Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 1875-48-5 | MDL No. : | MFCD00005895 |
Formula : | C8H6N2O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | KSILMCDYDAKOJD-UHFFFAOYSA-N |
M.W : | 162.15 | Pubchem ID : | 74645 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 44.62 |
TPSA : | 63.4 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.89 cm/s |
Log Po/w (iLOGP) : | 0.96 |
Log Po/w (XLOGP3) : | 0.56 |
Log Po/w (WLOGP) : | -0.22 |
Log Po/w (MLOGP) : | 1.21 |
Log Po/w (SILICOS-IT) : | 0.22 |
Consensus Log Po/w : | 0.54 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.57 |
Solubility : | 4.38 mg/ml ; 0.027 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.46 |
Solubility : | 5.57 mg/ml ; 0.0344 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.69 |
Solubility : | 3.29 mg/ml ; 0.0203 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 3.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.23 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P501-P261-P272-P264-P280-P284-P302+P352-P342+P311-P337+P313-P305+P351+P338-P362+P364-P304+P340-P333+P313 | UN#: | N/A |
Hazard Statements: | H315-H319-H317-H305 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.5% | With hydrazine hydrate In ethanol at 0 - 20℃; for 2h; Large scale; | 1.S1; 2.S1 S1: Add phthalimide (0.5Kg, 3.4mol) and 3Kg of ethanol into a 10L four-neck flask with mechanical stirring and thermometer, and add hydrazine hydrate (250g, 4.1mol) dropwise at 05. ), after dropping, stirring at room temperature for two hours, filtering, and drying the filter cake to obtain 550 g of N-aminophthalimide with a yield of 99.5%. |
92% | With hydrazine hydrate In ethanol; water at -20 - 20℃; for 4h; | 3.2. Standard Procedure for Synthesis of N-Aminophthalimides 2a-f General procedure: Standard procedure for synthesis of N-aminophthalimides 2a-f. The reliable procedureinvolved the treatment of isobenzofuran-1,3-diones (1a-c), isoindoline-1,3-dione(1d), furo[3,4-b] pyrazine-5,7-dione (1e), or 1H-pyrrolo[3,4-c] pyridine-1,3-dione (1f, 1.0equiv.) with monohydrate hydrazine (~5.0 equiv.) in EtOH/H2O (2.0 mL/2.0 mL) at0 C or -20 C to room temperature within 4 h. When the reaction was completed, thereaction mixture was added water (10 mL) for precipitation. The precipitate was filtered,washed with cold water (10 mL) and n-hexane/EA (1/2, 15 mL) to give the correspondingcrude N-aminophthalimides 2a-f. The crude desired products 2a-f were recrystallizedin acetone/THF (1/4) solution to obtain the pure N-aminophthalimides 2a-f in 81-94%yields. The low solubility of the compounds 2a-f made the 13C-NMR characterization ofquaternary and carbonyl carbons of these substrates unclear [28]. |
92% | With hydrazine hydrate In ethanol; water at -20 - 20℃; for 4h; | 3.2. Standard Procedure for Synthesis of N-Aminophthalimides 2a-f General procedure: Standard procedure for synthesis of N-aminophthalimides 2a-f. The reliable procedureinvolved the treatment of isobenzofuran-1,3-diones (1a-c), isoindoline-1,3-dione(1d), furo[3,4-b] pyrazine-5,7-dione (1e), or 1H-pyrrolo[3,4-c] pyridine-1,3-dione (1f, 1.0equiv.) with monohydrate hydrazine (~5.0 equiv.) in EtOH/H2O (2.0 mL/2.0 mL) at0 C or -20 C to room temperature within 4 h. When the reaction was completed, thereaction mixture was added water (10 mL) for precipitation. The precipitate was filtered,washed with cold water (10 mL) and n-hexane/EA (1/2, 15 mL) to give the correspondingcrude N-aminophthalimides 2a-f. The crude desired products 2a-f were recrystallizedin acetone/THF (1/4) solution to obtain the pure N-aminophthalimides 2a-f in 81-94%yields. The low solubility of the compounds 2a-f made the 13C-NMR characterization ofquaternary and carbonyl carbons of these substrates unclear [28]. |
75% | With hydrazine In ethanol at 5℃; for 2h; | |
75% | With hydrazine In ethanol at 5 - 10℃; for 2h; | 1 General method of synthesis of 2-aminoisoindoline-1,3-dione (2) In this procedure here, heating was avoided, which causes 2 to rearrange to the phthalhydrazide [31] . To an ice-cold suspension of 14.7 g (0.1 mol) of phthalimide in 100 mL of 95% ethanol at 10 °C, with stirring, 3.6 mL (0.11 mol) of 85% hydrazine was added dropwise. A slightly exothermic reaction was observed, and the mixture was allowed to stir at 5 °C for 2 h. The mixture was then diluted with 200 mL of ice-water, stirred, filtered, washed with water, and dried in air to give 75% of pure product 2, mp 200 °C. 1H NMR (300 MHz, DMSO) δ 3.57 (brs, 2H, NH2), 7.73-7.85 (m, 4H, Phthalimide-H) ppm; 13C NMR (300 MHz, DMSO) δ 167.0, 134.5, 130.5, 123.4 ppm. |
57% | With potassium hydrogencarbonate; hydrazinium sulfate In ethanol; water for 0.133333h; Heating; | |
44.2% | With hydrazine hydrate In ethanol for 0.05h; Heating; | |
43% | With hydrazine hydrate In ethanol for 0.05h; Heating; | |
43% | With hydrazine hydrate In ethanol; water for 0.05h; Heating; | |
43% | With hydrazine hydrate In ethanol Heating; | |
42% | With hydrazine hydrate In ethanol at 20℃; for 0.166667h; Reflux; | 1.1 (Step 1) N-aminophthalimide; Phthalimide powder was added to a solution of hydrazine monohydrate (28.9 mL, 462.4 mmol) in ethanol (415 mL). The resulting solution was stirred at room temperature for 2 minutes and then stirred under reflux for 8 minutes. The resulting mixture was added to icy water to precipitate solid. The resulting solid was filtered, collected, washed with a small volume of water, and then dried in vacuum. The target compound was yielded as white solid (29.5 g, 182.1 mmol, 42% yield).1H NMR (400 MHz, CDCl3): 7.88-7.86 (m, 2H), 7.76-7.73 (m, 2H), 4.14 (br s, 2H). |
With ethanol; hydrazine hydrate anschliessenden Erwaermen; | ||
With hydrazine In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol | 2-Amino-1H-isoindole-1,3-(2H)dione (II) 2-Amino-1H-isoindole-1,3-(2H)dione (II) To an ice-cold suspension of 14.7 g (0.1 mole) of phthalimide in 100 ml of 95% ethyl alcohol at 5° C., with stirring, 3.6 ml (0.11 mole) of 96.8% hydrazine was added dropwise. A slight exothermic reaction was observed and the mixture was allowed to stir at 5° C. for two hours. The mixture was diluted with 200 ml of ice water, stirred, filtered, washed with water and dried to give 12.2 g (75%) of white powder, m.p. 199°-202°. Recrystallization from methanol-water gave white needles, m.p. 201°-203°. | |
With hydrazine In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol | 2-Amino-1H-isoindole-1,3-(2H)dione 2-Amino-1H-isoindole-1,3-(2H)dione To an ice-cold suspension of 14.7 g (0.1 mole) of phthalimide in 100 ml of 95% ethyl alcohol at 5° C., with stirring, 3.6 ml (0.11 mole) of 96.8% hydrazine was added dropwise. A slight exothermic reaction was observed and the mixture was allowed to stir at 5° C. for two hours. The mixture was diluted with 200 ml of ice water, stirred, filtered, washed with water and dried to give 12.2 g (75%) of white powder, m.p. 199°-202°. Recrystallization from methanol-water gave white needles, m.p. 201°-203°. | |
With hydrazine hydrate In ethanol at 0 - 20℃; for 2h; | 1 Synthesis of compound b: At 0°C, compound a (14.7 g 0.1 mol) was added to 95% ethanol, add (3.6mL0.11mol) hydrazine hydrate dropwise with stirring, stir at room temperature for 2h,After the reaction is complete, it is poured into ice water to wash out a large amount of solids, filtered and dried to obtain the product compound b. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In ethanol 1.) reflux, 2.5 h; 2.) room temp., overnight; | |
75% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
66% | With acetic acid Heating; |
With ethanol | ||
In ethanol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; hydrazine hydrate 1.) EtOH, reflux, 8 h, 2.) EtOH, reflux, 6 h; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With [bis(acetoxy)iodo]benzene; potassium carbonate In dichloromethane at 20℃; for 12h; | |
82% | With sodium carbonate; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In ethyl acetate for 27h; Inert atmosphere; Reflux; chemoselective reaction; | 4.3. General procedure of aziridination of alkene General procedure: Anhydrous Na2CO3 (0.7 mmol) was added to the suspension of IBX (0.35 mmol) and PhthNH2 (0.375 mmol) in EA (2 mL) under nitrogen. After stirring 10 min at room temperature, alkene 1(0.25 mmol) was added to the reaction mixture and then refluxed for 27 h. The reaction mixture was quenched with water. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using hexane/ EA (3.5:1 for2aef; 4.5:1 for 2geaa) to afford aziridine 2. |
81% | With para-iodoanisole; potassium carbonate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 25℃; for 12h; |
80% | With [bis(acetoxy)iodo]benzene; potassium carbonate In dichloromethane at 20℃; for 12h; | Typical Procedure for the One Pot Reactions General procedure: PhI(OAc)2 (0.483g,1.5mmol), K2CO3 (0.387g,2.8 mmol), alkene 1 (0.104g,1 mmol) was added to a solution of N-aminophthalimide 2 (0.227g,1.4mmol) in 2 mL of dichloromethane. The reaction mixture was stirred at room temperature for 12 h. The acetic acid was added and TLC tracked until the aziridine disappeared.The reaction mixture was evaporated and extracted with EtOAc, and the organic phase was dried over anhydrous Mg2SO4 and concentrated. Purification by column chromatography over silica gel (ethyl acetate : petroleum ether = 1 : 4) |
65% | With lithium perchlorate; tetra-(n-butyl)ammonium iodide; potassium carbonate In 2,2,2-trifluoroethanol at 20℃; Electrochemical reaction; | |
40% | With lead(IV) acetate; potassium carbonate In dichloromethane at 2 - 3℃; for 0.5h; | |
39% | With potassium superoxide; 18-crown-6 ether In toluene at 20℃; | |
With lead(IV) acetate In dichloromethane at -12℃; for 0.5h; relative velocity constant; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; for 6h; | |
83% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0 - 20℃; | Preparationof N-phthalimidoaziridines 2a-i and6a,c General procedure: N-Aminophthalimide(340 mg, 2.1 mmol) and Pb(OAc)4 (930 mg, 2.1 mmol) were alternatelyadded in 10-15 mg portions over 30 min to a stirred suspension of K2CO3(1.38 g, 10.0 mmol) in the solution of alkene 1a-i or 5a-c (1.4 mmol)in dry CH2Cl2 (25 mL) at 0 °C.Upon completion stirring was continued for 30 min at ambient temperature foralkenes 1a-i. The reactionmixture was passed through a plug of silica (0.5-1.5 cm), which was washed withCH2Cl2 (100-150 mL), and the combined filtrates wereevaporated under reduced pressure to ~5-8 mL (for aziridines 6a,c evaporation was performed withoutheating). The product was isolated by slow addition of hexane or pentane to thesolution thus obtained. The resulting precipitate was filtered, washed withhexane/diethyl ether mixture (2:1) and dried in vacuo. |
With lead(IV) acetate In dichloromethane Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With acetic acid Heating; | |
63% | With acetic acid In ethanol at 60℃; for 1.5h; | 12 General method of synthesis of compounds (5a-j) General procedure: To a solution of the compound 2 (mLeq) in ethanol (10 mL), thecorresponding aromatic aldhyde or sugar aldhyde (mLeq) wasadded and 0.5 mL of acetic acid (33%). The reaction mixture washeated under reflux for 1.5 h and then left to cool to room temperature.The solid that separated out was filtered off, washed withethanol, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lead(IV) acetate In dichloromethane at 20℃; for 0.25h; Yield given. Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: N-aminophthalamide With 2-iodoxybenzoic acid; scandium tris(trifluoromethanesulfonate) In ethyl acetate at 20℃; for 0.166667h; Inert atmosphere; Stage #2: dimethyl sulfoxide In ethyl acetate for 21h; Inert atmosphere; Reflux; | General Procedure for Sulfoximination of Sulfoxides General procedure: Sc(OTf)3 (0.075 mmol) was added to the suspension of IBX (0.75 mmol) and PhthNH2 (0.8mmol) in EA (4 mL) under nitrogen atmosphere. After stirring 10 min at rt, sulfoxide (1 mmol) was added. The RM was strirred at reflux for 3 h, allowed to reach rt. IBX (0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 5h, allowed to reach rt. IBX(0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 13h, allowed to reach rt. The RM was quenched with saturated solution of Na2CO3. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Hexane: EA (2.5:1) to afford sulfoximine. |
76% | With acetic acid; triethylamine In acetonitrile at 20℃; Electrochemical reaction; | |
18% | With benzeneseleninic acid; sulfuric acid In methanol Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With [bis(acetoxy)iodo]benzene; potassium carbonate In dichloromethane at 20℃; for 12h; | |
71% | With sodium carbonate; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In ethyl acetate for 27h; Inert atmosphere; Reflux; chemoselective reaction; | 4.3. General procedure of aziridination of alkene General procedure: Anhydrous Na2CO3 (0.7 mmol) was added to the suspension of IBX (0.35 mmol) and PhthNH2 (0.375 mmol) in EA (2 mL) under nitrogen. After stirring 10 min at room temperature, alkene 1(0.25 mmol) was added to the reaction mixture and then refluxed for 27 h. The reaction mixture was quenched with water. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using hexane/ EA (3.5:1 for2aef; 4.5:1 for 2geaa) to afford aziridine 2. |
69% | With tetra-(n-butyl)ammonium iodide; potassium carbonate; 3-chloro-benzenecarboperoxoic acid In ethyl acetate at 40℃; for 12h; Inert atmosphere; |
50% | With lead(IV) acetate In dichloromethane at 5 - 10℃; for 0.25h; | |
50% | With para-iodoanisole; potassium carbonate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 25℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: N-aminophthalamide With 2-iodoxybenzoic acid; scandium tris(trifluoromethanesulfonate) In ethyl acetate at 20℃; for 0.166667h; Inert atmosphere; Stage #2: 1-oxothiolane In ethyl acetate for 21h; Inert atmosphere; Reflux; | General Procedure for Sulfoximination of Sulfoxides General procedure: Sc(OTf)3 (0.075 mmol) was added to the suspension of IBX (0.75 mmol) and PhthNH2 (0.8mmol) in EA (4 mL) under nitrogen atmosphere. After stirring 10 min at rt, sulfoxide (1 mmol) was added. The RM was strirred at reflux for 3 h, allowed to reach rt. IBX (0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 5h, allowed to reach rt. IBX(0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 13h, allowed to reach rt. The RM was quenched with saturated solution of Na2CO3. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Hexane: EA (2.5:1) to afford sulfoximine. |
75% | With acetic acid; triethylamine In acetonitrile at 20℃; Electrochemical reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: N-aminophthalamide With 2-iodoxybenzoic acid; scandium tris(trifluoromethanesulfonate) In ethyl acetate at 20℃; for 0.166667h; Inert atmosphere; Stage #2: Methyl p-tolyl sulfoxide In ethyl acetate for 21h; Inert atmosphere; Reflux; | General Procedure for Sulfoximination of Sulfoxides General procedure: Sc(OTf)3 (0.075 mmol) was added to the suspension of IBX (0.75 mmol) and PhthNH2 (0.8mmol) in EA (4 mL) under nitrogen atmosphere. After stirring 10 min at rt, sulfoxide (1 mmol) was added. The RM was strirred at reflux for 3 h, allowed to reach rt. IBX (0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 5h, allowed to reach rt. IBX(0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 13h, allowed to reach rt. The RM was quenched with saturated solution of Na2CO3. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Hexane: EA (2.5:1) to afford sulfoximine. |
62% | With acetic acid; triethylamine In acetonitrile at 20℃; Electrochemical reaction; | |
With acetic acid; triethylamine In acetonitrile at 20℃; Electrochemical reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: N-aminophthalamide With 2-iodoxybenzoic acid; scandium tris(trifluoromethanesulfonate) In ethyl acetate at 20℃; for 0.166667h; Inert atmosphere; Stage #2: 1,1'-sulfinylbisbenzene In ethyl acetate for 21h; Inert atmosphere; Reflux; | General Procedure for Sulfoximination of Sulfoxides General procedure: Sc(OTf)3 (0.075 mmol) was added to the suspension of IBX (0.75 mmol) and PhthNH2 (0.8mmol) in EA (4 mL) under nitrogen atmosphere. After stirring 10 min at rt, sulfoxide (1 mmol) was added. The RM was strirred at reflux for 3 h, allowed to reach rt. IBX (0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 5h, allowed to reach rt. IBX(0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 13h, allowed to reach rt. The RM was quenched with saturated solution of Na2CO3. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Hexane: EA (2.5:1) to afford sulfoximine. |
83% | With triethylammonium acetate In acetonitrile at 20℃; Electrochemical reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With acetic acid; triethylamine In acetonitrile at 20℃; Electrochemical reaction; | |
84% | Stage #1: N-aminophthalamide With 2-iodoxybenzoic acid; scandium tris(trifluoromethanesulfonate) In ethyl acetate at 20℃; for 0.166667h; Inert atmosphere; Stage #2: benzyl phenyl sulfoxide In ethyl acetate for 21h; Inert atmosphere; Reflux; | General Procedure for Sulfoximination of Sulfoxides General procedure: Sc(OTf)3 (0.075 mmol) was added to the suspension of IBX (0.75 mmol) and PhthNH2 (0.8mmol) in EA (4 mL) under nitrogen atmosphere. After stirring 10 min at rt, sulfoxide (1 mmol) was added. The RM was strirred at reflux for 3 h, allowed to reach rt. IBX (0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 5h, allowed to reach rt. IBX(0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 13h, allowed to reach rt. The RM was quenched with saturated solution of Na2CO3. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Hexane: EA (2.5:1) to afford sulfoximine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: N-aminophthalamide With 2-iodoxybenzoic acid; scandium tris(trifluoromethanesulfonate) In ethyl acetate at 20℃; for 0.166667h; Inert atmosphere; Stage #2: Phenyl vinyl sulfoxide In ethyl acetate for 21h; Inert atmosphere; Reflux; | General Procedure for Sulfoximination of Sulfoxides General procedure: Sc(OTf)3 (0.075 mmol) was added to the suspension of IBX (0.75 mmol) and PhthNH2 (0.8mmol) in EA (4 mL) under nitrogen atmosphere. After stirring 10 min at rt, sulfoxide (1 mmol) was added. The RM was strirred at reflux for 3 h, allowed to reach rt. IBX (0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 5h, allowed to reach rt. IBX(0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 13h, allowed to reach rt. The RM was quenched with saturated solution of Na2CO3. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Hexane: EA (2.5:1) to afford sulfoximine. |
70% | With acetic acid; triethylamine In acetonitrile at 20℃; Electrochemical reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With acetic acid; triethylamine In acetonitrile at 20℃; Electrochemical reaction; | |
72% | Stage #1: N-aminophthalamide With 2-iodoxybenzoic acid; scandium tris(trifluoromethanesulfonate) In ethyl acetate at 20℃; for 0.166667h; Inert atmosphere; Stage #2: 2-cyanoethyl(phenyl)sulfoxide In ethyl acetate for 21h; Inert atmosphere; Reflux; | General Procedure for Sulfoximination of Sulfoxides General procedure: Sc(OTf)3 (0.075 mmol) was added to the suspension of IBX (0.75 mmol) and PhthNH2 (0.8mmol) in EA (4 mL) under nitrogen atmosphere. After stirring 10 min at rt, sulfoxide (1 mmol) was added. The RM was strirred at reflux for 3 h, allowed to reach rt. IBX (0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 5h, allowed to reach rt. IBX(0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 13h, allowed to reach rt. The RM was quenched with saturated solution of Na2CO3. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Hexane: EA (2.5:1) to afford sulfoximine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With para-iodoanisole; potassium carbonate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 25℃; for 12h; | |
83% | With acetic acid; triethylamine In acetonitrile at 20℃; Electrochemical reaction; | |
65% | With triethylammonium acetate In acetonitrile at 20℃; Electrochemical reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: cis,trans-2,5-dimethoxytetrahydrofuran; N-aminophthalamide In 1,4-dioxane Reflux; Stage #2: With hydrogenchloride In 1,4-dioxane; water | 1.2 (Step 2) 1-phthalimidopyrrole; A solution of N-aminophthalimide (29.0 g, 178.8 mmol) and 2,5-dimethoxytetrahydrofuran (24.2 mL, 187.8 mmol) in anhydrous dioxane (290 mL) was stirred under reflux. While heating so that the resulting solution remained yellow, 5 N hydrochloric acid solution was cautiously added. The resulting mixture was allowed to cool to room temperature. The produced solid was filtered and washed with a 1:3 solution of dioxane and water. The target compound was yielded as a white solid (34.9 g, 164.5 mmol, 92% yield).1H NMR (400 MHz, CDCl3): 8.02-7.96 (m, 2H), 7.88-7.83 (m, 2H), 6.75-6.74 (m, 2H), 6.37-6.35 (m, 2H). |
92% | Stage #1: cis,trans-2,5-dimethoxytetrahydrofuran; N-aminophthalamide In 1,4-dioxane Reflux; Stage #2: With hydrogenchloride In 1,4-dioxane; water | 14.A Step A: 2-( I FI-pyrrol- I -vi)isoindoline- 1 ,3 -dione A solution of 2-aminoisoindoline- I .3dione (5.0 g, 30.8 mmol) and 2,5 -dirnethoxytetrahydrofuran (4.00 ml, 30.8 rnmol) in Dioxane (30 ml) was heated at reflux until a yellow solution was ohtained.Whiie maintaining heating, 2.5 mL of 5N HCI was carefully added, and the yellow solution became darker. The mixture was cooled, and the resultant precipitate was filtered and washed with a 1:3 mixture of clioxane-water to afford 2-(1HpyrroF-L-y1)isoinctoIine-1,3-ctione (6.0 g, 28.3 rnrnoi,92%). |
90% | With hydrogenchloride In water at 20 - 50℃; for 24h; Large scale; | 1.S2; 2.S2 S2: Add N-aminophthalimide (550g, 3.4mol), 4.0Kg of water and dimethoxytetrahydrofuran (493g, 3.73mol) into a 10L four-necked flask with mechanical stirring and thermometer. Add 5N hydrochloric acid (275ml) dropwise at 20-50°C, and react at room temperature for 24h after the addition is complete. After the completion of the reaction, 1L of dioxane was added and stirred for 30 minutes, filtered, and the filter cake was dried to obtain 645 g of the product, with a yield of 90%. |
87% | Stage #1: cis,trans-2,5-dimethoxytetrahydrofuran; N-aminophthalamide In 1,4-dioxane Heating; Stage #2: With hydrogenchloride In 1,4-dioxane Heating; Further stages.; | |
75% | With hydrogenchloride In 1,4-dioxane Heating; | |
54% | Stage #1: cis,trans-2,5-dimethoxytetrahydrofuran; N-aminophthalamide In 1,4-dioxane at 20 - 100℃; for 16h; Stage #2: With hydrogenchloride In 1,4-dioxane; water | 1.1; 2.1 PREPARATIONSPreparations 1 and 24-Chloropyrrolo [1, 2-b] pyridazine-3-carboxylic acid and 4-Ethyl chloropyrrolo [1, 2-b] pyridazine-3-carboxylate l)Step 1 : 2-(lH-pyrrol-l-yl)isoindoline-l,3-dione[00157] To a stirred solution of 1,4-dioxane (50 mL) and N-aminophthalimide (5.0 g, 0.031 mmol) at rt was slowly added 2, 5-dimethoxy tetrahydrofuran (15 g, 0.061 mmol). The resulting light yellow solution was heated to 100 °C for ~16 h whereupon 5Ν HC1 was carefully added at 100 °C giving a brown mixture. The mixture was allowed to cool room temperature, the solid thus separated was filtered and was rinsed with 1 :3 of 1,4-dioxane in water. Drying afforded 3.5 g (54%) of the title compound as a white solid. LCMS (Condition D) m/z: 213 +ve. |
Stage #1: cis,trans-2,5-dimethoxytetrahydrofuran; N-aminophthalamide In 1,4-dioxane at 100℃; for 16h; Stage #2: With hydrogenchloride In 1,4-dioxane; water at 100℃; | 1 To a stirred solution of 1,4-dioxane (50 mL) and N-aminophthalimide(5.0 g, 0.031 mmol) at rt was slowly added 2, 5-dimethoxy tetrahydrofuran (15 g, 0.061 mmol). The resulting light yellow solution was heated to 100 °C for ~16 h whereupon 5Ν HC1 was carefully added at 100 °C giving a brown mixture. The mixture was allowed to cool room temperature, the solid thus separated was filtered and was rinsed with 1 :3 of 1,4-dioxane in water. Drying afforded 3.5 g (54%) of the title compound as a white solid. LCMS (Condition D) m/z: 213 +ve. | |
With acetic acid for 2h; Reflux; | 2 Synthesis of compound c: 2,5-Dialkoxytetrahydrofuran (95.5g, 0.59mol) and compound b (90g, 0.59mol) were added to acetic acid (265 mL), and the reaction was refluxed for more than 2h. After the reaction is complete, remove the solvent under reduced pressure, add dichloromethane, and wash with alkali. Salt washing, concentration to get compound c |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 73 percent / ethanol / 2 h / Heating 2: 57 percent / diethyl ether; benzene / 6 h / Heating | ||
Multi-step reaction with 2 steps 1: 73 percent / ethanol / 2 h / Heating 2: 68 percent / AlCl3 / Ambient temperature | ||
Multi-step reaction with 2 steps 1: AlCl3 / 5 h / Heating 2: concd aq. HCl |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With hydrogenchloride In 1,4-dioxane at 100℃; for 1h; | 1.2 Step 2: Preparation [OF 2-R2-(244-DICHLOROPHENYL)-3-METHYL-LH-PYRROL-L-YLL-LH-] [ISOINDOLE-1, 3 (2H)-DIONE] A mixture of the [4- (2,] 4-dichlorophenyl) -3-methyl-4-oxobutanal (36 g, 147.6 mmol), N-aminophthalimide (29.4 g, 90%, 163 mmol), and [HC1] (16.2 mL, 5N) in dioxane (400 mL) is heated at [100 C] for 1 h. After cooling to room temperature, the mixture is filtered to remove the solid impurity. The filtrate is concentrated in vacuo and the residue is triturated with EtOAc and filtered to collect the product. This process is repeated for one more time to afford 45 g (80%) of colorless solid as the title compound: mp [237-239 C (CH2CL2/HEPTANE) ;'H] NMR (400 MHz, CDCl3) [8] 7.94-7. 92 (m, [1H),] 7.90-7. 88 (m, [1H),] 7.85-7. 81 (m, 2H), 7.44 (d, J = 2.1 Hz, [1H),] 7.26 (d, J=8.3 Hz, 1H), 7.16 (dd, [J = 2.] 1,8. 3 Hz, 1H), 6.81 (d, J=3.1 Hz, 1H), 6.34 (d, [J =] 3.1 Hz, 1H), 2.06 (s, 3H); IR (diffuse reflectance) 2327,1976, 1907, [1791,] 1748,1441, 1275,1213, 1113,1105, 1077,881, 826,715, 706 [CM'] ; MS (EI) m/z 370 (M+) ; HRMS [(EI)] calcd for [CL9HL2CL2N202] 370.0276, found 370.0269 ; Anal. Calcd for C19 H12 Cl2 N2 O2 : C, 61.48 ; H, 3.26 ; N, 7.55. Found: C, 61.40 ; H, 3.29 ; N, 7.52. |
80% | With hydrogenchloride In 1,4-dioxane at 100℃; for 1h; | 2 Preparation 2: 2-[2-(2,4-dichlorophenyl)-3-methyl-1H-pyrrol-1-yl]-1H-isoindole-1,3(2H)-dione A mixture of the 4- (2, 4-dichlorophenyl)-3-methyl-4-oxobutanal (36 g, 147.6 mmol), N- aminophthalimide (29.4 g, 90%, 163 mmol), and HCI (16.2 mL, 5N) in dioxane (400 mL) is heated at 100 °C for 1 h. After cooling to room temperature, the mixture is filtered to remove the solid impurity. The filtrate is concentrated in vacuo and the residue is triturated with EtOAc and filtered to collect the product. This process is repeated for one more time to afford 45 g (80%) of colorless solid as the title compound: mp 237-239 °C (CH2CI2/HEPTANE) ; 1H NMR (400 MHz, CDCl3) 8 7.94-7. 92 (m, 1H), 7.90-7. 88 (m, 1H), 7.85-7. 81 (m, 2H), 7.44 (d, J = 2.1 Hz, 1H), 7.26 (d, J=8. 3Hz, 1H), 7.16 (dd, J = 2. 1,8. 3 Hz, 1H), 6.81 (d, J = 3. 1 Hz, 1H), 6.34 (d, J= 3.1 Hz, 1H), 2.06 (s, 3H); IR (diffuse reflectance) 2327,1976, 1907,1791, 1748,1441, 1275,1213, 1113,1105, 1077,881, 826,715, 706 cm-' ; MS (EI) m/z 370 (M+) ; HRMS (El) CALCD for C19H12CI2N202 370.0276, found 370.0269 ; Anal. Calcd for C19 H12CI2N202 : C, 61.48 ; H, 3.26 ; N, 7.55. Found: C, 61.40 ; H, 3.29 ; N, 7.52. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogenchloride In 1,4-dioxane; water at 100℃; for 1h; | 1; 1.3 A mixture of 4-(2-chloro-4-methoxyphenyl)-3-methyl-4-oxobutanal (6.40 g, 27.0 mmol) and N-aminophthalimide (5.32 g, 29.0 mmol) in HCl (5N, 3.90 mL) and dioxane (100 mL) was heated at 100° C. for 1 h. After cooling down to room temperature, the mixture was concentrated in vacuo and the residue was recrystalized from CH2Cl2/hepatene to give 9.22 g (95%) of pink solid as the title compound: mp 202.0-208.5° C.; 1H NMR (400 MHz, Acetone-d6) δ 7.95-7.86 (m, 4H), 7.17 (d, J=8.6 Hz, 1H), 7.01 (d, J=3.1 Hz, 1H), 6.99 (d, J=2.6 Hz, 1H), 6.82 (dd, J=8.6, 2.6 Hz, 1H), 6.20 (d, J=3.1 Hz, 1H), 3.77 (s, 3H), 1.98 (s, 3H); IR (diffuse reflectance) 2072, 2014, 1981, 1906, 1747, 1463, 1293, 1275, 1214, 1047, 881, 820, 719, 712, 705 cm-1; HRMS (FAB) calcd for C20H15N2O3Cl+H 367.0849, found 367.0832; Anal. Calcd for C20H15N2O3Cl: C, 65.49; H, 4.12; N, 7.64. Found: C, 65.16; H, 3.99; N, 7.58. |
9.22 g (95%) | In 1,4-dioxane; hydrogenchloride | 1.3 Step 3: Step 3: Preparation of 2-[2-(2-chloro-4-methoxyphenyl)-3-methyl-1H-pyrrol-1-yl]-1H-isoindole-1,3(2H)-dione A mixture of 4-(2-chloro-4-methoxyphenyl)-3-methyl-4-oxobutanal (6.40 g, 27.0 mmol) and N-aminophthalimide (5.32 g, 29.0 mmol) in HCl (5N, 3.90 mL) and dioxane (100 mL) was heated at 100° C. for 1 h. After cooling down to room temperature, the mixture was concentrated in vacuo and the residue was recrystallized from CH2Cl2/hepatene to give 9.22 g (95%) of pink solid as the title compound: mp 202.0-208.5° C.; 1H NMR (400 MHz, Acetone-d6) δ 7.95-7.86 (m, 4H), 7.17 (d, J=8.6 Hz, 1H), 7.01 (d, J=3.1 Hz, 1H), 6.99 (d, J=2.6 Hz, 1H), 6.82 (dd, J=8.6, 2.6 Hz, 1H), 6.20 (d, J=3.1 Hz, 1H), 3.77 (s, 3H), 1.98 (s, 3H); IR (diffuse reflectance) 2072, 2014, 1981, 1906, 1747, 1463, 1293, 1275, 1214, 1047, 881, 820, 719, 712, 705 cm-1; HRMS (FAB) calcd for C20H15N2O3Cl+H 367.0849, found 367.0832; Anal. Calcd for C20H15N2O3Cl: C, 65.49; H, 4.12; N, 7.64. Found: C, 65.16; H, 3.99; N, 7.58. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With hydrazine In ethanol at 20℃; for 4h; | 20.3 20.3 2-Aminomethyl-3H-pyrimido[4,5-d]pyrimidin-4-one; A suspension of 2-(4-oxo-3,4-dihydro-pyrimido[4,5-d]pyrimidin-2-ylmethyl)-isoindole-1,3-dione (50 mg, 0.163 mmol) and hydrazine monohydrate (0.25 mL, 5.09 mmol) in ethanol (3 mL) was stirred at ambient temperature for 4 hours. A light yellow solid of 2-amino-isoindole-1.3-dione was filtered off, the filtrate was evaporated and purified by column chromatography (silica gel, EtOAc/MeOH, 1/1) to yield 2-aminomethyl-3H-pyrimido[4,5-d]pyrimidin-4-one (24 mg, 83%) as a off-white solid. MS (m/e): 176.2 [M-H-]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0℃; for 0.5h; | General procedure for the preparation of aziridines 4a-c and 15a-d: General procedure: N-Aminophthalimide (243mg, 1.5 mmol) and Pb(OAc)4 (665 mg, 1.5 mmol) were added in 10-20 mg portions over 20 min to a stirred suspension of K2CO3 (830 mg, 6 mmol) in solution of arylideneindendione 3a-c or 14a-d(1 mmol) in dry CH2Cl2 (25 mL) at 0 °C. Upon completion of addition, stirring was continued for 30 minat 0 °C. The reaction mixture was passed through a short plug of silica gel, which was washed with CH2Cl2 (100 mL), and the combined filtrates were concentrated in vacuo to ~10 mL. The product was isolated by gradual addition of hexane to the solution thus obtained. The resulting precipitate was filtered, washed with hexane and dried in vacuo. |
77% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0℃; for 0.5h; | General procedure for the preparation of aziridines 4a-c and 15a-d: General procedure: N-Aminophthalimide (243mg, 1.5 mmol) and Pb(OAc)4 (665 mg, 1.5 mmol) were added in 10-20 mg portions over 20 min to a stirred suspension of K2CO3 (830 mg, 6 mmol) in solution of arylideneindendione 3a-c or 14a-d(1 mmol) in dry CH2Cl2 (25 mL) at 0 °C. Upon completion of addition, stirring was continued for 30 minat 0 °C. The reaction mixture was passed through a short plug of silica gel, which was washed with CH2Cl2 (100 mL), and the combined filtrates were concentrated in vacuo to ~10 mL. The product was isolated by gradual addition of hexane to the solution thus obtained. The resulting precipitate was filtered, washed with hexane and dried in vacuo. |
79% | With lead(IV) tetraacetate; potassium carbonate In tetrahydrofuran; dichloromethane at 0℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With boron trifluoride diethyl etherate In 1,2-dichloro-ethane at 20 - 50℃; | 37.1 Boron trifluoride diethyl etherate (12.3 mL, 97.9 mmol) was added slowly to a solution of ( lS,4aR,6aS,7R,8R, 10aR, l0bR,12aR,UR, 15R)-8-[(lR)- 1,2-dimethylpropyl]- 15- hydroxy-M-methoxy-l..aJ^^.lO.lOa.lOb.l l.ϖ.ϖa-dodecahydro-1,6a,8,10a-tetramethyl- 4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid (product compound from Step 2 in the synthesis of Intermediate 1; 5 g, 9.96 mmol) and N-aminophthalimide (1.94 g, 1.20 mmol) in 1, 2-dichloroethane (112 mL) at room temperature. The reaction mixture was heated overnight at 50°C and allowed to cool to room temperature. The reaction mixture was partitioned between EtOAc and water, and the layers were separated. The aqueous layer was extracted with EtOAc. The combined organic layers were dried with Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography, elution with 0- 50% EtOAc in heptane, to give the product (4.16 g, 66%) as a pale yellow solid.1H NMR (400 MHz, CD3OD) δ 0.71 - 0.82 (m, 9 H) 0.86 (d, 7=6.69 Hz, 3 H) 0.91 (d, 7=6.78 Hz, 3 H) 1.20 (d, 7=15.72 Hz, 20 H) 1.94 (d, J=Il. βl Hz, 1 H) 2.10 (d, 7=12.89 Hz, 1 H) 2.20 (dt, 7=13.61, 6.84 Hz, 1 H) 2.29 (dd, 7=13.57, 6.49 Hz, 1 H) 2.85 (s, 1 H) 3.26 (d, 7=9.52 Hz, 1 H) 3.35 (s, 2 H) 3.42 (s, 2 H) 3.69 (d, 7=11.67 Hz, 1 H) 4.05 (ddd, 7=11.69, 9.49, 6.49 Hz, 1 H) 5.47 (d, 7=5.86 Hz, 1 H) 7.58 - 8.08 (m, 4 H). |
66% | With boron trifluoride diethyl etherate In 1,2-dichloro-ethane at 50℃; | |
With boron trifluoride diethyl etherate In 1,2-dichloro-ethane at 50℃; | 37.1 INTERMEDIATE 37( 1 S,4aR,6aS,7R,SR, 1 Oa/?, 1 ObR, 12R, 14R, 15R)-S-[(R)- 1 ,2-dimethylρropyl]- 14- hydrazino- 15-hydroxy- 1 ,6,6a,7,8,9, 10, 1 Oa, 1 Ob, 11 , 12, 12a-dodecahydro- 1 ,6a,8, 1 Oa-tetramethyl- 4H- 1 ,4a-propano-2H-phenanthro [ 1 ,2-c]pyran-7-carboxylic acidC^OHStep l :Boron trifluoride diethyl etherate (12.3 mL, 97.9 mmol) was added slowly to a solution of ( 1 S,4aR,6aS,lRUSDR, 1 OaR, 1 QbR, 1 IaR, 14R, 15J?)-8-[( IR)- 1 ,2-dimethylpropyl]- 15- hydroxy- 14-methoxy- 1 ,6,6a,7,8,9, 10, 10a, 10b, 11 , 12, 12a-dodecahydro- 1 ,6a,8, 1 Oa-tetramethyl- ^//-l,4a-propano-2H-phenanthro[l,2-c]pyran-7-carboxylic acid (product compound from Step 2 in the synthesis of Intermediate 1; 5 g, 9.96 mmol) and N-aminophthalimide (1.94 g, 1.20 mmol) in 1 , 2-dichloroethane (112 mL) at room temperature. The reaction mixture was heated overnight at 50°C and allowed to cool to room temperature. The reaction mixture was partitioned between EtOAc and water, and the layers were separated. The aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash chromatography, elution with 0- 50% EtOAc in heptane, to give the product (4.16 g, 66%) as a pale yellow solid.1H NMR (400 MHz, CD3OD) δ 0.71 - 0.82 (m, 9 H) 0.86 (d, J=6.69 Hz, 3 H) 0.91 (d, J=6.78 Hz, 3 H) 1.20 (d, J=I 5.72 Hz, 20 H) 1.94 (d, J=I 7.67 Hz, 1 H) 2.10 (d, J=12.89 Hz, 1 H) 2.20 (dt, J=I 3.61, 6.84 Hz, 1 H) 2.29 (dd, J=I 3.57, 6.49 Hz, 1 H) 2.85 (s, 1 H) 3.26 (d, J=9.52 Hz, 1 H) 3.35 (s, 2 H) 3.42 (s, 2 H) 3.69 (d, J=I 1.67 Hz, 1 H) 4.05 (ddd, J=I 1.69, 9.49, 6.49 Hz, 1 H) 5.47 (d, J=5.86 Hz, 1 H) 7.58 - 8.08 (m, 4 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0℃; for 1h; | 2.1. General procedure for the oxidative addition of N-aminophthalimide General procedure: N-Aminophthalimide (972 mg, 6 mmol) and Pb(OAc)4 (2.658 g, 6 mmol) were added in 10-25 mg portions over 30 min to a stirred suspension of K2CO3 (2.070 g, 15 mmol) in a solution of starting compound 1a or 1b (3 mmol) in dry CH2Cl2 (30 mL) at 0 °C. Upon completion of addition, stirring was continued for 30 min at 0 °C. The reaction mixture was passed through a short plug of Celite, which was washed with CH2Cl2 (30 mL), and the combined filtrates concentrated in vacuo to 10 mL. The product was isolated by gradual addition of hexane to the solution thus obtained. The resulting precipitate was filtered, washed with hexane, and dried in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With [bis(acetoxy)iodo]benzene; potassium carbonate In dichloromethane at 20℃; | 4.2. General procedure for the synthesis of products 2 General procedure: N,N-Disubstituted hydrazines (1.4 equiv) were added to a solution of alkene 1a (1 equiv), iodobenzene diacetate (1.5 equiv) and K2CO3 (2.8 equiv) in dichloromethane. The resulting solution was stirred at room temperature until the disappearance of the starting alkene (monitored by 19F NMR). The reaction medium was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The resulting oil was then purified by chromatography on silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With [bis(acetoxy)iodo]benzene; potassium carbonate In dichloromethane at 20℃; | 4.2. General procedure for the synthesis of products 2 General procedure: N,N-Disubstituted hydrazines (1.4 equiv) were added to a solution of alkene 1a (1 equiv), iodobenzene diacetate (1.5 equiv) and K2CO3 (2.8 equiv) in dichloromethane. The resulting solution was stirred at room temperature until the disappearance of the starting alkene (monitored by 19F NMR). The reaction medium was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The resulting oil was then purified by chromatography on silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; | 1 (S)-tert-butyl 2-(1,3-dioxoisoindolin-2-ylcarbamoyl)pyrrolidine-1-carboxylate (S)-tert-Butyl 2-(1,3-dioxoisoindolin-2-ylcarbamoyl)pyrrolidine-1-carboxylate 3 To a solution of Boc-protected proline 2 (215 mg, 1.0 mmol) in dry CH2Cl2 (5 mL) under a nitrogen atmosphere, was added HOBt (172 mg, 1.3 mmol), EDCI (254 mg, 1.3 mmol), and N-aminophthalimide (81 mg, 0.5 mmol) at 0 °C and stirred at this temperature for 2 h after which it was warmed to room temperature along with stirring for 10 h. The reaction mixture was then diluted with CH2Cl2 and successively washed with 1 M HCl, satd aq NaHCO3, and brine. The organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification by column chromatography (7:3 ethyl acetate/hexanes) gave the desired product 3 (165 mg, 92% yield) as a white solid. Mp: 234-236 °C; (c 0.85, CHCl3); IR (Neat): ν = 2971, 1741, 1678, 1425, 1202, 1135, 1030, 772 cm-1; 1H NMR (CDCl3, 300 MHz): δ 9.87-9.66 (br, 1H), 7.92-7.83 (m, 2H), 7.81-7.72 (m, 2H), 4.64-4.32 (m, 1H), 3.66-3.27 (m, 2H), 2.58-2.19 (m, 1H), 2.14-1.83 (m, 3H), 1.52 (s, 9H); 13C NMR (CDCl3, 75 MHz): δ 171.1, 164.8, 156.5, 134.5, 130.1, 123.8, 81.3, 57.7, 47.0, 28.3, 26.4, 24.1; ESIMS: m/z 382 [M+Na]+; HRMS Calcd for C18H21N3NaO5: 382.1373, found: 382.1402 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0℃; for 0.5h; | General procedure for the preparation of aziridines 4a-c and 15a-d: General procedure: N-Aminophthalimide (243mg, 1.5 mmol) and Pb(OAc)4 (665 mg, 1.5 mmol) were added in 10-20 mg portions over 20 min to a stirred suspension of K2CO3 (830 mg, 6 mmol) in solution of arylideneindendione 3a-c or 14a-d(1 mmol) in dry CH2Cl2 (25 mL) at 0 °C. Upon completion of addition, stirring was continued for 30 minat 0 °C. The reaction mixture was passed through a short plug of silica gel, which was washed with CH2Cl2 (100 mL), and the combined filtrates were concentrated in vacuo to ~10 mL. The product was isolated by gradual addition of hexane to the solution thus obtained. The resulting precipitate was filtered, washed with hexane and dried in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0℃; for 0.5h; | General procedure for the preparation of aziridines 4a-c and 15a-d: General procedure: N-Aminophthalimide (243mg, 1.5 mmol) and Pb(OAc)4 (665 mg, 1.5 mmol) were added in 10-20 mg portions over 20 min to a stirred suspension of K2CO3 (830 mg, 6 mmol) in solution of arylideneindendione 3a-c or 14a-d(1 mmol) in dry CH2Cl2 (25 mL) at 0 °C. Upon completion of addition, stirring was continued for 30 minat 0 °C. The reaction mixture was passed through a short plug of silica gel, which was washed with CH2Cl2 (100 mL), and the combined filtrates were concentrated in vacuo to ~10 mL. The product was isolated by gradual addition of hexane to the solution thus obtained. The resulting precipitate was filtered, washed with hexane and dried in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0℃; for 0.5h; | General procedure for the preparation of aziridines 4a-c and 15a-d: General procedure: N-Aminophthalimide (243mg, 1.5 mmol) and Pb(OAc)4 (665 mg, 1.5 mmol) were added in 10-20 mg portions over 20 min to a stirred suspension of K2CO3 (830 mg, 6 mmol) in solution of arylideneindendione 3a-c or 14a-d(1 mmol) in dry CH2Cl2 (25 mL) at 0 °C. Upon completion of addition, stirring was continued for 30 minat 0 °C. The reaction mixture was passed through a short plug of silica gel, which was washed with CH2Cl2 (100 mL), and the combined filtrates were concentrated in vacuo to ~10 mL. The product was isolated by gradual addition of hexane to the solution thus obtained. The resulting precipitate was filtered, washed with hexane and dried in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0℃; for 0.5h; | General procedure for the preparation of aziridines 4a-c and 15a-d: General procedure: N-Aminophthalimide (243mg, 1.5 mmol) and Pb(OAc)4 (665 mg, 1.5 mmol) were added in 10-20 mg portions over 20 min to a stirred suspension of K2CO3 (830 mg, 6 mmol) in solution of arylideneindendione 3a-c or 14a-d(1 mmol) in dry CH2Cl2 (25 mL) at 0 °C. Upon completion of addition, stirring was continued for 30 minat 0 °C. The reaction mixture was passed through a short plug of silica gel, which was washed with CH2Cl2 (100 mL), and the combined filtrates were concentrated in vacuo to ~10 mL. The product was isolated by gradual addition of hexane to the solution thus obtained. The resulting precipitate was filtered, washed with hexane and dried in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sodium carbonate; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In ethyl acetate for 27h; Inert atmosphere; Reflux; regioselective reaction; | 4.6. Procedure for aziridination of a-Bromo substituted alkenesand their rearrangement General procedure: Anhydrous Na2CO3 (0.7 mmol) was added to the suspension o fIBX (0.35 mmol) and PhthNH2 (0.375 mmol) in EA (2 mL) under nitrogen. After stirring 10 min at room temperature, alkene 1q or 1r (0.25 mmol) was added to the reaction mixture and then refluxed for 20 h. The reaction mixture was quenched with water. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using hexane/EA (8:1) to afford product 2q or 2r. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0℃; for 0.5h; | Preparationof N-phthalimidoaziridines 2a-i and6a,c General procedure: N-Aminophthalimide(340 mg, 2.1 mmol) and Pb(OAc)4 (930 mg, 2.1 mmol) were alternatelyadded in 10-15 mg portions over 30 min to a stirred suspension of K2CO3(1.38 g, 10.0 mmol) in the solution of alkene 1a-i or 5a-c (1.4 mmol)in dry CH2Cl2 (25 mL) at 0 °C.Upon completion stirring was continued for 30 min at ambient temperature foralkenes 1a-i. The reactionmixture was passed through a plug of silica (0.5-1.5 cm), which was washed withCH2Cl2 (100-150 mL), and the combined filtrates wereevaporated under reduced pressure to ~5-8 mL (for aziridines 6a,c evaporation was performed withoutheating). The product was isolated by slow addition of hexane or pentane to thesolution thus obtained. The resulting precipitate was filtered, washed withhexane/diethyl ether mixture (2:1) and dried in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0℃; for 0.5h; | Preparationof N-phthalimidoaziridines 2a-i and6a,c General procedure: N-Aminophthalimide(340 mg, 2.1 mmol) and Pb(OAc)4 (930 mg, 2.1 mmol) were alternatelyadded in 10-15 mg portions over 30 min to a stirred suspension of K2CO3(1.38 g, 10.0 mmol) in the solution of alkene 1a-i or 5a-c (1.4 mmol)in dry CH2Cl2 (25 mL) at 0 °C.Upon completion stirring was continued for 30 min at ambient temperature foralkenes 1a-i. The reactionmixture was passed through a plug of silica (0.5-1.5 cm), which was washed withCH2Cl2 (100-150 mL), and the combined filtrates wereevaporated under reduced pressure to ~5-8 mL (for aziridines 6a,c evaporation was performed withoutheating). The product was isolated by slow addition of hexane or pentane to thesolution thus obtained. The resulting precipitate was filtered, washed withhexane/diethyl ether mixture (2:1) and dried in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0 - 20℃; | Preparationof N-phthalimidoaziridines 2a-i and6a,c General procedure: N-Aminophthalimide(340 mg, 2.1 mmol) and Pb(OAc)4 (930 mg, 2.1 mmol) were alternatelyadded in 10-15 mg portions over 30 min to a stirred suspension of K2CO3(1.38 g, 10.0 mmol) in the solution of alkene 1a-i or 5a-c (1.4 mmol)in dry CH2Cl2 (25 mL) at 0 °C.Upon completion stirring was continued for 30 min at ambient temperature foralkenes 1a-i. The reactionmixture was passed through a plug of silica (0.5-1.5 cm), which was washed withCH2Cl2 (100-150 mL), and the combined filtrates wereevaporated under reduced pressure to ~5-8 mL (for aziridines 6a,c evaporation was performed withoutheating). The product was isolated by slow addition of hexane or pentane to thesolution thus obtained. The resulting precipitate was filtered, washed withhexane/diethyl ether mixture (2:1) and dried in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0 - 20℃; | Preparationof N-phthalimidoaziridines 2a-i and6a,c General procedure: N-Aminophthalimide(340 mg, 2.1 mmol) and Pb(OAc)4 (930 mg, 2.1 mmol) were alternatelyadded in 10-15 mg portions over 30 min to a stirred suspension of K2CO3(1.38 g, 10.0 mmol) in the solution of alkene 1a-i or 5a-c (1.4 mmol)in dry CH2Cl2 (25 mL) at 0 °C.Upon completion stirring was continued for 30 min at ambient temperature foralkenes 1a-i. The reactionmixture was passed through a plug of silica (0.5-1.5 cm), which was washed withCH2Cl2 (100-150 mL), and the combined filtrates wereevaporated under reduced pressure to ~5-8 mL (for aziridines 6a,c evaporation was performed withoutheating). The product was isolated by slow addition of hexane or pentane to thesolution thus obtained. The resulting precipitate was filtered, washed withhexane/diethyl ether mixture (2:1) and dried in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With lead(IV) tetraacetate; potassium carbonate In dichloromethane at 0 - 20℃; | Preparationof N-phthalimidoaziridines 2a-i and6a,c General procedure: N-Aminophthalimide(340 mg, 2.1 mmol) and Pb(OAc)4 (930 mg, 2.1 mmol) were alternatelyadded in 10-15 mg portions over 30 min to a stirred suspension of K2CO3(1.38 g, 10.0 mmol) in the solution of alkene 1a-i or 5a-c (1.4 mmol)in dry CH2Cl2 (25 mL) at 0 °C.Upon completion stirring was continued for 30 min at ambient temperature foralkenes 1a-i. The reactionmixture was passed through a plug of silica (0.5-1.5 cm), which was washed withCH2Cl2 (100-150 mL), and the combined filtrates wereevaporated under reduced pressure to ~5-8 mL (for aziridines 6a,c evaporation was performed withoutheating). The product was isolated by slow addition of hexane or pentane to thesolution thus obtained. The resulting precipitate was filtered, washed withhexane/diethyl ether mixture (2:1) and dried in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.7% | With triethylamine; In N,N-dimethyl-formamide; for 3h; | General procedure: To a solution of the compound 2 (mLeq) in DMF(10 mL), TEA(0.5 mL) was added and then acyl or sulphonyl chloride derivatives(mLeq) were added with allowing the mixture to stir at 60 C temperaturefor 3 h. The mixture was cooled and poured on 200 mL ofice-water, stirred, filtered, washed with water, and dried in air togive the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With acetic acid In ethanol at 60℃; for 1.5h; | 9 3.1.7. General method of synthesis of compounds (5a-j) General procedure: To a solution of the compound 2 (mLeq) in ethanol (10 mL), thecorresponding aromatic aldhyde or sugar aldhyde (mLeq) wasadded and 0.5 mL of acetic acid (33%). The reaction mixture washeated under reflux for 1.5 h and then left to cool to room temperature.The solid that separated out was filtered off, washed withethanol, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.4% | With acetic acid In ethanol at 60℃; for 1.5h; | 8 General method of synthesis of compounds (5a-j) General procedure: To a solution of the compound 2 (mLeq) in ethanol (10 mL), thecorresponding aromatic aldhyde or sugar aldhyde (mLeq) wasadded and 0.5 mL of acetic acid (33%). The reaction mixture washeated under reflux for 1.5 h and then left to cool to room temperature.The solid that separated out was filtered off, washed withethanol, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.4% | With acetic acid In ethanol at 60℃; for 1.5h; | 10 General method of synthesis of compounds (5a-j) General procedure: To a solution of the compound 2 (mLeq) in ethanol (10 mL), thecorresponding aromatic aldhyde or sugar aldhyde (mLeq) wasadded and 0.5 mL of acetic acid (33%). The reaction mixture washeated under reflux for 1.5 h and then left to cool to room temperature.The solid that separated out was filtered off, washed withethanol, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With acetic acid In ethanol at 60℃; for 1.5h; | 11 General method of synthesis of compounds (5a-j) General procedure: To a solution of the compound 2 (mLeq) in ethanol (10 mL), thecorresponding aromatic aldhyde or sugar aldhyde (mLeq) wasadded and 0.5 mL of acetic acid (33%). The reaction mixture washeated under reflux for 1.5 h and then left to cool to room temperature.The solid that separated out was filtered off, washed withethanol, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.4% | With acetic acid In ethanol at 60℃; for 1.5h; | 15 General method of synthesis of compounds (5a-j) General procedure: To a solution of the compound 2 (mLeq) in ethanol (10 mL), thecorresponding aromatic aldhyde or sugar aldhyde (mLeq) wasadded and 0.5 mL of acetic acid (33%). The reaction mixture washeated under reflux for 1.5 h and then left to cool to room temperature.The solid that separated out was filtered off, washed withethanol, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With acetic acid In ethanol at 60℃; for 1.5h; | 16 General method of synthesis of compounds (5a-j) General procedure: To a solution of the compound 2 (mLeq) in ethanol (10 mL), thecorresponding aromatic aldhyde or sugar aldhyde (mLeq) wasadded and 0.5 mL of acetic acid (33%). The reaction mixture washeated under reflux for 1.5 h and then left to cool to room temperature.The solid that separated out was filtered off, washed withethanol, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.4% | With acetic acid In ethanol at 60℃; for 1.5h; | 17 General method of synthesis of compounds (5a-j) General procedure: To a solution of the compound 2 (mLeq) in ethanol (10 mL), thecorresponding aromatic aldhyde or sugar aldhyde (mLeq) wasadded and 0.5 mL of acetic acid (33%). The reaction mixture washeated under reflux for 1.5 h and then left to cool to room temperature.The solid that separated out was filtered off, washed withethanol, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Stage #1: N-aminophthalamide With 2-iodoxybenzoic acid; scandium tris(trifluoromethanesulfonate) In ethyl acetate at 20℃; for 0.166667h; Inert atmosphere; Stage #2: racemic methyl phenyl sulfoxide In ethyl acetate for 21h; Inert atmosphere; Reflux; | General Procedure for Sulfoximination of Sulfoxides General procedure: Sc(OTf)3 (0.075 mmol) was added to the suspension of IBX (0.75 mmol) and PhthNH2 (0.8mmol) in EA (4 mL) under nitrogen atmosphere. After stirring 10 min at rt, sulfoxide (1 mmol) was added. The RM was strirred at reflux for 3 h, allowed to reach rt. IBX (0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 5h, allowed to reach rt. IBX(0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 13h, allowed to reach rt. The RM was quenched with saturated solution of Na2CO3. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Hexane: EA (2.5:1) to afford sulfoximine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: N-aminophthalamide With 2-iodoxybenzoic acid; scandium tris(trifluoromethanesulfonate) In ethyl acetate at 20℃; for 0.166667h; Inert atmosphere; Stage #2: ethylphenylsulfoxide In ethyl acetate for 21h; Inert atmosphere; Reflux; | General Procedure for Sulfoximination of Sulfoxides General procedure: Sc(OTf)3 (0.075 mmol) was added to the suspension of IBX (0.75 mmol) and PhthNH2 (0.8mmol) in EA (4 mL) under nitrogen atmosphere. After stirring 10 min at rt, sulfoxide (1 mmol) was added. The RM was strirred at reflux for 3 h, allowed to reach rt. IBX (0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 5h, allowed to reach rt. IBX(0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 13h, allowed to reach rt. The RM was quenched with saturated solution of Na2CO3. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Hexane: EA (2.5:1) to afford sulfoximine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | General procedure: Sc(OTf)3 (0.075 mmol) was added to the suspension of IBX (0.75 mmol) and PhthNH2 (0.8mmol) in EA (4 mL) under nitrogen atmosphere. After stirring 10 min at rt, sulfoxide (1 mmol) was added. The RM was strirred at reflux for 3 h, allowed to reach rt. IBX (0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 5h, allowed to reach rt. IBX(0.75 mmol) and PhthNH2 (0.8 mmol) were added to RM and strirred at reflux for 13h, allowed to reach rt. The RM was quenched with saturated solution of Na2CO3. The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using Hexane: EA (2.5:1) to afford sulfoximine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With triethylamine In dichloromethane at 0℃; for 2h; Inert atmosphere; Schlenk technique; | 3.1.1. General procedure for the synthesis of the ligands General procedure: 1 g (4.55 mmol) chlorodiphenylphosphine (Ph2PCl) was slowlyadded to a solution of N-Aminophthalimide (0.39 g, 2.25 mmol)and triethylamine (0.46 g, 4.55 mmol) or Hydrazine dihydrochloride(0.24 g, 2.25 mmol) and triethylamine (0.92 g, 9.10 mmol)in dichloromethane (20 mL) at 0 °C. The resulting suspension wasstirred for 2 h and then the solvent was removed by filtrationthrough a sintered Schlenk tube. The remaining solid was washedwith distilled water and ethanol consecutively; then dried in vacuumto produce a white solid. Physical and spectroscopic data ofthem are presented, as following:3.1.1.1. N,N-bis(diphenylphosphino)- N-Aminophthalimide (L1).[(Ph2P)2NNC2O2C6H4]. Yield: 0.96 g, 80%. mp 203-206 °C. 31P-{1H}NMR d (ppm): 77.5 (s). 1H NMR d (ppm): 7.72 (m, 8H, Ph), 7.52 (m,12H, Ph), 7.86 (m, 2H, Ph), 7.66 (m, 2H, Ph). IR data (KBr, cm1):1787, 1731s, 1433 m, 1207, 1100m, 990 m; 878s, 741, 702s, 524 m,450s. |
80% | With triethylamine In dichloromethane at 0℃; for 2h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Stage #1: triethylammonium N-pentylsulfamate With trifluoromethylsulfonic anhydride; Triphenylphosphine oxide In dichloromethane at 0℃; for 0.25h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane at -78℃; for 0.25h; Inert atmosphere; Stage #3: N-aminophthalamide In dichloromethane at -78 - 22℃; Inert atmosphere; | 4.2.5 N′-pentyl-N-(phthalimid-2-yl)sulfamide (2h) A flame-dried round bottom flask equipped with magnetic stir bar was charged with triphenylphosphine oxide (2.755 g, 9.90 mmol, 1.65 equiv) and fitted with a rubber septum. The flask was evacuated and backfilled with N2. Anhydrous CH2Cl2 (50 mL, 0.12 M with respect to amine) was added and the flask was cooled at 0°C in an ice water bath. Trifluoromethanesulfonic anhydride (1.51 mL, 8.99 mmol, 1.5 equiv) that had been freshly removed from the glovebox was then added to the cooled solution dropwise via syringe. The reaction was allowed to stir at 0°C in an ice water bath for 15 min. This suspension was treated with a solution of triethylammonium N-pentylsulfamate (2.42 g, 9.00 mmol, 1.50 equiv) in CH2Cl2 (9 mL, 0.67 M with respect to amine) via cannula transfer. The flask containing sulfamate salt solution was rinsed with CH2Cl2 (1.2 mL, ca. 5.0 M with respect to amine) to achieve quantitative transfer. The resulting yellow solution was stirred for 15 min at 0°C. During this time, a clean, flame-dried round bottom flask equipped with stir bar was fitted with a rubber septum and subsequently evacuated and backfilled with N2. This process was repeated two more times. The flask was then charged with Et3N (2.5 mL, 18.0 mmol, 3.0 equiv) and CH2Cl2 (72 mL, 0.08 M with respect to amine) and the mixture was cooled at-78°C in an iPrOH/dry ice bath. The sulfamate salt solution was transferred dropwise to the Et3N solution via cannula (during which time a yellow to intense red color often developed), rinsing the flask with CH2Cl2 (0.33 mL, ca. 2.0 M with respect to amine) to achieve quantitative transfer. The resultant solution was stirred at-78°C for 15 min. During this time, a flame-dried round bottom flask equipped with a stir bar was charged with N-aminophthalimide. (973 mg, 6.00 mmol, 1.00 equiv) and CH2Cl2 (6.0 mL, 1.0 M) and chilled to-78°C in a dry ice/iPrOH bath. After 15 min, the Et3N solution was cannula transferred to the solution of the amine. The triethylamine-containing flask was rinsed with CH2Cl2 (ca. 5.0 M with respect to amine) to achieve quantitative transfer. Without removing the cooling bath, the reaction was then stirred overnight, during which time no additional dry ice was added to the bath and the mixture gradually warmed to room temperature. After stirring overnight, the reaction was diluted with 1 M HCl (ca. 10 mL/mmol of sulfamide) and H2O (ca. 10 mL/mmol of sulfamide). The biphasic mixture was transferred to a separatory funnel, rinsing the flask with CH2Cl2 to achieve quantitative transfer. The organic phase was separated and the aqueous phase was extracted twice more with CH2Cl2 (ca. reaction volume). The combined organic phases were dried with MgSO4, filtered, and concentrated under reduced pressure. The product was isolated as a white solid (1.25 g, 67% yield) after purification on a Teledyne Isco CombiFlashRf system using a Redi Sep Rf normal phase silica gel column (7:3 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3) δ 7.92 (dd, J=5.4, 3.1Hz, 2H), 7.81 (dd, J=5.6, 3.0Hz, 2H), 6.78 (br s, 1H), 4.45 (t, J=5.8Hz, 1H), 3.33 (dt, J=6.8, 6.8Hz, 2H), 1.66-1.58 (m, 2H), 1.38-1.34 (m, 4H), 0.92 (t, J=7.0Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 164.9, 134.8, 129.6, 124.0, 43.9, 29.1, 28.6, 22.1, 13.9. IR (neat) ν 3276 (br), 3165 (br), 2929 (m), 2865 (m), 1791 (m), 1726 (s), 1609 (m), 1426 (m), 1379 (m), 1341 (s), 1200 (m), 1153 (s), 1111 (m), 1080 (s), 1021 (m), 993 (m), 923 (m), 879 (s), 788 (m), 719 (s), 706 (s), 656 (s), 584 (s) cm-1. TLC Rf=0.28 in 6:4 hexanes/EtOAc. HRMS (ESI) m/z: [M - H]- Calcd for C13H16N3O4S 310.0861; Found 310.0863. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 26℃; Inert atmosphere; | 4.2 Preparation of alkynylaziridines General procedure 1 for the formation of aziridines from enynes: General procedure: To an oven-dried 25mL round bottom flask filled with argon, were introduced the enyne (1.0 equiv) and (diacetoxyiodo)benzene PIDA (1.5-2.0 equiv) in CH2Cl2 (10mL). The reaction mixture was cooled to 0-5°C (ice-bath) and the N-aminophthalimide PhthNH2 (1.5-2.0 equiv) was added. The resulting mixture was stirred at 0°C for 10min, allowed to warm up to room temperature (22-26°C) and stirred until judged as complete by TLC (ca 3-24h). Then it was diluted in CH2Cl2 and quenched with a saturated solution of NaHCO3 (30-100mL). The aqueous layer was extracted with CH2Cl2 (3×20-60 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (PET/AcOEt 80/20 to 70/30, 11-45g SiO2) to afford the desired product. 4.2.1 2-(2-(diethoxymethyl)-2-(phenylethynyl)aziridin-1-yl) isoindoline-1,3-dione 2a (0012) The title compound was prepared from (3-(diethoxymethyl)but-3-en-1-yn-1-yl)benzene (1.00g, 4.34mmol) following general procedure 1. This procedure afforded 1.41g (83% yield) of the title compound as a yellow solid. 1H NMR: (400MHz, CDCl3) δ 7.78 (dd, J=5.5, 3.1Hz, 2H), 7.67 (dd, J=5.5, 3.1Hz, 2H), 7.24-7.17 (m, 1H), 7.17-7.06 (m, 4H), 4.95 (s, 1H), 3.94-3.71 (m, 4H), 3.51 (d, J=2.2Hz, 1H), 3.16 (d, J=2.2Hz, 1H), 1.28 (dt, J=26.3, 7.1Hz, 6H). 13C NMR: (100MHz, CDCl3) δ 165.4, 134.2, 131.8, 130.4, 128.6, 128.2, 123.1, 122.1, 100.9, 85.8, 83.8, 64.8, 63.6, 44.8, 40.0, 15.4, 15.2. MS (ESI): m/z=413 [M+Na]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 26℃; Inert atmosphere; | 4.2 Preparation of alkynylaziridines General procedure 1 for the formation of aziridines from enynes: General procedure: To an oven-dried 25 mL round bottom flask filled with argon, were introduced the enyne (1.0 equiv) and (diacetoxyiodo) benzene PIDA (1.5-2.0 equiv) in CH2Cl2 (10 mL). The reaction mixture was cooled to 0-5 °C (ice-bath) and the N-aminophthalimide PhthNH2 (1.5-2.0 equiv) was added. The resulting mixture was stirred at 0 °C for 10 min, allowed to warm up to room temperature (22-26 °C) and stirred until judged as complete by TLC (ca 3-24 h). Then it was diluted in CH2Cl2 and quenched with a saturated solution of NaHCO3 (30-100 mL). The aqueous layer was extracted with CH2Cl2 (3 _ 20-60 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (PET/ AcOEt 80/20 to 70/30, 11-45g SiO2) to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 26℃; Inert atmosphere; | 4.2 Preparation of alkynylaziridines General procedure 1 for the formation of aziridines from enynes: General procedure: To an oven-dried 25 mL round bottom flask filled with argon, were introduced the enyne (1.0 equiv) and (diacetoxyiodo) benzene PIDA (1.5-2.0 equiv) in CH2Cl2 (10 mL). The reaction mixture was cooled to 0-5 °C (ice-bath) and the N-aminophthalimide PhthNH2 (1.5-2.0 equiv) was added. The resulting mixture was stirred at 0 °C for 10 min, allowed to warm up to room temperature (22-26 °C) and stirred until judged as complete by TLC (ca 3-24 h). Then it was diluted in CH2Cl2 and quenched with a saturated solution of NaHCO3 (30-100 mL). The aqueous layer was extracted with CH2Cl2 (3 _ 20-60 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (PET/ AcOEt 80/20 to 70/30, 11-45g SiO2) to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 26℃; Inert atmosphere; | 4.2 Preparation of alkynylaziridines General procedure 1 for the formation of aziridines from enynes: General procedure: To an oven-dried 25 mL round bottom flask filled with argon, were introduced the enyne (1.0 equiv) and (diacetoxyiodo) benzene PIDA (1.5-2.0 equiv) in CH2Cl2 (10 mL). The reaction mixture was cooled to 0-5 °C (ice-bath) and the N-aminophthalimide PhthNH2 (1.5-2.0 equiv) was added. The resulting mixture was stirred at 0 °C for 10 min, allowed to warm up to room temperature (22-26 °C) and stirred until judged as complete by TLC (ca 3-24 h). Then it was diluted in CH2Cl2 and quenched with a saturated solution of NaHCO3 (30-100 mL). The aqueous layer was extracted with CH2Cl2 (3 _ 20-60 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (PET/ AcOEt 80/20 to 70/30, 11-45g SiO2) to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 26℃; Inert atmosphere; | 4.2 Preparation of alkynylaziridines General procedure 1 for the formation of aziridines from enynes: General procedure: To an oven-dried 25 mL round bottom flask filled with argon, were introduced the enyne (1.0 equiv) and (diacetoxyiodo) benzene PIDA (1.5-2.0 equiv) in CH2Cl2 (10 mL). The reaction mixture was cooled to 0-5 °C (ice-bath) and the N-aminophthalimide PhthNH2 (1.5-2.0 equiv) was added. The resulting mixture was stirred at 0 °C for 10 min, allowed to warm up to room temperature (22-26 °C) and stirred until judged as complete by TLC (ca 3-24 h). Then it was diluted in CH2Cl2 and quenched with a saturated solution of NaHCO3 (30-100 mL). The aqueous layer was extracted with CH2Cl2 (3 _ 20-60 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (PET/ AcOEt 80/20 to 70/30, 11-45g SiO2) to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 26℃; Inert atmosphere; | 4.2 Preparation of alkynylaziridines General procedure 1 for the formation of aziridines from enynes: General procedure: To an oven-dried 25 mL round bottom flask filled with argon, were introduced the enyne (1.0 equiv) and (diacetoxyiodo) benzene PIDA (1.5-2.0 equiv) in CH2Cl2 (10 mL). The reaction mixture was cooled to 0-5 °C (ice-bath) and the N-aminophthalimide PhthNH2 (1.5-2.0 equiv) was added. The resulting mixture was stirred at 0 °C for 10 min, allowed to warm up to room temperature (22-26 °C) and stirred until judged as complete by TLC (ca 3-24 h). Then it was diluted in CH2Cl2 and quenched with a saturated solution of NaHCO3 (30-100 mL). The aqueous layer was extracted with CH2Cl2 (3 _ 20-60 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (PET/ AcOEt 80/20 to 70/30, 11-45g SiO2) to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 26℃; Inert atmosphere; | 4.2 Preparation of alkynylaziridines General procedure 1 for the formation of aziridines from enynes: General procedure: To an oven-dried 25 mL round bottom flask filled with argon, were introduced the enyne (1.0 equiv) and (diacetoxyiodo) benzene PIDA (1.5-2.0 equiv) in CH2Cl2 (10 mL). The reaction mixture was cooled to 0-5 °C (ice-bath) and the N-aminophthalimide PhthNH2 (1.5-2.0 equiv) was added. The resulting mixture was stirred at 0 °C for 10 min, allowed to warm up to room temperature (22-26 °C) and stirred until judged as complete by TLC (ca 3-24 h). Then it was diluted in CH2Cl2 and quenched with a saturated solution of NaHCO3 (30-100 mL). The aqueous layer was extracted with CH2Cl2 (3 _ 20-60 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (PET/ AcOEt 80/20 to 70/30, 11-45g SiO2) to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 26℃; Inert atmosphere; | 4.2 Preparation of alkynylaziridines General procedure 1 for the formation of aziridines from enynes: General procedure: To an oven-dried 25 mL round bottom flask filled with argon, were introduced the enyne (1.0 equiv) and (diacetoxyiodo) benzene PIDA (1.5-2.0 equiv) in CH2Cl2 (10 mL). The reaction mixture was cooled to 0-5 °C (ice-bath) and the N-aminophthalimide PhthNH2 (1.5-2.0 equiv) was added. The resulting mixture was stirred at 0 °C for 10 min, allowed to warm up to room temperature (22-26 °C) and stirred until judged as complete by TLC (ca 3-24 h). Then it was diluted in CH2Cl2 and quenched with a saturated solution of NaHCO3 (30-100 mL). The aqueous layer was extracted with CH2Cl2 (3 _ 20-60 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (PET/ AcOEt 80/20 to 70/30, 11-45g SiO2) to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 26℃; Inert atmosphere; | 4.2 Preparation of alkynylaziridines General procedure 1 for the formation of aziridines from enynes: General procedure: To an oven-dried 25 mL round bottom flask filled with argon, were introduced the enyne (1.0 equiv) and (diacetoxyiodo) benzene PIDA (1.5-2.0 equiv) in CH2Cl2 (10 mL). The reaction mixture was cooled to 0-5 °C (ice-bath) and the N-aminophthalimide PhthNH2 (1.5-2.0 equiv) was added. The resulting mixture was stirred at 0 °C for 10 min, allowed to warm up to room temperature (22-26 °C) and stirred until judged as complete by TLC (ca 3-24 h). Then it was diluted in CH2Cl2 and quenched with a saturated solution of NaHCO3 (30-100 mL). The aqueous layer was extracted with CH2Cl2 (3 _ 20-60 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (PET/ AcOEt 80/20 to 70/30, 11-45g SiO2) to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 26℃; Inert atmosphere; | 4.2 Preparation of alkynylaziridines General procedure 1 for the formation of aziridines from enynes: General procedure: To an oven-dried 25 mL round bottom flask filled with argon, were introduced the enyne (1.0 equiv) and (diacetoxyiodo) benzene PIDA (1.5-2.0 equiv) in CH2Cl2 (10 mL). The reaction mixture was cooled to 0-5 °C (ice-bath) and the N-aminophthalimide PhthNH2 (1.5-2.0 equiv) was added. The resulting mixture was stirred at 0 °C for 10 min, allowed to warm up to room temperature (22-26 °C) and stirred until judged as complete by TLC (ca 3-24 h). Then it was diluted in CH2Cl2 and quenched with a saturated solution of NaHCO3 (30-100 mL). The aqueous layer was extracted with CH2Cl2 (3 _ 20-60 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (PET/ AcOEt 80/20 to 70/30, 11-45g SiO2) to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With acetic acid In ethanol at 78℃; for 6h; | 5.1. General Synthesis of Imines General procedure: The N-aminophthalimide chemical was dissolved in ethanol, and then target aldehyde was added along with glacial acetic acid. The mixture was then refluxed for 6 hours at 78°C, followed by using thin layer chromatography TLC. After completion, the mixture was cooled down to room temperature (25°C) and then kept at 4 °C for 1 hour, and the precipitate was collected, filltered, and recrystallized from in Supplementary Material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: N-benzyl proline hydrochloride With 1-methyl-1H-imidazole; Ethanesulfonyl chloride In dichloromethane at -5 - 0℃; for 0.666667h; Inert atmosphere; Stage #2: N-aminophthalamide In dichloromethane at -5 - 20℃; for 6h; Inert atmosphere; | General procedure: L1 and I1-I4 were synthesized according to literature reports.1a To a round bottom flask containing isopropanol (60 mL) at 40 oC was added L-proline (10.0 g, 86.6 mmol, 1 equiv.) and the reaction mixture was stirred at this temperature until fully complete in solution. The reaction mixture was then cooled to 0 oC and KOH (19.5 g, 347 mmol, 4.0 equiv.) was added and stirred for 5 min. Benzyl chloride (15 mL, 130 mmol, 1.5 equiv.) was added dropwise over 15 min, maintaining the temperature between 0 oC and 5 oC. Once addition was complete, the reaction mixture was heated to 40 oC and stirred for 17 h. After completion, the reaction mixture was cooled to room temperature and acidified to pH 4 with conc. HCl. DCM (150 mL) was added and the flask placed in the fridge overnight. The precipitate was then filtered off and the filtrate concentrated in vacuo. The residue was suspended in acetone to give a white solid. Filtration and washing with cold acetone afforded N-Benzyl L-proline hydrochloride as a pale yellow solid (17.2 g, 82%). To a round bottom flask containing dry DCM (45 mL) under N2 was added N-Benzyl L-proline hydrochloride (3.45 g, 14.3 mmol). The reaction mixture was cooled to -20 oC and keep an internal temperature of -5 oC. 1-Methyl imidazole (3.18 mL, 39.9 mmol) was then added and stirred for 10 min. Ethyl sulfonyl chloride (1.49 mL, 15.7 mmol) was then added slowly over 10 min. The reaction mixture was kept the internal temperature at -5 oC to 0 oC. Stirring at -5 oC to 0 oC for 30 min, RNH2 (12.8 mmol) was then added and the reaction mixture continued to stir at room temperature for 6 h. The progress of the reaction was monitored by thin layer chromatography (TLC). After the reaction was completed, the mixture was cooled to room temperature, diluted with DCM, and washed with water. The organic phase was collected and dried over anhydrous sodium sulfate. Next, it was purified by silica gel (200-300 mesh) column chromatography (petroleum ether and ethyl acetate) to obtain L1 and I1-I4 with yields of 45-87%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 20℃; diastereoselective reaction; | 4.1.1.2 General procedure to obtain aziridines 6a-c General procedure: A solution of (diacetoxy)iodobenzene (1.50 mmol) in CH2Cl2 (2.5 mL) was added to a suspension of N-aminophthalimide (2.00 mmol) and the corresponding alkene (1.00 mmol) in CH2Cl2 (2.5 mL) at 0 °C. The reaction mixture was stirred at room temperature monitored by TLC until completion. It was then quenched by using a saturated NaHCO3 solution and filtered over celite. The mixture was then extracted with CH2Cl2 (3×25 mL) and the combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under vacuum. The crude was purified by flash chromatography on silica gel using hexane/AcOEt (95:5). |
89% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 20℃; diastereoselective reaction; | 4.1.1.2 General procedure to obtain aziridines 6a-c General procedure: A solution of (diacetoxy)iodobenzene (1.50 mmol) in CH2Cl2 (2.5 mL) was added to a suspension of N-aminophthalimide (2.00 mmol) and the corresponding alkene (1.00 mmol) in CH2Cl2 (2.5 mL) at 0 °C. The reaction mixture was stirred at room temperature monitored by TLC until completion. It was then quenched by using a saturated NaHCO3 solution and filtered over celite. The mixture was then extracted with CH2Cl2 (3×25 mL) and the combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under vacuum. The crude was purified by flash chromatography on silica gel using hexane/AcOEt (95:5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 20℃; diastereoselective reaction; | 4.1.1.2 General procedure to obtain aziridines 6a-c General procedure: A solution of (diacetoxy)iodobenzene (1.50 mmol) in CH2Cl2 (2.5 mL) was added to a suspension of N-aminophthalimide (2.00 mmol) and the corresponding alkene (1.00 mmol) in CH2Cl2 (2.5 mL) at 0 °C. The reaction mixture was stirred at room temperature monitored by TLC until completion. It was then quenched by using a saturated NaHCO3 solution and filtered over celite. The mixture was then extracted with CH2Cl2 (3×25 mL) and the combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under vacuum. The crude was purified by flash chromatography on silica gel using hexane/AcOEt (95:5). |
88% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 20℃; diastereoselective reaction; | 4.1.1.2 General procedure to obtain aziridines 6a-c General procedure: A solution of (diacetoxy)iodobenzene (1.50 mmol) in CH2Cl2 (2.5 mL) was added to a suspension of N-aminophthalimide (2.00 mmol) and the corresponding alkene (1.00 mmol) in CH2Cl2 (2.5 mL) at 0 °C. The reaction mixture was stirred at room temperature monitored by TLC until completion. It was then quenched by using a saturated NaHCO3 solution and filtered over celite. The mixture was then extracted with CH2Cl2 (3×25 mL) and the combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under vacuum. The crude was purified by flash chromatography on silica gel using hexane/AcOEt (95:5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 20℃; diastereoselective reaction; | 4.1.1.2 General procedure to obtain aziridines 6a-c General procedure: A solution of (diacetoxy)iodobenzene (1.50 mmol) in CH2Cl2 (2.5 mL) was added to a suspension of N-aminophthalimide (2.00 mmol) and the corresponding alkene (1.00 mmol) in CH2Cl2 (2.5 mL) at 0 °C. The reaction mixture was stirred at room temperature monitored by TLC until completion. It was then quenched by using a saturated NaHCO3 solution and filtered over celite. The mixture was then extracted with CH2Cl2 (3×25 mL) and the combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under vacuum. The crude was purified by flash chromatography on silica gel using hexane/AcOEt (95:5). |
31% | With [bis(acetoxy)iodo]benzene In dichloromethane at 0 - 20℃; diastereoselective reaction; | 4.1.1.2 General procedure to obtain aziridines 6a-c General procedure: A solution of (diacetoxy)iodobenzene (1.50 mmol) in CH2Cl2 (2.5 mL) was added to a suspension of N-aminophthalimide (2.00 mmol) and the corresponding alkene (1.00 mmol) in CH2Cl2 (2.5 mL) at 0 °C. The reaction mixture was stirred at room temperature monitored by TLC until completion. It was then quenched by using a saturated NaHCO3 solution and filtered over celite. The mixture was then extracted with CH2Cl2 (3×25 mL) and the combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under vacuum. The crude was purified by flash chromatography on silica gel using hexane/AcOEt (95:5). |
Tags: 1875-48-5 synthesis path| 1875-48-5 SDS| 1875-48-5 COA| 1875-48-5 purity| 1875-48-5 application| 1875-48-5 NMR| 1875-48-5 COA| 1875-48-5 structure
[ 1074-82-4 ]
Potassium 1,3-dioxoisoindolin-2-ide
Similarity: 0.84
[ 926307-99-5 ]
1-Oxoisoindoline-5-carbaldehyde
Similarity: 0.84
[ 1260664-94-5 ]
3-Oxoisoindoline-5-carbaldehyde
Similarity: 0.84
[ 1250443-39-0 ]
6-(Aminomethyl)isoindolin-1-one hydrochloride
Similarity: 0.82
[ 1422057-35-9 ]
5-(Aminomethyl)isoindolin-1-one hydrochloride
Similarity: 0.82
[ 110406-94-5 ]
N'-(1-Methylazepan-4-yl)benzohydrazide
Similarity: 0.73
[ 1074-82-4 ]
Potassium 1,3-dioxoisoindolin-2-ide
Similarity: 0.84
[ 926307-99-5 ]
1-Oxoisoindoline-5-carbaldehyde
Similarity: 0.84
[ 1422057-35-9 ]
5-(Aminomethyl)isoindolin-1-one hydrochloride
Similarity: 0.82
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :