Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([N+:12]([O-:14])=[O:13])[CH:11]=1)[CH2:7][OH:8])([O-:3])=[O:2].[CH2:15](Br)[CH:16]=[CH2:17].[OH-].[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.O>[CH2:17]([O:8][CH2:7][C:6]1[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=1)[CH:16]=[CH2:15]
Reactant: O=[N+]([O-])c1cc(CO)cc([N+](=O)[O-])c1
Reactant: C=CCBr
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: C=CCOCc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.4 %

Procedure:
20.0 g (101 mmol) of 3,5-dinitrobenzyl alcohol, 22 ml (254 mmol) of allyl bromide and 2.0 g (5.89 g) of tetrabutylamonium hydrogensulfate were dissolved in 100 ml of tetrahydrofuran, and a solution of 8.0 g (200 mmol) of sodium hydroxide as dissolved in 16 ml of water was added thereto and stirred overnight at room temperature. The reaction solution was extracted with diethyl ether and the organic phase was taken out and dried with anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain a crude product, which was then purified by column chromatography with silica gel (using a developer of chloroform/hexane=1/l). As a result, 19.1 g of 3,5-dinitrobenzyl allyl ether having a structural formula of: ##STR32## was obtained as a yellow oil. Yield: 80%. The product was identified to have the above-mentioned structure by the following IR spectrum, 1H-NMR spectrum and elementary analysis.
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([OH:23])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:42]/[CH:43]=[CH:44]\[C:45]([CH2:56][CH3:57])([O:48][Si:49]([CH2:54][CH3:55])([CH2:52][CH3:53])[CH2:50][CH3:51])[CH2:46][CH3:47]>O1CCCC1>[Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([O:23][CH2:42]/[CH:43]=[CH:44]\[C:45]([CH2:56][CH3:57])([O:48][Si:49]([CH2:54][CH3:55])([CH2:50][CH3:51])[CH2:52][CH3:53])[CH2:46][CH3:47])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:37])([CH3:36])[CH3:38])([CH3:33])[CH3:34])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CCC(/C=C\CBr)(CC)O[Si](CC)(CC)CC
Reactant: C[C@@H](O)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCC(/C=C\CO[C@H](C)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C)(CC)O[Si](CC)(CC)CC
Yield: 98.9 %

Procedure:
Under the same conditions as in Example 83, 1α,3β-bis(tert-butyldimethylsilyloxy)-20(R)-hydroxypregna-5,7,16-triene (60.0 mg, 0.107 mmol), sodium hydride (60%, 17.1 mg, 0.428 mmol), 15-crown-5(10 μl) and (Z)-1-bromo-4-ethyl-4-triethylsilyloxy-2-hexene (103 mg, 0.321 mmol) were reacted in tetrahydrofuran (1 ml) and worked up, and then the residue was purified by preparative thin layer chromatography (0.5 mm×2, hexane:ethyl acetate=40:1, developed once) to give the title compound as a colorless oil (84.6 mg, 99%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:44])[C@H:15]([NH:24][C:25]([C@@H:27]2[CH2:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][N:28]2[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:26])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:10][CH2:9]1.N1C=CC=CC=1.[C:51]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[S:59](Cl)(=[O:61])=[O:60])#[N:52]>ClCCCl>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([CH2:16][C@@H:15]([NH:24][C:25]([C@@H:27]2[CH2:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][N:28]2[C:37]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:38])=[O:26])[C:14]([N:11]2[CH2:12][CH2:13][CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[NH:1][S:59]([C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=3[C:51]#[N:52])(=[O:61])=[O:60])[CH2:9][CH2:10]2)=[O:44])=[CH:22][CH:21]=1
Reactant: N#Cc1ccccc1S(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N1Cc2ccccc2C[C@H]1C(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCC(c2ccccc2N)CC1
Solvent: ClCCCl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N1Cc2ccccc2C[C@H]1C(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCC(c2ccccc2NS(=O)(=O)c2ccccc2C#N)CC1
Yield: 85.4 %

Procedure:
To a 50 mL round-bottomed flask equipped with stirring was added tert-butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)piperidyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl}carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (Example 20) (154 mg, 0.25 mmol), 1,2-dichloroethane (10 mL) and pyridine (0.03 mL, 0.3/5 mmol). The reaction mixture was stirred for 5 min at RT, treated with 2-cyanobenzenesulfonyl chloride (Lancaster Synthesis) (50 mg, 0.25 mmol) and stirred at RT for 16 h. The reaction was quenched with satd NH4Cl (10 mL), the organic layer separated, and the aqueous layer extracted with CH2Cl2 (2×10 mL). The organic fractions were combined, washed with satd NaCl (10 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (100% EtOAc) provided the title compound as a white foam (167 mg). MS (ESI, pos. ion) m/z: 782 (M+1); MS (ESI, neg. ion) m/z: 780 (M−1). Calc'd for C42H44ClN5O6S: 781.27.
Reaction SMILES: [ClH:1].[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C@@H:4]([NH:10][C:11]([C:13]1[S:14][C:15]3[CH:21]=[C:20](Br)[CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2.[CH:23]([C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)=[O:24].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C>[ClH:1].[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C@@H:4]([NH:10][C:11]([C:13]1[S:14][C:15]3[CH:21]=[C:20]([C:28]4[CH:29]=[CH:30][C:25]([CH:23]=[O:24])=[CH:26][CH:27]=4)[CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2
Reactant: O=C(N[C@H]1CN2CCC1CC2)c1cc2ccc(Br)cc2s1
Reactant: O=Cc1ccc(B(O)O)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: Cl
Solvent: CN(C)C=O
Product: O=Cc1ccc(-c2ccc3cc(C(=O)N[C@H]4CN5CCC4CC5)sc3c2)cc1
Temperature: 80 °C
Reaction time: 18 h

Procedure:
200 mg (0.50 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 11A) and 74.6 mg (0.50 mmol) of 4-formylphenylboronic acid are introduced into 2 ml of DMF. Addition of 0.75 ml of 2 M sodium carbonate solution and 20.3 mg (0.02 mmol) of PdCl2(dppf) is followed by heating to 80° C. After 18 h, the reaction mixture is filtered through kieselguhr and purified by preparative HPLC. The product fractions are concentrated, mixed with a 5:1 mixture of methanol and 4 N hydrogen chloride in dioxane and again concentrated. Drying under high vacuum results in 163.8 mg (75.0% of theory) of the title compound.
Reaction SMILES: [CH2:1]([C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[ClH:13]>CCO.[Pd]>[ClH:13].[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([CH2:9][NH2:10])=[CH:11][CH:12]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1ccc(C#N)cc1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: CCCCc1ccc(CN)cc1
Yield: 86 %

Procedure:
A solution of 4-butylbenzonitrile (30.09 g) in EtOH (380 mL) and HCl (4N in dioxane, 50 mL, 200 mmol) was hydrogenated at 50 psi on a Parr shaker in the presence of 10% palladium on carbon (6.09 g). The catalyst was removed via filtration through Celite® and the solution was concentrated in vacuo. The residue was suspended in Et2O and filtered to provide 4-butylbenzylamine hydrochloride as an off-white solid (32.47 g). 1H NMR (400 MHz, CD3OD) δ 7.33 (d, 2H), 4.04 (s, 2H), 2.60 (t, 2H), 1.56 (m, 2H), 1.31 (m, 2H), 0.89 (t, 3H).
Reaction SMILES: C1(NC2CCCCC2)CCCCC1.[C:14]1([S:20]([NH:23][C@H:24]([C:40](O)=[O:41])[CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:31])(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl.[CH2:44]([O:51][C:52](=[O:58])[C@@H:53]1[CH2:57][CH2:56][CH2:55][NH:54]1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[CH2:44]([O:51][C:52](=[O:58])[C@@H:53]1[CH2:57][CH2:56][CH2:55][N:54]1[C:40](=[O:41])[C@H:24]([CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])[NH:23][S:20]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)(=[O:22])=[O:21])[C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1
Reactant: O=C(NCCCC[C@H](NS(=O)(=O)c1ccccc1)C(=O)O)OCc1ccccc1
Reactant: O=C(OCc1ccccc1)[C@@H]1CCCN1
Agent: C1CCC(NC2CCCCC2)CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: O=C(NCCCC[C@H](NS(=O)(=O)c1ccccc1)C(=O)N1CCC[C@H]1C(=O)OCc1ccccc1)OCc1ccccc1
Reaction time: 2 h

Procedure:
Nα -benzenesulfonyl-Nε -benzyloxycarbonyl-L-lysine dicyclohexylamine (3.01 g, 5 mmole), proline benzylester hydrochloride (1.21 g, 5 mmole) and HOBT (0.68 g, 5 mmole) were dissolved in methylene chloride (30 ml) and WSC hydrochloride (0.96 g, 5 mmole) was added thereto at -30° C. The mixture was stirred for 2 hours at less than 0° C., and then overnight at room temperature, and methylene chloride (70 ml) was added to the solution. The solution was washed with 5% aqueous sodium bicarbonate (100 ml, twice), 5% aqueous citric acid (100 ml, twice) and water (100 ml) in the order given, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain Nα -benzenesulfonyl-Nε -benzyloxycarbonyl-L-lysyl-L-proline benzylester[(yield: 1.68 g. 55.3%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][CH3:10])[NH2:5].C[O:12][C:13]1C=CC=C(N)[CH:14]=1>>[NH2:5][C:4]1[CH:3]=[C:2]([Cl:1])[C:8]([O:9][CH3:10])=[CH:7][C:6]=1[C:13](=[O:12])[CH3:14]
Reactant: COc1ccc(N)cc1Cl
Reactant: COc1cccc(N)c1
Product: COc1cc(C(C)=O)c(N)cc1Cl
Yield: 50 %

Procedure:
1-(2-Amino-4-chloro-5-methoxy-phenyl)-ethanone 201g was synthesized from 3-chloro-4-methoxy-aniline 215g as a brown solid in 50% yield, according to the procedure as described for compound 215a. MS (ESI, EI+): m/z=200 (MH+).
Reaction SMILES: [C:1]1([S:7][CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])(C)(C)C.CCCCC.[CH:19]([C:21]1[CH2:25][CH2:24][CH2:23][CH:22]=1)=[O:20]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[C:21]1([CH:19]([OH:20])[CH2:8][S:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:25][CH2:24][CH2:23][CH:22]=1
Reactant: O=CC1=CCCC1
Reactant: CSc1ccccc1
Agent: [Li]C(C)(C)C
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: CCCCC
Solvent: C1CCOC1
Product: OC(CSc1ccccc1)C1=CCCC1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To a solution of thioanisol (3.73 g, 30 mmol) in a mixture of dry THF (50mL) and HMPA (14 mL) is added dropwise a solution of tert-butyllithium in pentane (30 mmol) at -78° C. over a period of 10 minutes. The resulting yellow-orange mixture is stirred at ambient temperature for an additional 45 minutes. A solution of 1-formyl-cyclopent-1-ene (2.88 g, 30 mmol) in dry THF (10 mL) is then added slowly. After stirring for 5 minutes, the reaction mixture is quenched with saturated ammonium chloride (20 mL), and allowed to warm to room temperature. The mixture is diluted with H2O (100 mL) and extracted with ethyl acetate (50 mL×3). The combined extracts are washed with H2O, dried (Na2SO4) and evaporated in vacuo to dryness. The residue is chromatographed over a silica gel column (5×30 cm) using toluene/EtOAc (9:1) as the eluent. The desired product is obtained as a pale yellow syrup, 5.0 g (76%). 1H NMR (CDCl3): δ1.66-1.99 (2H, m, CH2 -4'), 2.16-2.38 (4H, m, CH2 -3' and CH2 -5'), 2.61 (1H, brs, OH), 2.98 (1H, dd, J=8.21 Hz, J=13.45 Hz, Ha-2), 3.23 (1H, dd, J=4.39 Hz, J=13.45 Hz, Hb-2), 4.33 (1H, dd, J=4.39, J=8.21 Hz, H-1), 5.67 (1H, brs, H-1'), 7.14-7.45 (5H, m, Ph). Anal. Calc'd for C13H16OS: C, 70.87; H, 7.32; S, 14.34. Found: C, 70.88; H, 7.83; S, 14.37.
Reaction SMILES: [OH:1][C@@H:2]([C@H:4]1[C:39](=[O:40])[N:6]2[C:7]([C:26]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][C:33]([N+:36]([O-:38])=[O:37])=[CH:32][CH:31]=3)=[O:27])=[C:8](OP(C3C=CC=CC=3)(C3C=CC=CC=3)=O)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].[SH:41][C@@H:42]1[CH2:46][N:45]([C:47]([O:49][CH2:50][C:51]2[CH:56]=[CH:55][C:54]([N+:57]([O-:59])=[O:58])=[CH:53][CH:52]=2)=[O:48])[C@H:44]([C:60]([N:62]2[CH2:66][CH2:65][C@H:64]([CH2:67][N:68]([CH:82]3[CH2:84][CH2:83]3)[C:69]([O:71][CH2:72][C:73]3[CH:78]=[CH:77][C:76]([N+:79]([O-:81])=[O:80])=[CH:75][CH:74]=3)=[O:70])[CH2:63]2)=[O:61])[CH2:43]1.C(OCC)(=O)C>C(#N)C.C(N(CC)C(C)C)(C)C>[OH:1][C@@H:2]([C@H:4]1[C:39](=[O:40])[N:6]2[C:7]([C:26]([O:28][CH2:29][C:30]3[CH:31]=[CH:32][C:33]([N+:36]([O-:38])=[O:37])=[CH:34][CH:35]=3)=[O:27])=[C:8]([S:41][C@@H:42]3[CH2:46][N:45]([C:47]([O:49][CH2:50][C:51]4[CH:56]=[CH:55][C:54]([N+:57]([O-:59])=[O:58])=[CH:53][CH:52]=4)=[O:48])[C@H:44]([C:60]([N:62]4[CH2:66][CH2:65][C@H:64]([CH2:67][N:68]([CH:82]5[CH2:83][CH2:84]5)[C:69]([O:71][CH2:72][C:73]5[CH:74]=[CH:75][C:76]([N+:79]([O-:81])=[O:80])=[CH:77][CH:78]=5)=[O:70])[CH2:63]4)=[O:61])[CH2:43]3)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(OP(=O)(c3ccccc3)c3ccccc3)[C@H](C)[C@H]12
Reactant: O=C([C@@H]1C[C@H](S)CN1C(=O)OCc1ccc([N+](=O)[O-])cc1)N1CC[C@H](CN(C(=O)OCc2ccc([N+](=O)[O-])cc2)C2CC2)C1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Solvent: CCOC(C)=O
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C(=O)N4CC[C@H](CN(C(=O)OCc5ccc([N+](=O)[O-])cc5)C5CC5)C4)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
Yield: 369 %

Procedure:
To a solution of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-(diphenylphosphoryloxy)-1-carbapen-2-em-3-carboxylate (0.66 g) in anhydrous acetonitrile (7 ml), N,N-diisopropylethylamine (0.19 ml) and a solution of (2S,4S)-4-mercapto-1-(4-nitrobenzyloxycarbonyl)-2-[(3S)-3-(N-cyclopropyl-N-4-nitrobenzyloxycarbonylaminomethyl)pyrrolidin-1-ylcarbonyl]pyrrolidine (0.14 g) in anhydrous acetonitrile (8 ml) were added while stirring in an ice bath. The resulting mixture was allowed to react overnight at 0° C. To the reaction mixture, ethyl acetate was added. The resulting mixture was washed with water and saturated saline solution, dried over anhydrous sodium sulfate and then concentrated by evaporation under reduced pressure. The residue was purified by chromatography through a silica gel column (ethyl acetate/methanol=95/5), whereby 4-nitrobenzyl (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-[(2S,4S)-1-(4-nitrobenzyloxycarbonyl)-2-[(3S)-3-(N-cyclopropyl-N-4-nitrobenzyloxycarbonylaminomethyl)pyrrolidin-1-ylcarbonyl]pyrrolidin-4-ylthio]-1-carbapen-2-em-3-carboxylate (0.80 g) was obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:24]=[CH:23][C:7]([O:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15]C(=O)OC(C)(C)C)[CH:10]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:15][C:11]1[CH:10]=[C:9]([O:8][C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:24][CH:23]=2)[N:14]=[CH:13][N:12]=1
Reactant: CC(C)(C)OC(=O)Nc1cc(Oc2ccc([N+](=O)[O-])cc2)ncn1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Nc1cc(Oc2ccc([N+](=O)[O-])cc2)ncn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension of tert-butyl 6-(4-nitrophenoxy)pyrimidin-4-ylcarbamate (1.22 g, 85% purity, 3.12 mmol) in DCM (12.0 mL) was added TFA (1.4 mL, 18.4 mmol) and the reaction mixture stirred at RT for 1 hr. An additional aliquot of TFA (0.70 mL) was added and the mixture was kept at RT for 15 hr and was then evaporated in vacuo. The residue was partitioned between EtOAc (50 mL) and saturated aq NaHCO3 solution (50 mL) and the organic layer was separated and washed with brine (25 mL) and then dried (MgSO4). Evaporation of the volatiles in vacuo the title compound as a yellow solid (0.66 g, 89%); Rt 1.38 min (Method 2); m/z 233 (M−H)+ (ES+).
Reaction SMILES: O[CH2:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])O)[OH:4].S(=O)(=O)(O)O>O>[CH2:11]1[O:12][C@@H:5]2[C@@H:3]([OH:4])[CH2:2][O:8][C@@H:7]2[C@@H:9]1[OH:10]
Reactant: OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO
Agent: O=S(=O)(O)O
Solvent: O
Product: O[C@@H]1CO[C@H]2[C@@H]1OC[C@@H]2O
Temperature: 145 °C
Yield: 80 %

Procedure:
A stream of 45% by weight sorbitol (balance water) is introduced via inlet (1) at a rate of 8490 lb/hr. It contains 21 lb-moles of sorbitol and about 259 lb-moles of water. Aqueous sulfuric acid, 10% by weight, is injected via line (20) at a rate of 200 lb/hr in sufficient quantity to maintain sulfuric acid concentration at 0.5-0.6 wt % of the sorbitol feed (water-free basis). Heat input to stage heaters (51), (52), and (53) is adjusted to maintain the temperatures at 125, 135, and 145° C., respectively. Pressure in the head space above the third stage is maintained at about 18 to 20 mm Hg. The dehydration reaction through all the stages forms about 16.8 lb-moles of isosorbide (80% yield). 4.2 lb-moles of starting sorbitol go to byproducts comprising monoanhydro sorbitol derivatives, dimers, oligomeric and polymeric materials, and decomposition products. The total amount of water vapor produced from feed stream evaporation and the dehydration of sorbitol is about 312 lb-moles. Under the reaction conditions, about 80% of the isosorbide formed volatilizes in 98% purity into the water vapor. The bottoms are removed via line (12) at a rate of about 1110 lb/hr. Under these conditions, the hold up time is about 3 hours. The vapor stream, after contacting with about 10% internal reflux, is greater than 99% pure isosorbide (water-free basis) and leaves the reaction vessel via line (2) at 16 mm Hg pressure. It comprises 312 lb-moles/hr or 5616 lb/hr water vapor and 13.44 lb-moles/hr or 1962 lb/hr isosorbide. Upon condensation, it produces the nominal 15 to 16 million lb/year of isosorbide as about 25.9% aqueous solution. This may be concentrated or purified further depending on the intended use of the product.
Reaction SMILES: [K].Cl[C:3]1[CH:4]=[CH:5][C:6]([N+:11]([O-:13])=[O:12])=[C:7]([O:9][CH3:10])[CH:8]=1.[C:14]1(B(O)O)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CO.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Cl-].C(C1C=CC=C(C(C)C)C=1[N+]1C=CN(C2C(C(C)C)=CC=CC=2C(C)C)C=1)(C)C>[CH3:10][O:9][C:7]1[CH:8]=[C:3]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:4]=[CH:5][C:6]=1[N+:11]([O-:13])=[O:12]
Reactant: OB(O)c1ccccc1
Reactant: COc1cc(Cl)ccc1[N+](=O)[O-]
Agent: [Pd]
Agent: CC(C)c1cccc(C(C)C)c1-n1cc[n+](-c2c(C(C)C)cccc2C(C)C)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CO
Solvent: Cc1ccccc1
Product: COc1cc(-c2ccccc2)ccc1[N+](=O)[O-]
Temperature: 60 °C
Reaction time: 24 h
Yield: 114.8 %

Procedure:
A solution of potassium methoxyde (0.56 g, 7.98 mmol) in anhydrous methanol (5 mL) was added at 0° C. to a mixture of 5-chloro-2-nitroanisole (0.5 g, 2.66 mmol), phenylboronic acid (0.42 g, 3.44 mmol), bis(dibenzylideneacetone)palladium (47 mg, 0.082 mmol), 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (35 mg, 0.082 mmol) and tetrabutylammonium bromide (86 mg, 0.267 mmol) in anhydrous toluene (20 mL). The reaction mixture was stirred at 60° C. for 24 hours, and then was partitioned between ethyl acetate and water. The organic layer was separated and washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude residue was purified on a silica gel plug (EtOAc/hexane, 20/80) to give 0.7 g of 3-methoxy-4-nitro-biphenyl as a yellow oil.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([NH2:11])(=[O:10])=[O:9].P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C(OC1C=CC(C(O)CNC)=CC=1OC(C(C)(C)C)=O)=O)(C)C.Cl>CN(C)C=O.C(N(CC)CC)C.Cl[Pd]Cl.[Cu]I>[C:3]1([S:8]([NH2:11])(=[O:10])=[O:9])[CH:4]=[CH:5][CH:6]=[CH:7][CH:2]=1
Reactant: NS(=O)(=O)c1ccccc1I
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: CNCC(O)c1ccc(OC(=O)C(C)(C)C)c(OC(=O)C(C)(C)C)c1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: NS(=O)(=O)c1ccccc1

Procedure:
To a solution of 28.3 g (0.1 mole) of 2-iodophenylsulfonamide in 350 ml of dimethylformamide and 100 ml of triethylamine are added 1.0 g of palladium dichloro-bis(triphenylphosphite) complex, PdCl2 [P(C6H5)3 ]2, and 0.5 g of copper(I) iodide (CuI). Gaseous propine is then introduced into this solution until the starting material is completely reacted. The reaction mixture is filtered and the residue is concentrated in vacuo and then taken up in water. The precipitate is isolated and dried. Recrystallisation from ethyl acetate/hexane yields 15.6 g (80%) of 2-propyn-1-yl)phenylsulfonamide with a melting point of 147°-149° C.
Reaction SMILES: [Br:1]Br.[Br:3][C:4]1[CH:5]=[C:6]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)[CH:7]=[CH:8][CH:9]=1>C(O)(=O)C>[Br:1][C:12]1[S:11][C:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([Br:3])[CH:5]=2)=[CH:14][CH:13]=1
Reactant: Brc1cccc(-c2cccs2)c1
Reactant: BrBr
Solvent: CC(=O)O
Product: Brc1cccc(-c2ccc(Br)s2)c1
Yield: 68 %

Procedure:
A solution of bromine (8 g; 50 mM) in 20 mL of glacial acetic acid was added dropwise to a vigorously stirred solution of 2-(3'-bromophenyl)-thiophene (12 g; 50 mM) in 80 mL of glacial acetic acid. The resulting mixture was heated to reflux 5 hrs, cooled and poured onto ice. A solid separated which was filtered and washed with ice water, and purified on silica gel using hexane as solvent to give 68% of 2-bromo-5-[3'-bromophenyl]thiophene as an amorphous solid.
Reaction SMILES: C1(SC)C=CC=CC=1.FC(F)(F)C(O)=O.C([O:23][C:24]1[CH:51]=[CH:50][C:49]([N:52]2[CH2:57][CH2:56][S:55][CH2:54][CH2:53]2)=[CH:48][C:25]=1[C:26]([NH:28][C:29]1[CH:41]=[C:40]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:39]=[CH:38][C:30]=1[C:31]([O:33]C(C)(C)C)=[O:32])=[O:27])C1C=CC=CC=1>>[OH:23][C:24]1[CH:51]=[CH:50][C:49]([N:52]2[CH2:53][CH2:54][S:55][CH2:56][CH2:57]2)=[CH:48][C:25]=1[C:26]([NH:28][C:29]1[CH:41]=[C:40]([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH:39]=[CH:38][C:30]=1[C:31]([OH:33])=[O:32])=[O:27]
Reactant: CC(C)(C)OC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(N2CCSCC2)ccc1OCc1ccccc1
Solvent: CSc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1cc(-c2ccccc2)ccc1C(=O)O)c1cc(N2CCSCC2)ccc1O
Temperature: 25 °C
Reaction time: 24 h
Yield: 62.8 %

Procedure:
Thioanisole (1.0 mL) was added to a trifluoroacetic acid (2.0 mL) solution of tert-butyl 2-(2-(benzyloxy)-5-(thiomorpholin-4-yl)benzamido)-4-phenylbenzoate (0.10 g), followed by stirring at room temperature for 24 hours. The solvent was evaporated under reduced pressure, and a 4 mol/L hydrogen chloride-dioxane solution (0.5 mL) and ethyl acetate (1.0 mL) were added to the residue, followed by stirring at room temperature for 3 hours. The solid substance was collected by filtration, and water and ethyl acetate were added to the obtained solid substance. After adjusting the pH to 6.5 with a saturated aqueous solution of sodium bicarbonate, the organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: chloroform] to obtain 0.047 g of 2-(2-hydroxy-5-(thiomorpholin-4-yl)benzamido)-4-phenylbenzoic acid as a yellow solid.