WO2015102020A1 - Novel n-heterocyclic carbene compounds, their preparation and use - Google Patents

Novel n-heterocyclic carbene compounds, their preparation and use Download PDF

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WO2015102020A1
WO2015102020A1 PCT/IN2014/000804 IN2014000804W WO2015102020A1 WO 2015102020 A1 WO2015102020 A1 WO 2015102020A1 IN 2014000804 W IN2014000804 W IN 2014000804W WO 2015102020 A1 WO2015102020 A1 WO 2015102020A1
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heterocyclic carbene
formula
compound
ligand precursor
aryl
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WO2015102020A4 (en
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Srinivasa DUMBALA REDDY
Ravannath LAXMAN SUTAR
Vinod Kumar
Rahul DILIP SHINGARE
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Council of Scientific and Industrial Research CSIR
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
    • C07F15/006—Palladium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/04—Substitution
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/06—Peri-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
    • C07D487/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/027—Organoboranes and organoborohydrides

Definitions

  • the present invention relates to novel N-heterocyclic carbine compounds and process of the preparation thereof. More particularly, the present invention relates to novel N- heterocyclic carbenes compounds, their preparation and use of these novel N-heterocyclic carbenes as ligand in the Suzuki-Miyaura cross coupling reactions.
  • N-heterocyclic carbenes have emerged as an important class of ligands and catalysts because of their several attractive features, and they have thus received significant attention from the scientific community.
  • a transition metal carbene complex is an organometallic compound featuring a divalent carbene organic ligand. Carbene complexes for almost all transition metals have been reported and many reactions utilizing them have been reported.
  • NHCs are generally derived from persistent carbenes which are stable compound of divalent carbon.
  • N-heterocyclic carbene (NHC) ligands are widely used in chemistry due to their catalytic properties and applied for olefin metathesis among other reactions.
  • the enhanced application of this type of organometallics has over the last few years also triggered a steadily increasing number of studies in the fields of medicinal chemistry, which take advantage of the beautiful chemical properties of these complexes.
  • Spectroscopic and crystallographic data indicate that the principal plane of the NHC ligand in the achiral complexes is positioned orthogonally with respect to the Ir-Cl or Ir-P bonds, while the planes of NHC ligands in the corresponding chiral complexes are twisted by a torsion angle that depends on the size of the 2,9-substituents.
  • the main objective of the present invention is to provide novel N-heterocyclic carbene compounds of formula (I) and process for preparation thereof.
  • Another objective of the present invention is to provide novel N-heterocyclic carbene metal complexes of formula (II) and process for preparation thereof.
  • N-heterocyclic carbene ligand precursor compound comprising a compound of formula (I), metal complexes and derivatives thereof
  • R is H, alkyl, aryl, aralkyl; substituted alkyl and substituted aralkyl;
  • Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain hetero atoms like O, N, and S.
  • the process for the preparation of N- heterocyclic carbene ligand precursor comprising the following steps:
  • step (a) Adding a solution of 2 of step (a)in chlorobenzene to a suspension of (AICI3 ) Aluminium chloride in chlorobenzene followed by stirring at room temperature for 2h to obtain3;
  • step (b) Adding a solution of 3 of step (b) in THF to a suspension of Lithium aluminium hydride in THF followed by refluxing for lh which was again heating at reflux with 6 N aqueous HC1 for lh to obtain 4; d) Heating a solution of 4 of step (c) in triethyl orthofomate and HC1 at 80°C for 14 h under argon atmosphere and for 2 h at the same temparature in air to obtain N-heterocyclic carbene ligand precursor;
  • N-heterocyclic carbene metal complex comprising a compound of formula (II)
  • R is H, alkyl, aiyl, aralkyl; substituted Alkyl and substituted aralkyl;
  • Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain hetero atoms like O, N, S;
  • L is ligands L can be carbene having Formula (I) or any heterocycle containing Nitrogen which can be further substituted.
  • the process for the preparation of N- heterocyclic carbene metal complex further comprising refluxing the reaction mixture of N-heterocyclic carbene ligand precursor (5) and Pd(OAc) 2 in THF for 1 h to obtainN- heterocyclic carbene metal complex (8), or heating the reaction mixture of N-heterocyclic carbene ligand precursor (5), PdCl 2 and potassium carbonate in pyridine in microwave at 150°C for 30 min to obtain N- heterocyclic carbene metal complex (9).
  • the derivative of N-heterocyclic carbine compound comprising a compound of formula (III) T/IN2014/000804
  • R is H, alkyl, aryl, aralkyl; substituted alkyl and substituted aralkyl;
  • Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain hetero atoms like O, N, S;
  • X is O, S.
  • the derivative of N-heterocyclic carbene compound is selected from selected from l ,l,9,9-tetramethyl- l ,2,3,7,8,9- hexahydro-5H-imidazo[l,5,4,3-/mn][l , 10]phenanthroline-5-thione and 5- ⁇ 4 -boranyl)- l , l ,9,9-tetramethyl- l ,2,3,7,8,9-hexahydro-4- ⁇ 4 -imidazo-[3 ,4,5, 1-
  • the process for the preparation of derivative of N-heterocyclic carbene compound of formula (III) comprising the steps of a) stirring N-heterocyclic carbene ligand precursor 5 and sodium hydride (NaH) in THF for 1 h at room temparature; b) adding S 8 in THFfolowed by stirring at room temparature for further additional 2h to obtain 1 ,1,9,9-tetramethyl- 1 ,2,3, 7,8,9-hexahydro-5H- imidazo [ 1 ,5 ,4,3 -lmn] [1 ,10]phenanthroline-5 -thione (6).
  • R is H, alkyl, aryl, aralkyl; substituted alkyl and substituted aralkyl;
  • Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain heteroatoms like O, N, S;
  • a method of catalytic Suzuki- Miyaura cross-coupling of aryl halides with aryl boronic acids using novel N- heterocyclic carbenepalladium complex comprising stirring a solution of aryl boronic acids selected from the group consisting of phenyl boronic acid, (4-methoxyphenyl)boronic acid, (3-nitrophenyl)boronic acid, naphthalen-l-ylboronic acid, (4-(hydroxymethyl)phenyl)boronic acid, 4-boronobenzoic acid, (4-acetylphenyl)boronic acid, furan-2-ylboronic acid; aryl halides selected from the group consisting of l-(4-bromophenyl)ethan-l -one, l-bromo-4- methoxybenzene,chlorobenzene, 4-chlorophenol, 4-bromophenol, 3-bromopyridine, 2- brom
  • the present invention provides a method of catalytic Suzuki- Miyaura cross-coupling of aryl halides with arylboronic acids using novel N-heterocyclic carbene palladium complexat room temperature with very low catalyst loading.
  • the present invention provides anN-heterocyclic carbene ligand precursor of formula (I)
  • R is H, alkyl, aryl, aralkyl; substituted alkyl and substituted aralkyl;
  • Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain heteroatoms like O, N, and S.
  • the present invention provide a process for the preparation of N- heterocyclic carbene ligand precursor comprising the steps of:
  • step (b) Adding a solution of 3 of step (b) in THF to a suspension of Lithium aluminium hydride in THF followed by refluxing for lh. which was again heating at reflux with 6 N aqueous HC1 for lh to obtain 4;
  • step (c) Heating a solution of 4 of step (c) in triethyl orthofomate and HC1 at 80°C for 14 h under argon atmosphere and for 2 h at the same temparature in air to obtain N-heterocyclic carbene ligand precursor 5;
  • R is H, alkyl, aryl, aralkyl; substituted Alkyl and substituted aralkyl;
  • Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain heteroatoms like O, N, S;
  • L is ligands.
  • L can be carbene having Formula (I) or any heterocycle containing Nitrogen which can be further substituted.
  • N-heterocyclic carbene metal complexof formula (II) is selected from following compounds of formula 8 and 9 as shown below:
  • N-heterocyclic carbene metal complex of formula (8) comprising refluxing the reaction mixture of N-heterocyclic carbene ligand precursor (5) and Pd(OAc) 2 in THF for 1 h.
  • N-heterocyclic carbene metal complex of formula (9) comprising heating the reaction mixture of N-heterocyclic carbene ligand precursor (5), PdCl 2 and potassium carbonate in pyridine in microwave at 150°C for 30 min.
  • the present invention provide an derivatives of N-heterocyclic carbene of formula (III)
  • R H, alkyl, aryl, aralkyl
  • Alkyl and aralkyl can be further substituted
  • Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain heteroatoms like O, N, S;
  • N-heterocyclic carbene of formula (III) are preferably selected form 1 ,1 ,9,9-tetramethyl-l ,2,3,7,8,9-ta ⁇
  • the present invention provide an intermediate of formula (IV) which is used for the preparation of N-heterocyclic carbene of formula (I).
  • R H, alkyl, aryl, aralkyl; substituted Alkyl and substituted aralkyl;
  • Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain heteroatoms like O, N, S;
  • the present invention provide a method of catalytic Suzuki-Miyaura cross-coupling of aryl halides with arylboronic acids using novel N-heterocyclic carbene palladium complex, comprising stirring a solution of arylboronic acids, aryl halides, tripotassium phosphate K 3 P0 4 and N-heterocyclic carbene palladium complex in DMF at room temperature for 2 h.
  • the aryl halides as used herein are preferably selected froml- (4-bromophenyl)ethan- 1 -one, 1 -bromo-4-methoxybenzene,chlorobenzene, 4- chlorophenol,4-bromophenol, 3-bromopyridine,2-bromothiophene,2-bromoaniline.
  • the arylboronic acids as used herein are selected form Phenyl boronic acid, (4-methoxyphenyl)boronic acid,(3-nitrophenyl)boronic acid,naphthalen- 1 -y lboronic acid,(4-(hydroxymethyl)phenyl)boronic acid,4- boronobenzoic acid,(4-acetylphenyl)boronic acid,furan-2-ylboronic acid.
  • the diamine 4 (1.22 g, 5 mmol) was dissolved in triethyl orthofomate (85 mL) and treated with HC1 (0.42 mL,5 mmol). It was heated at 70 °C for 14 h under argon and for 2 h at the same temperature in air. The solution was cooled to room temperature and the salt was precipitated by addition of diethyl ether (50 mL). It was filtered through the Buckner funnel and dried under vacuum to yield 5 (1.25 g, 86%) as a white powder.
  • the benzimidazolium chloride 5 (58 mg, 0.2 mmol) and 60% sodium hydride NaH (8 mg, 0.2 mmol) were suspended in anhydrous THF (6 mL) and stirred at room temperature for 1 h. During this time, the suspension becomes yellow-orange. To this the supension of S 8 (51 mg, 0.2 mol) in anhdrous THF (5 mL) was added drowise to get almost a colourless reaction mixture. After stirring at room temperature for additional 2 h, ice-cold water was added and the reaction mixture was extracted with ethyl acetate (3 x 10 mL).
  • the benzimidazolium chloride 5 (290 mg, 1 mmol) and Pd(OAc) 2 (1 12 mg, 0.5 mmol) were charged in an oven dried two neck round bottom flask equipped with reflux condensor. The whole assembly was flushed with argon and anhydros THF (15 mL) was added to get white suspension. It was then heated at reflux for 1 h; during which color changes to pale grey. It was cooled to room temperature and volitiles were removed on rotavapor. The residue was redissolved in THF (10 mL) and the product was precipitated by addition of pet ether (40 mL). It was filtered through the Whatmann filter paper and dried under vacuum to get 8 (285 mg, 83%) as a light grey solid.
  • the benzimidazolium chloride 5 (100 mg, 0.34 mmol), PdCl 2 (60 mg, 0.34 mmol) and potassium carbonate (190 mg, 1.37 mmol) in pyridine (2.0 mL) were charged in an oven dried microwave vial. It was then heated in microwave at 150°C for 30 min. It was cooled to room temperature and the mixture was filtered through silica gel washing it with dichloromethane (3 mL). The volatiles were removed and the crude product was purified by column chromatography through a small pad of silica gel using dichloromethane as the eluent to yield 9 (145 mg, 80%) as a light yellow solid.

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Abstract

The present invention relates to novel N-heterocyclic carbenes compounds and process of the preparation thereof. The present invention further relates to the use of use of these novel N-heterocyclic carbenes as ligand in the Suzuki-Miyaura cross coupling reactions.

Description

NOVEL N-HETEROCYCLIC CARBENE COMPOUNDS, THEIR
PREPARATION AND USE FIELD OF THE INVENTION:
The present invention relates to novel N-heterocyclic carbine compounds and process of the preparation thereof. More particularly, the present invention relates to novel N- heterocyclic carbenes compounds, their preparation and use of these novel N-heterocyclic carbenes as ligand in the Suzuki-Miyaura cross coupling reactions.
BACKGROUND AND PRIOR ART:
Recently N-heterocyclic carbenes (NHCs) have emerged as an important class of ligands and catalysts because of their several attractive features, and they have thus received significant attention from the scientific community. A transition metal carbene complex is an organometallic compound featuring a divalent carbene organic ligand. Carbene complexes for almost all transition metals have been reported and many reactions utilizing them have been reported. NHCs are generally derived from persistent carbenes which are stable compound of divalent carbon.
Metal complexes with N-heterocyclic carbene (NHC) ligands are widely used in chemistry due to their catalytic properties and applied for olefin metathesis among other reactions. The enhanced application of this type of organometallics has over the last few years also triggered a steadily increasing number of studies in the fields of medicinal chemistry, which take advantage of the fascinating chemical properties of these complexes.
Article titled "Suzuki-Miyaura cross-Coupling reactions mediated by palladium/imidazoliumsalt systems" by GA Grasa et al. published in Organometallics, 2002, 21 (14), pp 2866-2873 reports nucleophilic N-heterocyclic carbenes (NHC) used as ancillary ligands in palladium-mediated Suzuki-Miyaura cross-coupling reactions involving aryl chlorides or aryl triflates with arylboronic acids. The scope of the coupling process using Pd(0) or Pd(II) sources and an imidazolium salt in the presence of a base, Cs2C03, was tested using various substrates. Article titled "A benzimidazole-based N-heterocyclic carbene derived from 1 ,10- phenanthroline" by C Metallinos et al. published in Org. Lett , 2004, 6 (20), pp 3641- 3644 reports a catalytically active palladium-complexed tetracyclic N-heterocyclic carbene (NHC) was prepared in three steps from commercially available 1 , 10- phenanthroline by using a reduction cyclization-deprotonation sequence. The new carbene framework is a prototype for the development of a series of chiral N-heterocyclic carbenes.
1 ,
Figure imgf000003_0001
Article titled "Reduction of substituted 1 ,10-phenanthrolines as a route to rigid chiral benzimidazolylidenes" by C Metallinos et al. published in Tetrahedron, Volume 62, Issue 48, 27 November 2006, Pages 11 145-1 1 157 reports substituted 1, 10-phenanthrolines which are reduced to octahydrophenanthrolines in moderate to good yields with NaBH3CN in acetic acid/methanol. The exact solvent composition is described to avoid the formation of tetrahydrophenanthrolines and N-alkylated by products, and to optimize the formation of octahydrophenanthrolines. Resolution of a racemic reduction product gives an enantiomerically pure C2-symmetric diamine from which the corresponding rigid benzimidazolylidene is prepared, whereas reduction of chiral phenanthrolines derived from bicyclic ketones affords diastereomerically pure diamines, which may also be converted to benzimidazolylidenes.
Figure imgf000003_0002
Article titled "Neutral and cationic iridium(I) complexes bearing chiral phenanthroline- derived benzimidazolylidenes: synthetic, structural, and catalytic studies" by C Metallinos et al. published in Organometallics, 2009, 28 (4), pp 1233-1242 reports a synthesis and characterization of series of neutral and cationic iridium(I) complexes bearing chiral and achiral phenanthroline-derived benzimidazolylidene ligands. Spectroscopic and crystallographic data indicate that the principal plane of the NHC ligand in the achiral complexes is positioned orthogonally with respect to the Ir-Cl or Ir-P bonds, while the planes of NHC ligands in the corresponding chiral complexes are twisted by a torsion angle that depends on the size of the 2,9-substituents. All of the new complexes showed varying degrees of catalytic activity and enantioselectivity toward hydrogenation of acetamidoacrylates, with the best results being achieved using 2,9- diphenyl-substituted (S,S)-20a, which afforded (-)-(R)-methyl 2-acetamidopropanoate (12a) in 97% yield and 81% ee.
Article titled "Preparation of NHC borane complexes by lewis base exchange with amine- and phosphine-boranes" by MM Brahmi el al. published in J Org. Chem. , 2010, 75 (20), pp 6983-6985 reports a versatile new method for the preparation of NHC boranes starting from two stable, readily available reactants— an heterocyclic salt and an amine or phosphine-borane. It uses a Lewis base exchange at boron and provides easy access to new NHC boranes, in particular B-substituted borane ones.
Only the group of Metallinos has reported the synthesis of fused tetracyclic NHCs and showed their application. Considering the importance of NHCs in several important reactions. Therefore there is a need to search for new NHCs with varying structural motifs by using simple and scalable chemistry.
OBJECTIVE OF INVENTION:
The main objective of the present invention is to provide novel N-heterocyclic carbene compounds of formula (I) and process for preparation thereof.
Another objective of the present invention is to provide novel N-heterocyclic carbene metal complexes of formula (II) and process for preparation thereof.
Yet another objective of the present invention is to providea derivatives of novel N- heterocyclic carbene of formula (III) and process for preparation thereof. Still another objective of the present invention is to provide a method of catalytic Suzuki- Miyaura cross-coupling of aryl halides with arylboronic acids using novel N-heterocyclic carbene palladium complex.
SUMMARY OF THE INVENTION:
Accordingly the present invention provides an N-heterocyclic carbene ligand precursor compound comprising a compound of formula (I), metal complexes and derivatives thereof
Figure imgf000005_0001
Formula (I)
Wherein, R is H, alkyl, aryl, aralkyl; substituted alkyl and substituted aralkyl; Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain hetero atoms like O, N, and S.
In an embodiment of the present invention, the process for the preparation of N- heterocyclic carbene ligand precursor comprising the following steps:
a) Adding a solution of l,3-dihydro-2H-benzo[i ]imidazol-2-one 1 in anhydrous DMF to a suspension of (NaH) sodium hydride in anhydrous DMF and stir for 30 min at 0°C followed by addition of a solution of 3,3- dimethylallyl bromide with constant stirring at room temperature for 6.5h to obtain 2;
b) Adding a solution of 2 of step (a)in chlorobenzene to a suspension of (AICI3 ) Aluminium chloride in chlorobenzene followed by stirring at room temperature for 2h to obtain3;
c) Adding a solution of 3 of step (b) in THF to a suspension of Lithium aluminium hydride in THF followed by refluxing for lh which was again heating at reflux with 6 N aqueous HC1 for lh to obtain 4; d) Heating a solution of 4 of step (c) in triethyl orthofomate and HC1 at 80°C for 14 h under argon atmosphere and for 2 h at the same temparature in air to obtain N-heterocyclic carbene ligand precursor;
In still another embodiment of the present invention, the N-heterocyclic carbene metal complex comprising a compound of formula (II)
Figure imgf000006_0001
Formula (II)
Wherein, R is H, alkyl, aiyl, aralkyl; substituted Alkyl and substituted aralkyl; Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain hetero atoms like O, N, S;
M is Pd,
L is ligands L can be carbene having Formula (I) or any heterocycle containing Nitrogen which can be further substituted.
In yet another embodiment of the present invention, the process for the preparation of N- heterocyclic carbene metal complex further comprising refluxing the reaction mixture of N-heterocyclic carbene ligand precursor (5) and Pd(OAc)2 in THF for 1 h to obtainN- heterocyclic carbene metal complex (8), or heating the reaction mixture of N-heterocyclic carbene ligand precursor (5), PdCl2 and potassium carbonate in pyridine in microwave at 150°C for 30 min to obtain N- heterocyclic carbene metal complex (9).
In still another embodiment of the present invention the derivative of N-heterocyclic carbine compound comprising a compound of formula (III) T/IN2014/000804
Figure imgf000007_0001
Formula (III)
Wherein, R is H, alkyl, aryl, aralkyl; substituted alkyl and substituted aralkyl;
Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain hetero atoms like O, N, S;
X is O, S.
In yet another embodiment of the present invention, the derivative of N-heterocyclic carbene compound is selected from selected from l ,l,9,9-tetramethyl- l ,2,3,7,8,9- hexahydro-5H-imidazo[l,5,4,3-/mn][l , 10]phenanthroline-5-thione and 5-^4-boranyl)- l , l ,9,9-tetramethyl- l ,2,3,7,8,9-hexahydro-4- λ 4-imidazo-[3 ,4,5, 1-
Imn] [ 1 , 10]phenanthroline.
In still another embodiment of the present invention,The process for the preparation of derivative of N-heterocyclic carbene compound of formula (III) comprising the step of stirring sodium bis(trimethylsilyl)amide and a suspension of of N-heterocyclic carbene ligand precursor 5 in tetrahydrofuran at -78 °C followed by addition of Borane tetrahydrofuran complex solution (BH3.THF) with constant stirring at room temparation for 5h to obtain 5-( λ 4-boranyl)-l ,l ,9,9-tetramethyl-l ,2,3,7,8,9-hexahydro-4 4-imidazo- [3 ,4,5 , 1 -Imn] [1 ,10]phenanthroline (7).
In yet another embodiment of the present invention,the process for the preparation of derivative of N-heterocyclic carbene compound of formula (III) comprising the steps of a) stirring N-heterocyclic carbene ligand precursor 5 and sodium hydride (NaH) in THF for 1 h at room temparature; b) adding S8in THFfolowed by stirring at room temparature for further additional 2h to obtain 1 ,1,9,9-tetramethyl- 1 ,2,3, 7,8,9-hexahydro-5H- imidazo [ 1 ,5 ,4,3 -lmn] [1 ,10]phenanthroline-5 -thione (6).
In still another embodiment of the present invention, a compound of formula (IV) for preparing N-heterocyclic carbene ligand precursor of formula (I)
Figure imgf000008_0001
Formula (IV)
Wherein, R is H, alkyl, aryl, aralkyl; substituted alkyl and substituted aralkyl; Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain heteroatoms like O, N, S;
In yet another embodiment of the present invention, a method of catalytic Suzuki- Miyaura cross-coupling of aryl halides with aryl boronic acids using novel N- heterocyclic carbenepalladium complex according to any of the previous claims, comprising stirring a solution of aryl boronic acids selected from the group consisting of phenyl boronic acid, (4-methoxyphenyl)boronic acid, (3-nitrophenyl)boronic acid, naphthalen-l-ylboronic acid, (4-(hydroxymethyl)phenyl)boronic acid, 4-boronobenzoic acid, (4-acetylphenyl)boronic acid, furan-2-ylboronic acid; aryl halides selected from the group consisting of l-(4-bromophenyl)ethan-l -one, l-bromo-4- methoxybenzene,chlorobenzene, 4-chlorophenol, 4-bromophenol, 3-bromopyridine, 2- bromothiophene, 2-bromoaniline; tripotassium phosphate K3P04and N-heterocyclic carbene palladium complex in DMF at room temperature for 2 h. In still another aspect, the present invention provides a method of catalytic Suzuki- Miyaura cross-coupling of aryl halides with arylboronic acids using novel N-heterocyclic carbene palladium complexat room temperature with very low catalyst loading.
DETAILED DESCRIPTION OF THE INVENTION:
The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.
In an embodiment, the present invention provides anN-heterocyclic carbene ligand precursor of formula (I)
Figure imgf000009_0001
Formula (I)
Wherein, R is H, alkyl, aryl, aralkyl; substituted alkyl and substituted aralkyl;
Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain heteroatoms like O, N, and S.
In another embodiment, the present invention providea process for the preparation of N- heterocyclic carbene ligand precursor comprising the steps of:
a) Adding a solution of l,3-dihydro-2H-benzo[^imidazol-2-one in anhydrous DMF to a suspension of Sodium hydride NaH in anhydrous DMF and stir for 30 min at 0°C followed by addition of a solution of 3,3- dimethylallyl bromide with constant stirring at room temperature for 6.5h to obtain 2; b) Adding a solution of 2 of step (a)in chlorobenzene to a suspension of aluminium chloride AICI3 in chlorobenzene followed by stirring at room temperature for 2h to obtain3;
c) Adding a solution of 3 of step (b) in THF to a suspension of Lithium aluminium hydride in THF followed by refluxing for lh. which was again heating at reflux with 6 N aqueous HC1 for lh to obtain 4;
d) Heating a solution of 4 of step (c) in triethyl orthofomate and HC1 at 80°C for 14 h under argon atmosphere and for 2 h at the same temparature in air to obtain N-heterocyclic carbene ligand precursor 5;
The process for the preparation of N-heterocyclic carbene ligand precursor is shown below in Scheme- 1 :
Figure imgf000010_0001
Carbenfi precursor
Scheme: 1 In still another embodiment, the present invention provide an N-heterocyclic carbene metal complex comprising a compound of formula (II)
Figure imgf000011_0001
Formula (II)
Wherein, R is H, alkyl, aryl, aralkyl; substituted Alkyl and substituted aralkyl;
Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain heteroatoms like O, N, S;
M is Pd,
L is ligands. L can be carbene having Formula (I) or any heterocycle containing Nitrogen which can be further substituted.
The N-heterocyclic carbene metal complexof formula (II) is selected from following compounds of formula 8 and 9 as shown below:
Figure imgf000011_0002
The process for the preparation of N-heterocyclic carbene metal complex of formula (8) comprising refluxing the reaction mixture of N-heterocyclic carbene ligand precursor (5) and Pd(OAc)2in THF for 1 h.
The process for the preparation of N-heterocyclic carbene metal complex of formula (8) is as shown in scheme 2 below:
Figure imgf000012_0001
Scheme: 2
The process for the preparation of N-heterocyclic carbene metal complex of formula (9) comprising heating the reaction mixture of N-heterocyclic carbene ligand precursor (5), PdCl2 and potassium carbonate in pyridine in microwave at 150°C for 30 min.
The process for the preparation of N-heterocyclic carbene metal complex of formula (9) is as shown i
Figure imgf000012_0002
NHC-Pd complex-ll
9
Scheme: 3
In one embodiment, the present invention provide an derivatives of N-heterocyclic carbene of formula (III)
Figure imgf000012_0003
Formula (III) Wherein, R = H, alkyl, aryl, aralkyl;
Alkyl and aralkyl can be further substituted
Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain heteroatoms like O, N, S;
X = 0, S;
The derivatives of N-heterocyclic carbene of formula (III) are preferably selected form 1 ,1 ,9,9-tetramethyl-l ,2,3,7,8,9-ta^
5-thioneand 5-^4-boranyl)-l ,l,9,9-tetramethyl-l ,2,3,7,8,9-hexahydro-4- 4-imidazo- [3 ,4,5, 1 -Imn] [1 ,10]phenanthroline.
The process for the preparation of 5-( 4-boranyl)-l ,l ,9,9-tetramethyl-l ,2,3,7,8,9- hexahydro-4^4-imidazo-[3,4,5,l-/w«][l ,10]phenanthrolinecomprising the step of stirring sodium bis(trimethylsilyl)amide and a suspension of of N-heterocyclic carbene ligand precursor 5 in tetrahydrofuran at -78 °C followed by addition of borane tetrahydrofuran complex BH3.THF with constatn stirring at room temparation for 5h to obtain 5-(λ4- boranyl)- 1 , 1 ,9,9-tetramethyl- 1 ,2,3 ,7,8,9-hexahydro-4^4-imidazo-[3 ,4,5,1- Imn] [1 , 10]phenanthroline.
The process for the preparation of 5-( 4-boranyl)-l ,l ,9,9-tetramethyl-l ,2,3,7,8,9- he ahydro-4-λ4-imidazo-[3,4,5,l - m«][l ,10]phenanthroline is as shown in scheme 4 below:
Figure imgf000013_0001
Scheme: 4 The process for the preparation of l ,l,9,9-tetramethyl-l ,2,3,7,8,9-hexahydro-5H- imidazo[l,5,4,3-/mn][l,10]phenanthroline-5-thionecomprising the step of:
a) Stirring N-heterocyclic carbene ligand precursor 5 and sodium hydride NaH in THF for 1 h at room temparature;
b) Adding S8in THF followed by stirring at room temparature for further additional 2h to obtain 1,1,9,9-tetramethyl- 1,2,3, 7,8,9-hexahydro-5H- imidazo [1,5,4, 3 -lmn] [1,10] phenanthroline-5 -thione (6) .
The process for the preparation of l,l,9,9-tetramethyl-l,2,3,7,8,9-hexahydro-5H- imidazo[l ,5,4,3-/w«][l ,10]phenanthroline-5-thione is as shown in scheme 5 below:
Figure imgf000014_0001
Scheme: 5
In one embodiment, the present invention provide an intermediate of formula (IV) which is used for the preparation of N-heterocyclic carbene of formula (I).
Figure imgf000014_0002
Formula (IV)
Wherein, R = H, alkyl, aryl, aralkyl; substituted Alkyl and substituted aralkyl;
Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain heteroatoms like O, N, S; In one embodiment, the present invention provide a method of catalytic Suzuki-Miyaura cross-coupling of aryl halides with arylboronic acids using novel N-heterocyclic carbene palladium complex, comprising stirring a solution of arylboronic acids, aryl halides, tripotassium phosphate K3P04 and N-heterocyclic carbene palladium complex in DMF at room temperature for 2 h.
In preferred embodiment, the aryl halides as used herein are preferably selected froml- (4-bromophenyl)ethan- 1 -one, 1 -bromo-4-methoxybenzene,chlorobenzene, 4- chlorophenol,4-bromophenol, 3-bromopyridine,2-bromothiophene,2-bromoaniline.
In another preferred embodiment, the arylboronic acids as used herein are selected form Phenyl boronic acid, (4-methoxyphenyl)boronic acid,(3-nitrophenyl)boronic acid,naphthalen- 1 -y lboronic acid,(4-(hydroxymethyl)phenyl)boronic acid,4- boronobenzoic acid,(4-acetylphenyl)boronic acid,furan-2-ylboronic acid.
The use of NHC-Pd complex (8) in catalysis of Suzuki-Miyaura coupling reaction is shown below in Scheme 6:
Figure imgf000015_0001
The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention. Examples:
Example 1: Synthesis of l,3-bis(3-methyIbut-2-en-l-yl)-l,3-dihydro-2H- benzo[rf]imidazol-2-one (2) :
Figure imgf000016_0001
2
In an oven dried 100 mL side armed flask, a suspension of 60% NaH (2.0 g, 50 mmol) in anhydrous DMF (10 mL) was cooled to 0°C. The solution of l,3-dihydro-2H- benzo[<sf]imidazol-2-one 1 (2.68 g, 20 mmol) in anhydrous DMF (15 mL) was added drop wise to it. After vigorous stirring for 30 min at the same temperature; the solution of 90% 3,3-dimethylallyl bromide (5.3 mL, 45 mmol) was added and the reaction mass was allowed to warm to room temperature. Following the completion of reaction (6.5 h) by TLC, it was quenched with ice cold solution of ammonium chloride and extracted with ethyl acetate (3 x 30 mL). The organic layer was washed with brine (30 mL), dried over anhydrous Na2S04 and concentrated. The residue obtained was purified by column chromatography using ethyl acetate: petroleum ether (1 :5) as the eluent to get 2 (4.42 g,
82%) as white solid. Mp 74-75°C; R (15% ethyl acetate/ hexane): 0.2; IR (Nujol) v/cm" ':2926, 2852, 1670, 1632; 1H NMR (400 MHz, CDC13) 8: 1.72 (s, 6H), 1.85 (s, 6H), 4.48 (d, J = 6.71 Hz, 4H), 5.27 (dd, J = 6.72 Hz, 2H), 6.94 (dd, J = 5.80, 3.35 Hz, 2H), 7.05 (dd, J = 5.80, 3.35 Hz, 2H); l3C NMR (100 MHz, CDC13) 6:28.4, 31.7, 36.5, 37.5, 115.4, 123.6, 125.8, 152.7; HRMS (ESI+) forC17H22N2O;Calculated:271.1810 [M+H]+;Found:271.1805. Example 2: Synthesis of l,l,9,9-tetramethyl-l,2,3>7,8,9-hexahydro-5H-Imidazo
[1,5,4,3/wwi] [l,10]phenanthrolin-5-one (3) :
Figure imgf000017_0001
3
To the ice cold suspension of Aluminum chloride A1C13 (5.6 g, 42 mol) in anhydrous chlorobenzene (15 mL), the solution of 2 (3.78 g, 14 mmol) in the same solvent (15 mL) was added. The wine red solution was stirred at room temperature and monitored by TLC. After completion of the reaction (2 h), it was poured on ice cold water (20 mL) containing IN HC1 (10 mL). White emulsion was extracted with ethyl acetate (3 * 25 mL) and organic layer was washed with saturated NaHC03 (30 mL) followed by brine (30 mL). It was dried over anhydrous Na2S04 and concentrated to get crude product, which was purified by column chromatography using ethyl acetate: pet ether (1 :3) as the eluent to result in 3 (2.8 g, 74%) as white solid. Mp 197-198°C; R/ (20% ethyl acetate/ hexane): 0.2;IR (Nujol) v/crn ' :2948, 2922, 2856, 1712, 1628, 1 134; Ή NMR (400 MHz, CDC13) δ: 1.34 (s, 12H), 1.89 (t, J = 5.80 Hz, 4H), 3.89 (t, J= 5.80 Hz, 4H), 6.89 (s, 2H); 13C NMR (100 MHz, CDC13) δ: 28.4, 31.8, 36.5, 37.6, 1 15.1 , 123.6, 125.8, 152.7; HRMS (ESI+) forCi7H22N2O;Calculated:271.1810 [M+H]+;Found:271.1805.
Example 3: Synthsis of 4,4,7,7-tetramethyl-l,2,3,4,7,8,9,10-octahydro-l,10- phenanthroline (4):
Figure imgf000017_0002
4
The solution of 3 (2.7 g, 10 mmol)in anhydrousTHF(30 mL) was dropwise added to the ice-cold suspension of 80% Lithium aluminium hydride (2.38 g, 50 mmol) in THF. The reaction mass was refluxed and monitored by TLC (1 h). The reaction mass was cooled to 0 °C and quinched by causious addition of cold water followed by NaOH. The white precipitate was filtered off and the filtrate and washings were dried over anhydrous Na2S04. The evaporation of solvent resulted in white solid which was dissolved in 6N HC1 (30 mL) and refluxed for lh. After cooling to room temperature, the reaction mass was washed with diethyl ether (30 mL) and aqueous layer was basicified with NaOH up to pH 1 1. It was extracted with ethyl acetate (3 χ 20 mL) and organic layer was washed with brine (30 mL). It was dried over anhydrous Na2S04 and concentrated to get crude product, which was purified by column chromatography using ethyl acetate: pet ether (1 :4) as the eluent to get 4 (1.42 g, 59%) as light red solid. Mp 136-137°C; R (15% ethyl acetate/ hexane): 0.3; IR (Nujol) v/cm'':3409, 3348, 3298, 2958, 2922, 1608, 1568; Ή NMR 400 MHz, CDC13) δ: 1.25 (s, 12H), 1.69 (t, J = 5.31 Hz, 4H), 3.26 (t, J = 5.81 Hz, 4H), 6.65 (s, 2H); 13C NMR ( 100 MHz, CDC13) δ: 31.8, 32.4, 38.9, 39.6, 1 17.1, 129.8, 132.3; HRMS (ESI+) forC,6H24N2;Calculated:245.2012 [M+H]+;Found:245.2006.
Example 4: Synthsis ofl,l,9,9-tetramethyl-l,2,3,7,8,9-hexahydroimidazo[l,5,4,3- Imn][l,10]phenanthrolin-4-ium chloride (5):
Figure imgf000018_0001
5
The diamine 4 (1.22 g, 5 mmol) was dissolved in triethyl orthofomate (85 mL) and treated with HC1 (0.42 mL,5 mmol). It was heated at 70 °C for 14 h under argon and for 2 h at the same temperature in air. The solution was cooled to room temperature and the salt was precipitated by addition of diethyl ether (50 mL). It was filtered through the Buckner funnel and dried under vacuum to yield 5 (1.25 g, 86%) as a white powder. Mp
> 295°C; IR (Nujol) v/cm"' :3323, 3242, 3115, 2953, 1641, 1623; 1H NMR (200 MHz, CDCI3) δ: 1.44 (s, 12H), 2.14 (t, J = 5.95 Hz, 4H), 4.76 (t, J= 5.94 Hz, 4H), 7.36 (s, 2H), 1 1.07 (s, 1H); 13C NMR (55 MHz, CDCI3) 6:28.0, 31.9, 37.3, 42.6, 121.2, 126.3, 131.6, 138.8; HRMS (ESI+) forC17H22ClN2;Calculated:255.1856 [M-Cl]+;Found:255.1853. Example 5: Synthsis of l,l,9,9-tetramethyl-l,2,3,7,8,9-hexahydro-5H- imidazo[l,5,4,3-//M«][l,10]phenanthroIine-5-thione (6):
Figure imgf000019_0001
6
The benzimidazolium chloride 5 (58 mg, 0.2 mmol) and 60% sodium hydride NaH (8 mg, 0.2 mmol) were suspended in anhydrous THF (6 mL) and stirred at room temperature for 1 h. During this time, the suspension becomes yellow-orange. To this the supension of S8 (51 mg, 0.2 mol) in anhdrous THF (5 mL) was added drowise to get almost a colourless reaction mixture. After stirring at room temperature for additional 2 h, ice-cold water was added and the reaction mixture was extracted with ethyl acetate (3 x 10 mL). The organic layer was washed with brine (5 mL) and dried over anhydrous Na2S04. Evaporation of solvent, followed by colum chromatographic purification of the crude product using ethyl acetate: petroleum ether (1 :4) as the eluent yielded 6(45 mg,
77%) as white solid. Mp 236-237°C; R/ (15% ethyl acetate/ hexane): 0.2; IR (Nujol) v/cm-':3018, 2963, 3298, 2958, 2922, 1608, 1568; 1H NMR (500 MHz, CDC13) δ: 1.36 (s, 12H), 1.99 (t, J = 5.78 Hz, 4H), 4.15 (t, J- 5.80 Hz, 4H), 7.01 (s, 2H); 13C NMR (125 MHz, CDC13) δ: 28.3, 32.0, 37.7, 39.3, 1 17.1, 126.9, 127.2, 165.3; HRMS (ESI+) forC17H22N2S;Calculated:287.1576 [M+H]+;Found:287.1572.
Example 6: Synthesis of 5-(i(4-boranyl)-l,l,9,9-tetramethyl-l,2,3,7,8,9-hexahydro-4 4-imidazo-[3,4,5,l-//M/i][l,10]phenanthroline (7) :
Figure imgf000019_0002
7 In an oven dried 25 mL two neck round bottom flask, the suspension of benzimidazolium chloride 5 (290 mg, 1 mmol) in anhydrous THF (10 mL) was cooled to -78°C. To this, 1 M solution of Sodium bis(trimethylsilyl)amide (NaHMDS) (1.0 mL) was added dropise and stirring continued at the same temperature for 1 h. The 1 M solution of Borane tetrahydrofuran complex solution (BH3.THF) (1.0 mL, 1 mmol) was then added dropwise and the reaction mass was slowly warmed to room temperature and stirred for additional 4h. The volitiles were removed on rotavapor and the crude product was purified by column chromatograpy through a small pad of silicagel using DCM as the eluent to yield 7 (128 mg, 48%) as a reddish solid. Mp 183-185°C; IR (Nujol) v/cm_1:3024, 2964, 1687, 1656, 1504; Ή NMR (400 MHz, CDC13) δ: 1.34 (s, 12H), 1.80 (t, J = 5.77 Hz, 4H), 3.89 (t, J = 6.02 Hz, 4H), 6.89 (s, 2H); 13C NMR (100 MHz, CDC13) δ: 28.4, 31.8, 36.5, 37.6, 1 15.4, 123.6, 125.8,152.7; Elemental analysis: C17H25BN2 requires: C, 76.13; H, 9.40; N, 10.44; found: C, 76.17; H, 9.35; N, 10.26 %
Example 7: Synthesis of NH -Palladium complex I (8) :
Figure imgf000020_0001
8
The benzimidazolium chloride 5 (290 mg, 1 mmol) and Pd(OAc)2 (1 12 mg, 0.5 mmol) were charged in an oven dried two neck round bottom flask equipped with reflux condensor. The whole assembly was flushed with argon and anhydros THF (15 mL) was added to get white suspension. It was then heated at reflux for 1 h; during which color changes to pale grey. It was cooled to room temperature and volitiles were removed on rotavapor. The residue was redissolved in THF (10 mL) and the product was precipitated by addition of pet ether (40 mL). It was filtered through the Whatmann filter paper and dried under vacuum to get 8 (285 mg, 83%) as a light grey solid. Compoud data indicates mixture of isomers. Mp 190°C (with decomposion); IR (Nujol) v/cm"':3014, 2974, 1596, 1475, 1403; 1H NMR (400 MHz, CDCI3) δ: 1.30-1.4.(m, 24H), 1.92 ( s, 4H), 2.09 ( s, 4H), 4.07 ( s, 4H), 4.93 ( s, 4H), 7.06 (s, 4H); 1JC NMR (100 MHz, CDC13) δ: 23.7, 28.4, 31.8, 43.1, 129.3, 147.5, 167.8, 182.7; Elemental analysis: C34H 4CI2N4PCI requires: C, 59.52; H, 6.46; N, 8.17; found: C, 59.22; H, 6.17; N, 8.13 %
Example 8: Synthesis of NHC-Palladium complex II (9):
Figure imgf000021_0001
NHC-Pd complex-ll
9
The benzimidazolium chloride 5 (100 mg, 0.34 mmol), PdCl2 (60 mg, 0.34 mmol) and potassium carbonate (190 mg, 1.37 mmol) in pyridine (2.0 mL) were charged in an oven dried microwave vial. It was then heated in microwave at 150°C for 30 min. It was cooled to room temperature and the mixture was filtered through silica gel washing it with dichloromethane (3 mL). The volatiles were removed and the crude product was purified by column chromatography through a small pad of silica gel using dichloromethane as the eluent to yield 9 (145 mg, 80%) as a light yellow solid. Mp 175 °C (with decomposition); IR (Nujol) v/cm-1 : 3014, 2915, 1596, 1491, 1350; 1H NMR (400 MHz, CDC13) δ: 9.03 (dd, J = 6.60, 1.71 Hz, 2H), 7.81 (tt, J = 7.58, 1.47 Hz, 1H), 7.40 (ddd, J = 7.58, 6.36, 1.47 Hz, 2H), 7.04 (s, 2H), 4.78 (t, J = 5.87, 4H), 2.10 (t, J - 6.12, 4H), 1.39 (s, 12H); 13C NMR (100 MHz, CDC13) 8: 155.1, 151.2, 138.0, 129.6, 128.9, 124.5, 1 17.6, 42.9, 38.1, 31.9, 28.4.Elemental analysis: C22H27Cl2N3Pd requires: C, 51.73; H, 5.33; N, 8.23; found: C, 51.36; H, 5.04; N, 8.02 %.
Crystallographic data for 9
(C22H27Ci2N3Pd): = 510.77, Crystal dimensions 0.68 x 0.32 x 0.1 1 mm3, triclinic, space group P-l a = 5.6847(6), b = 14.0640(14), c = 14.3961(14) A, □ = 108.211(4)°, □ = 95.732(4)°,□ = 95.371(4)°, V = 1078.32(19)A3, Z = 2, D caicd = 1.573 gcm-3, ^ (MO- D) = 1.121 mm-i, F(000) = 520, 2C = 50.00D , T= 150(2) K, 17520 reflections collected, 3781 unique reflections (Rim=0.0214), 3732 observed (/ > 2D (/)) reflections, 258 refined parameters, R value 0.0198, wR2 = 0.504, (all data R = 0.0202, wR2 = 0.0507), S = 1.149, minimum and maximum transmission 0.516 and 0.887; maximum and minimum residual electron densities +0.44 and -0.37 e A-3. All the H-atoms were placed in geometrically idealized position (C-H = 0.95 A for the phenyl H-atom, C-H = 0.99 A for the methylene H- atom and C-H = 0.98 A for the methyl H-atom) and constrained to ride on their parent atoms [ £/iso(H) = 1.2i/eq(C) for the phenyl and methylene groups and £/iso(H) = 1.5 Ueq(C) for the methyl group].
Figure imgf000022_0001
Example 9:Procedure for the conventional Suzuki-Miyaura cross-coupling reaction:
The 10 mL round bottom flask was charged with phenylboronic acid (122 mg, 1 mmol), 4-bromoacetophenone (199 mg, 1 mmol), tripotassium phosphate K3PO4 (424 mg, 2 mmol) and palladium complex 8 (3.5 mg, 0.005 mmol) under argon. DMF (2.0 mL) was added to form the white suspension which was stirred vigorously at room temperature and monitored by TLC for the consumption of 4-bromoacetophenone. The reaction mass turned yellow-red suspension after 1 h. After completion of the reaction (2 h), ice cold water was added to the reaction mass and it was extracted with ethyl acetate (3 χ 10 mL). The organic layer was washed with saturated NaHC03 (10 mL) and brine (10 mL) and dried over anhydrous Na2S04. The crude product was purified by column chromatography to yield 10 (185 mg, 94%) as white solid. Mp 121-123°C. 1H NMR (CDCI3, 200 MHz) δ: 8.05 (d, J = 8.40 Hz, 2H), 7.57-7.69 (m, 4H), 7.35-7.48 (m, 3H), 2.64 (s, 3H). Advantages of invention:
1. Novel N-Heterocyclic Carbene (NHC)
2. First and general synthesis of this kind NHC
3. Demonstrated the utility of this ligand in Suzuki-Miyaura coupling reaction through Pd complex under mild conditions.
4. It may be useful as catalysts or reagents in many transformations

Claims

We Claim,
1. An N-heterocyclic carbene ligand precursor compound comprising a compound of formula (I), metal com lexes and derivatives thereof
Figure imgf000024_0001
Formula (I)
Wherein, R is H, alkyl, aryl, aralkyl; substituted alkyl and substituted aralkyl; Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain hetero atoms like O, N, and S.
2. A process for the preparation of N-heterocyclic carbene ligand precursor according to claim 1 , comprising the following steps:
e) adding a solution of l,3-dihydro-2H-benzo[i ]imidazol-2-one 1 in anhydrous DMF to a suspension of sodium hydride NaH in anhydrous DMF and stir for 30 min at 0°C followed by addition of a solution of 3,3- dime thy lallyl bromide with constant stirring at room temperature for 6.5 h to obtain 2;
f) adding a solution of 2 of step (a)in chlorobenzene to a suspension of aluminium chloride A1C13 in chlorobenzene followed by stirring at room temperature for 2h to obtain3;
g) adding a solution of 3 of step (b) in THF to a suspension of Lithium aluminium hydride in THF followed by refluxing for lh. which was again heating at reflux with 6 N aqueous HC1 for lh to obtain 4; h) heating a solution of 4 of step (c) in triethyl orthofomate and HC1 at 70°C for 14 h under argon atmosphere and for 2 h at the same temparature in air to obtain N-heterocyclic carbene ligand precursor;
3. The N-heterocyclic carbene ligand precursor compound as claimed in claim 1, wherein the N-heterocyclic carbene metal complex comprising a compound of formula (II)
Figure imgf000025_0001
Formula (II)
Wherein, R is H, alkyl, aryl, aralkyl; substituted Alkyl and substituted aralkyl; Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain hetero atoms like O, N, S;
M isPd,
L is ligands. L can be carbene having Formula (I) or any heterocycle containing Nitrogen which can be further substituted.
4. The process for the preparation of N-heterocyclic carbene metal complex as claimed in claim 3 further comprising refluxing the reaction mixture of N- heterocyclic carbene ligand precursor (5) and Pd(OAc)2in THF for 1 h to obtain N-heterocyclic carbene metal complex (8),
or heating the reaction mixture of N-heterocyclic carbene ligand precursor (5), PdCl2 and potassium carbonate in pyridine in microwave at 150°C for 30 min to obtain N-heterocyclic carbene metal complex (9).
5. The N-heterocyclic carbene ligand precursor compound as claimed in claim 1 wherein the derivative of N-heterocyclic carbene comprising a compound of formula (III)
Figure imgf000025_0002
Formula (III)
Wherein, R is H, alkyl, aryl, aralkyl; substituted alkyl and substituted aralkyl; Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain hetero atoms like O, N, S;
X is O, S;
6. The derivative of N-heterocyclic carbene comprising a compound of formula (III) according to claim 5, wherein the derivative is selected from selected from l , l ,9,9-tetramethyl-l ,2,3,7,8,9-hexahydro-5H-imidazo[l ,5,4,3-
Imn] [1 , 10]phenanthroline-5-thione and 5-^4-boranyl)- 1 , 1 ,9,9-tetramethyl- l ,2,3,7,8,9-hexahydro-4- λ 4-imidazo-[3,4,5,l-/m«][l ,10]phenanthroline.
7. The process for the preparation of derivative of N-heterocyclic carbene compound of formula (III) as claimed in claim 6, wherein the process comprising the step of stirring sodium bis(trimethylsilyl)amide and a suspension of of N-heterocyclic carbene ligand precursor 5 in tetrahydrofuran at -78 °C followed by addition of BH3.THF with constant stirring at room temparation for 4h to obtain 5-( λ 4-boranyl)-l, l ,9,9-tetramethyl-l ,2,3,7,8,9- hexahydro-4 λ4-imidazo-[3,4,5,l- /w«][l ,10]phenanthroline (7).
8. The process for the preparation of derivative of N-heterocyclic carbene compound of formula (III) as claimed in claim 6, wherein the process comprising the step of
c) stirring N-heterocyclic carbene ligand precursor 5 and sodium hydride NaH in THF for 1 h at room temparature;
d) adding S8in THFfolowed by stirring at room temparature for further additional 2h to obtain l ,l ,9,9-tetramethyl-l ,2,3,7,8,9-hexahydro-5H- imidazo[ 1 ,5 ,4,3-lmn] [1 , 10]phenanthroline-5-thione (6).
9. A compound of formula (IV) for preparing N-heterocyclic carbene ligand precursor of formula (I) accordin to claim 1 ,
Figure imgf000026_0001
Formula (IV) Wherein, R is H, alkyl, aryl, aralkyl; substituted alkyl and substituted aralkyl;
Two R groups on same carbon or adjacent carbons can form a cyclic 3-8 membered ring which additionally may contain heteroatoms like O, N, S;
10. A method of catalytic Suzuki-Miyaura cross-coupling of aryl halides with aryl boronic acids using novel N-heterocyclic carbene palladium complex according to any of the previous claims, comprising stirring a solution of aryl boronic acids selected from the group consisting of phenyl boronic acid, (4- methoxyphenyl)boronic acid, (3-nitrophenyl)boronic acid, naphthalen-1- ylboronic acid, (4-(hydroxymethyl)phenyl)boronic acid, 4-boronobenzoic acid, (4-acetylphenyl)boronicacid, furan-2-ylboronic acid; aryl halides selected from the group consisting of l-(4-bromophenyl)ethan-l-one, l-bromo-4- methoxybenzene,chlorobenzene, 4-chlorophenol, 4-bromophenol, 3- bromopyridine, 2-bromothiophene, 2-bromoaniline; tripotassium phosphate 3P04 and N-heterocyclic carbene palladium complex in DMF at room temperature for 2 h.
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CN115448809A (en) * 2022-10-18 2022-12-09 陕西师范大学 Method for synthesizing diaryl compound under catalysis of triazine carbene palladium
CN115536817A (en) * 2022-09-30 2022-12-30 武汉工程大学 A class of naphthyl substituted asymmetric metal catalysts and their preparation and application
CN118834244A (en) * 2024-06-20 2024-10-25 常州大学 N-heterocyclic carbene-Schiff base type Csp2^Nsp2Bidentate ring palladium complex and synthetic method and application thereof

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CN106008946A (en) * 2016-05-30 2016-10-12 青岛科技大学 Preparation method and application of N-heterocyclic carbene metal aluminum compound
CN110483582A (en) * 2019-09-11 2019-11-22 陕西师范大学 Azepine Cabbeen palladium complex crystal and its synthetic method and preparing the application in amide compound
CN110483582B (en) * 2019-09-11 2023-02-10 陕西师范大学 Aza-carbene-palladium complex crystal, synthesis method thereof and application thereof in preparing amide compound
CN113024611A (en) * 2021-03-16 2021-06-25 上海理工大学 Novel N-heterocyclic carbene cyclic palladium compound and preparation method and application thereof
CN114702449A (en) * 2022-04-01 2022-07-05 西北大学 Synthetic method of N-heterocyclic carbene fluorescent free radical compound
CN115536817A (en) * 2022-09-30 2022-12-30 武汉工程大学 A class of naphthyl substituted asymmetric metal catalysts and their preparation and application
CN115448809A (en) * 2022-10-18 2022-12-09 陕西师范大学 Method for synthesizing diaryl compound under catalysis of triazine carbene palladium
CN115448809B (en) * 2022-10-18 2023-09-19 陕西师范大学 A method for synthesizing diaryl compounds using triazinecarbene palladium catalysis
CN118834244A (en) * 2024-06-20 2024-10-25 常州大学 N-heterocyclic carbene-Schiff base type Csp2^Nsp2Bidentate ring palladium complex and synthetic method and application thereof

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