Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:11][C:12]([OH:14])=[O:13])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].S(=O)(=O)(O)O.[CH3:20]O>>[OH:1][C:2]1[CH:3]=[C:4]([CH2:11][C:12]([O:14][CH3:20])=[O:13])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9]
Reactant: O=C(O)Cc1ccc([N+](=O)[O-])c(O)c1
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)Cc1ccc([N+](=O)[O-])c(O)c1
Temperature: 25 °C

Procedure:
To 3-hydroxy-4-nitrophenylacetic acid (5.45 g, 27.6 mol) and methanol (100 ml) was added concentrated sulfuric acid (0.5 ml). The mixture was then heated under reflux for 4 hours under stirring. After cooling to room temperature, the reaction mixture was distilled under reduced pressure to remove the solvent. Water (100 ml) was added to the residue, followed by extraction with ether (300 ml). The extract was washed successively with a saturated aqueous solution (100 ml) of sodium bicarbonate and saturated brine (100 ml), dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, whereby the title compound (4.90 g, 84%) was obtained as a yellow crystalline powder.
Reaction SMILES: [CH3:1][C:2]12[CH2:11][CH2:10][C@@H:9]([C:12]([CH3:14])=[CH2:13])[CH2:8][C:7]1=[CH:6][C:5](=[O:15])[CH2:4][CH2:3]2.S(=O)(=O)(O)[OH:17]>C(O)=O>[CH3:1][C:2]12[CH2:11][CH2:10][C@@H:9]([C:12]([OH:17])([CH3:14])[CH3:13])[CH2:8][C:7]1=[CH:6][C:5](=[O:15])[CH2:4][CH2:3]2
Reactant: C=C(C)[C@@H]1CCC2(C)CCC(=O)C=C2C1
Reactant: O=S(=O)(O)O
Solvent: O=CO
Product: CC12CCC(=O)C=C1C[C@H](C(C)(C)O)CC2

Procedure:
In Scheme V, treatment of (6R/S,9R)-6-methyl-9-(1-methylvinyl)-bicyclo[4,4,0]dec-1-ene-3-one (1) with mixture of sulfuric acid and formic acid at room temperature produces (6R/S,9R)-6methyl-9-(1-hydroxyisopropyl)-bicyclo[4.4.0]-dec-1-ene-3-one (14). Compound (14) reacts with organometallic reagent such Grignard reagent or organolithium reagent to form compound of formula (15) and the reaction is conducted in diethylether, tetrahydrofuran or any other solvent that does not interfere with the reaction at room temperature or cooled with ice bath or ice-salt mixture. Cyclization of compound of formula (15) to form compound of formula (Ie) is carried out in acidic medium, optionally with inorganic acid such as hydrochloric acid, sulfuric acid, or phosphoric acid in any solvent that does not interfere with the reaction such as water, methanol, ethanol, diethylether, benzene, toluene, methylene chloride, chloroform, ethylacetate, tetrahydrofuran, or a mixture thereof, particularly benzene-water, diethylether-water mixture. The reaction temperature is usually room temperature or lower.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15]2C(C(=O)NC3C=CC=CC=3)=CN=C(S(C)(=O)=O)N=2)[CH:9]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:15][O:14][C:10]1[CH:9]=[C:8]([CH:13]=[CH:12][CH:11]=1)[NH2:7]
Reactant: CC(C)(C)OC(=O)Nc1cccc(Oc2nc(S(C)(=O)=O)ncc2C(=O)Nc2ccccc2)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1cccc(N)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 287.6 %

Procedure:
To a stirred solution of 7 (0.15 g, 0.24 mmol) in dry CH2Cl2 (5 mL) at 0° C. was added CF3COOH (1.5 mL) and the reaction mixture was stirred at 0° C. for 30 min. The reaction was allowed to come to rt and stirred at it for 1 h. It was concentrated under reduced pressure and the residue was quenched with NaHCO3 solution (3 mL) and extracted with EtOAc (3×25 mL). The combined EtOAc extract was washed with water (20 mL), brine (10 mL) and dried over Na2SO4 and concentrated under reduced pressure to give 8 (0.085 g, 86.7%) as a white solid.
Reaction SMILES: C(O[C:5](=[O:7])[CH3:6])(=O)C.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([NH2:17])[CH3:16])=[CH:11][CH:10]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([NH:17][C:5](=[O:7])[CH3:6])[CH3:16])=[CH:11][CH:10]=1
Reactant: C[C@H](N)c1ccc(Br)cc1
Reactant: CC(=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(=O)N[C@@H](C)c1ccc(Br)cc1
Reaction time: 12 h

Procedure:
23.6 mL (250 mmol) acetic anhydride are added to 50.0 g (250 mmol) (S)-1-(4-bromophenyl)-ethylamine in 200 mL DCM while keeping the reaction temperature below 30° C. Stirring is continued for 12 h at rt. After that time, saturated NaHCO3-solution is added. The organic layer is separated, washed with water, dried over magnesium sulphate and the solvent is removed by evaporation.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([OH:11])[CH:3]=1.B>C1COCC1>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][OH:7])=[C:4]([OH:11])[CH:3]=1
Reactant: O=C(O)c1ccc(Cl)cc1O
Agent: B
Solvent: C1CCOC1
Product: OCc1ccc(Cl)cc1O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 82.1 %

Procedure:
To a solution of 4-chloro-2-hydroxybenzoic acid (2.0 g, 11.6 mmol, Aldrich) in THF (50 ml) was added dropwise 1 M borane in THF (20.9 ml, 20.9 mmol). The suspension was allowed to stir for 30 min at ambient temperature. The mixture was refluxed at 80° C. for 2.5 h. The solvent was removed in vacuo. The residue was loaded in dichloromethane and purified on silica 100 g using 0-100% ethyl acetate/cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white solid (1.51 g);
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH3:8])[C:3](=O)[CH2:4][C:5]#[N:6].[NH2:10][NH2:11].O>CCO>[C:2]([C:3]1[CH:4]=[C:5]([NH2:6])[NH:11][N:10]=1)([CH3:9])([CH3:8])[CH3:1]
Reactant: CC(C)(C)C(=O)CC#N
Reactant: NN
Solvent: CCO
Solvent: O
Product: CC(C)(C)c1cc(N)[nH]n1
Yield: 97 %

Procedure:
A solution of 4,4-dimethyl-3-oxopentanenitrile (Compound [CCLII]) (7 g, 55.9 mmol, 1.00 equiv) and NH2NH2.H2O (4.5 g, 140 mmol, 2.00 equiv) in EtOH (100 mL) was stirred for 7 h at 110° C. under nitrogen. The reaction progress was monitored by TLC (ethyl acetate/petroleum ether=1:2). After cooling, the resulting solution was concentrated under vacuum and diluted with 50 mL of water. The resulting solution was extracted with CH2Cl2, dried and concentrated under reduced pressure. The residue was loaded onto a silica gel column with ethyl acetate/petroleum ether as the eluent to Compound [CCXXXIV] as a yellowish oil: LCMS (m/e) 140 (M+H); 1H NMR (300 MHz, DMSO-d6) δ ppm 5.18 (s, 1H), 1.19 (s, 9H). Amount obtained: 7.6 g, 97% yield.
Reaction SMILES: [C:1]1([C:7]2[C:15]3[C:14](=O)[NH:13][CH:12]=[N:11][C:10]=3[O:9][C:8]=2[C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:19][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(Cl)([Cl:33])=O>C1C=CC=CC=1>[Cl:33][C:14]1[C:15]2[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[C:8]([C:17]3[CH:18]=[CH:19][C:20]([O:23][CH2:24][CH2:25][N:26]4[CH2:27][CH2:28][CH2:29][CH2:30]4)=[CH:21][CH:22]=3)[O:9][C:10]=2[N:11]=[CH:12][N:13]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=c1[nH]cnc2oc(-c3ccc(OCCN4CCCC4)cc3)c(-c3ccccc3)c12
Solvent: c1ccccc1
Product: Clc1ncnc2oc(-c3ccc(OCCN4CCCC4)cc3)c(-c3ccccc3)c12
Temperature: 25 °C

Procedure:
Into a 50 mL round bottom flask was placed 5-phenyl-6-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)furo[2,3-d]pyrimidin-4 (3H)-one 46 (132 mg, 0.329 mmol), and benzene (40 mL). The flask was equipped with a magnetic stir bar, dean-stark trap and a reflux condenser. The reaction was brought to reflux with some of the solvent having been distilled into the dean-stark trap. The reaction was allowed to cool to room temperature and phosphorous oxychloride (300 mg, 1.96 mmol) was added dropwise. The reaction was heated at reflux for 20 hours.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7])[CH3:2].[Cl:13][S:14](O)(=[O:16])=[O:15]>>[Cl:13][S:14]([C:10]1[CH:11]=[CH:12][C:4]([O:3][CH2:1][CH3:2])=[C:5]([CH:9]=1)[C:6]([OH:8])=[O:7])(=[O:16])=[O:15]
Reactant: O=S(=O)(O)Cl
Reactant: CCOc1ccccc1C(=O)O
Product: CCOc1ccc(S(=O)(=O)Cl)cc1C(=O)O
Temperature: 0 °C
Yield: 81.1 %

Procedure:
In a 250 ml three-neck flack, 2-ethoxy benzoic acid (50 g, 0.30 mol) was added dropwise to an ice-cooled mixtures of sulfoxide dichloride (22 ml, 0.30 mol) and chlorosulfonic acid (82.6 ml, 1.24 mol) under stirring. At the same time, the temperature of the reacting mixture was kept below 25° C. The resulting mixture was stirred at room temperature for 18 hours and then poured into ice water with stirring, and white deposit appeared. The reaction mixture was stirred for another 1 hour, filtered, washed with water, and dried in vacuum, which gave 64.4 g of crude product as white solid (II) (yield 81%). m.p. 108-110° C. The crude product was used directly in the next step without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[CH:8]=[C:9]([N+:11]([O-])=O)[CH:10]=1)=[O:4].Cl[Sn]Cl>>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[CH:8]=[C:9]([NH2:11])[CH:10]=1)=[O:4]
Reactant: COC(=O)c1cc(-c2ccc(C)cc2)cc([N+](=O)[O-])c1
Agent: Cl[Sn]Cl
Product: COC(=O)c1cc(N)cc(-c2ccc(C)cc2)c1

Procedure:
4′-Methyl-5-nitro-biphenyl-3-carboxylic acid methyl ester was reduced using SnCl2 using the procedure of step 4 of preparation 4 to afford 5-amino-4′-methyl-biphenyl-3-carboxylic acid methyl ester, MS (M+H)=242.
Reaction SMILES: C[O:2][C:3]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]([C:18]([NH2:20])=[O:19])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=1.C(O)(=O)C(O)=O.C(O)(C)C>O>[CH:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:18]([NH2:20])=[O:19])[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[C:3](=[O:2])[CH2:4][C:5]=2[CH:6]=1
Reactant: COC1=Cc2ccccc2N(C(N)=O)c2ccccc21
Agent: O=C(O)C(=O)O
Solvent: CC(C)O
Solvent: O
Product: NC(=O)N1c2ccccc2CC(=O)c2ccccc21
Temperature: 25 °C
Yield: 95 %

Procedure:
100 g of 10-methoxycarbamazepine in 1000 ml water and 69.24 g of oxalic acid solution were heated to 90° C. and maintained for about 17 hrs. After completion of the reaction the reaction mixture was cooled to room temperature (RT). The resulting reaction mass was filtered and washed with 1000 ml of DM water. The wet material obtained was charged with isopropyl alcohol and DM water. The obtained reaction mixture was heated to reflux for about 2 h. The reaction mixture was cooled to 15-25° C., filtered and washed with 100 ml of IPA-water mixture. The resulting compound is dried at 60° C. for 6 h to produce 90 g of Oxcarbazepine.
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[OH-:10].[Na+].Cl>>[Br:1][C:2]1[C:3]([OH:10])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1
Reactant: Clc1ncc(Br)c(Cl)n1
Reactant: [OH-]
Agent: Cl
Agent: [Na+]
Product: Oc1nc(Cl)ncc1Br
Temperature: 47.5 °C
Reaction time: 0.83 h

Procedure:
50.5 g of 5-bromo-2,4-dichloropyrimidine is mixed with 133 ml of 2N sodium hydroxide solution and stirred for 50 minutes at 45-50° C. After cooling, it is acidified with 21 ml of concentrated hydrochloric acid while being cooled with ice. The precipitate is suctioned off, washed with water and a little methylene chloride and dried at 25-35° C. 17.12 g (36.9% of theory) of the product with a melting point of 136-145° C. (decomposition) is obtained.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23](Br)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:32]1[O:33][CH:34]=[CH:35][CH:36]=1)CCC>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:32]4[O:33][CH:34]=[CH:35][CH:36]=4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccco1
Reactant: Brc1ccc2ncnc(Nc3ccc(OCc4ccccc4)cc3)c2c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1COCCO1
Product: c1ccc(COc2ccc(Nc3ncnc4ccc(-c5ccco5)cc34)cc2)cc1
Yield: 99.6 %

Procedure:
The (4-benzyloxy-phenyl)-(6-bromo-quinazolin-4-yl)-amine (300 mg, 0.74 mmol), 2-(tributylstannyl)-furan (290 mg, 0.81 mmol) and bis(triphenylphosphine)palladium(II) chloride (catalytic) were dissolved in dioxane (3.5 ml) and heated at reflux under nitrogen for 2 hr. The cooled reaction mixture was absorbed onto silica and purified by flash column chromatography (silica gel, eluting with 1:1 ethyl acetate/iso-hexane) to give the title product (290 mg, 79%) as a pale yellow solid; δH [2H6]-DMSO 9.94 (1H, b, NH), 8.85 (1H, s, 5-H), 8.53 (1H, s, 2-H), 8.21 (1H, d, 7-H), 7.91 (1H, d, furan-H), 7.81 (1H, d, 8-H), 7.72 (2H, d, 2′-H, 6′-H), 7.57-7.33 (5H, m, 5×Ph-H), 7.16 (1H, d, furan-H), 7.10 (2H, d, 3′-H, 5′-H), 6.72, (1H, dd, furan-4H), 5.17 (2H, s, CH2); m/z 394 (M+1)+.
Reaction SMILES: [CH2:1]([N:8]1[C:12](=[O:13])[C:11]2([CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]2)[N:10]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:32][C:33]([F:38])([F:37])[C:34]([OH:36])=[O:35]>>[F:32][C:33]([F:38])([F:37])[C:34]([OH:36])=[O:35].[CH2:1]([N:8]1[C:12](=[O:13])[C:11]2([CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[N:10]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCC2(CC1)C(=O)N(Cc1ccccc1)CN2c1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: O=C1N(Cc2ccccc2)CN(c2ccccc2)C12CCNCC2
Reaction time: 1 h
Yield: 91 %

Procedure:
3-Benzyl-8-(tert-butoxycarbonyl)-1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one (1.671 g) was added with trifluoroacetic acid (32 ml) with ice cooling and stirred at the same temperature for 1 hour. The solvent was evaporated under reduced pressure and then the residue was added with diisopropyl ether (50 ml) to precipitate the product. The precipitates was collected by filtration and dried to obtain 1.561 g of the title compound. Yield: 91%.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[O:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][CH2:12][NH:11]1.[CH:15](O)=O.C=O>>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[O:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[CH3:15]
Reactant: Cc1ccncc1OC[C@@H]1CCCN1
Reactant: O=CO
Agent: C=O
Product: Cc1ccncc1OC[C@@H]1CCCN1C

Procedure:
To a 330 mg sample of 4-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine (from Example 27 above) was added a solution of formic acid/formaldehyde (1:2, 2 mL). The mixture was heated at reflux for 5 hours, and the volatiles were removed by evaporation. The residue was dissolved in 1 mL of 20% NaOH. The solution was extracted with CH2Cl2 (3×), then the organic layer was dried (Na2SO4) and concentrated. The crude product was purified by chromatography over silica gel to afford 295 mg of the title compound. MS (DCI/NH3) m/e: 207 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ: 8.17 (s, 1H), 8.12 (d, J=5.5 Hz, 1H), 7.06 (d, J=5.5 Hz, 1H), 4.07 (dd, J=3.3, 10.6 Hz, 1H), 3.98 (dd, J=7.4, 10.6 Hz, 1H), 3.15-3.08 (m, 1H), 2.76-2.68 (m, 1H), 2.53 (s, 3H), 2.38-2.25 (m, 1H), 2.26 (s, 3H), 2.12-1.67 (m, 4H).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]2[C:14](=[O:15])[O:13][C:12]([CH3:17])([CH3:16])[O:11][C:10]2=[O:18])[CH:5]=[CH:6][CH:7]=1.[CH:19]1([Mg]Br)[CH2:21][CH2:20]1>C1COCC1>[CH:19]1([CH:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([OH:1])[CH:3]=2)[CH:9]2[C:10](=[O:18])[O:11][C:12]([CH3:16])([CH3:17])[O:13][C:14]2=[O:15])[CH2:21][CH2:20]1
Reactant: Br[Mg]C1CC1
Reactant: CC1(C)OC(=O)C(=Cc2cccc(O)c2)C(=O)O1
Solvent: C1CCOC1
Product: CC1(C)OC(=O)C(C(c2cccc(O)c2)C2CC2)C(=O)O1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 87.2 %

Procedure:
To a solution of 8.1 (2.0 g, 8.06 mmol) in THF, was added cyclopropylmagnesium bromide (available from Aldrich) (96.7 mL, 48.3 mmol) via cannula at 0° C. The resulting heterogeneous mixture was warmed to room temperature, stirred for 30 minutes, and quenched with 1 N aq. HCl. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel flash chromatography (10-35% EtOAc/hexane) to afford 8.2 (2.04 g, 87.2% yield) as a yellow oil.
Reaction SMILES: [C:1]([O-:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]CCCCC.[Al+3].[C:22]([O-])(=[O:40])[CH2:23]CCCCCCCCCCCCCCCC.C([O-])(=[O:60])CCCCCCCCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCCCCCCCC.[Na+]>C([O-])(=O)CCCCCCCCCCCCCCCCC.[Al+3].C([O-])(=O)CCCCCCCCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCCCCCCCC.[Pb+2].C([O-])(=O)CCCCCCCCCCCCCCCCC>[C:13]1(=[O:60])[O:40][CH2:22][CH2:23][O:20][C:1](=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1
Reactant: CCCCCCCCCCCCCCCCCC(=O)[O-]
Agent: [Al+3]
Agent: [Na+]
Agent: [Pb+2]
Product: O=C1CCCCCCCCCCCC(=O)OCCO1
Reaction time: 4 h
Yield: 95.9 %

Procedure:
To demonstrate the improved yields and increased reaction rates obtained utilizing the mixed metal catalysts of this invention, batch polymerizations were identically conducted using (a) a mixed metal catalyst comprised of aluminum stearate and sodium stearate (1:1 molar ratio), (b) aluminum stearate catalyst, and (c) lead stearate catalyst. These reactions were conducted in accordance with the procedure employed in Example II utilizing 74 grams poly(ethylene brassylate) and 0.5 mole percent of the catalyst. Reactions were carried out at 310°-320° C. and 0.1-0.5 mm Hg. for four hours. The amount of distillate (crude ethylene brassylate) recovered was recorded after the first hour of reaction. With the mixed metal catalyst, 45 mls. ethylene brassylate was obtained after 1 hour and the overall yield was 95.9%. With the aluminum stearate, 36 mls. crude ethylene brassylate was obtained in the first hour and the overall yield was only 78%. Using lead stearate only 25 mls distillate was obtained after 1 hour and the yield of crude ethylene brassylate was 69.1%.
Reaction SMILES: [C:1]([SiH2:5][O:6][C:7]([CH3:14])([CH3:13])[C:8]1[O:9][CH:10]=[CH:11][N:12]=1)([CH3:4])([CH3:3])[CH3:2].C(Br)(Br)(Br)[Br:16]>O1CCCC1.[Cl-].[NH4+]>[Br:16][C:10]1[O:9][C:8]([C:7]([CH3:14])([CH3:13])[O:6][SiH2:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[N:12][CH:11]=1
Reactant: BrC(Br)(Br)Br
Reactant: CC(C)(C)[SiH2]OC(C)(C)c1ncco1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(C)(C)[SiH2]OC(C)(C)c1ncc(Br)o1
Temperature: -40 °C
Reaction time: 2 h

Procedure:
To a solution of 2-(tert-Butyl-dimethyl-silanyloxymethyl)-oxazole) (0.35 g, 1.643 mmol) in dry tetrahydrofuran (8 mL) is added n-Butyl litihum (0.26 g, 4.107 mmol) drop wise under nitrogen atmosphere at −78° C. then stirred at −40° C. for 2 hours. The reaction mixture is again cooled to −78° C. then added carbontetrabromide (1.36 g, 4.107 mmol) and stirred to room temperature for 14 hours. Reaction mixture is diluted with saturated ammonium chloride solution and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, solvent is evaporated in vacuo and purified by column chromatography eluting 2% Ethyl acetate in hexane to afford the crude title compound (0.18 g), which is used in the next step without purification. LC-MS (m/z): [M+H]=294.2.
Reaction SMILES: [CH2:1]([CH:9]1[C:14](=[O:15])[NH:13][C:12](=[O:16])[NH:11][C:10]1=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[BrH:18]>O>[Br:18][C:9]1([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[C:14](=[O:15])[NH:13][C:12](=[O:16])[NH:11][C:10]1=[O:17]
Reactant: Br
Reactant: CCCCCCCCC1C(=O)NC(=O)NC1=O
Solvent: O
Product: CCCCCCCCC1(Br)C(=O)NC(=O)NC1=O
Temperature: 2.5 °C
Reaction time: 2 h

Procedure:
To a suspension of 5-octylbarbituric acid (20 g) in 120 ml of water, cooled at 0-5° C., are added 12 ml of 48% hydrobromic acid and successively are dropped 4.72 ml of brornine. After 2 hours under stirring, the white solid which separated is recovered by filtration, washed with water and partitioned between 200 ml of diethyl ether and 100 ml of water.
Reaction SMILES: [CH3:1][C:2]1[CH:12]=[CH:11][C:5]([CH:6]=[CH:7][C:8](O)=[O:9])=[CH:4][CH:3]=1.S(Cl)([Cl:15])=O>C(Cl)Cl>[CH3:1][C:2]1[CH:12]=[CH:11][C:5]([CH:6]=[CH:7][C:8]([Cl:15])=[O:9])=[CH:4][CH:3]=1
Reactant: Cc1ccc(C=CC(=O)O)cc1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: Cc1ccc(C=CC(=O)Cl)cc1

Procedure:
To a stirred mixture of 100 g (0.62 moles) p-methylcinnamic acid in methylene chloride (about 30 ml), 88 g (0.74 moles) thionyl chloride was added dropwise. The reaction mixture was then refluxed for 24 hours. The methylene chloride was removed under reduced pressure and heat to give the corresponding p-methylcinnamic acid chloride. Fresh methylene chloride was added to the acid chloride; half of which was used in Step (b).
Reaction SMILES: [NH2:1][C:2]([C:4]1([CH2:17][CH2:18][C:19]#[N:20])[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)=[O:3].C(O)(=O)C.[H][H]>[Pt]=O.Cl>[NH2:20][CH2:19][CH2:18][CH2:17][C:4]1([C:2]([NH2:1])=[O:3])[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2
Reactant: N#CCCC1(C(N)=O)c2ccccc2-c2ccccc21
Reactant: [H][H]
Agent: O=[Pt]
Agent: Cl
Solvent: CC(=O)O
Product: NCCCC1(C(N)=O)c2ccccc2-c2ccccc21

Procedure:
A 3.3 g. portion of 9-aminocarbonyl-9-(2-cyanoethyl)fluorene from Example 27 was hydrogenated in 95 ml. of glacial acetic acid under 4 atmospheres of hydrogen pressure for two hours at 24° C. in the presence of 1.5 g. of platinum oxide catalyst. The reaction mixture was filtered to remove the catalyst and the solvent was removed by evaporation under reduced pressure. The product which remained was dissolved in ethyl acetate and then extracted into 1 N hydrochloric acid. The aqueous acid layer was separated, made alkaline with 50% sodium hydroxide, and extracted several times with fresh ethyl acetate. The extracts were combined, washed with water and with brine, dried, and the solvent was removed by evaporation under reduced pressure to provide 2.3 g. of a white solid. The solid was dissolved in 1 N hydrochloric acid, filtered, and diluted with water to 100 ml. The aqueous acid solution was lyophilized to provide a white solid, which was crystallized from methanol and ethyl acetate was identified as 1.0 g. of 9-(3-aminopropyl)-9-aminocarbonylfluorene. m.p. 198°-200° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH:5]=[O:6].C(=O)([O-])[O-].[K+].[K+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C=O)C.O>[CH2:19]([O:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH:5]=[O:6])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=Cc1ccc([N+](=O)[O-])c(O)c1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=Cc1ccc([N+](=O)[O-])c(OCc2ccccc2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-Hydroxy-4-nitro-benzaldehyde (4.68 g, 28 mmol) is dissolved in DMF (27 mL) and to the solution is added with stirring powdered potassium carbonate (4.27 g, 30.1 mmol) and benzyl bromide (3.34 mL, 28.1 mmol). The mixture is stirred at RT overnight, diluted with water (200 mL) and extracted three times with EtOAc. The organic extracts are washed with 10% potassium carbonate and brine, dried over anhydrous MgSO4, decolorized with charcoal, filtered and evaporated to give 3-benzyloxy-4-nitro-benzaldehyde as an oil which is used in the next step without purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].N1C=CC=CC=1.[CH3:21][N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:25]2[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]2)(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]
Reactant: O=[N+]([O-])c1cc(S(=O)(=O)Cl)ccc1Cl
Reactant: CN1CCNCC1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CN1CCN(S(=O)(=O)c2ccc(Cl)c([N+](=O)[O-])c2)CC1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
17.1 2.5 g (9.763 mmol) of 4-chloro-3-nitrobenzenesulfonyl chloride are dissolved in 100 ml of DCM. 1.574 ml (19.5 mmol) of pyridine and 1.086 ml (9.760 mmol) of N-methylpiperazine are added, and the mixture is stirred at room temperature for 14 h. The reaction mixture is washed 3× with water, the organic phase is dried using sodium sulfate, filtered, and the solvent is removed, giving 1-(4-chloro-3-nitrobenzenesulfonyl)-4-methylpiperazine; EI-MS [M]+ 319.