt based catalyst of formula (I) in solvent at temperature in the range of 130 to 135 C. for the period in the range of 22 to 24 hrs to afford pyrazine derivative.

[0104] The process is carried out under argon atmosphere.

[0105] The present direct pyrazine synthesis catalyzed by phosphine free cobalt based catalyst of present invention is tested for gram-scale synthesis, and it worked excellently and gave 8 in 61% (1.02 g) isolated yield. [FIG. 5] This result implies that the phosphine free cobalt-based catalytic system of present invention has potential for the large-scale production of pyrazine under operationally simple, environmentally benign conditions.

EXAMPLES

[0106] Following examples are given by way of illustration therefore should not be construed to limit the scope of the invention.

Example 1: Synthesis of Ligands

a) Bis(2-(ethylthio)ethyl)amine (.SUP.Et.SNS; L1)

[0107] To a solution of bis(2-chloroethyl)amine hydrochloride (2.39 g, 13.4 mmol) in methanol (20 mL), 0.627 g of NaOH (15.7 mmol) and 2.5 g of sodium ethanethiolate (29.5 mmol) was added step wise. The resulting reaction mixture was allowed to stir for 12 h at 30 C., then the solvent was removed under reduced pressure, subsequently the reaction mixture was extracted with dichloromethane. The organic layer was collected and dried over anhyd. Na.sub.2SO.sub.4, then evaporated in vacuum under the reduced and the product (L1) was purified through neutral alumina column chromatography. Yield (0.862 g, 50%). .sup.1H NMR (500 MHz, CHLOROFORM-d) =2.83 (t, J=6.5 Hz, 4H), 2.69 (t, J=6.9 Hz, 4H), 2.55 (q, J=7.2 Hz, 4H), 1.98 (s, br, 1H), 1.26 (t, J=7.25 Hz, 6H). HRMS (EI): m/z Calcd for C.sub.8H.sub.19NS.sub.2 [M+H].sup.+: 194.0959; Found: 194.1043.

b) Bis(2-(isopropylthio)ethyl)amine (.SUP.iosPr.SNS; L2)

[0108] To a solution of bis(2-chloroethyl)amine hydrochloride (2.39 g, 13.4 mmol) in methanol (20 mL), 0.627 g of NaOH (15.7 mmol) and 2.9 g of sodium 2-propanethiolate (29.5 mmol) was added step wise. The resulting reaction mixture was allowed to stir for 12 h at 30 C., then the solvent was removed under reduced pressure, subsequently the reaction mixture was extracted with dichloromethane. The organic layer was collected and dried over anhyd.Na.sub.2SO.sub.4, then evaporated in vacuum under the reduced and the product (L2) was purified through neutral alumina column chromatography. Yield (1.42 g, 48%). .sup.1H NMR (500 MHz, CHLOROFORM-d) =2.94 (2H), 2.83 (t, J=6.9 Hz, 4H), 2.71 (t, J=6.5 Hz, 4H), 2.05 (s, br, 1H), 1.28 (d, J=6.5 Hz, 12H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =48.64, 34.81, 30.74, 23.49. HRMS (EI): m/z Calcd for C.sub.10H.sub.24NS.sub.2 [M+H].sup.+: 222.1345; Found: 222.1356.

Example 2: Synthesis of Cobalt-Complexes

a) Dimer of Co(II)chloride:bis(2-(diethyl-.SUP.3.-sulfanyl)ethyl)amine

[0109] ##STR00005##

[0110] Anhydrous CoCl.sub.2 (130 mg, 1 mmol) in methanol (2 mL) was added drop-wise to solution of .sup.EtSNS (L1) (193 mg, 1 mmol) in MeOH (2 mL) with stirring. The resulting reaction mixture was allowed to stir for 3 h at 30 C. The resulting solution was passed through syringe filter and dried in vacuo giving a blue crystalline powder. The crystal suitable for a single-crystal X-ray diffraction was obtained from MeOH: diethyl ether (by diffusion method) at 30 C. after one day.

[0111] Yield (249 mg, 77%); IR (KBr): 3213, 2936, 2868, 2792, 1625, 1462, 1412, 1377, 1306, 1268, 1093, 957, 731 cm.sup.1. The UV-Visible spectra of 1 recorded in acetonitrile show absorption centred at 589 and 680 nm. Elemental analysis calcd (%) for C.sub.16H.sub.38Cl.sub.4Co.sub.2N.sub.2S.sub.4: C 29.73; H 5.93; N 4.33; S 19.84; found: C 29.98; H 6.08; N 4.40; S 19.89. The formation of dimer is evidenced by MALDI-TOF mass spectrum (m/z=643.62). EPR study of 1 shows the paramagnetic nature of cobalt (II) complex and the g value is 2.58. Magnetic moment: 2.23 B.

b) Dimer of Co(II)chloride:bis(2-(isopropylthio)ethyl)amine

[0112] ##STR00006##

[0113] Anhydrous CoCl.sub.2 (130 mg, 1 mmol) in methanol (2 mL) was added drop-wise to solution of L2 (221 mg, 1 mmol) in MeOH (2 mL) with stirring. The resulting reaction mixture was allowed to stir for 3 h at 30 C. The resulting solution was passed through syringe filter and then kept for crystallization (diffusion method using diethyl ether). After 1 day, blue crystalline solid was obtained.

[0114] Yield (252 mg, 72%). IR (KBr): 3236, 2959, 2867, 2808, 2751, 1626, 1524, 1449, 1368, 1248, 1155, 997, 955, 725 cm.sup.1. The UV-Visible spectra of 2 recorded in acetonitrile show absorption centred at 588 and 680 nm. EPR study of 2 shows the paramagnetic nature of cobalt (II) complexes and having the g, and g.sub.y values 2.33 and 2.13, respectively, Elemental analysis calcd (%) for C.sub.20H.sub.46Cl.sub.4Co.sub.2N.sub.2S.sub.4: C 34.19; H 6.60; N 3.99; S 18.25; found: C 34.30; H 6.78; N 4.10; S 18.36. The formation of dimer is evidenced by MALDI-TOF mass spectrum (m/z=701.42). Magnetic moment: 2.29 B.

c) Dimer of Co(II)bromide:bis(2-(diethyl-.SUP.3.-sulfanyl)ethyl)amine

[0115] ##STR00007##

[0116] Anhydrous CoBr.sub.2 (219 mg, 1 mmol) in methanol (2 mL) was added dropwise to solution of SNS-L1 (193 mg, 1 mmol) in MeOH (2 mL) with stirring. The resulting reaction mixture was allowed to stir for 3 h at 30 C. The resulting solution was passed through syringe filter and collected in small glass vail and kept for crystallization via diffusion method using diethyl ether as external solvent, which afford blue crystalline solid material. Yield (267 mg, 65%); IR (KBr): 3212, 2964, 2928, 2867, 2788, 1463, 1412, 1377, 1305, 1268, 1230, 1148, 1093, 1051, 958 cm.sup.1.

d) Dimer of Co(II)bromide:bis(2-(isopropylthio)ethyl)amine

[0117] ##STR00008##

[0118] Anhydrous CoBr.sub.2 (219 mg, 1 mmol) in methanol (2 mL) was added dropwise to solution of SNS-L2 (221 mg, 1 mmol) in MeOH (2 mL) with stirring. The resulting reaction mixture was allowed to stir for 3 h at 30 C. The resulting solution was passed through syringe filter and collected in small glass vail and kept for crystallization via diffusion method using diethyl ether as external solvent, which afford blue crystalline solid material. Yield (254 mg, 58%); IR (KBr): 3217, 2958, 2922, 2865, 1464, 1412, 1368, 1307, 1247, 1148, 1055, 960, 726 cm.sup.1. HRMS (EI) or ESI mass are tried several times but in all case under the mass condition ligand is coming out from the metal center.

Example 3: Synthesis of Aromatic Heterocyclic of Formula (I) at Different Reaction Conditions

a) Reaction with Different Solvent.SUP.a

[0119] ##STR00009##

TABLE-US-00001 TABLE 1 Entry Solvent Yield (%).sup.b 1 Toluene 47 2 m-xylene 77 3 Mesitylene 57 4 n-octane 52 5 THF 32 .sup.a Reactions performed using amino alcohol 3c (0.125 mmol), 1-Phenyl ethanol 4a (0.15 mmol), catalyst 1 (2.5 mol %), KO.sup.tBu (1.1 equiv.) at 180 C. of bath temp. .sup.bYield determined by GC using 1,4-dibromo butane as an internal standard.

b) Reaction with Different Catalyst.SUP.a

[0120] ##STR00010##

TABLE-US-00002 TABLE 2 Entry Catalyst Yield (%).sup.b 1 Cat. 1 77 2 Cat. 2 34 3 CoCl.sub.2 trace 4 NR 5 RuCl.sub.2(PPh.sub.3)[HN(C.sub.2H.sub.4SEt).sub.2] 45 .sup.a Reactions performed using amino alcohol 3c (0.125 mmol), 1-Phenyl ethanol 4a (0.15 mmol), catalyst (2.5 mol %), KO.sup.tBu (1.1 equiv.) reflux at 150 C. to 180 C. .sup.bYield determined by GC using 1,4-dibromo butane as an internal standard. NR = No reaction.

c) Reaction with Different Base.SUP.a

[0121]

TABLE-US-00003 [00011] [00012] [00013] Entry Base Yield (%).sup.b 1 NaO.sup.tBu 63 2 NaO.sup.iPr 17 3 KOH 62 4 KO.sup.tBu 77 5 KHMDS 67 6 KH 71 7 K.sub.2CO.sub.3 NR 8 KOAc NR 9 NR .sup.aReactions performed using amino alcohol 3c (0.125 mmol), 1-Phenyl ethanol 4a (0.15 mmol), catalyst 1 (2.5 mol %), base (1.1 equiv.) reflux at 150 C. to 180 C. .sup.bYield determined by GC using 1,4-dibromo butane as an internal standard. NR = No reaction.

d) Reaction with Different Base Amount.SUP.a

[0122]

TABLE-US-00004 [00014] [00015] [00016] Entry Base (x equiv) Yield (%).sup.b 1 0.5 eq 20 2 1.1 eq 77 3 1.5 eq 55 4 2 eq 39 5 2.5 eq 35 .sup.aReactions performed using amino alcohol 3c (0.125 mmol), 1-Phenyl ethanol 4a (0.15 mmol), catalyst (2.5 mol %), KO.sup.tBu (equiv.) reflux at 150 C. to 180 C. .sup.bYield determined by GC using 1,4-dibromo butane as an internal standard.

e) Reaction with Different Temperature.SUP.a

[0123]

TABLE-US-00005 [00017] [00018] [00019] Entry Temperature Yield (%).sup.b 1 50 C. NR 2 80 C. trace 3 120 C. 23 4 150 C. 48 5 180 C. 77 (reflux) .sup.aReactions performed using amino alcohol 3c (0.125 mmol), 1-Phenyl ethanol 4a (0.15 mmol), catalyst (2.5 mol %), KO.sup.tBu (equiv.) at different (bath) temperature. .sup.bYield determined by GC using 1,4-dibromo butane as an internal standard. NR = No reaction.

f) Reaction with Different Alcohol and Amino Alcohol Ratio.SUP.a

[0124]

TABLE-US-00006 [00020] [00021] [00022] Alcohol/amino Entry alcohol ratio Yield (%).sup.b 1 1/1 69 2 1/1 (cat 2) 67 3 1.5/1 71 4 2/1 77 5 3/1 65 .sup.aReactions performed using amino alcohol 3c (0.125 mmol), 1-Phenyl ethanol 4a (0.15 mmol), catalyst (2.5 mol %), KO.sup.tBu (equiv.) reflux at 150 C. to 180 C. .sup.bYield determined by GC using 1,4-dibromo butane as an internal standard. NR = No reaction.

Example 4: Synthesis of Aromatic Heterocyclic Compound of Formula (I)

(a) General Procedure for the Synthesis of 1H-Pyrroles

[0125] To an oven-dried 15 mL ace pressure tube, 1,2 amino alcohol 3 (0.25 mmol), secondary alcohol 4 (0.5 mmol), Co-complex 1 (2.5 mol %) and m-xylene (2 mL) were added under a gentle stream of argon. The mixture was of heated at 150 C. to 180 C. for 24 h followed by cooling to room temperature. The reaction mixture was diluted with water (4 mL) and extracted with dichloromethane (35 mL). The resultant organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The crude mixture was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluting system.

i. 2-methyl-5-phenyl-1H-pyrrole (5a)

[0126] To an oven-dried 15 mL ace pressure tube, 2-aminopropan-1-ol (0.25 mmol), 1-phenylethanol (0.5 mmol), Co-complex 1 (2.5 mol %) and m-xylene (2 mL) were added under a gentle stream of argon. The mixture was of heated at 150 C. to 180 C. for 24 h followed by cooling to room temperature. The reaction mixture was diluted with water (4 mL) and extracted with dichloromethane (35 mL). The resultant organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The crude mixture was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluting system.

[0127] Colorless oil. Yield: 77%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.13 (s, br, 1H), 7.45 (d, J=7.2 Hz, 2H), 7.35 (t, J=7.2 Hz, 2H), 7.17 (t, J=7.2 Hz, 1H), 6.41 (s, 1H), 5.98 (s, 1H), 2.35 (s, 3H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =132.94, 129.02, 128.80, 125.64, 123.33, 107.93, 106.18, 13.19. HRMS (EI): m/z Calcd for C.sub.11H.sub.12N [M+H].sup.+: 158.0964; Found: 158.0965.

ii. 2-ethyl-5-phenyl-1H-pyrrole (5b)

[0128] Colorless oil. Yield: 81%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.15 (s, br, 1H), 7.45 (d, J=8.0 Hz, 2H), 7.36 (t, J=7.2 Hz, 2H), 7.18 (t, J=7.2 Hz, 1H), 6.44 (s, 1H), 6.01 (s, 1H), 2.71 (q, J=7.6 Hz, 2H), 1.31 (t, J=7.6 Hz, 3H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =135.60, 132.99, 130.58, 128.79, 125.65, 123.38, 106.23, 105.98, 21.00, 13.59. HRMS (EI): m/z Calcd for C.sub.12H.sub.12N [MH].sup.+: 170.0964; Found: 170.0964.

iii. 2-isopropyl-5-phenyl-1H-pyrrole (5c)

[0129] Colorless oil. Yield: 73%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.14 (s, br, 1H), 7.45 (d, J=7.2 Hz, 2H), 7.35 (t, J=7.6 Hz, 2H), 7.17 (t, J=7.2 Hz, 1H), 6.42 (s, 1H), 6.00 (s, 1H), 3.1-2.98 (m, 1H), 1.32 (d, J=6.9 Hz, 6H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =140.30, 133.03, 130.46, 128.79, 125.67, 123.43, 105.81, 104.97, 27.21, 22.66. HRMS (EI): m/z Calcd for C.sub.13H.sub.16N [M+H].sup.+: 186.1277; Found: 186.1279.

iv. 2-isobutyl-5-phenyl-1H-pyrrole (5d)

[0130] Colorless oil. Yield: 86%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.10 (s, br, 1H), 7.45 (d, J=7.6 Hz, 2H), 7.35 (t, J=7.6 Hz, 2H), 7.17 (t, J=7.2 Hz, 1H), 6.44 (s, 1H), 5.98 (s, 1H), 2.52 (d, J=7.2 Hz, 2H), 1.94-1.88 (m, 1H), 0.98 (d, J=6.9 Hz, 6H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =133.21, 133.00, 130.42, 128.79, 125.57, 123.30, 107.99, 106.04, 37.38, 29.27, 22.45. HRMS (EI): m/z Calcd for C.sub.14H.sub.16N [MH].sup.+: 198.1277; Found: 198.1277.

v. 2-sec-butyl-5-phenyl-1H-pyrrole (5e)

[0131] Colorless oil. Yield: 78%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.13 (s, br, 1H), 7.45 (d, J=7.6 Hz, 2H), 7.37 (t, J=7.6 Hz, 2H), 7.19 (t, J=7.2 Hz, 1H), 6.46 (s, 1H), 6.01 (s, 1H), 2.77-2.73 (m, 1H), 1.74-1.68 (m, 1H), 1.64-1.61 (m, 1H), 1.32 (d, J=6.9 Hz, 3H), 0.96 (t, J=7.2 Hz, 3H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =139.17, 133.05, 130.24, 128.77, 125.58, 123.34, 105.83, 105.64, 34.41, 30.23, 20.06, 11.82. HRMS (EI): m/z Calcd for C.sub.14H.sub.18N [M+H].sup.+: 200.1434; Found: 200.1432.

vi. 2,5-diphenyl-1H-pyrrole (5f)

[0132] Brown liquid. Yield: 58%. .sup.1H NMR (200 MHz, CHLOROFORM-d) =8.60 (s, br, 1H), 7.55 (d, J=7.7 Hz, 4H), 7.40 (t, J=7.3 Hz, 4H), 7.27 (t, J=7.3 Hz, 2H), 6.60 (d, J=2.5 Hz, 2H). HRMS (EI): m/z Calcd for C.sub.16H.sub.13N [M+H].sup.+: 219.1043; Found: 219.1043. (Known compound: Michlik, S.; Kempe, R. Nat. Chem. 2013, 5, 140).

vii. 2-benzyl-5-phenyl-1H-pyrrole (5g)

[0133] Light brown oil. Yield: 70%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.05 (s, br, 1H), 7.40 (d, J=7.6 Hz, 2H), 7.35-7.31 (m, 5H), 7.26 (d, J=7.2 Hz, 2H), 7.16 (t, J=7.2 Hz, 1H), 6.44 (s, 1H), 6.06 (s, 1H), 4.04 (s, 2H). HRMS (EI): m/z Calcd for C.sub.17H.sub.14N [MH].sup.+: 232.1121; Found: 232.1121. (Known compound: Michlik, S.; Kempe, R. Nat. Chem. 2013, 5, 140).

viii. 2-isopropyl-5-p-tolyl-1H-pyrrole (5h)

[0134] Colorless oil. Yield: 85%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.10 (s, br, 1H), 7.36 (d, J=8.5 Hz, 2H), 7.17 (d, J=7.9 Hz, 2H), 6.38 (s, 1H), 5.99 (s, 1H), 3.00-2.98 (m, 1H), 2.36 (s, 3H), 1.32 (d, J=7.3 Hz, 6H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =139.84, 135.33, 130.60, 130.31, 129.45, 123.44, 105.18, 104.76, 27.19, 22.66, 21.06. HRMS (EI): m/z Calcd for C.sub.14H.sub.18N [M+H].sup.+: 200.1434; Found: 200.1431.

ix. 2-(4-chlorophenyl)-5-isopropyl-1H-pyrrole (5i)

[0135] Colorless oil. Yield: 70%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.10 (s, br, 1H), 7.37 (d, J=8.4 Hz, 2H), 7.31 (d, J=8.4 Hz, 2H), 6.41 (s, 1H), 6.00 (s, 1H), 3.01-2.95 (m, 1H), 1.32 (d, J=6.9 Hz, 6H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =140.78, 131.52, 131.11, 128.92, 124.56, 123.43, 106.36, 105.23, 27.23, 22.64. HRMS (EI): m/z Calcd for C.sub.13H.sub.15ClN [M+H].sup.+: 220.0888; Found: 220.0886.

x. 2-isopropyl-5-(4-methoxyphenyl)-1H-pyrrole (5j)

[0136] White solid. Yield: 89%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.03 (s, br, 1H), 7.38 (d, J=8.4 Hz, 2H), 6.91 (d, J=8.4 Hz, 2H), 6.30 (s, 1H), 5.97 (s, 1H), 3.83 (s, 3H), 3.00-2.95 (m, 1H), 1.32 (d, J=6.9 Hz, 6H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =157.91, 139.58, 130.48, 126.22, 124.89, 114.26, 104.66, 55.30, 27.18, 22.68. HRMS (EI): m/z Calcd for C.sub.14H.sub.18ON [M+H].sup.+: 216.1383; Found: 216.1381.

xi. 4-(5-isopropyl-1H-pyrrol-2-yl)aniline (5k)

[0137] Light brown liquid. Yield: 67%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =7.99 (s, br, 1H), 7.26 (d, J=6.7 Hz, 2H), 6.69 (d, J=7.9 Hz, 2H), 6.24 (s, 1H), 5.95 (s, 1H), 3.65 (s, br, 3H), 2.99-2.94 (m, 1H), 1.31 (d, J=6.7 Hz, 6H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =144.48, 139.08, 131.03, 124.93, 124.31, 115.53, 104.45, 103.88, 27.16, 22.69. HRMS (EI): m/z Calcd for C.sub.13H.sub.17N.sub.2 [M+H].sup.+: 201.1386; Found: 201.1385.

xii. 2-isopropyl-5-m-tolyl-1H-pyrrole (5l)

[0138] Colorless oil. Yield: 70%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.15 (s, br, 1H), 7.76 (s, 1H), 7.28-7.26 (m, 2H), 7.03-7.01 (m, 1H), 6.42 (s, 1H), 6.01 (s, 1H), 3.03-2.97 (m, 1H), 2.40 (s, 3H), 1.34 (d, J=7.3 Hz, 6H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =140.12, 138.32, 133.69, 128.68, 128.40, 126.50, 124.18, 120.62, 105.67, 104.87, 27.21, 22.66, 21.52. HRMS (EI): m/z Calcd for C.sub.14H.sub.18N [M+H].sup.+: 200.1434; Found: 200.1432.

xiii. 2-isopropyl-5-(naphthalen-1-yl)-1H-pyrrole (5m)

[0139] Light yellow sticky liquid. Yield: 61%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.39-8.38 (m, 1H), 8.16 (s, br, 1H), 7.90-7.89 (m, 1H), 7.80-7.79 (m, 1H), 7.51 (m, 4H), 6.44 (s, 1H), 6.12 (s, 1H), 3.11-3.03 (m, 1H), 3.37 (d, J=6.5 Hz, 6H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =139.82, 134.10, 131.84, 131.28, 128.89, 128.39, 127.05, 126.19, 125.85, 125.62, 125.45, 109.34, 104.34, 27.17, 22.67. HRMS (EI): m/z Calcd for C.sub.17H.sub.18N [M+H].sup.+: 236.1434; Found: 236.1425.

xiv. 2-isopropyl-5-octyl-1H-pyrrole (5n)

[0140] Ration of alcohol/amino alcohol=1.5/1 has taken under the identical reaction condition. Colorless oil. Yield: 45%. .sup.1H NMR (200 MHz, CHLOROFORM-d) =5.79 (d, J=2.3 Hz, 2H), 2.96-2.82 (m, 1H), 2.56 (t, J=7.3 Hz, 2H), 1.62 (m, 2H), 1.27 (m, 16H), 0.89 (t, J=5.0 Hz, 3H). HRMS (EI): m/z Calcd for C.sub.15H.sub.28N [M+H].sup.+: 222.2216; Found: 222.2213. The product contains dehydrogenated product derived from secondary alcohol (Product: other dehydrogenated products=1:1.5).

xv. 2-isobutyl-5-(naphthalen-2-yl)-1H-pyrrole (5o)

[0141] Light yellow sticky liquid. Yield: 74%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.26 (s, br, 1H), 7.83-7.79 (m, 4H), 7.66 (d, J=8.8 Hz, 1H), 7.47 (t, J=7.2 Hz, 1H), 7.43 (t, J=7.2 Hz, 1H), 6.58 (s, 1H), 6.04 (s, 1H), 2.56 (d, J=6.9 Hz, 2H), 1.98-1.93 (m, 1H), 1.01 (d, J=6.5 Hz, 6H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =133.85, 131.81, 130.43, 128.45, 127.70, 127.51, 126.36, 125.06, 123.06, 120.02, 108.23, 106.84, 37.44, 29.29, 22.51. HRMS (EI): m/z Calcd for C1.sub.8H.sub.20N [M+H].sup.+: 250.1590; Found: 250.1583.

b) General Procedure for the Synthesis Pyridine Derivatives

[0142] To an oven-dried 15 mL ace pressure tube, 1,2 amino alcohol 6 (0.25 mmol), secondary alcohol 4 (0.5 mmol), Co-complex 1 (2.5 mol %) and m-xylene (1 mL) were added under a gentle stream of argon. The mixture was heated at 150 C. to 180 C. for 24 h followed by cooling to room temperature. The reaction mixture was diluted with water (4 mL) and extracted with dichloromethane (35 mL). The resultant organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The crude mixture was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluting system.

i. 2-Phenyl Pyridine (7a)

[0143] To an oven-dried 15 mL ace pressure tube, (2-aminophenyl)methanol 6 (0.25 mmol), 1-phenylethan-1-ol 4 (0.5 mmol), Co-complex 1 (2.5 mol %) and m-xylene (1 mL) were added under a gentle stream of argon. The mixture was heated at 150 C. to 180 C. for 24 h followed by cooling to room temperature. The reaction mixture was diluted with water (4 mL) and extracted with dichloromethane (35 mL). The resultant organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The crude mixture was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluting system.

[0144] Colorless oil. Yield: 68%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.71 (d, J=4.9 Hz, 1H), 8.01 (d, J=7.6 Hz, 2H), 7.73 (m, 2H), 7.49 (t, J=8.0 Hz, 2H), 7.43 (t, J=7.2 Hz, 1H), 7.23-7.21 (m, 1H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =157.35, 149.57, 139.31, 136.64, 128.86, 128.65, 126.81, 121.99, 120.45. HRMS (EI): m/z Calcd for C.sub.11H.sub.10N [M+H].sup.+: 156.0808; Found: 156.0807.

ii. 2-p-tolyl Pyridine (7b)

[0145] Colorless oil. Yield: 79%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.69 (d, J=4.6 Hz, 1H), 7.90 (d, J=8.4 Hz, 2H), 7.76-7.71 (m, 2H), 7.29 (d, J=8.0 Hz, 2H), 7.21 (t, J=5.3 Hz, 1H), 2.42 (s, 3H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =157.49, 149.58, 138.93, 136.67, 129.46, 126.76, 121.78, 120.26, 21.25. HRMS (EI): m/z Calcd for C.sub.12H.sub.12N [M+H].sup.+: 170.0964; Found: 170.0964.

iii. 2-(4-methoxyphenyl) Pyridine (7c)

[0146] Colorless oil. Yield: 83%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.66 (d, J=4.2 Hz, 1H), 7.96 (d, J=9.2 Hz, 2H), 7.72 (t, J=7.6 Hz, 1H), 7.69 (t, J=7.6 Hz, 1H), 7.18 (t, J=7.2 Hz, 1H), 7.01 (d, J=8.8 Hz, 1H), 3.88 (s, 3H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =160.46, 157.13, 149.54, 136.64, 132.04, 128.15, 121.39, 119.80, 114.11, 55.35. HRMS (EI): m/z Calcd for C.sub.12H.sub.12ON [M+H].sup.+: 186.0913; Found: 186.0912.

iv. 2-m-tolylpyridine (7d)

[0147] Colorless oil. Yield: 69%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.70 (d, J=4.6 Hz, 1H), 7.85 (s, 1H), 7.77-7.72 (m, 3H), 7.38 (t, J=7.6 Hz, 1H), 7.24 (t, J=7.2 Hz, 2H), 2.45 (s, 3H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =157.65, 149.60, 139.35, 138.43, 136.70, 129.71, 128.63, 127.65, 123.99, 122.01, 120.64, 21.51. HRMS (EI): m/z Calcd for C.sub.12H.sub.12N [M+H].sup.+: 170.0964; Found: 194.1043.

v. 2-octyl Pyridine (7e)

[0148] Ration of alcohol/amino alcohol=1.5/1 has taken under the identical reaction condition.

[0149] Colorless oil. Yield: 60%. .sup.1H NMR (200 MHz, CHLOROFORM-d) =8.53 (d, J=4.8 Hz, 1H), 7.59 (t, J=9.3 Hz, 1H), 7.16-7.07 (m, 2H), 2.79 (t, J=8.1 Hz, 2H), 1.73 (m, 2H), 1.28 (m, 10H), 0.89 (t, J=6.7 Hz, 3H). HRMS (EI): m/z Calcd for C.sub.13H.sub.22N [M+H].sup.+: 192.1747; Found: 192.1744. The product contains dehydrogenated product derived from secondary alcohol (Product: other dehydrogenated products=1:1.8). (Known compound: Nakamura, Y.; Yoshikai, N.; lies, L.; Nakamura, E. Org. Lett. 2012, 14, 12).

vi. 2-decyl Pyridine (7f)

[0150] Ration of alcohol/amino alcohol=1.5/1 has taken under the identical reaction condition. Colorless oil. Yield: 63%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.53 (d, J=4.6 Hz, 1H), 7.58 (t, J=7.6 Hz, 1H), 7.14 (d, J=7.6 Hz, 1H), 7.08 (t, J=5.7 Hz, 1H), 2.78 (t, J=7.6 Hz, 2H), 1.76-1.68 (m, 2H), 1.26 (m, 14H), 0.88 (t, J=6.9 Hz, 3H). HRMS (EI): m/z Calcd for C.sub.15H.sub.26N [M+H].sup.+: 220.2060; Found: 220.2057. Unable to isolate complete pure product, product identified from its unreacted secondary alcohol. Product: unreacted secondary alcohol=1:1.6. (Known compound: Vandromme, L.; ReiBig, H.-U.; Groper, S.; Rabe, J. P. Eur. J. Org. Chem. 2008, 2049-2055).

vii. 2-phenyl Quinoline (7g)

[0151] White solid. Yield: 81%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.21 (t, J=9.2 Hz, 4H), 7.88 (d, J=8.4 Hz, 1H), 7.83 (d, J=8.0 Hz, 1H), 7.75 (t, J=8.0 Hz, 1H), 7.57-7.53 (m, 3H), 7.49 (t, J=7.2 Hz, 1H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =157.29, 148.24, 139.64, 136.70, 129.70, 129.59, 129.26, 128.79, 127.52, 127.41, 127.13, 126.22, 118.94. (Known compound: Rao, M. L. N.; Dhanorkar, R. J. Eur. J. Org. Chem. 2014, 5214-5228).

viii. 2-(3-methoxyphenyl) Quinoline (7h)

[0152] Colorless oil. Yield: 75%. .sup.1H NMR (200 MHz, CHLOROFORM-d) =8.22-8.19 (m, 2H), 7.87-7.80 (m, 3H), 7.74 (t, J=8.5 Hz, 2H), 7.54 (t, J=7.3 Hz, 1H), 7.45 (t, J=7.9 Hz, 1H), 7.04 (d, J=8.5 Hz, 1H), 3.94 (s, 3H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =160.08, 157.04, 148.15, 141.09, 136.68, 129.74, 129.68, 129.58, 127.39, 126.25, 119.95, 119.02, 115.30, 112.66, 55.34. HRMS (EI): m/z Calcd for C.sub.16H.sub.14ON [M+H].sup.+: 236.1070; Found: 236.1068.

ix. 2-(4-fluorophenyl)quinoline (7i)

[0153] White solid. Yield: 72%. .sup.1H NMR (400 MHz, CHLOROFORM-d) =8.21-8.15 (m, 4H), 7.82 (d, J=8.5 Hz, 2H), 7.74 (t, J=6.7 Hz, 1H), 7.54 (t, J=7.3 Hz, 1H), 7.22 (t, J=8.5 Hz, 2H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =164.76, 162.77, 156.77, 148.19, 136.85, 136.85, 135.78, 129.74, 129.39, 129.33, 127.43, 127.04, 126.30, 118.58, 115.80, 115.63. HRMS (EI): m/z Calcd for C.sub.15H.sub.11NF [M+H].sup.+: 224.0870; Found: 224.0869.

x. 2-(4-(trifluoromethyl)phenyl)quinoline (7j)

[0154] White solid. Yield: 67%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.29 (d, J=8.4 Hz, 2H), 8.25 (d, J=8.4 Hz, 1H), 8.20 (d, J=8.4 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.85 (d, J=8.0 Hz, 1H), 7.80-7.75 (m, 3H), 7.58 (t, J=8.0 Hz, 1H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =155.62, 148.25, 142.92, 137.08, 129.96, 129.83, 127.80, 127.50, 126.82, 125.72, 125.69, 118.73. HRMS (EI): m/z Calcd for C.sub.16H.sub.11NF.sub.3 [M+H].sup.+: 274.0838; Found: 274.0838.

xi. 2-(naphthalen-2-yl)quinoline (7k)

[0155] White solid. Yield: 87%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =8.64 (s, 1H), 8.40 (d, J=8.8 Hz, 1H), 8.25 (d, J=8.4 Hz, 1H), 8.05-8.01 (m, 3H), 7.93-7.91 (m, 1H), 7.85 (d, J=8.0 Hz, 1H), 7.77 (t, J=6.9 Hz, 1H), 7.57-7.54 (m, 3H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =157.12, 148.35, 136.94, 136.76, 133.84, 133.48, 129.72, 129.68, 128.79, 128.54, 127.70, 127.46, 127.19, 127.11, 126.67, 126.30, 125.03, 119.11. HRMS (EI): m/z Calcd for C.sub.19H.sub.14N [M+H].sup.+: 256.1121; Found: 256.1120.

Example 5: General Procedure for the Synthesis of Pyrazine Derivative

[0156] To an oven-dried 15 mL ace pressure tube, 1,2 amino alcohol 3f (0.25 mmol), Co-complex 1 (2.5 mol %) and m-xylene (1 mL) were added under a gentle stream of argon. The mixture was heated at 135 C. (bath temperature). After 24 h, the reaction mixture was diluted with water (4 mL) and extracted with dichloromethane (35 mL). The resultant organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The crude mixture was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluting system.

[0157] Gram-scale synthesis: The present cobalt-catalyzed direct pyrazine synthesis was tested for the gram-scale synthesis, and it worked excellently and gave 8 in 61% (1.02 g) isolated yield.

a. 2,5-Diphenyl Pyrazine (8)

[0158] To an oven-dried 15 mL ace pressure tube, 2-amino-2-phenylethan-1-ol 3f (0.25 mmol), Co-complex 1 (2.5 mol %) and m-xylene (1 mL) were added under a gentle stream of argon. The mixture was heated at 135 C. (bath temperature). After 24 h, the reaction mixture was diluted with water (4 mL) and extracted with dichloromethane (35 mL). The resultant organic layer was dried over anhydrous Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The crude mixture was purified by silica gel column chromatography (230-400 mesh size) using petroleum-ether/ethyl acetate as an eluting system.

[0159] White solid. Yield: 68%. .sup.1H NMR (500 MHz, CHLOROFORM-d) =9.10 (s, 2H), 8.08 (d, J=7.2 Hz, 4H), 7.55 (t, J=7.2 Hz, 4H), 7.50 (q, J=7.2 Hz, 2H). .sup.13C NMR (126 MHz, CHLOROFORM-d) =150.68, 141.25, 136.27, 129.77, 129.07, 126.79. (Known compound: Gnanaprakasam, B.; Balaraman, E.; Ben-David, Y.; Milstein, D. Angew. Chem. Int. Ed. 2011, 50, 12240).

Advantages of the Invention

[0160] Use of a new, air-stable molecularly defined SNS-cobalt (II) complex. [0161] This tandem annulation reaction operates under mild, eco-benign conditions with the liberation of hydrogen gas and water as the sole by-products. [0162] Excellent step-economy and high atom-efficiency. [0163] A simple, phosphine ligand-free Co (II)-complex as a precatalyst for the preparation of diverse N-heterocycles via dehydrogenative annulation of unprotected -aminoalcohols with secondary alcohols. [0164] Cobalt (II)-complexes are air-stable and their synthesis has the practical advantages of being straightforward, conveniently performed in open air atmosphere, and can be scaled up.