| 95.5% |
Stage #1: adamantane With oxygen; nitric acid; trifluoroacetic acid at 50℃; for 2.5h; Autoclave;
Stage #2: acetonitrile for 4h; Autoclave; |
1-11
General procedure: 1) Add 20g adamantane, 120mL solvent I and 0.16g initiator into the reaction kettle, and pass oxidant gas into it, and react for 2.5h at 50°C;2). Add 6.63 g of nitrile compound in step 1) and react for 4 hours. After the reaction is completed, solvent I is recovered to obtain solid A sinking to the bottom of the kettle;3). The solid A obtained in step 2) is slurried and washed with 50 mL of water, and filtered to obtain acetylamantadine |
| 94% |
With sulfuric acid In 1,2-dichloro-ethane at 60℃; for 19h; Green chemistry; |
2; 2-1-2-25; 5; 3-6 Example 2: Synthesis of 1-Acetylaminoadamantane (Compound 2)
The polyionic liquid PIL-1 (1g) was added with acetonitrile (7.533g). [0.1835 mol]. To the mixture, adamantane (10g), 32 ml of 1,2-dichloroethane, then slowly added dropwise H2SO4(98%), (7.193g, 0.0734 µM) at 60 °C until the total time 19h. The reaction was completed, the acid catalyst was distilled off under reduced pressure 10 °C under reduced pressure.0.09 mpa. The flask was distilled off and cooled in a vacuum 60 °C and then distilled off under reduced pressure at room temperature -0.1 mpa, and then deionized water 10 °C 200 g was added dropwise. After 1h is added dropwise, the temperature 10 °C in the bottle keeps stirring 1h. for stirring, suction filtration and water leaching are finally obtained 13.335g, GC purity 99%. yield is 94%. theoretical output, 14.187g. |
| 92% |
Stage #1: adamantane With trifluoroacetic acid; sodium nitrite at 10 - 25℃; for 4.66h;
Stage #2: acetonitrile at 80℃; for 12h; |
1 Preparation of 1-acetamidoadamantane
120 ml (184 g, 1.62 mol) of trifluoroacetic acid and 6 g (0.0441 mol) of adamantane were charged in a 250 ml three-necked reaction flask equipped with a stirrer and a thermometer,The reaction flask was stirred under an ice-water bath to reduce the temperature of the solution to 10 ° C, followed by the addition of 1.2 g (0.0174 mol) of sodium nitrite, gradually warming to 25 ° C in 40 min,After the reaction was continued at 25 ° C for 4 h, 7.2 g (0.176 mol) of acetonitrile was added to the reaction solution and heated to 80 ° C. The reaction was carried out for 12 hours and cooled to 25 ° C ,The reaction droplets were added to a 500 ml reaction flask equipped with 360 ml of water, followed by extraction with methylene chloride three times (100 ml each)The combined extracts were washed with saturated brine and saturated aqueous sodium bicarbonate (100 ml each), dried over magnesium sulfate,The anhydrous magnesium sulfate was removed by filtration and the solvent evaporated to dryness to give 7.83 g of product as a white solid in 92% yield and 98% pure GC. |
| 85% |
With sodium azide at 30℃; |
|
| 82% |
With sulfuric acid at 25 - 65℃; for 4.5h; Large scale; Green chemistry; |
|
| 75% |
With lithium tetrafluoroborate; water Inert atmosphere; Electrochemical reaction; |
|
| 74% |
With nitric acid In tetrachloromethane at 25℃; for 5h; |
|
| 74% |
With boron trifluoride diethyl etherate; fluorine at 20℃; for 0.0833333h; |
|
| 64% |
With aluminium trichloride In chloroform 1) reflux, 5 h, 2) r.t., 11 h.; |
|
| 60% |
With nitrosyl hexafluorophosphate; [BMIM(SO3H)][PF6] at 90℃; for 14h; Inert atmosphere; Ionic liquid; |
General procedure for the synthesis of N-adamantylamides (entries 1-3; Table 5):
The [BMIM][PF6] (2.0-2.2 mL), adamantane (1mmol) and NOPF6 (2.0-3.5 mmol) were charged into an oven-dried Schlenk tube under nitrogen and the reaction mass was stirred for 15 minutes at r.t. before adding the selected nitrile (1 mmol; 5mmol in the case of MeCN) under nitrogen. The reaction mixture was stirred at 90 OC for 14-18h and the progress of the reaction was monitored by TLC and GC-MS. After completion, the reaction mass was quenched with distilled water, followed by neutralization with dilute NaHCO3 solution. The product was extracted in diethyl ether (10 mL, 3-4 times), dried over anhydrous MgSO4, the ether layer was evaporated in vacuum and the crude product was chromatographed with hexane-ethyl acetate mixture (80:20) to afford pure amides. The aqueous phase was carefully removed from the ionic liquid, and the IL was dried under high vacuum overnight. It was recycled and re-used in subsequent reactions (in 2 cycles). The use of excess [BMIM][PF6] (4-5ml) permits its recovery and reuse in more cycles (typically 5-6 runs). |
| 17.2% |
Stage #1: adamantane With sulfuric acid; nitric acid at 0 - 20℃; for 4h;
Stage #2: acetonitrile at 20℃; for 4h; Further stages.; |
|
| 10% |
With sodium ortho-iodobenzenesulfonate; Oxone; tetra(n-butyl)ammonium hydrogensulfate at 60℃; for 24h; Inert atmosphere; |
|
|
With sulfuric acid; <i>tert</i>-butyl alcohol In hexane |
|
|
With sulfuric acid; bromine |
|
|
With nitrosyl hexafluorophosphate; water 1.) CH2Cl2, 5 h, room temp.; Yield given; |
|
|
Stage #1: adamantane With sulfuric acid at -5 - 0℃; for 0.5h; Large scale;
Stage #2: acetonitrile at -5 - 35℃; for 3.5h; Large scale;
Stage #3: adamantane at 20℃; for 3.5h; Large scale; |
Example :
Example : New process of the preparation of a kind of 1-acetamidodamantanecomprising of the following steps : (1)Preparation of raw materials (2) Specifications of the 1st reactor : 50L. Advance cooling.Gradually add 25L (47.5kg) fuming sulfuric acid. Stir for 10min. At -5°C, add, by batch, 7.5kg of adamante.During the addition, the temperature must not exceed 0°C.After addition, continue stirring for half an hour. (3) At -5°C,add,dropwise, 6.5L (5.2kg) of acetonitrile.During the addition, the temperature must not exceed 0°C.After addition, continue stirring for half an hour. Slowly heat to 35°C(room temperature). Incubate for 3h. (4) After the reaction liquid turns clear, slowly add 2.5kg adamantane. During the addition, keep thetemperature from rising. After addition, stir for 3h. Add again then heat to 20°C. Stir for half an hour. Allow to stand for about half anhour. Separate the dichloromethane layer (lower layer) then add 17kgdichloromethane again. Stir for half an hour. Allow to stand for about half anhour. Separate dichloromethane layer.Pump combined dichloromethane layer into reactor. Add measured in advance. pH is around10. Separate dichloromethane layer. Distill dichloromethane under reducedpressure to obtain amide product. (5) Add 120kg water into 300L 2nd reactor. Undergo coolingwater circulation system. Lower reactor temperature to below 0°C. Add, dropwise, to thereaction liquid obtained from step 4. Control temperature must not exceed 10°. After addition, continue stirring forhalf an hour. (6) Add 34kg dichloromethane to 2nd reactor. Heat to 20°C. Continue stirring forhalf an hour. Allow to stand for half an hour for phase separation. Thedichloromethane extract located in the lower phase is introduced to the 3rdreactor. (7) Add 17kg dichloromethane to 2nd reactor. Continue stirringfor half an hour. Allow to stand for half an hour for phase separation. Thedichloromethane extract located in the lower phase is introduced to the 100L 3rdreactor. Add 30kg lye (containing 2% sodium hydroxide) to the 3rdreactor. pH is10. Separate dichloromethane layer. Distill dichloromethane under reducedpressure to obtain 1-acetamidodamantane product. |
|
Stage #1: adamantane With sulfuric acid at -5 - 0℃; for 0.5h; Large scale;
Stage #2: acetonitrile at -5 - 35℃; for 3.5h; Large scale; |
1 (1) preparation of 1-acetamidoadamantane
(1) preparation of the raw materials; will be a 50L specifications for the first reactor, pre-cooling in advance,Gradually add fuming sulfuric acid 25L (47.5kg),, Stirred for 10 minutes, 7.5 kg of adamantane was added in portions at -5 ° C,Feeding process temperature can not exceed 0 ,Stirring is continued for half an hour; (3). At the temperature of-5 ° C, 6.5 L (5.2 kg) of acetonitrile was added dropwise,The temperature can not exceed 0 during the dropping process;Drop finished stirring for half an hour,The temperature was slowly raised to 35 ° C (room temperature)Incubation reaction 3 hours; (4). 2.5kg of adamantane was slowly added when the reaction liquid became clear;Feeding process to keep the temperature does not rise,After stirring, the mixture was further stirred for 3 hours. Was added, and the temperature was raised to 20 ° C.Stir for half an hour.Standing stratified about half an hour.Separate the methylene chloride layer (in the lower layer), then add methylene chloride 17kg, stirring for half an hour, standing stratified about half an hour.The dichloromethane layer was separated.The combined methylene chloride layers were drawn into the reaction vessel,In advance with the good,So that the PH value of 10 or so.The dichloromethane layer was separated,Methylene chloride is reduced in steam.The product amide. (5), in 300L of the second reactor by adding 120kg of water,Through the water-cooling cycle system,Cooling the reaction kettle to below 0 DEG C;The reaction solution obtained in step (4) was added dropwise so that the control temperature was not more than 10 ° C,And then continued stirring for half an hour; (6) in the second reactor by adding methylene chloride 34kg,And the temperature was raised to 20 ° C,Stirring was continued for half an hour,Standing for half an hour there stratification,Introducing the methylene chloride located in the lower layer into a third reactor; (7). in the second reactor by adding methylene chloride 17kg,Stirring was continued for half an hour,Standing for half an hour there stratification,The methylene chloride located in the lower layer was withdrawn and introduced into a third reactor of 100 L;In the third reactor by adding 30kg alkaline water (containing sodium hydroxide 2%),To give a pH of 10, the dichloromethane layer was separated,The methylene chloride was distilled off under reduced pressure,The product 1-acetyl amido adamantane. |
|
With sulfuric acid; sulfur trioxide at 20℃; for 3h; |
1A-3A Example 1: Step A, amidation reaction:
Under ice-water bath conditions, add 40ml of SO3 with a mass fraction of 10% fuming sulfuric acid to a four-necked flask. Under stirring conditions, add 4g of adamantane until the adamantane is complete After dissolution, 4ml of acetonitrile was slowly added to control the temperature of the reaction system to not exceed 20°C. After the addition, the system was transferred to room temperature and reacted for 3 hours to obtain a reaction liquid containing 1-acetamidoadamantane. |
|
Stage #1: adamantane; acetonitrile With fuming sulphuric acid In dichloromethane at 30℃;
Stage #2: With water In dichloromethane at 0℃; |
1-7
General procedure: (1) The temperature of the first microchannel reactor 1 is adjusted to 30°C, and the temperature of the second microchannel reactor 2 is adjusted to 0 ; (2) Inject the mixture of adamantane, acetonitrile, halogenated alkanes, and oleum (20% concentration) into the first microchannel reactor 1 with a metering pump; (3) Inject water into the first microchannel reactor 1 with a metering pump The second microchannel reactor 2 is washed with water; (4) the effluent of the second microchannel reactor 2 is collected, separated, and the organic phase is removed by distillation to obtain the product acetylamantadine.The weight ratio of adamantane, acetonitrile and haloalkane is 1:0.5:25, the injection speed is 5ml/min, the haloalkane is methylene chloride; the concentration of oleum is 20%, and the injection speed is 0.6ml/min; The outlet of the microreactor I is connected to an extension tube with an inner diameter of 1.0mm and a length of 20m; the water injection rate in the microreactor II is 5ml/min. |
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