There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Structure of 17329-87-2
*Storage: {[sel_prStorage]}
*Shipping: {[sel_prShipping]}
The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
*For Research Use Only !
Change View
Size | Price | VIP Price | US Stock |
Global Stock |
In Stock | ||
{[ item.pr_size ]} |
Inquiry
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.discount_usd) ]} {[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]} |
Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]} | Inquiry {[ item.pr_usastock ]} In Stock Inquiry - | {[ item.pr_chinastock ]} {[ item.pr_remark ]} In Stock 1-2 weeks - Inquiry - | Login | - + | Inquiry |
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days
1-2weeks
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd,1,item.mem_rate,item.pr_is_large_size_no_price, item.pr_usd) ]}
Inquiry
{[ getRatePrice(item.pr_usd,item.pr_rate,1,item.pr_is_large_size_no_price, item.vip_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
{[ getRatePrice(item.pr_usd, 1,1,item.pr_is_large_size_no_price, item.pr_usd) ]}
In Stock
- +
Please Login or Create an Account to: See VIP prices and availability
US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
CAS No. : | 17329-87-2 |
Formula : | C8H7ClN2O3 |
M.W : | 214.61 |
SMILES Code : | O=C(NC1=CC=C([N+]([O-])=O)C=C1)CCl |
MDL No. : | MFCD00031337 |
InChI Key : | AZURFBCEYQYATI-UHFFFAOYSA-N |
Pubchem ID : | 140220 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H301-H311-H331-H341 |
Precautionary Statements: | P201-P202-P261-P264-P270-P271-P280-P302+P352-P304+P340-P308+P313-P310-P330-P361-P403+P233-P405-P501 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅲ |
* 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 |
---|---|---|
98% | In tetrahydrofuran; at 50℃; | General procedure: To a stirred solution of 12b (4.6 g, 20 mmol) in THF (50 mL) was added N,N-dimethylamine (2M solution in THF, 1.8 g, 20 mL, 40 mmol) dropwise at rt. The resulting mixture was stirred at 50 C overnight and was then evaporated to dryness under reduced pressure. The residue was triturated with a saturated aqueous solution of NaHCO3, and the solid product was collected by filtration, washed with water followed by hexane, and dried to give 14a. Yield: 4.1 g (87%) |
b.The amide from step a (150 g) was suspended in toluene (1.5 L). Piperidine (138 mL) was added slowly and the solution heated to reflux for 1 hour. The solution was cooled and concentrated. DCM (500 mL) was added, and then 2N aqueous HCI, and the resulting precipitate was removed by filtration and washed with a further portion of HCI. The precipitate was dissolved in water (2 L) and basified with NaOH pellets to pH 14. The resulting precipitate was removed by filtration and washed with water to give the product as a white solid. Drying in a vacuum oven gave the product (72%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57.5% | In methanol; at 50℃; for 20h; | (1) the compound 2-chloro-N-(4-nitrophenyl)acetamide 6.01 g (28.00mmol), anhydrous methanol 50.0 ml, dipropyl amine 11.10 g (109.69mmol), is added to the 100 ml flask in three, heating to 50 C reaction 20h, fluid evaporation of the reaction, ethyl acetate is dissolved and washed with water, the organic phase dried anhydrous magnesium sulfate, concentrated to obtain 4.50 g yellow colored product 2-(dipropylamino)-N-(4-nitrophenyl)acetamide, the yield is 57.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In toluene;Product distribution / selectivity; | a.4-nitro-aniline (150 g) was suspended in toluene (1.5 L) and stirred. Chloroacetyl chloride (87 ml_) was dissolved in toluene (100 ml_) and added dropwise to the aniline suspension. The reaction mixture was stirred overnight and then washed with aqueous sodium carbonate solution (2 x), 1N aqueous HCI (2 x), and water. The organics were dried over sodium sulfate and concentrated to give the product (96%). |
95% | With triethylamine; In tetrahydrofuran; at 20℃; for 2h;Cooling with ice; | Add p-nitroaniline (276mg, 2mmol) and triethylamine (303mg, 3mmol) to tetrahydrofuran (10mL),Chloroacetyl chloride (226mg, 2mmol) was added dropwise under ice water bath.After dropping, stirring at room temperature for 2h, TLC (CH2Cl2:MeOH=10:1) detected that the reaction was complete.Add 1N HCl (20mL) to the reaction solution, continue to stir for 15 min,Suction filtration, drying, yellow powder 4-35a, 408mg, yield 95%. |
93.3% | With triethylamine; In 1,4-dioxane; at 5 - 20℃;Product distribution / selectivity; | a. Preparation of 2-Chloro-N-(4-nitrophenyl)acetamide; 4-Nitroaniline (250.0 g, 1.8 mol) and triethylamine (276 mL, 1.98 mol) were dissolved in 1 ,4-dioxane (1.5 L) and cooled to 50C. This stirred, cooled solution was then added to a solution of chloroacetyl chloride in 1 ,4-dioxane keeping the temperature <20C. After stirring overnight, an extra equivalent of triethylamine and chloroacetyl EPO <DP n="52"/>chloride was added and the reaction was stirred once again overnight before being poured into water (5 L). After being stirred for 15 min, the resultant solid was filtered off, washed with water, and dried to give 358.8 g (93%) of 2-chloro-Λ/-(4- nitrophenyl)acetamide: solid; mp 185-187C; Rf 0.14 (1 :2 EtOAc/hexane) |
93% | P-nitroaniline 138g (1.0mol), toluene 600mL, sodium carbonate 1.59g (1.5mol) water 400mL was added to the reaction flask, stirred for 30 minutes, control temperature 15 ± 5 slowly add 124g (1.1mol) chloroacetyl chloride, After dripping in about 2 hours, stirring at room temperature for 2 hours, filtering and drying to obtain 200g of 2-chloro-N-p-nitrophenylacetamide, yield 93%, HPLC purity 98.3%, no further purification can be directly Used for the next reaction. | |
92% | In tetrahydrofuran; at 20℃; | General procedure: To a solution of 3-nitroaniline 10a (13.8 g, 100 mmol) in THF (50 mL), chloroacetyl chloride (200 mmol) was added dropwise at rt, and the resulting mixture was stirred at rt for 8-10 h. The reaction mixture was evaporated under reduced pressure, and the solid residue was triturated with a saturated aqueos solution of NaHCO3 and filtered. The solid was washed successively with water and hexane and dried to yield 12a. Yield: 19.62 g (92%); |
91% | With Sodium hydrogenocarbonate; In dichloromethane; at 0℃; for 1h; | General procedure: Propionyl chloride (6.0mmol) in dry CH2Cl2 (10mL) was added dropwise to a mixture of 4-methoxybenzenamine (5.0mmol), sodium bicarbonate (12.5mmol) and dry CH2Cl2 (15mL). The mixture was stirred in ice water bath for 1h and poured into water and then extracted with CH2Cl2 (3×30mL). The combined organic layer was washed with brine and dried over anhydrous MgSO4. The solvent was evaporated to dryness to afford the compound 4a. Others amide derivatives 4b-4s were synthesized similarly. Physical constants and spectral data of compounds 4a-4s are summarized below. |
90% | With triethylamine; In tetrahydrofuran; at -15 - 20℃; for 14.5h; | 2-Chloro-N-(4-nitro-phenyl)-acetamide, (14).; 4-Nitroaniline (61 g, 443mmol) was dissolved in THF (3 L) and cooled to -15C in a salt-ice bath. To this stirred mixture was added TEA (44.7g, 443mmol), followed by the addition of Chloroacetylchloride (10Og, 885mmol) in THF (1.5 L) dropwise over 30 min. The reaction was then allowed to warm up to RT, then stirred overnight. The reaction was monitered by TLC, and when complete (approx. 14 hr), <n="22"/>the insoluble precipitate of NH4CI was removed by filtration. The filtrate was the basified with sat. NaHCO3(aq) soln. (500 ml_), the solid formed was then removed by filtration. This was then successively washed with water (2 x 1 L) portions, then Acetone (2 x 500 ml_) portions. This gave the pure product, a pale yellow solid (84.43 g, 90%); R, = 0.05 (5% MeOH/ 95% DCM), m/p 187-1911C, IR (film) 3272.90, 3225.90, 3162.90, 3103.87, 2939.90, 1682.77 cm"1, 1H NMR (DMSO, 400MHz) δ: 4.34 (s, 2H), 7.84 (d, 2H1 J = 9.2 Hz), 8.25 (d, 2H, J = 9.2 Hz), 10.88 (s, 1 H). 13C NMR (DMSO, 100MHz) δ: 43.53, 119.10, 125.00, 142.63, 144.54, 165.56, HRMS [ES+] calcd for C8H7CIN2O3215.0218 [M+H] +, found 215.0220. |
88% | With anhydrous Sodium acetate; In acetic acid; for 0.5h;Cooling with ice; | General procedure: Initially, appropriate amine (0.05mol) was dissolved in glacial acetic acid (25ml) containing saturated solution of sodium acetate (25ml). In case, if the substance did not dissolve completely then the mixture was warmed and the resultant solution was cooled in an ice-bath with stirring. To the ice cold solution chloroacetyl chloride (4.8ml, 0.06mol) was added drop wise with continuous stirring to avoid the vigorous reaction. After half an hour, a white colored product was separated out and filtered. The product was firstly washed with 50% aqueous acetic acid and finally with water. The crude product was then recrystallized from ethanol. The product so obtained was dried under vacuum to obtain the series of intermediate compounds (12a-o). |
85% | With triethylamine; In dichloromethane; at 0 - 20℃; | General procedure: To the mixture of substituted aromatic amine (0.020 mol)and Et3N (0.024 mol), solubilized in 20 mL of CH2Cl2at a temperature of 0 C, maintained by an ice bath,2-chloroacetyl chloride (0.024 mol) was slowly added. Theice bath was then removed, and the reaction stayed underagitation for 6 h at room temperature. The reaction mixturewas monitored by TLC (hexane/methyl acetate 1:1). At theend of reaction, the reaction mixture was concentrated atreduced pressure and cold water was added to the reactionmixture, causing the formation of a solid. The solid wasthen filtered and washed with cold water (3 × 20 mL), andthe final product was purified by recrystallization with anethanol/water (1:1) mixture. α-Chloro-N-phenylacetamide (2a)Yield: 93%, |
85% | With triethylamine; In dichloromethane; at 0 - 20℃; | General procedure: Chloroacetyl chloride (0.024 mol) was slowly added to the mixture of substituted aromatic amine (0.020 mol) and Et3N(0.024 mol), solubilized in 20 mL of CH2Cl2 at a temperature of 0 C,maintained by an ice bath. The ice bath was then removed, and the reaction kept under agitation for 6 h at room temperature. The reaction mixture was monitored by TLC (hexane/methyl acetate 1:1).At the end of the reaction, the reaction mixture was concentrated at reduced pressure and cold water was added to the reaction mixture, causing the formation of a solid. The solid was then nfiltered and washed with cold water (3 20 mL), and the final product was purified by recrystallization with an ethanol/water(1:1) mixture [41]. |
80% | With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 17h;Inert atmosphere; | [00397] Step 1 : To a mixture of 4-nitroaniline (5.0 g, 36 mmol) and TEA (5.0 mL, 36 mmol) in THF (100 mL) stirred at 0 C was added 2-chloroacetyl chloride (1.9 mL; 24 mmol), and the mixture was allowed to warm to room temperature and stirred for 17 h. The mixture was partitioned between 1 :9 MeOH/EtOAc and aq. NaHC03 (ca. 100 mL each; 50%> NaHC03 saturation), and the organic layer was washed with aq. brine (ca. 100 mL; 50%> saturation), separated and dried over anhydrous Na2S04 and concentrated whereupon a precipitate formed. The precipitate was filtered and washed with EtOAc to afford the desired product 2-chloro-N-(4-nitrophenyl)acetamide as a yellow solid (6.17 g, 80% yield).1H NMR (DMSO-d6, 400 MHz) δ 10.90 (br s, 1H), 8.25 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 9.2 Hz, 2H), 4.34 (s, 2H); MS (ESI): calcd for C8H7C1N203 : 214, found: weak signal. |
80% | General procedure: In a 50 mL flask, 20 mmol of p-substituted arylamineand 24 mmol of triethylamine (Et3N) were added to 20 mLdichloromethane, under constant stirring, at a temperatureof 0 C, which was controlled by a crushed ice bath. Aftera brief period, 24 mmol of 2-chloro-acetyl/3-chloropropylchloride was added slowly. Then, the ice bathwas removed, and the reaction remained under constantstirring and at room temperature for 24 h. At the end ofthe reaction, the solvent was removed, under reducedpressure. The resulting precipitate was washed withdistilled water, vacuum filtered, and recrystallized in asuitable ethanol/water solution. This procedure yieldeda crystalline form. | |
76% | With potassium carbonate; In acetone;Reflux; | General procedure: Chloroacetyl chloride (0.06 mol) was added dropwise toa mixture of the appropriate amine (0.05 mol) and K2CO3(0.06 mol) in acetone (50 ml) at room temperature. Thereaction mass was refluxed for 4-8 h, and then progress of reaction was monitored by TLC using ethyl acetate-hexane(8:2) solvent system as eluent. Then the reaction mixture was cooled and poured into 100 ml of ice water. The resulting white precipitates were filtered off and dried under the vacuum condition and purified by recrystallization from alcohol. Similarly, other compounds (5a-5j) were prepared by using various substituted amines. |
75% | With potassium carbonate; In acetone;Reflux; | General procedure: Chloroacetyl chloride (0.06 mol) was added dropwise to a mixture of the appropriate amine (0.05 mol) and K2CO3 (0.06 mol) in acetone (50 mL) at room temperature. The reaction mixture was refluxed for 4-8 h, then, after cooling to room temperature, it was slowly poured into 100 mL of ice water. A solid was formed thereafter. The precipitate was separated by filtration and washed successively with water. The product was dried under vacuum to obtain 2a-k. The progress of the reaction was monitored by Thin Layer Chromatography using toluene: acetone (8:2) solvent system. |
74% | With anhydrous Sodium acetate; acetic acid; In water monomer;Cooling with ice; | General procedure: An appropriate primary aryl amine (0.137g, 1mmol) was added dropwise with a dropping funnel in glacial acetic acid (15ml) in 100ml R.B. kept at ice bath. Chloroacetyl chloride (112μl, 1mmol) was slowly added to the reaction mixture with vigorous stirring. When the addition was completed, 0.33M aqueous sodium acetate (25ml) was added. Further 50ml of chilled water was added directly to the round bottom flask and solution was stirred thoroughly for 20min, a residue/precipitate was obtained. Precipitate was filtered and washed with cold water. The crude product was dried and recrystallized with ethanol to obtain pure 2-Haloacetamide (2-chloroacetamide, corresponding products are 2a for M series, 2b for P series and 2c for N series). |
73% | With triethylamine; In tetrahydrofuran; at 0 - 20℃; | 4-nitroaniline (5.66 g, 40.98 mmol) was dissolved in THF (150 ml) and cooled to 0 0C prior to TEA (11.42 ml, 81.95 mmol, 2 equiv.) being added and the drop wise addition of 2-chloroacetyl chloride (4.89 ml, 61.464 mmol, 1.5 equiv.). The mixture was stirred overnight at room temperature under N2. The precipitate was filtered, the THF removed in vacuo and the resulting oil suspended in sat. NaHCO3 (aq.) (200 ml). The solid product was filtered and oven dried to a brown solid (6.42 g, 30.05 mmol, 73%). Rf 0.35 [DCM]. Mp. 177 - 180 0C. 1H NMR (400 MHz, dtf-DMSO) δ 10.94 (IH, s, NH), 8.25 (2H, d, J=9.3 Hz, 2ArH), 7.85 (2H, d, J=9.1 Hz, 2ArH), 4.35 (2H, s, CH2) ppm. 13C NMR (100 MHz, d6-OMSO) δ 165.6 (C=O), 144.6 (ArC), 142.6 (ArC), 125.0 (2ArCH), 119.1 (2ArCH), 43.5 (CH2) ppm. IR (neat) υmax 3274, 3227, 3162, 3103, 2941, 1683, 1565, 1494, 1332, 849 cm"1. MS m/z calc. C8H7ClN2O3 [M] 214.0, found [M-I] 212.9. |
69% | With pyridine; In dichloromethane; at 20℃; for 12h; | General procedure: The solution of arylamine (1.0 equiv.) and pyridine (1.0 equiv.) in DCM (concentration, 0.4 M) was cooled in an ice bath. Thesolution of 2-chloroacetyl chloride or 2-bromoacetyl bromide (1.1 equiv.) in DCM (concentration, 0.5 M) was added dropwise to theabove solution according to the references [1-3]. The resulting reaction mixture was warmed to room temperature and stirred for 12 h.The reaction mixture was diluted with DCM and then washed with 1M HCl and brine. The organic layer was dried over anhydrousMgSO4, filtered and concentrated in vacuo. The crude product was purified by crystallization from a mixture of solvent DCM andpetroleum ether. |
66% | In dichloromethane; | General procedure: Substituted aniline (0.01 mol) I (i-xi) and Dichloromethane (20 ml) were mixed in a conical flask and Chloroacetylchloride (1.02 ml; 0.01 M) in a separating funnel was added drop by drop to the conical flask. The reaction mixture was stirred for 4-6 h resulting in the formation of white precipitate. The product obtained was filtered, and washed with a little cold water and recrystallized from water or from methanol or ethanol either alone or dilute with water. |
60% | With triethylamine; In dichloromethane; at 15℃; for 2h;Inert atmosphere; | To an ice-cooled solution of 4-nitroaniline (2.0 g, 14.4 mmol) and TEA (2.2 g, 21.6 mmol) in DCM (30 mL) was added 2-chloroacetyl chloride (2.0 g, 17.4 mmol). The mixture was stirred at 15 oC for 2 h. The mixture was washed with 1 N HCl (50 mL), brine (50 mL), dried over sodium sulfate and concentrated to give a crude product, which was triturated with EA (20 mL) to give the title product (1.8 g, 60%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ = 10.91 (s, 1 H), 8.25 (d, J = 8.3 Hz, 2 H), 7.84 (d, J = 8.2 Hz, 2 H), 4.35 (s, 2 H) ppm. |
56.7% | With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 0.333333h; | General procedure: In a round bottom flask, 10mmol aniline derivitives (4a-n) and 20mmol potassium carbonate were suspended in 15mL DMF and cooled to 0C. Then 12mmol chloroacethylchloride was added. The reaction mixture was then stirred at room temperature for 20min; quenched with saturated sodium hydrogen carbonate (10mL) and washed with water. The organic layer was separated and dried over sodium sulfate. The organic layer was evaporated under reduced pressure, and the crude reaction mixture was purified by column chromatography using chloroform and methanol as a mobile phase to obtain a pure compound [36-39]. The CAS-numbers and yield of synthesized compounds were reported in the supplementary file (Table S1). |
In ethyl acetate; | a. 2-Chloro-N-(4-nitrophenyl)-acetamide p-Nitroaniline (10.0g) and chloroacetyl chloride (15 ml) were refluxed together 1 hour, mixed with ethyl acetate and washed with water 3 times to yield 11.5 g; mp 183-185C. | |
With triethylamine; In acetonitrile; at 5 - 20℃; for 20h; | To a solution of 4-nitroaniline (27.62 g) and triethylamine (24.3 g) in acetonitrile (280 ml) was added dropwise chloroacetyl chloride (24.8 g) at 5C and the mixture was stirred at ambient temperature for 20 hours. The precipitates were collected by filtration and washed with water and diisopropyl ether, and dried in vacuo over phosphorus pentoxide to give 2-chloro-N- (4- nitrophenyl) acetamide (33.99 g) as a yellow powder. 1H-NMR (DMSO-d6): 8 4. 35 (2H, s), 7.75-7. 9 (2H, m), 8.2-8. 3 (2H, M), 10. 91 (1H, s) (-) APCI-MS (m/z): 213 (M-H)- | |
With triethylamine; In dichloromethane; at 0 - 20℃;Product distribution / selectivity; | a.A solution of 4-nitro-aniline (200 g, 1.4492 mol) in DCM (2 L) was cooled to 0 0C, and treated with Et3N (175 g, 1.739 mol) and then chloroacetyl chloride (180 g, 1.594 mol). After the addition was complete, the temperature was allowed to rise to room temperature, and the reaction mixture was stirred overnight. The reaction mixture was filtered, and the solids washed with water and then dried under vacuum and then by evaporation from toluene to yield the product (190 g). | |
With potassium carbonate; In acetone;Reflux; | General procedure: To 0.05 mol of each amine derivative (1a-k) and 0.06 mol of anhydrous K2CO3 in 50 mL of acetone, 0.06 mol of chloroacetyl chloride (0.06 mol) was added dropwise at room temperature and mixture was allowed to reflux for 4 to 8 h. The reaction progress was monitored by TLC using toluene : acetone (V/V, 8:2) solvent system. After the completion of the reaction, the mixture was cooled and poured into crushed ice. A solid thus obtained was filtered, washed with water and dried on vacuum oven to get 2a-k. | |
With triethylamine; In acetic acid; at -5 - 30℃; for 4.5h; | General procedure: In a 250 mL round bottom flask, charge aromatic amine (0.033 mol) and 12.5 ml glacial acetic acid at 25C to 30C. The reaction mixtures was completely dissolved in glacial acetic acid and drop wise addition of chloroacetyl chloride (3.0 mL, 0.037 mol) in reaction mixture at -5C to 0C completed within 1 hr. The reaction mixture was stirred for 3 hr at 25C to 30C. The reaction mixture was poured into saturated sodium acetate solution. The product was filtered and washed with cold water. Crystallization from ethanol/water (ratio 80:20) mixture yielded crystalline mass. | |
With potassium carbonate; In acetone;Reflux; | General procedure: Chloroacetyl chloride (0.06 mol) was added dropwise to a mixture of the appropriate amine (0.05 mol) and K2CO3 (0.06 mol) in acetone (50 mL) at room temperature. The reaction mixture was refluxed for 4 to 8 h, then, after cooling to room temperature, it was slowly poured into 100 mL of ice water. The solid that formed was separated byfiltration and washed repeatedly with water. The product was dried under vacuum to obtain 2a-k.8-12 The progress of the reaction was monitored by TLC using toluene: acetone (8 : 2) solvent system. | |
In benzene; for 6h;Reflux; | General procedure: Compound 1 (1.0 equiv.) and chloroacetyl chloride (1.0 equiv.) were taken in benzene and the reaction mixture was refluxed for 6 h after completion of the reaction monitored by TLC, the reaction mixture was diluted with EtOAc and washed with sat NaHCO3, H2O and brine. The combined organic layer was dried over anhyd. Na2SO4, evaporated to get compound corresponding 2a-o. | |
A suspension of 4-nitroaniline (7 g, 0.051 mol) and anhydrouspotassium carbonate (7 g, 0.051 mol) in dichloromethane (30 mL)was stirred for 30 min at room temperature. The reaction mixturewas cooled on an ice bath. To this was added an ice-cooled solutionof chloroacetylchloride (5.7 g, 0.051 mol) in dichloromethane(20 mL) drop wise over a period of 30 min. The reaction mixturewas stirred overnight at room temperature followed by reflux foradditional 30 min. Excess solvent was removed and the residuewas neutralized with aqueous sodium bicarbonate solution (5%w/v). The product obtained was filtered off and washed thoroughlywith cold water. The crude product obtained was dried under vacuum(10 g, yield: 92%). TLC (chloroform, Rf = 0.5). The product wassufficiently pure and used in the next step directly. | ||
With anhydrous Sodium acetate; acetic acid; at 0 - 25℃; for 2h; | General procedure: A substituted aniline (34.3 mmol) was added to 12.5 mL of a saturated solution ofsodium acetate, followed by 12.5 mL acetic acid. The suspension was cooled to 0 C, and 2-chloroacetyl chloride (34.4 mmol, 2.75 ml) was added dropwise to the suspension at ≤5 C.During the addition of 2-chloroacetyl chloride, the suspension dissipated and the mixtureclarified. Before the addition of 2-chloroacetyl chloride was complete, a white precipitatebegan to form. Upon completion of the addition, the heterogeneous mixture was brought to 25C and stirred at room temperature for 2 h. The white precipitate was filtered, washed withdistilled water (2×5 mL) and dried under vacuum to afford the crude product. Recrystallizationof crude 2a-g from absolute ethanol gave the desired 2a-g, respectively. The physical,analytic and spectral data of 2a-g are summarized in the Supplementary material to thispaper | |
With triethylamine; In dichloromethane; at 0 - 20℃; for 20h; | General procedure: In an ice bath, substituted aniline (20 mmol) wasdissolved along with triethylamine (24 mmol) in 20 mL of dichloromethane (DCM) at 0 C, and then 2-chloroacetylchloride (24 mmol) was slowly added. The ice bath wasremoved and the reaction was kept stirring for 20 h at roomtemperature. After this time, the reaction mixture wasconcentrated at reduced pressure, the residue was washedwith cold water (3 × 20 mL) and the precipitate was filtered.The product was recrystallized with ethanol/water. | |
With triethylamine; In tetrahydrofuran; at 0 - 25℃; for 1h; | General procedure: Chloroacetyl chloride(33 mmol, 2.63 mL) was added dropwise with stirring to a mixtureof triethylamine (33 mmol, 4.63 mL) and 2-aminobenzothiazole oraniline derivative (30 mmol) in THF (100 mL) at 0 C. After thecompletion of dropping, the mixturewas allowed to stir for 1 h. Thesolvent was evaporated under reduced pressure. The residue waswashed with water to remove trimethylamine hydrochloride, driedand recrystallized from EtOH [59,60]. | |
With triethylamine; In dichloromethane; at 0 - 25℃; for 20h; | General procedure: 2-Chloroacetyl chloride (24 mmol) wasslowly added dropwise to a mixture of various anilines(20 mmol) and Et3N (24 mmol) in anhydrous CH2Cl2(20 mL) at 0 C. The reaction mixture was warmed to roomtemperature and stirred for an additional 20 h. After the solventwas removed under reduced pressure, the residue waswashed with ice water, and the precipitate was separatedby filtration. The crude product was purified by crystallizationusing a mixture of ether/hexane (2a-r). | |
at 20℃; for 4h; | General procedure: Ice-cold chloroacetyl chloride (52 mL, 0.46 mol) was addeddrop-wise to substituted aniline (0.2 mol) (1a-e) with stirring,under anhydrous conditions. The reaction mixture wasstirred at room temperature for 4 h. The semisolid residuewas neutralized with sodium bicarbonate solution. Thecontents were filtered off and washed thoroughly with coldwater. The crude mass was air dried and recrystallized fromethanol. | |
With triethylamine; In dichloromethane; at 30℃; | General procedure: Chloroacetyl chloride (1.23 g, 11 mmol), Et3N (1.11 g, 11 mmol) and different amines (10 mmol)were added to CH2Cl2 (20 mL) and the resulting mixture was stirred at 30 C for 2-8 h. Then, thesolvent was evaporated in vacuo, water was added (15 mL), the mixture was filtered and the residuewas washed with water to obtain the different intermediates (Scheme 2). | |
In acetic acid; at 0 - 20℃; | General procedure: Various substituted anilines were dissolved in glacial acetic acidat 0 C, to this was added over 30 min choloroacetylchloride (2equivalents). The reaction mixture was brought to room temperatureand stirred overnight. Saturated sodium bicarbonate solutionwas added till complete neutralization. The resulting precipitatewas filtered off and washed with n-hexane and dried. The resultantproduct was used further without any purification. Either of 3-hydroxy benzaldehyde, 4-hydroxy benzaldehyde, vanillin or isovanillin(1 equivalent) was dissolved in acetone and potassiumcarbonate (2 equivalents) was added. Then correspondingsubstituted acetamide was mixed to the stirring solution. Finally,potassium iodide (1.5 equivalent) was added. The reaction mixturewas refluxed for 8-10 h. After completion of reaction, the resultantmixture was concentrated and treated with water and extractedwith ethyl acetate (3 x 20 mL). The organic layers were combinedand treated with brine and dried over sodium sulfate andconcentrated. The crude mixture was purified over silica gel(60-120) using petroleum ether: ethyl acetate (9:1). | |
With acetic acid; at 0 - 20℃; | General procedure: Various substituted anilines were dissolved in glacial acetic acid at0 C, to this was added over 30 min choloroacetyl chloride (2 equivalents).The reaction mixture was brought to room temperature andstirred overnight. Saturated sodium bicarbonate solution was added tillcomplete neutralization. The resulting precipitate was filtered off andwashed with n-hexane and dried. The resultant product (1) was usedfurther without any purification. Either of 4-hydroxy benzaldehyde(2a), vanillin (2b) or isovanillin (2c) (1 equivalent) was dissolved inacetone and potassium carbonate (2 equivalents) was added. Thencorresponding substituted acetamide (1) was mixed to the stirring solution.Finally, potassium iodide (1.5 equivalent) was added. The reactionmixture was refluxed for 8-10 h. After completion of reaction,the resultant mixture was concentrated and treated with water andextracted with ethyl acetate (3×20 mL). The organic layers werecombined and treated with brine and dried over sodium sulfate andconcentrated. The crude mixture was purified over silica gel (60-120)using petroleum ether: ethyl acetate (9:1). | |
With triethylamine; In chloroform; for 4h; | General procedure: In a round bottom flask, respective aniline (1a-e) (0.1 mol) was allowed to react with 2-chloroacetyl chloride (2) (0.1 mol) in presence of basetriethyl amine in 2-3 ml of chloroform and stirred at 0 C temperature for 4 hrs. The progress of the reaction was monitored by TLC using ethylacetate: hexane (1:9) as a solvent system. After completion of the reaction, the reaction mixture was poured on crushed ice and neutralised byadding acetic acid into it. The obtained solid intermediates that is 2-chloro-N-phenylacetamide derivatives (3a-e) of respective aniline (1a-e) werefiltered, dried and crystallised in ethanol. The melting points of all the compounds shows good agreement with the reported.1 | |
In N,N-dimethyl-formamide; at 20℃; for 0.5h; | General procedure: A mixture of aniline derivatives 5a - h and chloroacetyl chloride 6 in DMF was stirred at room temperature for 30 min.Then, the reaction mixture was diluted with water, poured intocrashed ice, and the obtained precipitate were filtered off.Finally, residue was washed with cold water to obtain pureN-phenyl-2-chloroacetamides 7a - h. | |
With potassium carbonate; at 20℃;Cooling with ice; | General procedure: We have previously reported preparation, purification and characterization of 2a-2k in our research papers [36,37]. Briefly, Chloroacetyl chloride (0.1mol) was added drop wise to a mixture of appropriate amines (0.05mol) and anhydrous potassium carbonate (K2CO3) (0.075mol) in dichloromethane or chloroform in an ice-cold condition. The reaction mixture was then stirred at room temperature. After completion of reaction, solvent was evaporated under reduced pressure, ice cold water was added to the obtained dry mass and the insoluble product was filtered and dried and purified by recrystallization with appropriate solvents. | |
In N,N-dimethyl-formamide; at 20℃; for 0.5h; | General procedure: A solution of amines 4a-n (1 mmol) and chloroacetyl chloride 5 (1.1 mmol) in DMF (15 mL) was stirred at RT for 30 min. Then, the mixture was diluted with cold water, poured into ice, and the obtained precipitates were filtered off. The residue was washed with water to obtain pure N-phenyl (or benzyl)-2-chloroacetamide 6a-n. | |
With triethylamine; at 0 - 20℃; for 4h; | General procedure: In a round bottom flask, primary or secondary amines (0.1 mol) and triethyl amine weredissolved in DCM and stirred at 0 C. 2-Chloroacetyl chloride (0.1 mol) was added to reaction mixture drop wise with continuous stirring on magnetic stirrer. After the addition,the ice bath was removed and the reaction mixture was stirred at room temperature for 4 h.The progress of the reaction was monitored by TLC using ethyl acetate: hexane (1:9) as asolvent system. After completion of the reaction, the reaction mixture was poured on crushedice and neutralised by adding acetic acid to it. The obtained solid intermediates of respectiveamines were filtered, dried and crystallised in ethanol. | |
With potassium carbonate; In dichloromethane; at 20℃; for 24h; | General procedure: The synthetic procedure for the synthesis of various acetamide have been described in our various reports. Briefly, aromatic or heteroaromatic amines were added to chloroacetyl chloride (1:1.5) under cold conditions along with a base in chloroform or dichloromethane for a day. On completion of reaction, the solvent was evaporated, and product was washed with water. Dried product was recrystallized using ethanol. | |
In acetone; at 20℃; | General procedure: To a solution of variousaniline (1.0 equiv ) in acetone were added chloroacetylchloride (1.1 equiv ) and reaction mixture stirredat room temperature for 2-3 h, reaction was monitoredby TLC, after completion of reaction mixture poured incold water, the separated solid product collected andwashed with cold water and dry in vacuum filter toafford 2-chloro-N-phenylacetamide derivatives. | |
With triethylamine; In dichloromethane; at 0 - 20℃; for 2h; | General procedure: To a solution of substituted aniline 5 (10.00mmol) in DCM (20mL) were added Et3N (20.00mmol), and chloroacetic chloride (12.00mmol) was added at 0C slowly. The solvent was removed in vacuo and the crude residue was purified by flash column chromatography on silica gel to give amide 6. | |
With triethylamine; In dichloromethane; at 0 - 25℃; for 20h;Inert atmosphere; | Assembly for synthesis includes oven-dried flat bottom flask fa- cilitated with a Teflon-coated magnetic stirring bar, rubber septa, nitrogen balloon and cooling bath. An appropriate primary amine (1.0 mmol) was added drop wise to a mixture of triethylamine (1.2 mmol) in dichloromethane (4.5 mL) under nitrogen atmosphere at 0 C. Chloroacetyl chloride (1.2 mmol) was added drop wise at 0 C, then the reaction mixture was stirred at ambient temperature for 20 h. Consumption of starting material was monitored by TLC in Ethyl acetate: Hexane (80:20), and ninhydrin spraying reagent. The reaction mixture was concentrated under reduced pressure and the residue washed with ice water (3 ×20 mL) and filtered. Precipi- tates of desired compound were dried in oven at 48 C temp and was carried on without further purification [34] . | |
In acetone; at 20℃; for 0.5h; | General procedure: Chloroacetyl chloride (1.1 equiv)was added dropwise with constant stirring to a solutionof the corresponding amine (1.0 equiv) in acetone. Themixture was stirred for 30 min at room temperature(TLC) and poured onto crushed ice. The solid productwas filtered off, washed with water, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In tetrahydrofuran; at 50℃; | General procedure: To a stirred solution of 12b (4.6 g, 20 mmol) in THF (50 mL) was added N,N-dimethylamine (2M solution in THF, 1.8 g, 20 mL, 40 mmol) dropwise at rt. The resulting mixture was stirred at 50 C overnight and was then evaporated to dryness under reduced pressure. The residue was triturated with a saturated aqueous solution of NaHCO3, and the solid product was collected by filtration, washed with water followed by hexane, and dried to give 14a. Yield: 4.1 g (87%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | In tetrahydrofuran; at 50℃; | General procedure: To a stirred solution of 12b (4.6 g, 20 mmol) in THF (50 mL) was added N,N-dimethylamine (2M solution in THF, 1.8 g, 20 mL, 40 mmol) dropwise at rt. The resulting mixture was stirred at 50 C overnight and was then evaporated to dryness under reduced pressure. The residue was triturated with a saturated aqueous solution of NaHCO3, and the solid product was collected by filtration, washed with water followed by hexane, and dried to give 14a. Yield: 4.1 g (87%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With sodium hydroxide; In acetonitrile; for 6h;Reflux; | General procedure: A mixture of chloroacetamide (1 eq) and NaOH (2 eq) in acetonitrile (50 mL) was stirred in a round bottom flask and refluxed for 6 h. The solvent was evaporated in a vacuum, the residue suspended in ethyl acetate and washed with water. The suspension was filtered, the filter cake washed with water and col- lected, affording 1,4-diphenylpiperazine-2,5-diones ( 1, 2 or 3 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In benzene; for 8h;Reflux; | To a refluxing solution of 2-chloro-N-(4-nitrophenyl)acetamide(2.14 g, 10.0 mmol) in benzene (25 mL) was added triphenylphospine(2.62 g, 10.0 mmol) solution in benzene(5 mL). After the reaction mixture was refluxed for 8 h, the temperature of reaction mixture was reduced to room temperature. Filtration of reaction mixture and washing with ethyl acetate gave triphenylphosphomium salt (4.0 g) in 84% yield. To a solution of triphenylphosphomium salt (2 g, 4.2 mmol)) obtained above in chloroform (15 mL)was added solution of 4-DMAP (6.3 mmol, 800 mg) in chloroform(5 mL). After all starting materials were dissolved, 1H-pyrrole-2-carbaldehyde (4.2 mmol, 200 mg) was added. After the reactionmixture was stirred for 8 h at room temperature, the solvent wasevaporated in vacuo. The residue material was washed with diethylether, and purified by column chromatography (5% methanol indichloromethane). The desired product (213 mg) was obtained in40% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.3% | P-nitroaniline 138g (1.0mol), toluene 600mL, sodium carbonate 1.59g (1.5mol) water 400mL was added to the reaction flask, stirred for 60 minutes, control temperature 15 ± 5 chloroacetic anhydride 191g (1.1mol) was added in portions, After the addition, the mixture was stirred at room temperature for 4 hours, filtered, and dried to obtain 192 kg of 2-chloro-N-p-nitrophenylacetamide, a yield of 89.3%, and a HPLC purity of 96.8%.It can be used directly in the next reaction without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | In tetrahydrofuran; at 50℃; | General procedure: To a stirred solution of 12b (4.6 g, 20 mmol) in THF (50 mL) was added N,N-dimethylamine (2M solution in THF, 1.8 g, 20 mL, 40 mmol) dropwise at rt. The resulting mixture was stirred at 50 C overnight and was then evaporated to dryness under reduced pressure. The residue was triturated with a saturated aqueous solution of NaHCO3, and the solid product was collected by filtration, washed with water followed by hexane, and dried to give 14a. Yield: 4.1 g (87%) |
86% | In methanol; at 20℃;Heating / reflux; | 2-chloro-N-(4-nitrophenyl)acetamide (1) (2.00 g, 9.319 mmol) was dissolved in MeOH (100 ml) and to this was added pyrrolidine (1.56 ml, 18.634 mmol, 2 equiv.) and the mixture heated at reflux for 4 hours and stirred at room temperature overnight. The MeOH was removed in vacuo and the resulting oil suspended in 5% NH3 (aq.) (50 ml), and the observed precipitate was isolated by filtration as a brown solid (2.00 g, 8.014 mmol, 86%). Rf 0.58 [MeOH]. Mp. 78 - 81 0C. 1H NMR (400 MHz, d6-OMSO) δ 10.39 (IH, s, NH), 8.26 (2H, d, J=9.6 Hz, 2ArH), 7.98 (2H, d, J= 9.4 Hz, 2ArH), 3.37 (2H, s, CH2), 2.64 (4H, m, 2CH2), 1.80 (4H, m, 2CH2) ppm. 13C NMR (100 MHz, d6-OMSO) δ 169.8 (C=O), 144.9 (ArC), 142.2 (ArC), 124.8 (2ArCH), 119.1 (2ArCH), 59.5 (CH2), 53.6 (2CH2), 23.4 (2CH2) ppm. IR (neat) υmax 3237, 2970, 2868, 2820, 2798, 1738, 1697, 1600, 1503, 1307, 1109, 851 cm"1. MS m/z calc. Ci2H15N3O3 [M] 249.1, found [M-I] 248.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | In tetrahydrofuran; at 50℃; | General procedure: To a stirred solution of 12b (4.6 g, 20 mmol) in THF (50 mL) was added N,N-dimethylamine (2M solution in THF, 1.8 g, 20 mL, 40 mmol) dropwise at rt. The resulting mixture was stirred at 50 C overnight and was then evaporated to dryness under reduced pressure. The residue was triturated with a saturated aqueous solution of NaHCO3, and the solid product was collected by filtration, washed with water followed by hexane, and dried to give 14a. Yield: 4.1 g (87%) |
52% | In isopropyl alcohol; at 80℃; for 17h;Inert atmosphere; | [00398] Step 2: A mixture of 2-chloro-N-(4-nitrophenyl)acetamide (500 mg, 2.33 mmol) and morpholine (2.0 mL, 23 mmol) in isopropanol (ca. 5 mL) was stirred at 80 C for ca. 17h. The mixture was partitioned between EtOAc and aq. NaHC03 (ca. 10 mL each; 50% NaHC03 saturation), and the organic layer was separated and dried over anhydrous Na2S04 to afford the desired product as a yellow solid (323 mg, 52% yield). 1H NMR (DMSO-d6, 400 MHz) δ 10.36 (br s, 1H), 8.24-8.21 (m, 2H), 7.92-7.89 (m, 2H), 3.63 (d, J = 3.2 Hz, 4H), 3.31 (br s, 4H), 3.21 (s, 2H); MS (ESI): calcd for C12H15N304: 265, found: 266 (MH+). |
With potassium carbonate; In N,N-dimethyl-formamide; at 15 - 40℃; for 2h;Inert atmosphere; | To a solution of 2-chloro-N-(4-nitrophenyl)acetamide (600 mg, 2.8 mmol) and morpholine (487 mg, 5.6 mmol) in DMF (10 mL) was added K2CO3 (772 mg, 5.6 mmol) at 15 oC. The mixture was heated to 40 oC and stirred at that temperature for 2 h. The mixture was poured into water (100 mL) and extracted with DCM (50 mL*2). The combined organic layers were washed with brine (100 mL*2), dried over sodium sulfate and concentrated to give the crude product (600 mg, crude) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ = 9.46 (br s, 1 H), 8.24 (d, J = 8.2 Hz, 2 H), 7.77 (d, J = 8.2 Hz, 2 H), 3.85 - 3.78 (m, 4 H), 3.21 (s, 2 H), 2.70 - 2.64 (m, 4 H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With chloroacetyl chloride; In tetrahydrofuran; for 1h; | To a solution of 4-nitroaniline (1 g, 7.2 mmol) in tetrahydrofuran(5 mL) was added solution of chloroacetyl chloride (1.15 ml in 5 mltetrahydrofuran 14.5 mmol). After the reaction mixture was stirredfor an hour, 20mL of coldwater was poured to the reaction mixtureand the mixture was stirred another 1 h. The precipitate wasfiltered and washed with water. After drying the solid at roomtemperature, a yellow solid 4 (1.43 g) was obtained in 93% yield. 1HNMR (DMSO-d6, 500 MHz) 4.30 (s, 2H), 7.84 (d, 2H, J 9.25), 8.23(d, 2H, J 9.25), 10.79(s, 1H) 13CNMR (DMSO-d6, 125 MHz) d 166.0,145.0, 143.0, 125.4, 119.5, 44.0 Mp > 220 C. IR (cm_1): 3276, 3230,3165, 3105, 2943, 1684, 1566, 1334 HRMS (ESI), m/z calcd forC8H7O3N2Cl Na: 237.0035, Found: 237.0037. |
With triethylamine; In water; ethyl acetate; chloroacetyl chloride; | (a) N-(4-nitrophenyl)-2-chloroacetamide 4-nitroaniline (13.8 g) in ethyl acetate (200 ml) was treated with triethyl amine (15 ml) and then treated in portions with chloroacetyl chloride (8 ml). The resulting mixture was stirred for 10 minutes. The mixture was then treated with water (200 ml) and ethyl acetate (100 ml). The mixture was warmed until all solids were dissolved, and the layers separated. The ethyl acetate layer was then concentrated to 100 ml whilst hot, and cooled to room temperature. The next day the mixture was filtered, and the solids washed with ethyl acetate and air dried to give N-(4-nitrophenyl)-2-chloroacetamide, m.p. 183-185 C., 14.83 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18 g (74%) | With sodium hydrogencarbonate; In chloroform; acetone; | EXAMPLE 8 4-Nitro-α-[4-(2-methoxyphenyl)-1-piperazinyl]-acetanilide (I: R=R1 =R2 =R4 =H, R3 =NO2, n=o) 12.46 g of 1-(2-methoxyphenyl)-piperazine in 75 ml of acetone was added to 13.95 g of 4-nitro-α-chloro-acetanilide and 5.47 g of sodium bicarbonate in 75 ml of acetone. The whole was refluxed under stirring for 8 hours. At the end of the reaction, 20 ml of chloroform was added in order to maintain in solution all the organic product, and the inorganic salts were removed by filtration. The solvent was evaporated off in vacuo and the residue was crystallized from ethyl acetate:hexane to give 18 g (74%) of the title compound, mp 148-149 C. The corresponding hydrochloride melted at 232-233 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2h; | b. A solution of the product from step a (90 g, 0.4196 mol) in DMF (900 mL) was treated with powdered K2CO3 (115.8 g, 0.840 mol), followed by dimethylamine hydrochloride (51.3 g, 0.62937 mol). The reaction mixture was heated to 60 0C and stirred at that temperature for 2 hours. Water was added to the reaction mixture, and the product was extracted with EtOAc (3 x 350 mL). The organic layers were combined and EPO <DP n="56"/>OOwashed with water (2 x 250 mL) and brine, dried (Na2SO4), filtered and concentrated to a light brown solid (72 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In methanol; at 5℃; | b. Preparation of N2-(2-Hvdroxyethyl)-N-(4-nitroDhenyl)αlvcinamide; 2-Chioro-Λ/-(4-nitrophenyl)acetamide (160.9 g, 1 mol) was suspended in methanol (2.25 L) under an atmosphere of argon. The mixture was cooled to 50C and ethanolamine (458.1 g, 10 mol) was added. The reaction mixture was stirred overnight and the resultant solid was filtered off, washed in methanol, and dried to give 149.5 g (83%) of Λ/2-(2-hydroxyethyl)-Λ/-(4-nitrophenyl)glycinamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | In ethanol; for 4h;Heating / reflux; | To a suspension of 2.946g (13.73mmol) of 2-chloro-N-(4-nitrophenyl)acetamide in 30mL of ethanol was added 3.31mL (41.18mmol) of 2-(methyamino)ethanol and the mixture was refluxed for 4 hours. After the reaction mixture was cooled to room temperature and condensed, then, the residue was treated with ethyl acetate. The organic layer was washed with water and dried over with anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (eluent: dichloromethane/methanol = 40/1) to give 2.05g (59%) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a suspension of sodium hydride (60% oil dispersion) (1.32 g) in N, N-dimethylformamide (40 ml) was added a solution of pyrazole (2.25 g) in N, N-dimethylformamide (20 ml) at 5C and the mixture was stirred at ambient temperature for an hour. To this mixture was added dropwise a solution of 2-chloro-N- (4-nitrophenyl) acetamide (6.44 g) in N, N-dimethylformamide (40 ml) and stirred at 50C for 8 hours. The mixture was poured into a mixture of ethyl acetate and ice-water and the separated organic layer was washed with water and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel eluting with hexane: ethyl acetate (1: 2 v/v) to give N- (4- NITROPHENYL)-2-(LH-PYRAZOL-1-YL) acetamide (3.49 g) as a yellow powder. 1H-NMR (DMSO-d6): 8 5.11 (2H, s), 6.30 (1H, dd, J=2.3 Hz, 1.6 HZ), 7.48 (1H, d, J=1.6 Hz), 7.79 (1H, d, J=2.3 Hz), 7.85-7. 95 (2H, m), 8.2-8. 3 (2H, M), 10.94 (1H, s) (+) ESI-MS (m/z) : 247 (M+H) + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium carbonate; In acetone;Reflux; | General procedure: To a 0.05 mol of 5-((1H-benzo[d]imidazol-1-yl)methyl)-1,3,4-oxadiazole-2-thiol (5) in 25 mL of acetone, 0.05 mol of 2-chloro-N-(substituted)phenyl acetamide (2a-k) in acetone and 0.05 mol of K2CO3 was added and the reaction mixture was refluxed for 6-12 h, then, after cooling to room temperature, it was slowly poured into 100 mL of ice water and the resulting solid was separated by filtration and washed successively with water. The product was dried under vacuum to obtain 6a-k[40]. The progress of the reaction was monitored by Thin Layer Chromatography using n-hexane: ethyl acetate (8:2) solvent system. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With triethylamine; In ethanol;Reflux; | General procedure: 4-Amino benzoic acid (PABA) (0.01 mol) was dissolved in ethyl alcohol followed by addition of III (i-xi) (0.01 M) and triethylamine (0.1 mol). The reaction mixture was refluxed for 7-8 h. The solution was poured on crushed ice. The resulting solid was separated, dried, and recrystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With triethylamine; In ethanol;Reflux; | General procedure: 4-Amino butanoic acid (GABA) was dissolved in ethyl alcohol followed by addition of II (i-xi) (0.01 M) and triethylamine (0.01 mol). The reaction mixture was refluxed for 6-7 h. The reaction mixture was poured on crushed ice. The resulting solid was separated, dried, and recrystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | General procedure: The mixture of potassium methyl cyanimidodithiocarbonate 1 (1 equiv.) and 2-halo-N-arylacetamides 2 (1 equiv.) was heated for 2-4 h using various alcohols (ROH) as reaction solvents. After that, 2 equivalents of triethyl amine were added and the resulted reaction mixture was refluxed for further 4-8 h. The solvent was removed in vacuo. The crude material was then purified by silica gel column chromatography using ethyl acetate/petroleum ether as eluent system to afford compounds of 4a-4d and 4k-4r. 4-Amino-2-ethoxy-N-(4-nitrophenyl)thiazole-5-carboxamide 4n: Bright yellow solid, yield 58%; mp 240-242 oC; 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 8.22 (d, 2H, J = 9.2 Hz), 7.86 (d, 2H, J = 8.8 Hz), 7.00 (brs, 2H), 4.16 (q, 2H, J = 6.8 Hz), 1.21 (t, 3H, J = 6.8 Hz); 13C NMR (100 MHz, DMSO-d6): δ 163.74, 163.32, 145.83, 141.16, 125.23, 117.38, 59.23, 14.58; HRMS (ESI) Calcd. for C12H13N4O4S [M+H+]: 309.0652; found: 309.0653. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | In tetrahydrofuran; at 50℃; | General procedure: To a stirred solution of 12b (4.6 g, 20 mmol) in THF (50 mL) was added N,N-dimethylamine (2M solution in THF, 1.8 g, 20 mL, 40 mmol) dropwise at rt. The resulting mixture was stirred at 50 C overnight and was then evaporated to dryness under reduced pressure. The residue was triturated with a saturated aqueous solution of NaHCO3, and the solid product was collected by filtration, washed with water followed by hexane, and dried to give 14a. Yield: 4.1 g (87%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | General procedure: Acridone (10) (195mg, 1mmol) was added portion wise to a stirred suspension of NaH (56mg, 1.2mmol, 50% of mineral oil) in dry DMF (10ml) at 0C. The reaction mixture was stirred for 2h. Afterward, 2-chloro-N-(substituted)phenyl acetamides 12a-o (2mmol) and KI (33.2mg, 0.2mmol) were added to the reaction mixture with stirring for different time intervals. After completion of the reaction (TLC), the reaction mixture was poured into crushed ice (50g) with constant stirring. The precipitated solid was collected and then extracted with chloroform. The combined organic extracts were washed with brine and water and finally dried with anhydrous sodium sulfate. Pure compounds were isolated after column chromatography and recrystallized from suitable solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetonitrile;Reflux; | General procedure: One intermediate of 4a-4s (1.2mmol) was added to a mixture of compound 3 (1.0mmol), potassium carbonate (2.0mmol) and dry CH3CN (20mL). The mixture was reflux for 5-6h. After cooling, the resulting mixture was filtrated. The filtrate was evaporated to dryness, and the residue was chromatographed with silica gel column chromatography (eluting with ethyl acetate/petroleum ether=2/1), then the product was salified with HCl gas in CH3CN to afford the target compound. The yield, melting point and spectral data of compounds 5a-5s are given below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With potassium carbonate; In acetone;Reflux; | General procedure: To 50 mL of acetone, 0.05 mol of aryl acetamides derivatives (2a-k), 0.05 mol of 1,3,4-oxadiazole derivative (4) and equimolecular amount of K2CO3 were mixed and the resulted mixture was allowed to reflux for 6 to 12 h. The completion of each reaction was justified by TLC technique using n-hexane : ethyl acetate (8:2) solvent system. When the reaction got completed, the reaction mixture was cooled to room temperature and poured onto crushed ice. The solid mass thus separated out was collected by filtration on vacuum pump, dried on vacuum oven to furnish final products 5a-k [23]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | General procedure: In a 250 mLround bottom flask, dibenzo[b,f][1,4]thiazepin-11(10H)-one (1.0 mol) in 25 mLdimethyl formamide at -5C to 0C was added. Sodium hydride (2.5 mol, 60 % w/w) was lot wise added in reaction mixture at -5C to 0C within 25 min. The temperature of reaction mixture was maintained at -5C to 0C for 30 min. Addition of 2-chloro N-phenylacetamide solution (1.2 mol) (I1-13) in reaction mixture within 30 min at -5C to 0C was completed. The temperature of reaction mixture was maintained at 25C to 30C for 12-15 hr. The reaction mixture was poured into crushed ice, filtered, dried and crystallized from ethyl acetate. Similarly other compounds were prepared by using dibenzo[b,f][1,4]thiazepin-11(10H)-one 4 and various N-chlorosubstituted phenylacetamide (I1-13). The synthesized compounds were recrystallized in ethyl acetate. Practical yield and physicochemical parameter are reported below. |
A713985 [10147-71-4]
2-Chloro-N-(3-nitrophenyl)acetamide
Similarity: 0.98
A463963 [2653-16-9]
2-Chloro-N-methyl-N-(4-nitrophenyl)acetamide
Similarity: 0.94
A653306 [16346-60-4]
2,2-Dichloro-N-(4-nitrophenyl)acetamide
Similarity: 0.92
A462593 [10147-70-3]
2-Chloro-N-(2-nitrophenyl)acetamide
Similarity: 0.90
A713985 [10147-71-4]
2-Chloro-N-(3-nitrophenyl)acetamide
Similarity: 0.98
A463963 [2653-16-9]
2-Chloro-N-methyl-N-(4-nitrophenyl)acetamide
Similarity: 0.94
A653306 [16346-60-4]
2,2-Dichloro-N-(4-nitrophenyl)acetamide
Similarity: 0.92
A462593 [10147-70-3]
2-Chloro-N-(2-nitrophenyl)acetamide
Similarity: 0.90
A713985 [10147-71-4]
2-Chloro-N-(3-nitrophenyl)acetamide
Similarity: 0.98
A463963 [2653-16-9]
2-Chloro-N-methyl-N-(4-nitrophenyl)acetamide
Similarity: 0.94
A653306 [16346-60-4]
2,2-Dichloro-N-(4-nitrophenyl)acetamide
Similarity: 0.92
A462593 [10147-70-3]
2-Chloro-N-(2-nitrophenyl)acetamide
Similarity: 0.90
A713985 [10147-71-4]
2-Chloro-N-(3-nitrophenyl)acetamide
Similarity: 0.98
A463963 [2653-16-9]
2-Chloro-N-methyl-N-(4-nitrophenyl)acetamide
Similarity: 0.94
A653306 [16346-60-4]
2,2-Dichloro-N-(4-nitrophenyl)acetamide
Similarity: 0.92
A462593 [10147-70-3]
2-Chloro-N-(2-nitrophenyl)acetamide
Similarity: 0.90
A713985 [10147-71-4]
2-Chloro-N-(3-nitrophenyl)acetamide
Similarity: 0.98
A463963 [2653-16-9]
2-Chloro-N-methyl-N-(4-nitrophenyl)acetamide
Similarity: 0.94
A653306 [16346-60-4]
2,2-Dichloro-N-(4-nitrophenyl)acetamide
Similarity: 0.92
A462593 [10147-70-3]
2-Chloro-N-(2-nitrophenyl)acetamide
Similarity: 0.90