Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH:2]([CH2:6][CH3:7])[C:3](Cl)=[O:4].[Cl-].[Al+3].[Cl-].[Cl-].[C:12]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH3:24][CH:25]([CH2:29][CH3:30])[C:26]([O-:28])=[O:27].Cl>[N+](C1C=CC=CC=1)([O-])=O>[CH3:1][CH:2]([CH2:6][CH3:7])[C:3]([C:21]1[CH:22]=[CH:23][C:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:19][CH:20]=1)=[O:4].[CH3:24][CH:25]([CH2:29][CH3:30])[C:26]([O-:28])=[O:27]
Reactant: c1ccc(-c2ccccc2)cc1
Reactant: CCC(C)C(=O)Cl
Agent: CCC(C)C(=O)[O-]
Agent: Cl
Agent: [Al+3]
Solvent: O=[N+]([O-])c1ccccc1
Product: CCC(C)C(=O)c1ccc(-c2ccccc2)cc1
Temperature: 0 °C
Reaction time: 70 h
Yield: 54.1 %

Procedure:
Then, 4.0 g of (+)-2-methyl butanoyl chloride and 7 ml of nitrobenzene were charged into a flask and cooled to 0° C., added with 10.74 g (80 mmol) of anhydrous aluminum chloride and further with a solution of 4.97 g (19.6 mmol) of (+)-biphenyl-2-methylbutanoate in 9 ml of nitrobenzene, which was stirred at room temperature for 70 hours. After the addition of 2 normal hydrochloric acid and ice, the extraction with chloroform was performed. The extracted chloroform phase was washed with water, dried on anhydrous magnesium sulfate, and the solvent was distilled off. The residue was purified through a column chromatography of silica gel after distillation off of the solvent to obtain 3.60 g (yield: 54%) of an oily (+)-4-(2-methylbutanoyl) biphenyl-2-methylbutanoate. The NMR analytical values of this product were as follows.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[N:11]1[C:15](=[O:16])[NH:14][N:13]=[N:12]1.[H-].[Na+].I[CH2:20][CH3:21]>CS(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[N:11]1[C:15](=[O:16])[N:14]([CH2:20][CH3:21])[N:13]=[N:12]1
Reactant: CCI
Reactant: COc1cc(-n2nn[nH]c2=O)c(Cl)cc1F
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CCn1nnn(-c2cc(OC)c(F)cc2Cl)c1=O
Yield: 85.6 %

Procedure:
In the manner of Example 2, Step F, the reaction of 1.33 g (0.0054 mole) of 1-(2-chloro-4-fluoro-5-methoxyphenyl)-1,4-dihydro-5H-tetrazol-5-one with 0.26 g (0.0054 mole) of sodium hydride and 1.6 g (0.01 mole) of iodoethane in 60 mL of dimethylsulfoxide produced 1.26 g of 1-(2-chloro-4-fluoro-5-methoxyphenyl)-1,4-dihydro-4-ethyl-5H-tetrazol-5-one, compound 105, 79°-80° C. Compound 106 was prepared in a similar manner.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([NH2:13])=[O:12])[C:6](=[O:14])[CH2:5]2.[CH3:15][S:16]([C:19]1[S:23][C:22]([C:24](Cl)=[O:25])=[CH:21][CH:20]=1)(=[O:18])=[O:17]>CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([NH2:13])=[O:12])[C:6](=[O:14])[CH:5]2[C:24](=[O:25])[C:22]1[S:23][C:19]([S:16]([CH3:15])(=[O:18])=[O:17])=[CH:20][CH:21]=1
Reactant: CS(=O)(=O)c1ccc(C(=O)Cl)s1
Reactant: NC(=O)N1C(=O)Cc2cc(Cl)ccc21
Agent: CN(C)c1ccncc1
Product: CS(=O)(=O)c1ccc(C(=O)C2C(=O)N(C(N)=O)c3ccc(Cl)cc32)s1
Yield: 70 %

Procedure:
The title compound was prepared according to the procedure of Example 32. A 2.06 g (10.0 mmoles) sample of 5-methylsulfonyl-2-thiophenecarboxylic acid (prepared according to Cymerman-Craig, J., et al., J. Chem. Soc.:237 (1954)) reacted with 10 ml of thionyl chloride to give 2.14 g of crude acid chloride as a solid. The reaction of 1.75 g (8.33 mmoles) of 5-chloro-2-oxindole-1-carboxamide with 5-methylsulfonyl-2-thiophenecarbonyl chloride in the presence of 3.05 g (25.0 mmoles) of 4-(N,N-dimethylamino)pyridine gave 3.17 g of crude product after acidic workup. A single recrystallization from acetic acid gave 2.31 g (5.80 mmoles, 70% yield) of pure 5-chloro-3-(5-methylsulfonyl-2-thenoyl)-2-oxindole -1-carboxamide as a deep-orange solid, m.p. 212°-14° C.
Reaction SMILES: Cl.[CH3:2][CH:3]1[CH:9]([CH3:10])[CH2:8][N:7]([C:11](=[O:24])[C:12]2[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:13]=2[N:19]2[N:23]=[CH:22][CH:21]=[N:20]2)[CH2:6][CH2:5][NH:4]1.Cl[C:26]1[N:35]=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([F:36])[CH:32]=2)[N:27]=1.C(N(CC)CC)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[CH3:10][CH:9]1[CH:3]([CH3:2])[N:4]([C:26]2[N:35]=[CH:34][C:33]3[C:28](=[CH:29][CH:30]=[C:31]([F:36])[CH:32]=3)[N:27]=2)[CH2:5][CH2:6][N:7]([C:11](=[O:24])[C:12]2[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:13]=2[N:19]2[N:23]=[CH:22][CH:21]=[N:20]2)[CH2:8]1
Reactant: Cc1ccc(-n2nccn2)c(C(=O)N2CCNC(C)C(C)C2)c1
Reactant: Fc1ccc2nc(Cl)ncc2c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: Cc1ccc(-n2nccn2)c(C(=O)N2CCN(c3ncc4cc(F)ccc4n3)C(C)C(C)C2)c1
Temperature: 130 °C

Procedure:
Compound 1-7 (75 mg, 0.21 mmol) was combined with 2-chloro-6-fluoroquinazoline 1-8 (39 mg, 0.21 mmol; see example 1-D), triethylamine (30 uL, 0.21 mmol), and potassium carbonate (296 mg, 2.1 mmol) in toluene (2 mL) and heated in a sealed tube to 130° C. overnight. The reaction was concentrated in vacuo and the residue purified by reverse phase preparative chromatography on a C-18 column (5 to 75% acetonitrile in water with 0.1% TFA buffer). The clean fractions were combined and made basic with 20% sodium carbonate solution. This was extracted with ethyl acetate two times and the combined organics washed with brine and dried with sodium sulfate. Concentration in vacuo gave the titled compound as a solid. Data for 1-9: LC/MS: m/z (M+Na)=460.2 found; 460.5 calculated.
Reaction SMILES: [O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH:3]([NH:11][C:12]([C:14]2[CH:36]=[CH:35][C:17]([O:18][C:19]3[CH:28]=[C:27]4[C:22]([CH:23]([C:29]([O:31]C)=[O:30])[CH2:24][CH2:25][O:26]4)=[CH:21][C:20]=3[C:33]#[N:34])=[CH:16][CH:15]=2)=[O:13])[CH2:2]1.O[Li].O.O1CCOCC1.Cl>C1COCC1>[O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH:3]([NH:11][C:12]([C:14]2[CH:15]=[CH:16][C:17]([O:18][C:19]3[CH:28]=[C:27]4[C:22]([CH:23]([C:29]([OH:31])=[O:30])[CH2:24][CH2:25][O:26]4)=[CH:21][C:20]=3[C:33]#[N:34])=[CH:35][CH:36]=2)=[O:13])[CH2:2]1
Reactant: COC(=O)C1CCOc2cc(Oc3ccc(C(=O)NC4COc5ccccc5C4)cc3)c(C#N)cc21
Agent: Cl
Agent: [Li]O
Solvent: C1CCOC1
Solvent: C1COCCO1
Solvent: O
Product: N#Cc1cc2c(cc1Oc1ccc(C(=O)NC3COc4ccccc4C3)cc1)OCCC2C(=O)O
Temperature: 25 °C
Reaction time: 17 h
Yield: 79.1 %

Procedure:
Methyl 7-(4-(chroman-3-ylcarbamoyl)phenoxy)-6-cyano-3,4-dihydro-2H-chromene-4-carboxylate (27.6 mg, 0.0570 mmol) was dissolved in THF (3 ml) and 1M solution of LiOH—H2O (114 μL, 0.114 mmol) was added. The mixture was stirred for 17 hours at ambient temperature. The mixture was quenched with 4M HCl dioxane (42.7 μL, 0.171 mmol). The crude mixture was purified on silica gel (MeOH in dichloromethane with 1% acetic acid gradient) to provide 21.2 mg of the title compound as white a solid (79%). MS (apci) m/z=471.0 (M+H).
Reaction SMILES: [CH3:1][CH:2]([CH3:14])[C:3]([C:5]1[NH:13][C:8]2=[CH:9][N:10]=[CH:11][CH:12]=[C:7]2[CH:6]=1)=O.[C:15]([NH:18][NH2:19])([NH2:17])=[NH:16].[ClH:20].Cl>C(O)C>[ClH:20].[ClH:20].[CH3:1][CH:2]([CH3:14])[C:3](=[N:19][NH:18][C:15]([NH2:17])=[NH:16])[C:5]1[NH:13][C:8]2=[CH:9][N:10]=[CH:11][CH:12]=[C:7]2[CH:6]=1
Reactant: N=C(N)NN
Reactant: CC(C)C(=O)c1cc2ccncc2[nH]1
Agent: Cl
Solvent: CCO
Product: CC(C)C(=NNC(=N)N)c1cc2ccncc2[nH]1
Temperature: 25 °C
Reaction time: 2 h
Yield: 33.3 %

Procedure:
To a solution of 2-methyl-1-(1H-pyrrolo[2,3-c]pyridin-2-yl)-1-propanone (Example 80) (100 mg, 0.53 mmol) in ethanol (5 mL) were added aminoguanidine hydrochloride (58 mg, 0.53 mmol) and 6 N HCl (0.2 mL). The reaction mixture was heated to reflux under N2. After 2 h, heating was terminated and the reaction mixture was cooled to room temperature. Purification by column chromatography (silica gel, 5 to 20% methanol in methylene chloride) produced [[2-methyl-1-(1H-pyrrolo[2,3-c]pyridin-2-yl)propylidene]amino]guanidine dihydrochloride (28 mg, 26%) as a yellow solid: mp 242-245° C.; 1H NMR (500 MHz, CD3OD) δ 1.49 (6H, d, J=7.1 Hz), 3.50-3.54 (1H, m), 7.15 (1H, s), 7.72 (1H, d, J=5.5 Hz), 8.11 (1H, d, J=5.6 Hz), 8.77 (1H, s); ESI MS m/z 245 [C12H16N6+H]+; HPLC (Method A) >99% (AUC) tR=11.9 min.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[CH:10][C:9]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.[OH-].[Na+].Cl>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:12])[CH:9]([C:13]2[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=2)[C:10]#[N:11])=[CH:6][CH:7]=1
Reactant: Clc1ccc(-c2oncc2-c2ccncc2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: N#CC(C(=O)c1ccc(Cl)cc1)c1ccncc1
Temperature: 25 °C
Yield: 97.5 %

Procedure:
A solution of 5-(4-chlorophenyl)-4-(pyridin-4-yl)isoxazole (20.5 g, 79.9 mmol) and 150 mL of a 1N sodium hydroxide solution was stirred at 60° C. for 1 hour. The reaction mixture was cooled to room temperature and adjusted to pH 6 with concentrated hydrochloric acid. The precipitates were filtered, washed with water and ethanol, and dried to give 3-(4-chlorophenyl)-3-oxo-2-(pyridin-4-yl)propanenitrile (20.0 g, quantitative yield). m.p. 225.4-234.9° C. 1H NMR (CDCl3/CD3OD/300 MHz) δ 8.12 (brs, 2H), 7.73-7.59 (m, 5H), 7.30 (d, 3H). ESLRMS m/z 257 (M+H). ESHRMS m/z 257.0481 (M+H, C14H9N20Cl requires 257.0482).
Reaction SMILES: [O:1]1[CH:13]2[C@@:14]34[CH2:16][CH2:17][N:18]([CH3:19])[C@@H:8]([C@:9]3([OH:21])[CH2:10][CH2:11][C:12]2=[O:20])[CH2:7][C:6]2=[C:15]4[C:2]1=[CH:3][CH:4]=[CH:5]2.[Br:22]Br>CC(O)=O>[Br:22][C:3]1[CH:4]=[CH:5][C:6]2[CH2:7][C@H:8]3[N:18]([CH3:19])[CH2:17][CH2:16][C@:14]45[C:15]=2[C:2]=1[O:1][CH:13]4[C:12](=[O:20])[CH2:11][CH2:10][C@@:9]35[OH:21]
Reactant: CN1CC[C@]23c4c5cccc4OC2C(=O)CC[C@@]3(O)[C@H]1C5
Reactant: BrBr
Solvent: CC(=O)O
Product: CN1CC[C@]23c4c5ccc(Br)c4OC2C(=O)CC[C@@]3(O)[C@H]1C5

Procedure:
1.1 g (3.8 mmol) of 4,5-epoxy-14-hydroxy-17-methylmorphinan-6-one in 50 ml of glacial AcOH were treated with 3.8 ml of a 1M solution of Br2 in AcOH as described in Preparation 5, yielding 1.1 g of the title product.
Reaction SMILES: Cl.Cl.[CH2:3]([C@:5]1([C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=3)[CH2:15][CH2:14]2)=[O:12])[CH2:9][CH2:8][C@H:7]([NH2:10])[CH2:6]1)[CH3:4].[CH3:29][CH:30]1[C:35](=O)[CH2:34][CH2:33][O:32][CH2:31]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH2:3]([C@:5]1([C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=3)[CH2:15][CH2:14]2)=[O:12])[CH2:9][CH2:8][C@H:7]([NH:10][CH:35]2[CH2:34][CH2:33][O:32][CH2:31][CH:30]2[CH3:29])[CH2:6]1)[CH3:4]
Reactant: CC1COCCC1=O
Reactant: CC[C@]1(C(=O)N2CCN(c3cc(C(F)(F)F)ccn3)CC2)CC[C@H](N)C1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC[C@]1(C(=O)N2CCN(c3cc(C(F)(F)F)ccn3)CC2)CC[C@H](NC2CCOCC2C)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 40.6 %

Procedure:
To a solution of (1S,3S)-3-ethyl-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentanamine dihydrochloride (100 mg, 0.20 mmol), 3-methyltetrahydro-4H-pyran-4-one (96 mg, 0.71 mmol), and triethylamine (0.11 mL, 0.79 mmol) in methylene chloride (3 mL) was added sodium triacetoxyborohydride (96 mg, 0.45 mmol). After being stirred at room temperature overnight, the reaction was quenched with saturated NaHCO3 and extracted with methylene chloride three times. The combined organics were dried (MgSO4), filtered, concentrated, purified by flash column chromatography (NH4OH/MeOH/EtOAc) to yield the desired product (38 mg, 40%). MS calculated for C24H35F3N4O2: (M+H) 469.3; found 469.3.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[NH:13][C:12]([C:14]([C:46]4[CH:51]=[CH:50][C:49]([OH:52])=[CH:48][CH:47]=4)=[C:15]4[N:45]=[C:18]([C:19]([C:38]5[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=5)=[C:20]5[NH:37][C:23](=[C:24]([C:30]6[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=6)[C:25]6[CH:26]=[CH:27][C:28]=2[N:29]=6)[CH:22]=[CH:21]5)[CH:17]=[CH:16]4)=[CH:11][CH:10]=3)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH3:69]>CN(C=O)C>[OH:52][C:49]1[CH:48]=[CH:47][C:46]([C:14]2[C:12]3[NH:13][C:9]([C:8]([C:5]4[CH:6]=[CH:7][C:2]([O:1][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH3:69])=[CH:3][CH:4]=4)=[C:28]4[N:29]=[C:25]([C:24]([C:30]5[CH:31]=[CH:32][C:33]([OH:36])=[CH:34][CH:35]=5)=[C:23]5[NH:37][C:20](=[C:19]([C:38]6[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=6)[C:18]6[CH:17]=[CH:16][C:15]=2[N:45]=6)[CH:21]=[CH:22]5)[CH:26]=[CH:27]4)=[CH:10][CH:11]=3)=[CH:51][CH:50]=1
Reactant: CCCCCCCCCCBr
Reactant: Oc1ccc(-c2c3nc(c(-c4ccc(O)cc4)c4ccc([nH]4)c(-c4ccc(O)cc4)c4nc(c(-c5ccc(O)cc5)c5ccc2[nH]5)C=C4)C=C3)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCOc1ccc(-c2c3nc(c(-c4ccc(O)cc4)c4ccc([nH]4)c(-c4ccc(O)cc4)c4nc(c(-c5ccc(O)cc5)c5ccc2[nH]5)C=C4)C=C3)cc1
Reaction time: 1.5 h

Procedure:
5,10,15,20-tetrakis-(4-Hydroxy-phenyl)-porphyrin (100 mg, 0.15 mmol) is dissolved and K2CO3 (230 mg) is suspended in DMF (30 mL). To the vigorously stirred reaction mixture a solution of 1-bromodecane (0.016 mL, 0.11 mmol) in DMF (10 mL) is added dropwise at 70° C. during 30 mins and the mixture is stirred for 1.5 h. After evaporation of solvent, the residue is dissolved in toluene:ethanol (1:1 by vol., ca. 3 mL) and purified by chromatography on a column (150 g) of silica gel (Merck 60) using toluene as eluent. After elution of the first 3 fractions, the column is eluted with toluene:ethyl acetate (2:1 by vol.) and the 5th fraction eluted is collected, the solvent removed and the residue dried under high vacuum to give the product as violet crystals.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([O:12]C)=O)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[NH2:14][NH2:15]>CCO>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([NH:14][NH2:15])=[O:12])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: COC(=O)c1ccc2[nH]ccc2c1
Reactant: NN
Solvent: CCO
Product: NNC(=O)c1ccc2[nH]ccc2c1
Yield: 77.4 %

Procedure:
To a solution of methyl 1H-indole-5-carboxylate (0.9 g, 5.142 mmol) in EtOH (10 mL) was added NH2NH2 (1.8 mL, 38.11 mmol). The reaction was heated at reflux for 12 h. The solvent was removed in vacuo to give a yellow solid, which was recrystallized with 60% EtOAc in n-hexane (10 mL) to afford 1H-indole-5-carbohydrazide (0.7 g, 3.98 mmol, 77.8%). MS (ESI, pos. ion) m/z: 176 (M+1).
Reaction SMILES: C(S)C1C=CC=CC=1.C(S[CH2:22][CH2:23][C:24]([O:26][CH:27]([CH2:42][S:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50]CCCCC)[CH2:28][S:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]CCCCC)=[O:25])CCCCCCCCCCC.C([O-])(=O)C=C.O>C(O)C>[C:24]([O:26][CH:27]([CH2:28][S:29][CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[CH2:42][S:43][CH2:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)(=[O:25])[CH:23]=[CH2:22]
Reactant: CCCCCCCCCCCCSCCC(=O)OC(CSCCCCCCCCCCCC)CSCCCCCCCCCCCC
Agent: C=CC(=O)[O-]
Agent: SCc1ccccc1
Solvent: O
Solvent: CCO
Product: C=CC(=O)OC(CSCc1ccccc1)CSCc1ccccc1

Procedure:
1,3-bis-(benzylthio)-2-propyl acrylate was prepared by using benzyl mercaptan in place of dodecanethiol in the procedure described in Steps (1) and (2) of Example 1. A solution of 14 grams of the acrylate, 5.8 grams of benzyl mercaptan and 1 milliliter of "Triton B" in 75 milliliters of ethanol was heated under reflux for 71/4 hours. The reaction mixture was allowed to cool and was then poured into water. The oil which precipitated was separated by extraction with toluene and the toluene solution was stripped on a rotary evaporator. There remained 21.0 grams of a light colored oil which was identified as 1,3-bis-(benzylthio)-2-propyl 3-(benzylthio)propionate by means of its NMR spectrum.
Reaction SMILES: [C:1]([O:4][CH2:5][CH:6]([NH:12][C:13]([C:15]1[C:16]([I:45])=[C:17]([NH:37][C:38](=[O:44])[O:39][CH2:40][CH:41]2[CH2:43][O:42]2)[C:18]([I:36])=[C:19]([C:22]([NH:24][CH:25]([CH2:31][O:32][C:33](=[O:35])[CH3:34])[CH2:26][O:27][C:28](=[O:30])[CH3:29])=[O:23])[C:20]=1[I:21])=[O:14])[CH2:7][O:8][C:9](=[O:11])[CH3:10])(=[O:3])[CH3:2].N1C=CC=CC=1>C(OCC)(=O)C>[C:1]([O:4][CH2:5][CH:6]([NH:12][C:13]([C:15]1[C:16]([I:45])=[C:17]([N:37]2[CH:41]([CH2:43][OH:42])[CH2:40][O:39][C:38]2=[O:44])[C:18]([I:36])=[C:19]([C:22]([NH:24][CH:25]([CH2:31][O:32][C:33](=[O:35])[CH3:34])[CH2:26][O:27][C:28](=[O:30])[CH3:29])=[O:23])[C:20]=1[I:21])=[O:14])[CH2:7][O:8][C:9](=[O:11])[CH3:10])(=[O:3])[CH3:2]
Reactant: CC(=O)OCC(COC(C)=O)NC(=O)c1c(I)c(NC(=O)OCC2CO2)c(I)c(C(=O)NC(COC(C)=O)COC(C)=O)c1I
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: CC(=O)OCC(COC(C)=O)NC(=O)c1c(I)c(C(=O)NC(COC(C)=O)COC(C)=O)c(I)c(N2C(=O)OCC2CO)c1I
Yield: 76.2 %

Procedure:
A solution of oxiranylmethyl [3,5-bis[[[2-(acetyloxy)-1-[(acetyloxy)methyl]ethyl]amino]carbonyl]-2,4,6-triiodophenyl]carbamate of Example 3a (12.1 g, 12.4 mmol) in freshly distilled anhydrous pyridine (120 ml) was heated at 75° C. for 45 minutes. Pyridine was removed under diminished pressure at 45° C. and the residue was co-evaporated twice with toluene (75 ml). The solid thus obtained was dissolved in ethyl acetate (250 ml) and the solution was washed with H2O (1×100 ml). The organic layer was dried (MgSO4). It was then filtered and the solvent removed to obtain the title compound as a yellow solid (9.2 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9]O)=[CH:4][CH:3]=1.P(Br)(Br)[Br:12]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][Br:12])=[CH:4][CH:3]=1
Reactant: OCCc1ccc(F)cc1
Reactant: BrP(Br)Br
Solvent: Cc1ccccc1
Product: Fc1ccc(CCBr)cc1
Temperature: 25 °C
Reaction time: 120 h
Yield: 64.8 %

Procedure:
To a solution of 2-(4-fluorophenyl)ethyl alcohol (13.4 mL, 107 mmol) in dry toluene (150 mL) at 0° C. was added phosphorous tribromide (21.1 mL, 224 mmol). The resulting mixture was stirred at ambient temperature for 5 days and then recooled to 0° C. and crushed ice (200 g) added. The aqueous layer was extracted with ether (2×120 mL) and the combined organic extracts were then washed with saturated aqueous sodium bicarbonate solution (2×30 mL), dried (MgSO4) and concentrated in vacuo. Distillation afforded 2-(4-fluorophenyl)ethyl bromide as a colorless oil (14.08 g, 31%); b.p. 103° C. @ 12 mm Hg.
Reaction SMILES: [CH3:1][N:2]1[CH2:10][C:9]2([C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=3)[CH:4]([CH:5]3[CH2:18][CH:8]2[CH:7]=[CH:6]3)[CH2:3]1.N([O-])=O.[Na+].[N-:23]=[N+:24]=[N-].[Na+]>O>[N:17]([C:14]1[CH:15]=[CH:16][C:11]([C:9]23[CH:8]4[CH2:18][CH:5]([CH2:6][CH2:7]4)[CH:4]2[CH2:3][N:2]([CH3:1])[CH2:10]3)=[CH:12][CH:13]=1)=[N+:23]=[N-:24]
Reactant: CN1CC2C3C=CC(C3)C2(c2ccc(N)cc2)C1
Reactant: [N-]=[N+]=[N-]
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: CN1CC2C3CCC(C3)C2(c2ccc(N=[N+]=[N-])cc2)C1
Temperature: 5 °C
Reaction time: 1 h

Procedure:
A 200 mg portion of 4-(1,2,3,4,7,7a-hexahydro-2-methyl-4,7-methano-3aH-isoindol-3a-yl)benzenamine was suspended in 35 ml of water, the pH was adjusted to 1.6 and the solution was cooled to 5° C. A 59 mg portion of sodium nitrite was added and the mixture was stirred for one hour at 5° C. A 54 mg portion of sodium azide was added, the cooling bath removed and the reaction protected from light for one hour. Still protected from light, the mixture was diluted with ether, made basic with sodium hydroxide and evaporated at reduced pressure, giving 210 mg of the desired product as a brown oil.
Reaction SMILES: [CH3:1][CH:2]([OH:6])[CH:3]([OH:5])[CH3:4]>C(O)(=O)C>[C:3]([O:5][CH:3]([CH:2]([O:6][C:2](=[O:6])[CH3:1])[CH3:1])[CH3:4])(=[O:5])[CH3:4]
Reactant: CC(O)C(C)O
Solvent: CC(=O)O
Product: CC(=O)OC(C)C(C)OC(C)=O

Procedure:
As a by-product in the 1,3-propanediol fermentation, 2,3-butanediol also is an important raw material in chemical industry. It is a colorless and flavorless liquid, and may be used as fuels, and used to prepare polymers, inks, perfumes, antifreezers, fumigants, humidizers, softening agent, plasticizer, explosives, chiral vehicles for pharmaceuticals and the like. Also, 2,3-butanediol may serve as a very valuable raw material in chemical industry to synthesize other chemicals, for example, dehydrating 2,3-butanediol to form methyl ethyl ketone with quite extensive applications, and further dehydrating to form 1,3-butadiene. 2,3-Butanediol can be polymerized to produce styrene via a Diels-Alder reaction. 2,3-Butanediol and methyl ethyl ketone may condense and then subject to a hydrogenating reaction to form octane, which can be used to produce high quality materials for flight. 2,3-Butanediol reacts with acetic acid to form 2,3-butanediol diacetate, which can be added to butters to improve flavor. Generally, 2,3-butanediol, however, is not be separated and purified as a product due to its low yields in the 1,3-propanediol fermentation.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:9][S:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:3][C:4]([N:6]([CH3:8])[CH3:7])=O.CO.Cl>C1COCC1>[NH2:1][C@@H:2]([CH2:9][S:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH2:3][CH2:4][N:6]([CH3:8])[CH3:7]
Reactant: CN(C)C(=O)C[C@@H](N)CSc1ccccc1
Agent: Cl
Solvent: C1CCOC1
Solvent: CO
Product: CN(C)CC[C@@H](N)CSc1ccccc1
Reaction time: 8 h
Yield: 54.9 %

Procedure:
A solution of EXAMPLE 1L (8.68 g, 36.5 mmol) in THF (200 mL) was treated with BH3-dimethylsulfide (18.2 mL, 182.5 mmol) at room temperature, stirred overnight, treated slowly with methanol (20 mL), followed by 2N HCl (50 mL), stirred overnight, and concentrated. The resulting residue was purified by silica gel chromatography eluting with 5% 7N NH3/CH3OH in dichloromethane to give the desired product (4.50 g, 55%). MS (CI) m/e 224 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:11])[CH3:10])=[CH:5][CH:4]=1.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(N(CC)CC)C.[CH:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[S:40][CH:41]([C:45](O)=[O:46])[C:42](O)=[O:43])([CH3:33])[CH3:32]>C(Cl)Cl>[OH:46][C:45]1[CH:10]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[O:11][C:42](=[O:43])[C:41]=1[S:40][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=1[CH:31]([CH3:33])[CH3:32]
Reactant: CC(C)c1ccccc1SC(C(=O)O)C(=O)O
Reactant: COc1ccc(C(C)=O)cc1
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(-c2cc(O)c(Sc3ccccc3C(C)C)c(=O)o2)cc1

Procedure:
The title compound was prepared by Method A using 4'-methoxyacetophenone (2.26 g, 15.1 mmol), trimethylsilyl triflate (3.5 mL, 18.1 mmol), triethylamine (4.26 mL, 30.6 mmol), methylene chloride (30 mL), and diethyl ester of [(2-isopropylphenyl)thio]propanedioic acid (3.11 g, 10.0 mmol) m.p. 221-223° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.25 (d, 6H), 3.40 (m, 1H), 3.85 (s, 3H), 6.78 (s, 1H), 6.92 (m, 1H), 7.10 (m, 4H), 7.27 (m, 1H), 7.81 (d, 2H), 12.38 (brs, 1H).
Reaction SMILES: [CH3:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([N+:13]([O-])=O)[CH:5]=[CH:4][CH:3]=1>C(O)(=O)C.C(O)C.O.[Fe]>[NH2:13][C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]
Reactant: CCOC(=O)c1c(C)cccc1[N+](=O)[O-]
Agent: [Fe]
Solvent: CCO
Solvent: CC(=O)O
Solvent: O
Product: CCOC(=O)c1c(C)cccc1N

Procedure:
A reaction mixture of 185 g of ethyl 6-methyl-2-nitrobenzoate and 176 g of powdered iron in 343 mL of glacial acetic acid and 2200 mL of ethanol was heated at reflux for 5 hours. The reaction mixture was allowed to cool, diluted with excess water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated to an orange oil 148.3 g.