Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[C:7]2[CH:8]=[CH:9][S:10][C:6]=2[C:5](=[S:11])[N:4]=[C:3]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[I:18][CH3:19]>>[I-:18].[CH3:1][N+:2]1[C:7]2[CH:8]=[CH:9][S:10][C:6]=2[C:5]([S:11][CH3:19])=[N:4][C:3]=1[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CI
Reactant: Cn1c(-c2ccccc2)nc(=S)c2sccc21
Product: CSc1nc(-c2ccccc2)[n+](C)c2ccsc12
Product: [I-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
500 mg 1-Methyl-2-phenyl-1H-thieno(3,2-d)pyrimidine-4-thione was slowly added to 5 ml (80 mmol) iodomethane at 0° C. and stirred for 1 h at room temperature. The solution was filtrated and the residue washed with dichloromethane.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH2:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].ClC(Cl)(Cl)[CH:16](O)[OH:17].C(Cl)(Cl)Cl>O>[CH:16]([NH:13][CH2:12][CH2:11][C:5]1[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=1)=[O:17]
Reactant: OC(O)C(Cl)(Cl)Cl
Reactant: COc1ccc(CCN)cc1OC
Solvent: ClC(Cl)Cl
Solvent: O
Product: COc1ccc(CCNC=O)cc1OC
Temperature: 120 °C
Reaction time: 0.33 h

Procedure:
First, 2-(3,4-dimethoxyphenyl)-ethylamine (181.2 g, 1 mol) and chloral hydrate (181 g, 1.1 mol) are mixed together and heated to 120° C., with stirring, for 20 minutes and any volatile components (chloroform and water) are eliminated in a water jet vacuum at an oil bath temperature of 140° C. An oil is left behind which is further processed without any purification.
Reaction SMILES: [O:1]=[C:2]1[N:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][N:12]=2)=[CH:7][CH:3]1C(O)=O.N1C2C(=CC=CC=2)C=CC=1>CCOCC>[N:14]1[CH:15]=[CH:16][C:11]([C:8]2[CH:7]=[CH:3][C:2](=[O:1])[NH:10][CH:9]=2)=[N:12][CH:13]=1
Reactant: O=C(O)C1C=C(c2ccncn2)C=NC1=O
Solvent: CCOCC
Solvent: c1ccc2ncccc2c1
Product: O=c1ccc(-c2ccncn2)c[nH]1
Reaction time: 0.5 h

Procedure:
90.8 g of 2-oxo-5-(4-pyrimidinyl)nicotinic acid was mixed with 900 ml of quinoline and then heated to reflux overnight. The mixture was then cooled and poured into 1800 ml of anhydrous ether. The mixture was stirred for 30 minutes, filtered and the solid was washed with 2 liters of ether. The solid was dried, recrystallized in 100 ml of hot dimethylformamide and dried to yield 5-(4-pyrimidyl)-2(1H)pyridone m.p. 250° C.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]3[N:13]([N:17]=[C:18]([NH2:20])[N:19]=3)[CH:14]=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].Br[C:22]1[CH:23]=[C:24]([NH:28][C:29](=[O:31])[CH3:30])[CH:25]=[CH:26][CH:27]=1>>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]3[N:13]([N:17]=[C:18]([NH:20][C:22]4[CH:23]=[C:24]([NH:28][C:29](=[O:31])[CH3:30])[CH:25]=[CH:26][CH:27]=4)[N:19]=3)[CH:14]=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)(=[O:3])=[O:4]
Reactant: CC(=O)Nc1cccc(Br)c1
Reactant: CS(=O)(=O)c1ccc(-c2cccn3nc(N)nc23)cc1
Product: CC(=O)Nc1cccc(Nc2nc3c(-c4ccc(S(C)(=O)=O)cc4)cccn3n2)c1

Procedure:
N-{3-[8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-phenyl}-acetamide was prepared from 8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (70.6 mg, 0.245 mmol) and N-(3-bromo-phenyl)-acetamide (52.4 mg, 0.245 mmol) in a manner analogous to Example 2d. Product isolated as a white lyophilate (19 mg, 18%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.89 (s, 1H), 9.77 (s, 1H), 8.83 (d, J=6.5 Hz, 1H), 8.46 (d, J=8.4 Hz, 2H), 8.07 (d, J=8.6 Hz, 2H), 7.99-7.95 (m, 2H), 7.40 (d, J=8.0 Hz, 1H), 7.21-7.12 (m, 3H), 3.29 (s, 3H), 2.06 (s, 3H). MS=422 (MH)+.
Reaction SMILES: [CH2:1]([C:5]1[NH:6][C:7]2[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=2[N:9]=1)[CH2:2][CH2:3][CH3:4].Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:23]([C:28]([O:30][CH3:31])=[O:29])=[CH:24][CH:25]=[CH:26][CH:27]=2)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+].ClCCl>CN(C)C=O>[CH2:1]([C:5]1[N:6]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[C:23]([C:28]([O:30][CH3:31])=[O:29])=[CH:24][CH:25]=[CH:26][CH:27]=3)=[CH:18][CH:17]=2)[C:7]2[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=2[N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: COC(=O)c1ccccc1-c1ccc(CBr)cc1
Reactant: CCCCc1nc2ccccc2[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CCCCc1nc2ccccc2n1Cc1ccc(-c2ccccc2C(=O)OC)cc1
Yield: 45.4 %

Procedure:
A mixture of 2-butylbenzimidazole (2.6 g), the bromomethyl compound (C) (5.0 g) and potassium carbonate (1.55 g) in N,N-dimethylformamide (DMF) (40 ml) was heated at 100° C. for 3 hours. Dichloromethane (200 ml) was added and insoluble material was removed by filtration. The filtrate was concentrated and the residue purified by flash chromatography, eluting with triethylamine/ethyl acetate/hexane (1:40:60 v/v), to give methyl 4'-[2-butyl-1H-benzimidazol-1-yl)methyl]biphenyl-2-carboxylate (A) as a clear oil (2.7 g); NMR (CDCl3): 0.95(t,3H), 1.45(m,2H), 2.9(t,2H), 3.6(s,3H), 5.4(s,2H), 7.2(d,2H), 7.2-7.6 (complex m,3H), 7.8(m,2H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[CH2:7][NH:8]N1C=CC=CC1N.Cl.[Cl:17][CH2:18][C:19](=[NH:23])OCC.[C:24](O)(=O)[CH3:25]>>[Cl:17][CH2:18][C:19]1[N:8]([CH2:7][C:2]2[CH:3]=[N:4][CH:5]=[CH:6][N:1]=2)[C:2]2=[N:1][CH:6]=[CH:24][CH:25]=[C:3]2[N:23]=1
Reactant: CCOC(=N)CCl
Reactant: CC(=O)O
Reactant: NC1C=CC=CN1NCc1cnccn1
Agent: Cl
Product: ClCc1nc2cccnc2n1Cc1cnccn1
Temperature: 25 °C
Reaction time: 21 h
Yield: 100 %

Procedure:
To a stirred solution of 3.6 parts of N-(2-pyrazinylmethyl)-1,2-pyridinediamine in 30 parts of acetic acid were added 4.24 parts of ethyl 2-chloroethanimidate monohydrochloride. The reaction mixture was stirred first for 21 hours at room temperature and then for a few minutes at 90° C. The whole was evaporated and the residue was taken up in water. The aqueous layer was treated with sodium carbonate and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated, yielding 3.9 parts (100%) of 2-(chloromethyl)-3-(2-pyrazinylmethyl)-3H-imidazo[4,5-b]pyridine as a residue (int. 29).
Reaction SMILES: [F:1][C:2]1[CH:19]=[CH:18][C:5](/[CH:6]=[N:7]/[C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH2:10][O:11][C:12]3=[O:17])=[CH:4][CH:3]=1.[CH3:20][N:21]1[CH:25]=[N:24][N:23]=[C:22]1[CH:26]=O.[O-:28][CH2:29][CH3:30].[Na+].C(O)C>C(OCC)(=O)CC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]2[CH:26]([C:22]3[N:21]([CH3:20])[CH:25]=[N:24][N:23]=3)[C:29](=[O:28])[C:30]3[C:13]([C:12]([O:11][CH2:10][CH3:9])=[O:17])=[CH:14][CH:15]=[CH:16][C:8]=3[NH:7]2)=[CH:18][CH:19]=1
Reactant: Cn1cnnc1C=O
Reactant: CC[O-]
Reactant: O=C1OCc2c(/N=C/c3ccc(F)cc3)cccc21
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(=O)CC
Product: CCOC(=O)c1cccc2c1C(=O)C(c1nncn1C)C(c1ccc(F)cc1)N2
Temperature: 0 °C
Reaction time: 2.5 h
Yield: 11 %

Procedure:
A mixture of compound (E)-4-(4-fluorobenzylideneamino)isobenzofuran-1(3H)-one (690 mg, 2.7 mmol) and 4-methyl-4H-1,2,4-triazole-3-carbaldehyde (300 mg, 2.7 mmol) in ethyl propionate (20 mL) was cooled to 0° C. Then a solution of sodium ethoxide in ethanol [sodium (250 mg, 10.8 mmol) in ethanol (10 mL)] was added dropwise. After the addition the mixture was stirred at room temperature for 2.5 hr, then was quenched with water (20 mL) and solvent was removed in vacuum. The residue was dissolved in water and extracted with ethyl acetate three times, washed with water and brine, and then evaporated to give the crude product, which was purified by chromatography to obtain a yellow solid (120 mg, yield 11%). LC-MS (ESI) m/z: 395 (M+1)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:14](O)[CH2:15][CH2:16][CH:17]([C:19]2[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=2)[OH:18])[CH:6]=[C:7]([I:13])[C:8]=1[O:9][CH2:10][CH2:11][OH:12].FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@H:14]2[CH2:15][CH2:16][C@H:17]([C:19]3[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=3)[O:18]2)[CH:6]=[C:7]([I:13])[C:8]=1[O:9][CH2:10][CH2:11][OH:12]
Reactant: COc1cc(C(O)CCC(O)c2cc(OC)c(OC)c(OC)c2)cc(I)c1OCCO
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: COc1cc([C@H]2CC[C@H](c3cc(OC)c(OC)c(OC)c3)O2)cc(I)c1OCCO
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To 1-(3-methoxy-4-hydroxyethoxy-5-iodophenyl)-4-(3,4,5-trimethoxyphenyl)-1,4-butanediol (11.8 g, 21.5 mmol) in chloroform (100 mL) at 0° C. was added dropwise trifluoroacetic acid (9.82 g, 86.1 mmol) in chloroform (100 mL) over 30 minutes. The solution was stirred at 0° C. for 2 hours and then at room temperature for 1 hour. The reaction mixture was quenched with 1N NaOH and chloroform (100 mL) was added. The organic layer was washed with 1N NaOH solution, water and saturated NaCl solution, and then dried over MgSO4, filtered and evaporated in vacuo to an oil which was a cis and trans mixture. The trans isomer was isolated by column chromatography (silica, 1:1 hexane/ethyl acetate) (4.7 g, 41.4%) as the faster eluting isomer. 1H NMR (CDCl3) δ1.99 (m, 2 H); 2.47 (m, 2 H); 3.83 (t, 2 H); 3.84 (s, 3 H); 3.87 (s, 3 H); 3.89 (s, 6 H); 4.16 (t, 2 H); 5.18 (m, 2 H); 6.62 (s, 2 H); 6.96 (d, 1 H); 7.39 (d, 1 H).
Reaction SMILES: [OH:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:11](=[O:13])[CH3:12].[F:14][C:15]([F:25])([F:24])[C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[CH:18]=O.[OH-].[K+].Cl>CCO>[OH:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:11](=[O:13])/[CH:12]=[CH:18]/[C:17]1[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=1[C:15]([F:14])([F:24])[F:25]
Reactant: CC(=O)c1cccc([N+](=O)[O-])c1O
Reactant: O=Cc1ccccc1C(F)(F)F
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: O=C(/C=C/c1ccccc1C(F)(F)F)c1cccc([N+](=O)[O-])c1O
Temperature: 0 °C
Yield: 94.3 %

Procedure:
A solution of 1-(2-Hydroxy-3-nitrophenyl)ethanone 1 (788 mg, 4.4 mmol), 2-(trifluoromethyl)benzaldehyde 8 (1.1 g, 6.5 mmol) and 25% aq KOH (90 mL) in EtOH (90 mL) was stirred for 12 h at room temperature. The reaction mixture was poured into ice-water and the pH was adjusted to 2 using conc. HCl. The resulting precipitate was collected by filtration, rinsed with H2O and dried under vacuum to give 9 as a yellow solid (1.4 g, 95% yield).
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[C:10](=O)[C:9](=[CH:12]N3CCOCC3)[CH2:8][CH2:7][C:5]=2[N:6]=1.[N+]([O-])(O)=O.[CH3:23][N:24]([CH3:35])[C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]([NH2:34])=[NH:33])=[CH:27][CH:26]=1.[OH-].[Na+]>COCCO>[CH3:23][N:24]([CH3:35])[C:25]1[CH:26]=[CH:27][C:28]([NH:31][C:32]2[N:34]=[CH:12][C:9]3[CH2:8][CH2:7][C:5]4[N:6]=[C:2]([CH3:1])[S:3][C:4]=4[C:10]=3[N:33]=2)=[CH:29][CH:30]=1
Reactant: CN(C)c1ccc(NC(=N)N)cc1
Reactant: Cc1nc2c(s1)C(=O)C(=CN1CCOCC1)CC2
Agent: [Na+]
Agent: [OH-]
Solvent: COCCO
Solvent: O=[N+]([O-])O
Product: Cc1nc2c(s1)-c1nc(Nc3ccc(N(C)C)cc3)ncc1CC2
Temperature: 100 °C
Yield: 9.2 %

Procedure:
A mixture of 2-methyl-6-morpholin-4-ylmethylene-5,6-dihydro-4H-benzothiazol-7-one (119 mg, 4.5 mmol), N-(4-dimethylamino-phenyl)-guanidine nitrate (137 mg, 4.5 mmol), NaOH (18 mg, 4.5 mmol), and 2-methoxyethanol (2 mL) was heated at 100° C. for 5 h. The reaction mixture was concentrated under vacuum. Flash column chromatography (20% EtOAc:hexane) gave the title product as a dark yellow solid (140 mg, 92%): mp 176-177° C. Anal. RP-HPLC: tR 11.9 min (0-60% MeCN, purity 100%). 1H-NMR (DMSO-d6): δ 9.23 (s, 1H, NH), 8.28 (s, 1H, Py-H), 7.60 (d, 2H, J 9.2, Ph-H), 6.75 (d, 2H, J 9.2, Ph-H), 3.02 (m, 4H, CH2—CH2), 2.88 (s, 6H, NMe2), 2.75 (s, 3H, CH3). 13C-NMR (DMSO-d6): δ 168.90, 159.67, 159.08, 155.77, 146.32, 131.16, 120.65, 115.25, 113.32, 41.14, 25.15, 23.45, 19.79. MS (ESI+): m/z 338.10 (M+H)+.
Reaction SMILES: CN(C)C1NC(=O)[C:6](CCO)=[C:5]([CH3:13])N=1.[Cl:15][CH2:16][CH2:17][C:18]1[C:19](=[O:29])[N:20]([CH3:28])[C:21]([N:25]([CH3:27])C)=[N:22][C:23]=1[CH3:24].ClCCC1C(=O)N(CCC)C(N(C)C)=NC=1C.Cl.ClCCC1C(=O)N(CC)C(N(C)C)=NC=1C>>[CH2:27]([NH:25][C:21]1[N:20]([CH3:28])[C:19](=[O:29])[C:18]([CH2:17][CH2:16][Cl:15])=[C:23]([CH3:24])[N:22]=1)[CH2:6][CH2:5][CH3:13]
Reactant: Cc1nc(N(C)C)[nH]c(=O)c1CCO
Reactant: Cc1nc(N(C)C)n(C)c(=O)c1CCCl
Agent: CCCn1c(N(C)C)nc(C)c(CCCl)c1=O
Agent: CCn1c(N(C)C)nc(C)c(CCCl)c1=O
Agent: Cl
Product: CCCCNc1nc(C)c(CCCl)c(=O)n1C

Procedure:
and further, following the same procedures 2-dimethylamino-5-(2-hydroxyethyl)-6-methyl-4(3H)-pyrimidinone (Coll. Czech. Chem. Commun., 32, 1582, 1967) was converted into 5-(2-chloroethyl)-2-(dimethylamino)-3,6-dimethyl-4(3H)-pyrimidinone (interm. 32); 5-(2-chloroethyl)-2-(dimethylamino)-6-methyl-3-propyl-4(3H)-pyrimidinone (interm. 33); and 5-(2-chloroethyl)-2-(dimethylamino)-3-ethyl-6-methyl-4(3H)-pyrimidinone monohydrochloride (interm. 34).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:17]3[O:18][CH:19]=[CH:20][CH:21]=3)=[C:11]([CH2:13][C:14]([OH:16])=[O:15])[N:12]=2)=[CH:4][CH:3]=1.[CH2:22](Br)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].C(N(CC)CC)C.O>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:17]3[O:18][CH:19]=[CH:20][CH:21]=3)=[C:11]([CH2:13][C:14]([O:16][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[O:15])[N:12]=2)=[CH:4][CH:3]=1
Reactant: CCCCCCCBr
Reactant: O=C(O)Cc1nc(-c2ccc(Cl)cc2)oc1-c1ccco1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCOC(=O)Cc1nc(-c2ccc(Cl)cc2)oc1-c1ccco1
Reaction time: 4 h
Yield: 42.8 %

Procedure:
To a solution of 1.5 g of 2-[2-(4-chlorophenyl)-5-(2-furyl)-4-oxazolyl]acetic acid and 1.0 g of n-heptyl bromide in 25 ml of dimethylformamide is dropwise added 0.92 g of triethylamine at room temperature. The mixture is stirred at 30° to 40° C. for 4 hours. Then, the mixture is poured into water, and the aqueous mixture is extracted with a mixture of diethyl ether and ethyl acetate (1:1). The extract is treated in the same manner as described in Example 27, whereby 0.85 g of n-heptyl 2-[2-(4-chlorophenyl)-5-(2-furyl)-4-oxazolyl]acetate is obtained. Yield: 42.7%
Reaction SMILES: C([O:3][C:4]([C:6]1([S:16]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)(=[O:18])=[O:17])[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:8][CH2:7]1)=[O:5])C>CO.[OH-].[Na+]>[CH2:12]([N:9]1[CH2:8][CH2:7][C:6]([S:16]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)(=[O:18])=[O:17])([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]1)[CH2:13][CH2:14][CH3:15]
Reactant: CCCCN1CCC(C(=O)OCC)(S(=O)(=O)c2ccc(OC)cc2)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCCCN1CCC(C(=O)O)(S(=O)(=O)c2ccc(OC)cc2)CC1

Procedure:
1-Butyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid was prepared starting from 1-butyl-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester (6.42 g 16.8 mmol) dissolved in methanol (200 ml) and 10 N NaOH (20 ml). The resulting reaction mixture was worked up as outlined in example 83. Yield 1.6 (27%); white powder; mp 206 ° C.; MS: 356.4 (M+H)+.
Reaction SMILES: [CH-:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH-:6]1[CH:10]=[CH:9][CH:8]=[CH:7]1.[Zr+2:11].C[Li]>C(OCC)C>[CH3-:1].[CH3-:6].[CH-:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH-:6]1[CH:10]=[CH:9][CH:8]=[CH:7]1.[Zr+4:11]
Reactant: [Zr+2]
Agent: [Li]C
Agent: c1cc[cH-]c1
Solvent: CCOCC
Product: [CH3-]
Product: [Zr+4]

Procedure:
60 ml of dried diethyl ether and 5.34 g of zirconocene dichlol were mixed together at a temperature of -20° C. in an argon atmosphere, and then 1.5M of methyl lithium was added little by little to the resultant solution over 70 minutes with stirring. After further stirring the mixture for 30 minutes at a temperature of 0° C., the diethyl ether was removed thereby obtaining a white solid which was then sublimated to obtain zirconocene dimethyl.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10].[CH3:11][O:12][C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[C:16](O)=[O:17]>O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH:6]=[CH:5][C:4]=1[O:9][CH3:10])[C:16]([C:15]1[CH:19]=[CH:20][C:21]([O:22][CH3:23])=[C:13]([O:12][CH3:11])[CH:14]=1)=[O:17]
Reactant: COc1ccccc1OC
Reactant: COc1ccc(C(=O)O)cc1OC
Solvent: O
Product: COc1ccc(C(=O)c2ccc(OC)c(OC)c2)cc1OC
Temperature: 60 °C
Yield: 98.4 %

Procedure:
16.92 g (120 mmol) of 1,2-dimethoxybenzene and 22.08 g (120 mmol) of 3,4-dimethoxybenzoic acid were stirred in 100 g of polyphosphoric acid (d=2.1 g/ml) at 80° C. for 30 min. The reaction mixture was then cooled to 60° C., and 250 ml of water was added dropwise over the course of 30 min. The resulting mixture was further cooled using ice, and the resulting precipitate was filtered off, washed with 2×60 ml of water and finally dried under reduced pressure to give 35.7 g of a reddish product. The yield of the product was 98 percent of theory.
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH2:11][CH3:12])=[CH:5][CH:4]=1.C(O[CH2:16][CH3:17])C.[Cl:18][Si:19]([Cl:22])([Cl:21])[Cl:20]>C1(C)C=CC=CC=1>[CH2:9]([C:6]1[CH:7]=[CH:8][C:3]([Si:19]([Cl:21])([Cl:20])[Cl:18])=[CH:4][CH:5]=1)[CH2:10][CH2:11][CH3:12].[CH2:9]([C:6]1[CH:7]=[CH:8][C:3]([Si:19]([C:3]2[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH2:16][CH3:17])=[CH:5][CH:4]=2)([Cl:22])[Cl:18])=[CH:4][CH:5]=1)[CH2:10][CH2:11][CH3:12]
Reactant: CCCCc1ccc(Br)cc1
Reactant: Cl[Si](Cl)(Cl)Cl
Reactant: CCOCC
Agent: [Mg]
Solvent: Cc1ccccc1
Product: CCCCc1ccc([Si](Cl)(Cl)Cl)cc1
Product: CCCCc1ccc([Si](Cl)(Cl)c2ccc(CCCC)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A 3 L-volume four-necked flask equipped with a Dimroth condenser, a dropping funnel and a stirrer was charged with magnesium (15.7 g, 0.645 moles, in a flaky state), and the inside of the flask was purged with nitrogen. Diethyl ether (200 mL) was poured while keeping the inside of the flask at a positive pressure, and one piece of iodine was added while stirring. Furthermore, 1-bromo-4-butylbenzene (141.6 g, 0.665 moles) and diethyl ether (500 mL) were charged into the dropping funnel while keeping the inside of the flask at a positive pressure. When the diethyl ether was heated, and refluxing started, the diethyl ether solution of 1-bromo-4-butylbenzene was dropped from the dropping funnel under mild refluxing over about 4.5 hours, and the mixture was stirred for one hour as it was. After finishing stirring under heating, the reaction solution was cooled to room temperature and diluted with 300 mL of toluene. Tetrachlorosilane (44.6 g, 0.263 moles) and toluene (200 mL) were charged into the dropping funnel while keeping the inside of the flask at a positive pressure and dropped at room temperature over about 30 minutes. After completion of the dropping, stirring of the reaction solution was continued at room temperature overnight. A formed crystal of magnesium bromide was filtered, the obtained filtrate was concentrated, and the concentrated liquid was distilled in vacuo. 4-Butylphenyl trichlorosilane as an initial distillate and 48.5 g of pale yellow bis(4-butylphenyl)dichlorosilane (153 to 155° C./4 to 5 Torr) as a major distillate were obtained. This compound was confirmed to be the desired silane compound (aromatic monomer (B1)) from chemical shift, branching and integration values of signals obtained by the 1HNMR measurement (using chloroform as a heavy solvent at 400 MHz) (see FIG. 2). In the following polymerization reaction, a purified material obtained by vacuum distillation of this major distillate just before that was provided. Also, all of the solvents to be used were dried by a molecular sieve and then used.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[C:14]([Cl:15])=[CH:13][C:12]([C:16]([F:19])([F:18])[F:17])=[CH:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1>>[Cl:15][C:14]1[C:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([NH:1][S:27]([C:24]3[CH:25]=[CH:26][C:21]([Cl:20])=[CH:22][CH:23]=3)(=[O:29])=[O:28])[CH:3]=2)=[N:10][CH:11]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:13]=1
Reactant: Nc1cc(-c2ncc(C(F)(F)F)cc2Cl)ccc1Cl
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Product: O=S(=O)(Nc1cc(-c2ncc(C(F)(F)F)cc2Cl)ccc1Cl)c1ccc(Cl)cc1
Yield: 30.6 %

Procedure:
In a similar way to Example 37, reaction of 2.5 g of 2-(3-amino-4-chlorophenyl)-3-chloro-5-trifluoromethylpyridine and 1.9 g of 4-chlorobenzenesulfonyl chloride, and purification of the crude product by recrystallization from ether, resulted in 1.2 g of colorless crystals. Yield: 31%; melting point: 156°-157° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[OH:19])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=1)[C:10]([OH:12])=[O:11])=[O:6].[CH3:20]O>>[CH3:20][O:11][C:10](=[O:12])[C:9]1[CH:13]=[CH:14][CH:15]=[C:7]([C:5](=[O:6])[C:4]2[CH:16]=[CH:17][C:18]([OH:19])=[C:2]([OH:1])[CH:3]=2)[CH:8]=1
Reactant: O=C(O)c1cccc(C(=O)c2ccc(O)c(O)c2)c1
Reactant: CO
Product: COC(=O)c1cccc(C(=O)c2ccc(O)c(O)c2)c1
Reaction time: 8 h

Procedure:
A solution of 2.9g of 3-(3,4-dihydroxybenzoyl)-benzoic acid in 100 ml of methanol is mixed with 7g of Amberlyst 15® and refluxed with stirring for 8 hours. The reaction mixture is filtered on diatomaceous earth, the filtrate concentrated by evaporation, taken up in ethyl acetate and shaken out with 10% sodium bicarbonate solution. The organic phase is dried on sodium sulfate and concentrated by evaporation. 1.4g of 3-(3,4-dihydroxybenzoyl)-benzoic acid methyl ester is obtained as oily crude product. 272 mg of this crude product is dissolved in 2.5 ml of dimethylformamide, mixed with 269 mg of (1E)-6-bromo-l-(4-methoxyphenyl)-1-hexene and 185 mg of lithium carbonate and the mixture is heated for 18 hours to 50°-60° C. with stirring. The reaction mixture is filtered, washed with dichloromethane, the filtrate is concentrated by evaporation and the residue is chromatographed on silica gel with hexane/ethyl acetate=98/2. 230 mg of 3-[3-hydroxy- 4-[6-(4-methoxyphenyl)-(5E)-5-hexenyloxy]benzoyl]-benzoic acid methyl ester is obtained as oil.
Reaction SMILES: [CH3:1][C:2]1[N:3]([NH:13][CH:14]=[NH:15])[CH:4]=[C:5]([C:7]2[CH:8]=[N:9][N:10]([CH3:12])[CH:11]=2)[N:6]=1.[C:16](N1C=CN=C1)(N1C=CN=C1)=[O:17]>O1CCCC1>[CH3:1][C:2]1[N:3]2[C:4]([C:16](=[O:17])[NH:15][CH:14]=[N:13]2)=[C:5]([C:7]2[CH:8]=[N:9][N:10]([CH3:12])[CH:11]=2)[N:6]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Cc1nc(-c2cnn(C)c2)cn1NC=N
Solvent: C1CCOC1
Product: Cc1nc(-c2cnn(C)c2)c2c(=O)[nH]cnn12
Temperature: 65 °C
Reaction time: 2.5 h

Procedure:
N-[2-Methyl-4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]imidoformamide (58.3 g, 285 mmol) was combined with 1,1′-carbonyldiimidazole (98%, 59.0 g, 357 mmol) in tetrahydrofuran (1140 mL) at 63° C., and the suspension was stirred for 2.5 hours at 65° C. The mixture was cooled and concentrated in vacuo; the resulting solid was slurried with methanol (400 mL), warmed to reflux for 20 minutes and cooled to 7° C. The solid was collected to provide C1 as a pale yellow solid. Yield: 45.9 g, 199 mmol, 70%. LCMS m/z 231.1 (M+1). 1H NMR (500 MHz, DMSO-d6) δ 2.48 (s, 3H), 3.88 (s, 3H), 7.79 (s, 1H), 8.08 (s, 1H), 8.37 (s, 1H), 11.59 (br s, 1H).
Reaction SMILES: C([O-])(=O)C.[Na+].Cl.[S:7]([CH:11]([NH2:15])[C:12]([OH:14])=[O:13])([OH:10])(=[O:9])=[O:8].CO[CH:18]1[CH2:22][CH2:21][CH:20](OC)O1>C(O)(=O)C.C(OC(=O)C)C>[S:7]([CH:11]([N:15]1[CH:18]=[CH:22][CH:21]=[CH:20]1)[C:12]([OH:14])=[O:13])([OH:10])(=[O:9])=[O:8]
Reactant: COC1CCC(OC)O1
Reactant: NC(C(=O)O)S(=O)(=O)O
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: O=C(O)C(n1cccc1)S(=O)(=O)O

Procedure:
To a solution of sodium acetate (0.1 mole) in about 300 ml of glacial acetic acid is added about 0.05 mole of α-sulfo-α-aminoacetic acid hydrochloride. The solution is heated to reflux for 5 minutes, 2,5-dimethoxytetrahydrofuran (1 equivalent based on α-sulfo-α-aminoacetic acid hydrochloride) is added as quickly as possible, and the solution refluxed for an additional 2 minutes. The acetic acid is flash evaporated leaving a residue which is taken up in ethylacetate. The ethyl acetate is filtered, dried and evaporated to give α-sulfo-α-(1-pyrryl) acetic acid.