Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][C@@H:10]2[CH2:14][N:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH2:19][O:18][C:17]3[CH:26]=[CH:27][CH:28]=[CH:29][C:16]2=3)=[CH:5][CH:4]=1.[Cl:32]CCl>>[ClH:32].[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][C@@H:10]2[CH2:14][N:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH2:19][O:18][C:17]3[CH:26]=[CH:27][CH:28]=[CH:29][C:16]2=3)=[CH:30][CH:31]=1
Reactant: ClCCl
Agent: COc1ccc(CCN2CCC[C@@H]2CN2c3ccccc3COc3ccccc32)cc1
Product: Cl
Reaction time: 0.08 h

Procedure:
A hydrogen chloride ether saturated solution was added to a solution of 2.9 g (7.0 mmols) of (R)-(+)-5,11-dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine in 20 ml of dichloromethane, and the mixture was stirred for 5 minutes. Then, the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from a mixed solvent of dichloromethane and diethyl ether to give 2.9 g of (R)-(+)-5,11-dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]-dibenzo[b,e][1,4]oxazepine hydrochloride as a colorless prism crystal in a yield of 93%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][C@H:10]2[CH2:14][N:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH2:19][O:18][C:17]3[CH:26]=[CH:27][CH:28]=[CH:29][C:16]2=3)=[CH:5][CH:4]=1.[Cl:32]CCl>>[ClH:32].[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][C@H:10]2[CH2:14][N:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH2:19][O:18][C:17]3[CH:26]=[CH:27][CH:28]=[CH:29][C:16]2=3)=[CH:30][CH:31]=1
Reactant: ClCCl
Agent: COc1ccc(CCN2CCC[C@H]2CN2c3ccccc3COc3ccccc32)cc1
Product: Cl

Procedure:
A hydrogen chloride ether saturated solution was added to a solution of 12.0. g (23.2 mmols) of (S)-(-)-5,11-dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine in 50 ml of dichloromethane, and the mixture was stirred for 5 minutes. Then, the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from a mixed solvent of acetone and diethyl ether to give 9.5 g of (S)-(-)-5,11-dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine hydrochloride as a colorless prism crystal in a yield of 73%.
Reaction SMILES: [CH3:1][C:2]1[S:3][CH:4]=[C:5]2[C:11](=[O:12])[NH:10][C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[NH:7][C:6]=12.[C:17](Cl)([Cl:19])=[O:18]>ClCCl.C1(C)C=CC=CC=1>[Cl:19][C:17]([N:7]1[C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[NH:10][C:11](=[O:12])[C:5]2=[CH:4][S:3][C:2]([CH3:1])=[C:6]12)=[O:18]
Reactant: O=C(Cl)Cl
Reactant: Cc1scc2c1Nc1ccccc1NC2=O
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: Cc1scc2c1N(C(=O)Cl)c1ccccc1NC2=O
Temperature: 25 °C
Reaction time: 168 h

Procedure:
8.2 g (0.036 mol) of 4,9-dihydro-3-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one were suspended in 365 ml of dichloromethane and after the addition of 40 ml (0.08 mol) of a 20% phosgene solution in toluene the mixture was stirred for 7 days at ambient temperature. The solution formed was washed three times, each time with 80 ml of water, dried over sodium sulphate and the solvent was eliminated in vacuo. The desired compound was freed from contaminants by column chromatography on MN silica gel 60 (70-230 mesh ASTM) using dichloromethane/ethyl acetate/petroleum ether 5/5/4 (v/v) as eluant. 6.1 g (58% of theory) of colourless crystals were obtained, m.p. 238°-239° C., RF 0.77 (Macherey-Nagel, PolygramRSIL G/UV254, pre-coated plastic sheets for TLC, eluant: dichloromethane/ethyl acetate/petroleum ether 5/5/4 v/v).
Reaction SMILES: [OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].[Br:13][CH2:14][CH2:15][CH2:16]Br.C(N(CC)CC)C>CN(C=O)C>[C:3]1(=[O:12])[N:2]([O:1][CH2:16][CH2:15][CH2:14][Br:13])[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]12
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: BrCCCBr
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1OCCCBr
Temperature: 47.5 °C
Reaction time: 5.5 h

Procedure:
A mixture of N-hydroxyphthalimide (16.3 g, 100 mmol) and 1,3-dibromopropane (20.19 g, 100 mmol) in dry DMF (150 mL) and triethyl amine (15.33 mL, 110 mmol) is stirred at 20 to 75° C. for 1 to 10 hours. After filtration, the mixture is evaporated to dryness in vacuo. The residue is purified by silica gel flash column chromatography to give the title compound.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]([CH2:9][C:10]#[N:11])[CH:6]=[CH:7][CH:8]=1.B(Br)(Br)Br.O>ClCCl>[OH:2][C:3]1[CH:4]=[C:5]([CH2:9][C:10]#[N:11])[CH:6]=[CH:7][CH:8]=1
Reactant: COc1cccc(CC#N)c1
Agent: BrB(Br)Br
Solvent: O
Solvent: ClCCl
Product: N#CCc1cccc(O)c1
Temperature: 25 °C
Reaction time: 20 h
Yield: 70.7 %

Procedure:
To a solution of 2-(3-methoxyphenyl)acetonitrile (2 g; 13.59 mmol) in 13 mL of dry dichloromethane (DCM) cooled at 0° C. under an inert atmosphere, a 1M solution of BBr3 in DCM (28.54 mmol; 28.54 mL) is slowly added dropwise. The mixture is stirred at room temperature for 20 hours. The reaction mixture is then poured into ice, water is added and the organic phase is extracted three times with dichloromethane, washed with brine and dried over anhydrous Na2SO4. After evaporation, the crude mixture is purified by flash-chromatography on silica gel using petroleum ether/EtAc (80/20) as an eluant, affording 1.28 g (71%) of 2-(3-hydroxyphenyl)acetonitrile.
Reaction SMILES: [CH3:1][CH:2]([CH3:19])[CH2:3][NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]2[N:15]=[N:16][N:17]=[C:7]2[C:6]=1[NH2:18].[C:20](OC(OCC)OCC)(=O)C.[Na]>O>[CH3:1][CH:2]([CH3:19])[CH2:3][N:4]1[C:5]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]3[N:15]=[N:16][N:17]=[C:7]3[C:6]=2[N:18]=[CH:20]1
Reactant: CCOC(OCC)OC(C)=O
Reactant: CC(C)CNc1c(N)c2nnnn2c2ccccc12
Agent: [Na]
Solvent: O
Product: CC(C)Cn1cnc2c1c1ccccc1n1nnnc21

Procedure:
N5-(2-Methylpropyl)tetrazolo[1,5-a]quinoline-4,5-diamine (0.2 g, 0.78 mmole, Example 16) was combined with diethoxymethyl acetate (2 mL) and heated on a steam bath for 3 hours. Water (10 mL) and 10% sodium hdyroxide (2 mL) were added and the reaction mixture was heated on a steam bath for 1 hour. A solid was isolated by filtration then recrystallized from methanol/ethyl acetate to provide 0.16 g of 6-(2-methylpropyl)-6H-imidazo[4,5-c]tetrazolo[1,5-a]quinoline as a white crystalline solid, m.p. 210-212° C. Analysis: Calculated for C14H14N6; %C, 63.14; %H, 5.30; %N, 31.56; Found: %C, 63.12; %H, 5.32; %N, 31.61.
Reaction SMILES: Br[C:2]1[CH:15]=[CH:14][C:5]2[O:6][C:7]3[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[C:16]1([N:22]2[C:34]3[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][C:29]=3[C:28]3[C:23]2=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:13][C:10]1[CH:11]=[CH:12][C:7]2[O:6][C:5]3[CH:14]=[CH:15][C:2]([C:31]4[CH:32]=[CH:33][C:34]5[N:22]([C:16]6[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=6)[C:23]6[C:28]([C:29]=5[CH:30]=4)=[CH:27][CH:26]=[CH:25][CH:24]=6)=[CH:3][C:4]=3[C:8]=2[CH:9]=1
Reactant: OB(O)c1ccc2c(c1)c1ccccc1n2-c1ccccc1
Reactant: Brc1ccc2oc3ccc(Br)cc3c2c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: Brc1ccc2oc3ccc(-c4ccc5c(c4)c4ccccc4n5-c4ccccc4)cc3c2c1
Temperature: 90 °C
Yield: 55 %

Procedure:
A mixture of 2,8-dibromodibenzo[b,d]furan (2.868 g, 10 mmol), (9-phenyl-9H-carbazol-3-yl)boronic acid (3.26 g, 10 mmol), Pd(PPh3)4 (0.30 g, 0.26 mmol) and potassium carbonate (4.1 g, 30 mmol) in dioxane/water (50 mL/10 mL) was degassed and heated at about 90° C. overnight. The resulting mixture was worked up with ethyl acetate/brine, dried over Na2SO4, purified by flash column (hexanes to hexanes/ethyl acetate 40:1). The desired fraction was collected and concentrated, filtration and dried in air to give a white solid (2.70 g, in 55% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([CH:17]=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1.CC(C)=[O:21].OS(O)(=O)=O.O=[Cr](=O)=O.O>CC(C)=O.[O-2].[O-2].[O-2].[Cr+6]>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([C:17]([OH:21])=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1
Reactant: O=CC12CC(c3ccccc31)c1ccc(Cl)cc12
Reactant: CC(C)=O
Agent: O=[Cr](=O)=O
Agent: [Cr+6]
Agent: O=S(=O)(O)O
Solvent: O
Product: O=C(O)C12CC(c3ccccc31)c1ccc(Cl)cc12
Temperature: 25 °C

Procedure:
To a cooled solution (0° C.) of 2-chloro-9-formyl-9,10-dihydro-9,10-methanoanthracene (described in example 1i) (20.0 g, 78.5 mmol) in acetone (260 mL) was added Jones reagent (24 mL; 27 g chromium trioxide, 23 mL water diluted up to 100 mL of reagent solution) in portions. The reagent was added until an orange color persists. The reaction, containing a significant amount of reduced chromium salts, was warmed to room temperature. The solvents were removed in vacuo and replaced with water (300 mL) saturated with sodium chloride. The aqueous phase was extracted with ethyl acetate (3×300 mL). Combined organic extracts were extracted with 2.5N NaOH (3×400 mL). The basic aqueous extracts were acidified with 3N HCl, saturated with sodium chloride, and extracted with ethyl acetate (4×300 mL). Combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and reduced to a off-white solid. The procedure yielded 26.66 g (quantitative) of the title compound. No additional purification was required. 1H NMR (D6 -DMSO, 300 MHz) 13.2 (donfield) 7.46 (br s, 1H), 7.36 (m, 3H), 7.02 (m, 3 H), 4.45 (s, 1H), 2.67 (s, 2H) MS (CI, CH4) m/z 271 (M+1,100), 273 (34), 299 (M+29,17), 253 (33), 243 (22), 227 (20)
Reaction SMILES: Cl.[C:2]1([C:8]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:27](#[N:30])[CH:28]=[CH2:29]>>[C:2]1([C:8]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:9][CH2:10][N:11]([CH2:29][CH2:28][C:27]#[N:30])[CH2:12][CH2:13]2)[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(C2(c3ccccc3)CCNCC2)cc1
Reactant: C=CC#N
Agent: Cl
Solvent: CCN(CC)CC
Product: N#CCCN1CCC(c2ccccc2)(c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 82.2 %

Procedure:
To a suspension of 4,4-diphenylpiperidine hydrochloride (195 mg, 0.712 mmol, 1.0 equiv) in ETOh (1.5 mL) was added triethylamine (0.25 mL, 1.83 mmol, 2.6 equiv) followed by acrylonitrile (0.13 mL, 2.01 mmol, 2.8 equiv). The resulting solution was stirred at room temperature under argon for 15 minutes and then concentrated. Water was added, and the mixture was extracted three times with EtOAc. The combined organic extracts were dried over MgSO4 and concentrated to give 170 mg (87%) of tan solid, which was used for the next reaction without purification. m.p. 95-96° C.; 1H NMR (300 MHz, CDCl3) δ2.37 (m, 2H), 2,46 (m, 4H), 2.52 (m, 6H), 7.12 (m, 2H), 7.23 (m, 8H); 13C NMR (75 MHz, CDCl3) δ16.65, 36.71. 45.08, 50.78, 54.13, 119.70, 126.48, 127.78, 129.11, 147.87; IR (neat) 2944.4, 2821.0, 1495.5, 1445.9 cm−1.
Reaction SMILES: C[O:2][C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)=[N:14][O:15][CH:16]=2)=[N:6][CH:5]=1.COC(=O)C1C=CC(OCC2C(C3C=CC(F)=CC=3)=NOC=2)=NC=1>>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([C:13]2[C:12]([CH2:11][O:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([OH:24])=[O:2])=[CH:5][N:6]=3)=[CH:16][O:15][N:14]=2)=[CH:22][CH:21]=1
Reactant: COC(=O)c1ccc(OCc2conc2-c2ccc(Cl)cc2)nc1
Agent: COC(=O)c1ccc(OCc2conc2-c2ccc(F)cc2)nc1
Product: O=C(O)c1ccc(OCc2conc2-c2ccc(Cl)cc2)nc1
Yield: 99.1 %

Procedure:
As described for example 331a, 6-[3-(4-chloro-phenyl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (4.0 g, 11.6 mmol) was converted, instead of 6-[3-(4-fluoro-phenyl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester, to the title compound (3.8 g, 100%) which was obtained as a light yellow solid. MS: m/e=331.1 [M−H]−.
Reaction SMILES: Cl[C:2]1[CH2:6][CH2:5][CH2:4][C:3]=1[CH:7]=O.[CH2:9]([O:11][C:12](=[O:22])[CH2:13][NH:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:10]>>[CH2:15]([N:14]1[C:13]([C:12]([O:11][CH2:9][CH3:10])=[O:22])=[CH:7][C:3]2[CH2:4][CH2:5][CH2:6][C:2]1=2)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: O=CC1=C(Cl)CCC1
Reactant: CCOC(=O)CNCc1ccccc1
Product: CCOC(=O)c1cc2c(n1Cc1ccccc1)CCC2
Temperature: 110 °C

Procedure:
25 g (0.191 mol) of 2-chloro-1-formylcyclopent-1-ene are added to 73.9 g (0.382 mol) of N-benzylglycine ethyl ester at room temperature and the mixture is then heated to 110° C. Working-up is carried out as indicated in Example 1.
Reaction SMILES: Cl.[Cl:2][CH2:3][CH2:4][CH2:5][NH2:6].C([O-])([O-])=O.[K+].[K+].[C:13]([C:17]([C:20]([C:23]([C:26]([C:29]([CH2:32][CH2:33][S:34](Cl)(=[O:36])=[O:35])([F:31])[F:30])([F:28])[F:27])([F:25])[F:24])([F:22])[F:21])([F:19])[F:18])([F:16])([F:15])[F:14]>COCCOC>[C:13]([C:17]([C:20]([C:23]([C:26]([C:29]([CH2:32][CH2:33][S:34]([NH:6][CH2:5][CH2:4][CH2:3][Cl:2])(=[O:36])=[O:35])([F:30])[F:31])([F:28])[F:27])([F:25])[F:24])([F:22])[F:21])([F:19])[F:18])([F:16])([F:15])[F:14]
Reactant: NCCCCl
Reactant: O=S(=O)(Cl)CCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Product: O=S(=O)(CCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)NCCCCl
Temperature: 75 °C

Procedure:
3-chloropropyl amine hydrochloride (4.7 g), K2CO3 (6.9 g) and 1,2-dimethoxyethane (19.3 g) solvent were placed in the round bottom flask equipped with mechanical stirring under nitrogen. Solution of 2-(perfluorohexyl)ethanesulfonyl chloride CF3(CF2)5(CH2)2SO2Cl (10.1 g), in 1,2-dimethoxyethane (10 g) solvent was added dropwise during 1 hour at room temperature while stirring at 250 rpm. After the addition was completed, the reaction was gradually heated to 75° C. and reacted for 12 h. The reaction was monitored by GC to ensure the complete conversion of CF3(CF2)5(CH2)2SO2Cl. The final reaction mixture with pH=3.5 was cooled down and filtered from solids through 2 mm layer of CELITE 545. The solids were washed with 1,2-dimethoxyethane (10 mL) and combined filtrate was evaporated in vacuum to obtain 8.2 g of CF3(CF2)5(CH2)2SO2NH(CH2)3Cl. The product was additionally dissolved in hot toluene (8 g) and washed with 15.5 mL of 1 wt % HCl aqueous solution.
Reaction SMILES: [Br-:1].[CH3:2][O:3][C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([C:11]#[C:12]/[C:13](/[CH3:35])=[CH:14]\[CH2:15][P+:16]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:6]([CH3:36])[C:5]=1[CH3:37].[H][H]>CO.[Pd].S([O-])([O-])(=O)=O.[Ba+2]>[Br-:1].[CH3:2][O:3][C:4]1[CH:9]=[C:8]([CH3:10])[C:7](/[CH:11]=[CH:12]\[C:13](\[CH3:35])=[CH:14]/[CH2:15][P+:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)=[C:6]([CH3:36])[C:5]=1[CH3:37]
Reactant: COc1cc(C)c(C#C/C(C)=C\C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)c(C)c1C
Reactant: [H][H]
Agent: [Pd]
Agent: O=S(=O)([O-])[O-]
Agent: [Ba+2]
Solvent: CO
Product: COc1cc(C)c(/C=C\C(C)=C/C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)c(C)c1C
Yield: 54.6 %

Procedure:
In a manner analagous to Example 2, a solution of 3.42 g of (Z)-[5-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-2-penten-4-ynyl]triphenylphosphonium bromide in 240 ml of methanol was hydrogenated in the presence of 1.8 g of palladium/barium sulphate (5%). 188 ml of hydrogen were taken up within 2 hours. The crude product (3.4 g) of (2Z,4Z)-[5-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-2,4-pentadienyl]triphenylphosphonium bromide (chemical yield 54.6% in accordance with HPLC) obtained after filtration and evaporation was dissolved in 20 ml of methylene chloride and crystallized by the dropwise addition of 50 ml of ethyl acetate while stirring. The suspension was left to stand at 0° C. overnight and filtered. The crystals were washed with a small amount of ethyl acetate/methylene chloride (volume ratio 5:1) and dried at room temperature/0.01 mbar. There was thus obtained 1.0 g of 94.9% (2Z,4Z)-[5-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-2,4-pentadienyl]triphenylphosphonium bromide; m.p. 202°-205° C.
Reaction SMILES: [NH2:1][C:2]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[C:9]([C:14]([O:16][CH3:17])=[O:15])[CH:8]=[CH:7]2)=O.O>P(OC)(OC)(OC)=O>[C:2]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[C:9]([C:14]([O:16][CH3:17])=[O:15])[CH:8]=[CH:7]2)#[N:1]
Reactant: COC(=O)c1ccc2cc(C(N)=O)ccc2c1
Solvent: O
Solvent: COP(=O)(OC)OC
Product: COC(=O)c1ccc2cc(C#N)ccc2c1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 92.2 %

Procedure:
A suspension of Example 8C (31 g, 135 mmole) in trimethyl phosphate (450 mL) was treated with triphosgenie (27 g, 136 mmole), stirred for 20 min at room temperature and heated in an oil bath at 80° C. for 1 h. The product precipated from the solution while cooling to room temperature. The thick slutty was treated with water and filtered, and the white solid was thoroughly washed with water and dried under vacuum to provide 26.3 g of the title compound.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([O:12][CH:13]([CH3:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].C(O)C.ClCCl.[BH4-].[Na+]>C1COCC1>[OH:3][CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([O:12][CH:13]([CH3:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])=[CH:6][CH:5]=1)[CH3:2]
Reactant: CC(=O)c1ccc(C(=O)OC(C)c2ccccc2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: CCO
Product: CC(O)c1ccc(C(=O)OC(C)c2ccccc2)cc1
Temperature: 0 °C
Yield: 96.9 %

Procedure:
32.17 g (0.12 mol) of methylbenzyl 4-acetylphenylcarboxylate, 50 ml of ethanol, 100 ml of dichloromethane and 50 ml of THF were supplied into a four-necked flask provided with a stirrer and a thermometer. Then 2.3 g (0.06 mol) of sodium borohydride was added at 15°-25° C. over a period of 10 minutes. The mixture was maintained at the same temperature for 2 hours and the reaction mixture was poured into ice-water and treated according to Example 19 to obtain 31.43 g (97% yield) of methylbenzyl 4-(1-hydroxyethyl)phenylcarboxylate (III-22).
Reaction SMILES: N1C=CC=CC=1.[CH2:7](Cl)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Cl:15][SiH:16]([Cl:18])[Cl:17]>>[CH2:7]([Si:16]([Cl:18])([Cl:17])[Cl:15])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: Cl[SiH](Cl)Cl
Reactant: ClCc1ccccc1
Solvent: c1ccncc1
Product: Cl[Si](Cl)(Cl)Cc1ccccc1
Yield: 10.6 %

Procedure:
In the same apparatus and procedure as Example 1 above, 0.08 g (1.0 mmol) of pyridine, 0.63 g (5.0 mmol) of benzyl chloride, and 3.41 g (25.2 mmol) of trichlorosilane were reacted at 200° C. for 6 hrs. The resulting mixture was distilled to give 0.12 g of benzyltrichlorosilane (yield; 11%).
Reaction SMILES: [CH:1]1[C:6]2=[N:7][S:8][N:9]=[C:5]2[C:4]([NH:10][C:11]2[NH:15][CH2:14][CH2:13][N:12]=2)=[C:3]([Cl:16])[CH:2]=1.[C:17]([OH:24])(=[O:23])[CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>C(O)C>[CH:1]1[C:6]2=[N:7][S:8][N:9]=[C:5]2[C:4]([NH:10][C:11]2[NH:15][CH2:14][CH2:13][N:12]=2)=[C:3]([Cl:16])[CH:2]=1.[C:17]([O-:24])(=[O:23])[CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: CCCCCC(=O)O
Agent: Clc1ccc2nsnc2c1NC1=NCCN1
Solvent: CCO
Product: CCCCCC(=O)[O-]
Temperature: 2.5 °C

Procedure:
To 5 ml of ethanol, 3.0 g of the tizanidine base (99.15% HPLC) and 2.5 g of hexanoic acid are added. After brief heating to boil a yellowish solution results, from which a precipitated product starts to separate. After cooling to 0 to 5° C. and aspiration 3.25 g of tizanidine hexanoate are obtained.
Reaction SMILES: [CH:1]([CH:3]=[CH2:4])=[O:2].[CH3:5][CH:6]([CH2:9]O)[CH2:7][OH:8]>>[CH:3]([CH:1]1[O:8][CH2:7][CH:6]([CH3:9])[CH2:5][O:2]1)=[CH2:4]
Reactant: CC(CO)CO
Reactant: C=CC=O
Product: C=CC1OCC(C)CO1

Procedure:
Acrolein and 2-methyl-1,3-propanediol were condensed to produce 2-vinyl-5-methyl-1,3-dioxane in accordance with the procedure of Example I.
Reaction SMILES: [CH3:1][CH:2]([CH2:5][OH:6])[CH2:3][OH:4].[CH:7]([CH:9]=[CH2:10])=O>O1CCCC1>[CH:9]([CH:10]1[O:6][CH2:5][CH:2]([CH3:1])[CH2:3][O:4]1)=[CH2:7]
Reactant: CC(CO)CO
Reactant: C=CC=O
Solvent: C1CCOC1
Product: C=CC1OCC(C)CO1

Procedure:
One or more objects of the present invention are accomplished by the provision of a process for producing tetrahydrofuran which comprises (1) condensing 2-methyl-1,3-propanediol with acrolein to form 2-vinyl-5-methyl-1,3 dioxane; (2) converting the 2-vinyl-5-methyl-1,3-dioxane under hydroformylating conditions to a mixture of 2(5'-methyl-1',3'-dioxane)propionaldehyde and 3-(5'-methyl-1',3'-dioxane)propionaldehyde; and (3) hydrogenating said mixture of propionaldehydes in the presence of a hydrogenation catalyst and water in a reaction medium having a pH between about 0.1 and 5 to yield tetrahydrofuran and 2-methyl-1,3-propanediol.
Reaction SMILES: CC1N=C2SC=CN2C(=O)C=1.II.ClC1C=CC(/C=[CH:22]/[C:23]2[N:24]=[C:25]3[S:33][CH:32]=[CH:31][N:26]3[C:27](=[O:30])[C:28]=2[I:29])=CC=1>C(#N)C>[I:29][C:28]1[C:27](=[O:30])[N:26]2[CH:31]=[CH:32][S:33][C:25]2=[N:24][C:23]=1[CH3:22]
Reactant: O=c1c(I)c(/C=C/c2ccc(Cl)cc2)nc2sccn12
Agent: Cc1cc(=O)n2ccsc2n1
Agent: II
Solvent: CC#N
Product: Cc1nc2sccn2c(=O)c1I

Procedure:
A stirred solution of Step 1 Intermediate (20 g, 120.463 mmol) in acetonitrile (200 ml) was treated with ceric ammonium nitrate (33 g, 60.233 mmol) and iodine (18 g, 72.281 mmol) at room temperature according to the procedure outlined in Intermediate 1, Step 3 to give 35 g of the product as a light yellow solid; 1H NMR (300 MHz, DMSO-d6) δ 2.56 (s, 3H), 7.52 (d, J=5.1 Hz, 1H), 7.97 (d, J=4.8 Hz, 1H); ESI-MS (m/z) 291.29 (M−H)−.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[NH:11]1[CH:15]=[N:14][N:13]=[N:12]1.C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[N:11]1[N:12]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[N:13]=[N:14][CH:15]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: c1nnn[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: O=[N+]([O-])c1ccc(-n2ncnn2)cc1
Temperature: 90 °C
Reaction time: 24 h
Yield: 31.1 %

Procedure:
4-Fluoronitrobenzene (2 g, 0.014 mol), tetrazole (1 g, 0.014 mol), potassium carbonate (1.96 g, 0.014 mol) were dissolved in DMSO (50 ml) and stirred at 90° C. for 24 h under dry conditions. The yellow suspension was poured into water (150 ml), the resulting yellow solid filtered of and dried in vacuo to afford the title compound (831 mg, 31%).
Reaction SMILES: [Br-:1].[Li+].[C:3](=[O:11])([O:7][CH:8](Cl)[CH3:9])[O:4][CH2:5][CH3:6].O>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.ClCCl>[C:3](=[O:11])([O:7][CH:8]([Br:1])[CH3:9])[O:4][CH2:5][CH3:6]
Reactant: [Br-]
Reactant: CCOC(=O)OC(C)Cl
Agent: CCCCCCCCCCCCCCCC[N+](C)(C)C
Agent: [Li+]
Solvent: ClCCl
Solvent: O
Product: CCOC(=O)OC(C)Br
Temperature: 35 °C
Reaction time: 24 h
Yield: 75.9 %

Procedure:
A mixture of lithium bromide (43 g, 0.5 m), ethyl alphachloroethyl carbonate (15.3 g, 0.1 m); water (100 ml), dichloromethane (100 ml) and cetyl trimethyl ammonium bromide (1.5 g) was stirred at ambient temperature for 24 hours. The aqueous layer was removed and replaced by a fresh solution of lithium bromide (26 g, 0.3 m) in water (40 ml) containing cetyl trimethyl ammonium bromide (1 g). After stirring for a further 24 hours during which time the temperature was raised to 35° C., the organic layer was separated, dried and vacuum distilled to afford after repeated fractionation the new compound, ethyl alpha-bromoethyl carbonate (15.0 g, 76% yield) having a boiling point of 90°-92° C. at 35 mms of mercury pressure.