* 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.
With 1,4-dibenzyl-1,4-diazoniabicyclo[2.2.2]octane dichloroiodate In neat (no solvent) at 20℃; for 0.166667 h;
General procedure: General procedure for the iodination of aryl amines under solvent-free conditions.DBDABCODCI (0.5 mmol) and aryl amine (1 mmol) were triturated together in a porcelainmortar at room temperature. After completing reaction which monitored by TLC, the ethylacetate added to mixture and filtered, the organic layer washed with 5percent aqueous sodiumthiosulfate, and dried over MgSO4. The solvent was removed in vacuum and the crude mixturewas purified by column chromatography using ethyl acetate and hexane mixture and analyzedby m.p. and 1H NMR spectroscopy.
80%
With iodine; sodium carbonate In cyclohexane; water at 20℃; for 2 h;
General procedure: To a clean 50 mL round bottomed flask equipped with a large stir bar was added the substrate (10 mmol) followed by cyclohexane (ca. 6.0 mL to maintain the reaction concentration of 1.67 M) and an aqueous saturated solution of sodium carbonate (2.8 mL). Finally, iodine beads (11 mmol) were added as a solid and the flask was sealed with a septum and vented with a needle to the open atmosphere. The reaction was allowed to stir for the specified time at room temperature unless otherwise noted (see refPreviewPlaceHolderTable 1). The reaction mixture was poured into a separatory funnel with the aid of ethyl acetate or MTBE (2-3 mL) with additional aqueous saturated sodium carbonate (1 mL). The organic layer was washed twice with an aqueous saturated solution of sodium bisulfite (4 mL) and brine (5 mL), dried over sodium sulfate, and concentrated in vacuo to provide crude iodinated product. The products were purified by crystallization (if crystalline) from hexanes. Column chromatography (ethyl acetate/hexanes) was performed on the oils.
Reference:
[1] Organic Letters, 2001, vol. 3, # 7, p. 991 - 992
[2] Journal of Organic Chemistry, 2018, vol. 83, # 15, p. 7606 - 7621
[3] Bulletin of the Chemical Society of Ethiopia, 2015, vol. 29, # 1, p. 157 - 162
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[5] Bulletin of the Chemical Society of Japan, 2012, vol. 85, # 11, p. 1239 - 1243
[6] Canadian Journal of Chemistry, 2009, vol. 87, # 12, p. 1675 - 1681
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[8] Tetrahedron Letters, 2011, vol. 52, # 52, p. 7141 - 7145
[9] Tetrahedron, 1994, vol. 50, # 17, p. 5139 - 5146
[10] Organic and Biomolecular Chemistry, 2011, vol. 9, # 8, p. 2987 - 2991
[11] Journal of the Chinese Chemical Society, 1996, vol. 43, # 1, p. 95 - 99
[12] Molecules, 2004, vol. 9, # 7, p. 617 - 621
[13] Molecules, 2002, vol. 7, # 12, p. 867 - 870
[14] Synthesis, 2004, # 3, p. 441 - 445
[15] Journal of Materials Chemistry, 2004, vol. 14, # 3, p. 292 - 295
[16] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1988, vol. 42, # 7, p. 448 - 454
[17] Synthetic Communications, 2004, vol. 34, # 19, p. 3579 - 3585
[18] Patent: US2003/201429, 2003, A1, . Location in patent: Page/Page column 4-5
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[23] Journal of the American Chemical Society, 2018, vol. 140, # 33, p. 10553 - 10561
2
[ 62404-59-5 ]
[ 60577-34-6 ]
Yield
Reaction Conditions
Operation in experiment
90%
With triethyl borane; sodium hydroxide In hexane at 80℃; for 6 h; Inert atmosphere; Sealed tube
Under argon atmosphere, NaOH and triethyl boron were first stirred at room temperature to form a clear clear solution at a concentration of 1 M / L; Subsequently, 20 mmol (4 molpercent) of the above-mentioned triethylboron solution, 5 mmol of amide substrate, 15 mmol of silane, 2 mL of solvent Into a 10 mL sealed tube and placed in an oil bath at 80 ° C for 6 hours with heating. The reaction was completed and the reaction was exposed to air quenching, followed by The yield was determined by column chromatography and gas chromatography and a pure product was obtained. When using polymethylhydrogensiloxane (PMHS) and When the tetrahydrofuran was used as the silane and the solvent, the yields of the products A and B were 90percent and 0percent, respectively. When the triethoxysilane And n-hexane as silane and solvent, respectively, the yield of products A, B were: 94percent, 4percent
Reference:
[1] Patent: CN107235845, 2017, A, . Location in patent: Paragraph 0034; 0035; 0036; 0037
[2] Organic and Biomolecular Chemistry, 2017, vol. 15, # 10, p. 2246 - 2252
3
[ 62404-59-5 ]
[ 60577-34-6 ]
Yield
Reaction Conditions
Operation in experiment
94%
With triethyl borane; Triethoxysilane; sodium hydroxide In hexane at 80℃; for 6 h; Inert atmosphere; Sealed tube
Under argon atmosphere, NaOH and triethyl boron were first stirred at room temperature to form a clear clear solution at a concentration of 1 M / L; Subsequently, 20 mmol (4 molpercent) of the above-mentioned triethylboron solution, 5 mmol of amide substrate, 15 mmol of silane, 2 mL of solvent Into a 10 mL sealed tube and placed in an oil bath at 80 ° C for 6 hours with heating. The reaction was completed and the reaction was exposed to air quenching, followed by The yield was determined by column chromatography and gas chromatography and a pure product was obtained. When using polymethylhydrogensiloxane (PMHS) and When the tetrahydrofuran was used as the silane and the solvent, the yields of the products A and B were 90percent and 0percent, respectively. When the triethoxysilane And n-hexane as silane and solvent, respectively, the yield of products A, B were: 94percent, 4percent
Reference:
[1] Patent: CN107235845, 2017, A, . Location in patent: Paragraph 0034; 0035; 0036; 0037
4
[ 698-70-4 ]
[ 60577-34-6 ]
Yield
Reaction Conditions
Operation in experiment
59%
Stage #1: With tert.-butylhydroperoxide In toluene for 0.0333333 h; Inert atmosphere Stage #2: With triethylamine In toluene at 110℃; for 3 h; Inert atmosphere
General procedure: A round-bottom flask was chargedwith N,N-dialkyl aniline dissolved in toluene solution, under N2 condition. TBHP was added drop wise and reaction was stirred for 2 min. Triethylamine was added thereafter, and then the contents of the reaction were stirred for 3 h at 110 °C under inert N2 condition. The reaction mixture was washed 2–3 times with H2O and ethyl acetate. The upper organic layer was separated and dried over sodium sulphate and then subjected to rotavapour. The crude mixture was purified by column chromatography on silica gel (60–120).
Reference:
[1] Journal of Chemical Sciences, 2016, vol. 128, # 9, p. 1469 - 1473
5
[ 616-38-6 ]
[ 540-37-4 ]
[ 60577-34-6 ]
Yield
Reaction Conditions
Operation in experiment
76%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In 1-methyl-pyrrolidin-2-one at 250℃; for 0.2 h; Flow reactor
General procedure: Selective N-monomethlyation reactions were performed in a Vapourtec E-series continuous flow system equipped with a high temperature tube reactor (10 mL, stainless steel, 0.03'' i.d., Fig. 2 ) and a membrane back pressure regulator (Zaiput). Stock solutions of aniline (20 mmol, 1.0 equiv, 2 M), DMC (5.05 mL, 60 mmol, 3.0 equiv, 6 M), and DBU (4.47 mL, 30 mmol, 1.5 equiv, 3 M) were prepared in oven-dried 10 mL volumetric flasks using NMP as the solvent. The solutions were transferred to screw-thread vials with septum caps and reagents were pumped directly from the vials. After the high temperature coiled tube reactor was heated to 250 °C, peristaltic pumps (Vapourtec V-3) were used to pump the reactant solutions into the system (0.277 mL/min each for a 12 min residence time). The solutions were mixed with a cross-mixer (0.4″ i.d.), passed though the high temperature coiled tube reactor. Upon exiting the reactor, the reaction stream was passed through a short segment of stainless steel tubing to enable the reaction to cool and then exited the system by passage through the back pressure regulator (Note: PFA fittings should not be used at the exit of the reactor as they will deform due to the high temperature of the reaction stream and cause leaks in the system. Stainless steel connectors and tubing (12'') were used in our system.). After the flow system was equilibrated for 18 min, the product stream was collected for 5 min (2.77 mmol of aniline). The crude mixture was dissolved in ethyl acetate and washed with brine. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (Biotage 25 g Ultra-sil, 3–15percent ethyl acetate in hexanes) to afford the desired product.
[6-[(Bis-tert-butoxycarbonylmethyl-amino)-methyl]-4-(4-methylamino-phenylethynyl)-pyridin-2-ylmethyl]-tert-butoxycarbonylmethyl-amino}-acetic acid tert-butyl ester[ No CAS ]
With 1,4-dibenzyl-1,4-diazoniabicyclo[2.2.2]octane dichloroiodate; In neat (no solvent); at 20℃; for 0.166667h;
General procedure: General procedure for the iodination of aryl amines under solvent-free conditions.DBDABCODCI (0.5 mmol) and aryl amine (1 mmol) were triturated together in a porcelainmortar at room temperature. After completing reaction which monitored by TLC, the ethylacetate added to mixture and filtered, the organic layer washed with 5% aqueous sodiumthiosulfate, and dried over MgSO4. The solvent was removed in vacuum and the crude mixturewas purified by column chromatography using ethyl acetate and hexane mixture and analyzedby m.p. and 1H NMR spectroscopy.
80%
With iodine; sodium carbonate; In cyclohexane; water; at 20℃; for 2h;
General procedure: To a clean 50 mL round bottomed flask equipped with a large stir bar was added the substrate (10 mmol) followed by cyclohexane (ca. 6.0 mL to maintain the reaction concentration of 1.67 M) and an aqueous saturated solution of sodium carbonate (2.8 mL). Finally, iodine beads (11 mmol) were added as a solid and the flask was sealed with a septum and vented with a needle to the open atmosphere. The reaction was allowed to stir for the specified time at room temperature unless otherwise noted (see refPreviewPlaceHolderTable 1). The reaction mixture was poured into a separatory funnel with the aid of ethyl acetate or MTBE (2-3 mL) with additional aqueous saturated sodium carbonate (1 mL). The organic layer was washed twice with an aqueous saturated solution of sodium bisulfite (4 mL) and brine (5 mL), dried over sodium sulfate, and concentrated in vacuo to provide crude iodinated product. The products were purified by crystallization (if crystalline) from hexanes. Column chromatography (ethyl acetate/hexanes) was performed on the oils.
With iodine; sodium hydrogencarbonate;
EXAMPLE 1 [0057] Preparation of an EO Chromophore with One Polymerizable Group.[0058] The following reaction scheme, illustrated in FIG. 1, describes the preparation of a monoepoxy-functional EO chromophore according to the present invention. Similar reactions were carried out to prepare episulfide, oxetane and thietane containing EO chromophores. The examples given herein are for illustration purposes and are not to be taken as limiting the invention. The preparation of the electron withdrawing portion of the chromophore is described in PCT International Publication No. WO 01/98287 A1; and additional description for preparing chromophores is. [0059] The reactions shown in FIGS. 1 and 2 were carried out using methods well known by one skilled in the art. For example, solvents such as tetrahydrofuran or other ethers were used for the lithiation, aldehyde formation and conversion, and reduction reactions shown in FIG. 1, Step 1. The palladium chloride-catalyzed condensation reaction of FIG. 1, Step 3, was carried out in an ether such as tetrahydrofuran or other suitable solvent. All reactions were carried out in standard laboratory glassware under an argon atmosphere. [0060] Referring now to FIG. 1, in Step 1 a 3,4-dialkylthiophene was treated with two equivalents of butyllithium and dimethylformamide, followed by hydrolysis, to form a 3,4-dialkylthiophene-1,4-dialdehyde. In FIG. 1, Step 1, while the alkyl groups (R1 and R1a as shown in Structure II) are shown as being hexyl (C6H13), other alkyl groups in the C1-C10 range can also be used. The 3,4-dialkyl thiophene-1,4-dialdehyde was then treated with methyltriphenylphosphonium bromide and sodium hydride to convert one of the aldehyde groups into a vinylic group (-CH-CH2) attached to the thiophene ring as shown in compound A. [0061] In Step 2, N-methylaniline was reacted with iodine in the presence of sodium bicarbonate to form 4-iodo-N-methyaniline. This product was subsequently reacted with epichlorohydrin to form 4-iodo-N-methyl-N-(3-chloro-2-hydroxypropyl)aniline. The resulting chlorohydrin moiety was then dehydrohalogenated to form the corresponding epoxide (Compound B). [0062] In Step 3, compounds A and B were coupled using a palladium chloride catalyst to form Product C. [0063] In Step 4, Product C was reacted with a furan derivative, herein called 1-(dicyanomethylene)-2-cyano-4-(4-cyclohexylphenyl)furan, to yield the monoepoxy functional EO chromophore having the following Structure III.EMI7.0[0064] Compounds containing polymerizable episulfide, oxetane and thietane groups are similarly prepared.
3-(3-{4'-[(3-{3-[4'-(tert-butoxycarbonylmethylamino)biphenyl-3-ylsulfanyl]benzyl}-3H-imidazole-4-carbonyl)methylamino]biphenyl-3-ylsulfanyl}benzyl)-3H-imidazole-4-carboxylic acid methyl ester[ No CAS ]
[6-((1S,2R,4S)-1-Bicyclo[2.2.1]hept-5-en-2-ylmethoxy)-hexyl]-{4-[(E)-3,4-bis-(tert-butyl-dimethyl-silanyloxymethyl)-6-(4-nitro-phenyl)-hex-3-ene-1,5-diynyl]-phenyl}-methyl-amine[ No CAS ]
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 4h;
Part D: The product obtained above was dissolved in dichloromethane (100 mL), to which DIEA (12 mL) and chloroacetyl chloride (12 mL) were slowly added at 0 C. The reaction was stirred from 0 C. to rt for 4 hours, washed with 1.0 N HCl (2*) and brine, and dried over magnesium sulfate. After solvent removal, the crude product was purified by chromatography using ethyl acetate/hexane as eluent (2:8 to 4:6 ethyl acetate:hexane) to give the desired 2-chloro-N-(4-iodo-phenyl)-N-methyl-acetamide as a brown solid. MS found: (M+1)+=310.23.
With water; potassium carbonate; In methanol; at 20℃; for 6h;
Part C: The product obtained above was dissolved in methanol/water (2:1, 100 mL) and potassium carbonate (15.75 g, 114.1 mmol) was added. The mixture was stirred at rt for 6 hours. Dichloromethane (100 mL) was added, and the organic layer was separated, washed with water and brine, and dried over magnesium. Removal of the solvent gave the desired (4-iodo-phenyl)-methyl-amine as a dark colored, low-melting solid. MS found: (M+1)+=234.11.
EXAMPLE 1 [0057] Preparation of an EO Chromophore with One Polymerizable Group.[0058] The following reaction scheme, illustrated in FIG. 1, describes the preparation of a monoepoxy-functional EO chromophore according to the present invention. Similar reactions were carried out to prepare episulfide, oxetane and thietane containing EO chromophores. The examples given herein are for illustration purposes and are not to be taken as limiting the invention. The preparation of the electron withdrawing portion of the chromophore is described in PCT International Publication No. WO 01/98287 A1; and additional description for preparing chromophores is. [0059] The reactions shown in FIGS. 1 and 2 were carried out using methods well known by one skilled in the art. For example, solvents such as tetrahydrofuran or other ethers were used for the lithiation, aldehyde formation and conversion, and reduction reactions shown in FIG. 1, Step 1. The palladium chloride-catalyzed condensation reaction of FIG. 1, Step 3, was carried out in an ether such as tetrahydrofuran or other suitable solvent. All reactions were carried out in standard laboratory glassware under an argon atmosphere. [0060] Referring now to FIG. 1, in Step 1 a 3,4-dialkylthiophene was treated with two equivalents of butyllithium and dimethylformamide, followed by hydrolysis, to form a 3,4-dialkylthiophene-1,4-dialdehyde. In FIG. 1, Step 1, while the alkyl groups (R1 and R1a as shown in Structure II) are shown as being hexyl (C6H13), other alkyl groups in the C1-C10 range can also be used. The 3,4-dialkyl thiophene-1,4-dialdehyde was then treated with methyltriphenylphosphonium bromide and sodium hydride to convert one of the aldehyde groups into a vinylic group (-CH-CH2) attached to the thiophene ring as shown in compound A. [0061] In Step 2, N-methylaniline was reacted with iodine in the presence of sodium bicarbonate to form 4-iodo-N-methyaniline. This product was subsequently reacted with epichlorohydrin to form 4-iodo-N-methyl-N-(3-chloro-2-hydroxypropyl)aniline. The resulting chlorohydrin moiety was then dehydrohalogenated to form the corresponding epoxide (Compound B). [0062] In Step 3, compounds A and B were coupled using a palladium chloride catalyst to form Product C. [0063] In Step 4, Product C was reacted with a furan derivative, herein called 1-(dicyanomethylene)-2-cyano-4-(4-cyclohexylphenyl)furan, to yield the monoepoxy functional EO chromophore having the following Structure III.EMI7.0[0064] Compounds containing polymerizable episulfide, oxetane and thietane groups are similarly prepared.
methyl 6-iodo-1-methyl-2-oxo-1,2-dihydro-4-quinolineacetate[ No CAS ]
[ 7677-24-9 ]
[ 60577-34-6 ]
methyl 6-cyano-1-methyl-2-oxo-1,2-dihydro-4-quinolineacetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%
tetrakis(triphenylphosphine)palladium (0); In water; triethylamine; toluene;
7.1. Methyl 6-cyano-1-methyl-2-oxo-1,2-dihydro-4-quinolineacetate 1.1 ml of trimethylsilyl cyanide (8.4 mmol) followed by 0.15 g (0.13 mmol) of tetrakistriphenylphosphinepalladium are added to a solution of 0.50 g (1.4 mmol) of methyl 6-iodo-1-methyl-2-oxo-1,2-dihydro-4-quinolineacetate (prepared from <strong>[60577-34-6]N-methyl-4-iodoaniline</strong> according to the method described in Example 1) in 6 ml of anhydrous triethylamine. The reaction medium is then heated to reflux for 4 hours under a nitrogen atmosphere. After cooling to room temperature, the medium is poured into 60 ml of toluene and 60 ml of water. The organic phase is washed with water and the initial aqueous phase is re-extracted with dichloromethane. The organic phases are combined, dried over sodium sulphate and concentrated under vacuum. The residue is purified by flash chromatography on silica, eluding with a methanol/dichloromethane (5:95) mixture. 0.313 g of the expected nitrile is obtained. Yield=87%; Melting point=202-203 C.
The product so obtained (5.96 g), iodine (5.08 g) and iodic acid (2.29 g) were heated in glacial acetic acid (30 ml) and concentrated sulphuric acid (4 ml) at 85 C. for 3.5 hours. The mixture was then cooled to ambient temperature and ethyl acetate (125 ml) and water (75 ml) were added. Solid sodium bicarbonate was added to neutralise the mixture which was then washed with water (75 ml) and brine (75 ml). After drying (MgSO4) the solvent was evaporated to leave 4'-iodo-N-methylacetanilide (7.04, 64%), m.p. 140-141 C. (recrystallized from ethyl acetate/hexane). A solution of the product so obtained (6.05 g) in 2N aqueous sodium hydroxide solution (30 ml) and ethanol (30 ml) was refluxed for 8 hours. The solvent was evaporated and the residue partitioned between ethyl acetate (110 ml) and water (100 ml). The organic phase was washed with brine (75 ml), dried (MgSO4) and the solvent evaporated to give 4-iodo-N-methylaniline as an oil (4.97 g, 97%). NMR Spectrum 2.80 (3H, s), 6.40 (2H, d), 7.45 (2H, d).
4-cyano-2,3,5,6-tetrafluorophenyl-N-(4-iodophenyl)-N-methylcarbamodithioate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
64%
General procedure: Compound 1a (0.2 mmol, 39.5 mg), carbon disulfide 2 (0.4mmol, 30.4 mg), and K3PO4 (0.3 mmol, 63.5 mg) were weighted to a dried 10 mL schlenk flask under air. Then DMSO (2.0 mL) was added. The mixture was stirred at room temperature for approximately two hours. After substrate 1a completely disappeared (monitored by TLC), pentafluorobenzonitrile 3a (0.26 mmol, 50.4 mg) was added and the mixture continued stirring for another two hours. After the completion of the reaction (by TLC), water (5.0 mL) was added to the reaction media and extracted with CH2Cl2 (3×10.0 mL). The combined organic layers were washed with brine, and dried over anhydrous MgSO4. After removal of the solvent, the residue was purified by flash column chromatography on silica gel to give the desired product 4a.
(2R,3S,4R,5R)-3,4-Bis-benzyloxy-2-benzyloxymethyl-5-iodomethyl-6-methoxy-tetrahydro-pyran[ No CAS ]
methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-[4-iodophenyl(methyl)amino]methyl}-α,β-D-glucoside[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61%
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 36h;Inert atmosphere;
General procedure: To a solution of glycosyl 13/methyl glucoside37,38 20/33 (0.175 mmol) in dry DMF was added aniline or N-alkylated aniline (0.262 mmol), respectively, followed by anhyd K2CO3 (0.436 mmol). The mixture was stirred at 60 C under a N2 atmosphere until TLC analysis indicated the disappearance of the carbohydrate starting material (12-36 h). After completion of the reaction, the mixture was allowed to cool down to r.t. The solution was then diluted with water (10 mL) and the aqueous phase was extracted with Et2O (3 × 10 mL). The combined organic phases were washed with brine, dried (MgSO4), filtered, and evaporated. The residue was purified by column chromatography (silica gel; EtOAc-hexane, 1:9).
With triethyl borane; sodium hydroxide; In hexane; at 80℃; for 6h;Inert atmosphere; Sealed tube;
Under argon atmosphere, NaOH and triethyl boron were first stirred at room temperature to form a clear clear solution at a concentration of 1 M / L; Subsequently, 20 mmol (4 mol%) of the above-mentioned triethylboron solution, 5 mmol of amide substrate, 15 mmol of silane, 2 mL of solvent Into a 10 mL sealed tube and placed in an oil bath at 80 C for 6 hours with heating. The reaction was completed and the reaction was exposed to air quenching, followed by The yield was determined by column chromatography and gas chromatography and a pure product was obtained. When using polymethylhydrogensiloxane (PMHS) and When the tetrahydrofuran was used as the silane and the solvent, the yields of the products A and B were 90% and 0%, respectively. When the triethoxysilane And n-hexane as silane and solvent, respectively, the yield of products A, B were: 94%, 4%
With triethyl borane; Triethoxysilane; sodium hydroxide; In hexane; at 80℃; for 6h;Inert atmosphere; Sealed tube;
Under argon atmosphere, NaOH and triethyl boron were first stirred at room temperature to form a clear clear solution at a concentration of 1 M / L; Subsequently, 20 mmol (4 mol%) of the above-mentioned triethylboron solution, 5 mmol of amide substrate, 15 mmol of silane, 2 mL of solvent Into a 10 mL sealed tube and placed in an oil bath at 80 C for 6 hours with heating. The reaction was completed and the reaction was exposed to air quenching, followed by The yield was determined by column chromatography and gas chromatography and a pure product was obtained. When using polymethylhydrogensiloxane (PMHS) and When the tetrahydrofuran was used as the silane and the solvent, the yields of the products A and B were 90% and 0%, respectively. When the triethoxysilane And n-hexane as silane and solvent, respectively, the yield of products A, B were: 94%, 4%
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In 1-methyl-pyrrolidin-2-one; at 250℃; for 0.2h;Flow reactor;
General procedure: Selective N-monomethlyation reactions were performed in a Vapourtec E-series continuous flow system equipped with a high temperature tube reactor (10 mL, stainless steel, 0.03'' i.d., Fig. 2 ) and a membrane back pressure regulator (Zaiput). Stock solutions of aniline (20 mmol, 1.0 equiv, 2 M), DMC (5.05 mL, 60 mmol, 3.0 equiv, 6 M), and DBU (4.47 mL, 30 mmol, 1.5 equiv, 3 M) were prepared in oven-dried 10 mL volumetric flasks using NMP as the solvent. The solutions were transferred to screw-thread vials with septum caps and reagents were pumped directly from the vials. After the high temperature coiled tube reactor was heated to 250 C, peristaltic pumps (Vapourtec V-3) were used to pump the reactant solutions into the system (0.277 mL/min each for a 12 min residence time). The solutions were mixed with a cross-mixer (0.4? i.d.), passed though the high temperature coiled tube reactor. Upon exiting the reactor, the reaction stream was passed through a short segment of stainless steel tubing to enable the reaction to cool and then exited the system by passage through the back pressure regulator (Note: PFA fittings should not be used at the exit of the reactor as they will deform due to the high temperature of the reaction stream and cause leaks in the system. Stainless steel connectors and tubing (12'') were used in our system.). After the flow system was equilibrated for 18 min, the product stream was collected for 5 min (2.77 mmol of aniline). The crude mixture was dissolved in ethyl acetate and washed with brine. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (Biotage 25 g Ultra-sil, 3-15% ethyl acetate in hexanes) to afford the desired product.