Org Prep Daily

September 24, 2006

p-Anisylmethylsulfone

Filed under: procedures — milkshake @ 10:24 pm

sulfone.gif

p-Anisylmethylsulfide 11.25g (72.94mmol) was dissolved in methanol (0.3L), Oxone solid 135g (219mmol, 6 eq. of persulfate) was added in one portion and the mixture was stirred for 3 hours. (The reaction was complete in 2 hours by HPLC). The solids were removed by filtration and washed with methanol, the filtrates were evaporated. The solid residue was re-crystallized from a mix of ethanol 100mL and water 400mL (to R.T., overnight). The crystallized product was collected by flitration, washed with water, dried by suction and on highvac. Y=11.898g (87.5%) of pearl-shiny white flakes. (A second crop could be obtained from supernatants but I was lazy).

1H(d6-DMSO, 400MHz): 7.847(app d, 8.9Hz, 2H), 7.160(app d, 8.9Hz, 2H), 3.857(s, 3H), 3.152(s, 3H)

5-Cl-4-Aminobenzodioxole

Filed under: procedures — milkshake @ 12:50 am

 

aminodioxol.gif

 

The chlorobenzodioxole acid 5.00g (24.93mmol) and triethylamine 4.9mL solution in anh. THF (220mL) was cooled to 0C and ethyl chloroformate 2.9mL (30mmol) was added dropwise over 5 min. The mixture was stirred at 0C for 90 min, ice-cooled solution of sodium azide 8.2g in water 80mL was added, followed by ice-cold water 120mL. The cooling bath was removed and the mixture was stirred at ambient temperature for 10 hours (overnight). The reaction mixture was extracted twice with ether (2x250mL), the extracts were washed with brine (250mL), combined, dried (MgSO4) and evaporated. The crude product (yellow solid, 3.89g) was applied onto a column of silica (80g) in hexane, and eluted with EtOAc gradient, 0 to 30% (in hexane). Y= 3.278g (76.5%) of a pale-yellow crystalline solid.

 

1H(d6-DMSO, 400MHz): 6.739(d, 8.4Hz, 1H), 6.241(d, 8.4Hz, 1H), 5.976(s, 2H), 5.117(very br s, 2H); 13C(d6-DMSO, 100MHz): 146.03, 133.79, 129.28, 121.60, 111.80, 106.96, 101.04. 97.79

 

 

September 22, 2006

5-Cl-Benzodioxole-4-carboxylic acid

Filed under: procedures — milkshake @ 6:41 pm

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Butyllithium 70 mmol (28mL of 2.5M solution in hexanes) was added to a diisopropylamine 10mL (70.8mmol) solution in anh.THF (200mL) at –78 C. After 20 minutes, 5-chlorobenzodioxole 7.5mL (64mmol) was added dropwise and the mixture was stirred at –78 C for 1 hour. The reaction mixture was then saturated with a CO2 stream (generated from dry ice in a separate flask) at –78 C for 40 min. Water 10mL was added dropwise, the mixture was removed from the cooling bath and stirred until gas evolution ceased (30 min). The mixture was evaporated to dryness, the residue was dissolved in water 400mL, two small spoons of charcoal were added, the mixture was heated to reflux, cooled and filtered. The filtrates were acidified with conc. HCl (20mL), the resulting slurry was allowed to settle for 15 minutes. The precipitated solids were collected by filtration, washed with a copious amount of water and dried by suction. The crude product (11.77g) was re-crystallized from a mixture of ethanol (100mL) and water (300mL). Y=10.186g (79%) of a white crystalline solid (HPLC purity about 95%).

1-H(d6-DMSO, 400MHz): 13.686(br s, 1H), 7.013(dAB, 8.3Hz, 1H), 6.965(dAB, 8.3Hz, 1H), 6.144(s, 2H)

(S)-3-Me-morpholine

Filed under: procedures — milkshake @ 2:02 am

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Oven-dried 2L flask with a large egg-shaped stirbar was flushed with Ar and 95% sodium hydride 3.484g (138mmol) was quickly added (fire hazard!) followed by anh. THF 0.5L. Neat L-alaninol 9.865g (131.3 mmol) was added over 5 min (H2 evolution) without cooling. The obtained slurry of sodium aminoalcoholate was stirred under Ar for 45 min, then Ethyl chloroacetate 16.177g (132 mmol) was added. The mixture was stirred for 30 min at ambient temperature, then refluxed for 3 hours. The flask was cooled on ice bath, LAH 12g was carefully added in several portions (3x1g, then 3x3g) with cooling. 15 min after complete addition, the flask was placed on oil bath 95-100C and refluxed for 3 hours 30 min.The reaction mixture was cooled on ice bath, carefully quenched by dropwise addition of water 12 mL, diluted with THF (300mL), 15% NaOH 36 mL was added and the mixture was stirred overnight (16 hours). The solids were removed by filtration (and washed with additional THF) and the filtrates were carefully concentrated (ambient water bath, 60 Torr) The residue was distilled at normal pressure under Ar. After a smallTHF fraction, the pure product distilled, b.p. 136-8C (oil bath was 160-200C). Y=6.513g (49% th) of a clear liquid.

1H(CDCl3, 400MHz): 3.777 (br m, 1H), 3.732 (dd, 11.0Hz, 2.7Hz, 1H), 3.465 (app td, 11.4Hz(t), 2.3Hz(d), 1H), 3.083 (app t, 10.1Hz, 1H), 2.983(app td, 11.7Hz(t), 3.5Hz(d), 1H), 2.901(m, 1H), 2.805(br m, 1H), 0.958 (d, 6.3Hz, 3H);  13C-NMR(CDCl3, 100MHz): 73.99, 67.45, 50.62, 46.52, 18.11

In humid places like Florida, oil-free sodium hydride should be avoided because of its risk of self-ignition. It is helpful to use a dry test tube with a septa, as a disposable reagent container when weighing flammable powder reagents (NaH, LAH, etc.). The material in test tube is dumped into Ar-filled flask in a single portion. For LAH gradual addition, it is convenient to pre-weight several separate dump-portions and keep them under septa in a dessicator.

September 21, 2006

My Struggle

Filed under: Uncategorized — milkshake @ 11:22 pm

WordPress, the software behind this blog (and also the company running the hosting service) is not very friendly to structures of organic molecules. It mangles them. I have been trying to fight the problem desperately, by importing high-pixel images – but this only bogged down this blog. So I would like to apologize to everybody who arrived here, just to see a bunch of closed icons. Reading Org Prep Daily must have been like swimming in cold porridge and I am sorry for the aggravation. 

I think I finally figured out a tolerable way of putting up the structures. (200-400% enlarged ChemDraw structures exported as gif-files). This alternative is more gentle to the Worpress servers, producing only 8-10k gif files per scheme. The resulting pictures are still bit fuzzy around the edges – and I have to put up structures in large size to avoid disappearing atoms and jagged bonds.

I will try to improve graphical quality of this blog. Meanwhile, you should be able to open a new window with picture-perfect structures when klicking on fuzzy mangled ones throughout the blogtext. 

Also, I compared Firefox with IE and Org Prep Daily does not seem to be much slower in Firefox now. Please, let me know about any further nuisance experienced here.  

Update: It looks like one can get a decent upload of Chemdraw structures if they were scaled in Chemdraw (Object-Scale) from the original ACS-document settings (0.20 in) to exactly 0.30in bond median. (“Scale selected object to 0.3in median bond”). The document is then saved as gif file. The gif file is uploaded to WordPress (as full size) and the size is set using the picture editor in WordPress compose menu to exactly match the gif original size. This technique works well also for the 0.40in bond median size but the produced reaction schemes are too big to properly display in the blog on 17-inch monitor and would not fit page on printout.   

September 20, 2006

3-Amino-2,4,6-collidine

Filed under: procedures — milkshake @ 9:48 pm

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2,4,6-collidine 15.0g (0.1238 mol) was added dropwise into 20% oleum 70mL in a 0.5L flask on ambient oil bath. (Quite exothermic). The mixture was brought up to 100 C and powdered potassium nitrate 30g was slowly added in small portions over 15 minutes (nitrous gas evolution). The mixture was stirred under a reflux condenser at 100 C for 5 hous, then cooled and poured on ice (400g). The mixture was made alkaline by adding concentrated aq. ammonia (300mL), cooled and extracted with dichloromethane (3x100mL). The combined extracts were dried (MgSO4) and evaporated. The residue (18g) was re-crystallized from pentane (60mL) at -20C (freezer 14 hours) to obtain 15.75g of pure nitrocollidine. A second crop (1.40g) was obtained by concentrating and cooling the supernatants. Y=17.15g (83.5%) of the nitrocollidine as a light-yellow crystalline solid.

 

The nitrocollidine 8.00g was hydrogenated in anhydrous ethanol 120mL over 10% Pd-C (3.6g) at 50psi in a Parr shaker for one day. (The hydrogen consumption ceased within 1 hour). The mixture was filtered through a pad of celite, filtrates evaporated and dried on highvac. The solid residue was dissolved in refluxing hexane, filtered while hot, diluted with additional hexane (50mL) and the allowed to crystallize in freezer at -20C overnight (16h). The supernatants were decanted off and the obtained pure aminocollidine was dried on highvac. Y=6.029g (92%) of a white shiny hygroscopic crystalline solid. 1H-NMR(CD3CN, 400MHz): 6.715(s,1H), 3.784(br s, 2H), 3.377(s, 3H), 2.265(s, 3H), 2.081(s, 3H)

 

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