Dimethyl 2-fluoromalonate

Dimethyl 2-fluoromalonate

Dimethyl malonate (19.8 g, 0.15 mol) and Cu(NO₃)₂·2.5H₂O (3.50 g, 15 mmol) were dissolved in acetonitrile (85 mL), the mixture was cooled to 0–5 °C and stirred at 650 rpm using an overhead stirrer. After purging the system with N₂ for 5 minutes, fluorine gas (20% v/v in N₂, 50 mL min⁻¹, 170 mmol) was introduced into the reaction mixture for 7 h. After purging with nitrogen for 20 minutes, the solvent was removed in vacuo and the residue was partitioned between water (30 mL) and ethyl acetate (20 mL). The aqueous phase was extracted with ethyl acetate (2 × 20 mL) and the combined organic layer was washed with saturated brine (20 mL). After drying over sodium sulphate, the solvent was evaporated under reduced pressure to give dimethyl 2-fluoromalonate (21.8 g, 97% yield, 95% purity) as a colourless oil;

IR (neat, cm⁻¹) 2962, 1748, 1438, 1250, 1206, 1112, 1016;  

δ_H (CDCl₃, 400 MHz) 3.85 (6H, s, CH₃), 5.31 (1H, d, ²J_HF 48.0, CHF);

δ_F (CDCl₃, 376 MHz): −195.73 (d, ²J_HF 48.0, CH–F);

δ_C (CDCl₃, 100 MHz) 53.48 (CH₃), 85.19 (d, ¹J_CF 197.2, C–F), 164.39 (d, ²J_CF 24.0, CO);  

m/z (EI⁺) 150 (3%, [M]⁺), 119 (42%, [M − OMe]⁺), 91 (73%, [M − COOMe]⁺), 59 (100%, [COOMe]⁺). Spectroscopic data in agreement with previously published data.

 N. Ishikawa, A. Takaoka and M. K. Ibrahim, J. Fluorine Chem., 1984, 25, 203–212
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Top 10 Most Exotic Places to Travel

If you are in the mood to travel off the beaten path, check out these unique exotic places.

10

Bagan

Bagan is home to the largest and densest concentration of Buddhist temples and stupas in the world. Once a mighty city was eventually sacked by the mongols. Interestingly its not a UNESCO World Heritage Site.

9

Arashimaya Bamboo Forest, Japan

The famous forest is literally littered with famous tombs, temples is close to the “Moon Crossing Bridge”.  Its worth exploring.

8

Mendenhall Ice Caves

After watching the film “Frozen”, I felt compelled to include an icy wonderland. The ice caves fit the bill. The caves exists because the glacier is melting and that means this place wont last long, enjoy it while you can.

7

Białowieża Forest

Ever wondered how Europe looked like pre-14th century? Even if you didn’t this is your answer. This is one of the best preserved forests in the world, and you can finally see what type of environment King Arthur saw when he was off exploring.

6

Phowintaung

This is a Buddhist cave complex in Burma. Yes, I know this list has a lot of Buddhism related items, but these places are truly one of a kind. It contains 947 richly decorated caves in the complex.

5

North Tanzania

Now for something completely different. Tanzania is one of the best places to go for a safari and home to Mount Kilimanjaro. Make sure to visit the Tarangire National Park, one of the last undiscovered jewels of Africa.

4

Caño Cristales

Known as the most beautiful river in the world, and even the “Liquid Rainbow”, is someplace you have to visit if you travel to South America. The river itself has no fish at all. Should be fun to swim in.

3

Mount Roraima

Say hello to the inspiration behind Conan Doyle’s Lost World and The Avatar. This place is literally out of this world. This mountain is in South America and is the basis of many of the legends of the indigenous people who lived there before the Europeans arrived. According to them this is the stump of a mighty tree that once held all the fruits and vegetables in the world.

2

Angkor

The capital of the ancient Khmer empire, is home to the majestic Angkor Wat, the largest temple in the world. This is one of the best places to visit in Cambodia. It also seems like the jungle is taking back the temple.

1

Kawachi Fuji Gardens, Japan

This place is a little difficult to find. Its five hours away from Tokyo if you take the Nozomi high speed train. Its a 15 km long tunnel, which you should visit in April.

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Diethyl fluoromalonate

Diethyl malonate fluorination: general reaction

Diethyl malonate (3.20 g, 20 mmol) and copper nitrate hydrate (Cu(NO₃)₂·2.5H₂O; 0.46 g, 2 mmol) were dissolved in acetonitrile (17 mL) and placed into the fluorination reactor and the mixture was cooled to 0–5 °C. After purging the system with N₂ for 5 minutes, fluorine gas (10% v/v in N₂, 45 mL min⁻¹, 22 mmol) was passed into the stirred mixture for 2 h. The reactor was purged with nitrogen for 10 minutes, the solvent was removed in vacuo and the residue partitioned between water (10 mL) and ethyl acetate (10 mL). The aqueous phase was extracted with ethyl acetate (10 mL) and the combined organic layers were washed with saturated brine (10 mL). After drying over sodium sulfate, the solvent was evaporated to leave diethyl 2-fluoromalonate (3.37 g, 94% yield, 93.5% purity) as a colourless liquid.

IR (neat, cm⁻¹): 2986, 1747, 1243, 1187, 1097, 1020;  

δ_H (CDCl₃, 400 MHz) 1.31 (6H, t, ³J_HH 7.2, CH₃), 4.31 (4H, q, ³J_HH 7.2, CH₂), 5.26 (1H, d, ²J_HF 48.3, CHF); δ_F (CDCl₃, 376 MHz): – 195.58 (d, ²J_HF 48.3, CH–F); 

δ_C (CDCl₃, 100 MHz) 14.04 (CH₃), 62.80 (CH₂), 85.39 (d, ¹J_CF 198.2, C–F), 164.20 (d, ²J_CF 24.1, CO);  

m/z (EI⁺) 179 (5%, [M + H]⁺), 133 (44%, [M − OEt]⁺), 105 (49%, [M − COOEt]⁺), 78 (100%, [CH₂FCOOH]⁺). 

Spectroscopic data were identical with those previously reported  ^SEE  and side products were identified from their reported ¹⁹F NMR shifts.

 SEE.....

1. (a) R. D. Chambers, J. Hutchinson and J. Thomson, J. Fluorine Chem., 1996, 78, 165–166 CrossRef CAS; (b) R. D. Chambers, M. A. Fox, D. Holling, T. Nakano, T. Okazoe and G. Sandford, Chem. Eng. Technol., 2005, 28, 344–352 CrossRef CAS; (c) R. D. Chambers and J. Hutchinson, J. Fluorine Chem., 1998, 92, 45–52

 

Diethyl fluoromalonate large scale fluorination

Diethyl malonate (40.0 g, 0.25 mol) and copper nitrate hydrate (Cu(NO₃)₂·2.5H₂O; 5.81 g, 25 mmol) were dissolved in acetonitrile (200 mL) and placed in 500 mL fluorination vessel, cooled to 0–5 °C and stirred at 650 rpm using an overhead stirrer. After purging the system with N₂ for 5 minutes, fluorine gas (20% v/v in N₂, 80 mL min⁻¹, 265 mmol) was introduced into the mixture for 6 hours and 30 minutes. The reactor was purged with nitrogen for 10 minutes, the solvent removed in vacuo and the residue partitioned between water (50 mL) and ethyl acetate (50 mL). The aqueous phase was extracted once more with ethyl acetate (50 mL) and the combined organic layers were washed with saturated NaHCO₃ (25 mL) and brine (20 mL). After drying over sodium sulfate, the solvent was evaporated to leave diethyl 2-fluoromalonate (44.4 g, 99% yield, 95% purity) as a light yellow, transparent liquid. This crude product was distilled to afford high purity fluoromalonate (34.7 g, 77% yield, 99%+ purity) as a colourless liquid,

bp. 102–103 °C (18 mbar), (lit.: 110–112 °C, 29 mbar), spectroscopic data as above.
N. Ishikawa, A. Takaoka and M. K. Ibrahim, J. Fluorine Chem., 1984, 25, 203–212
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Buluan Island, Zamboanga Sibugay, Ipil, philippines

Location: Ipil, Zamboanga Sibugay

“Buluan Island, a gem of a piece of land off Barangay Buluan in Zamboanga Sibugay’s municipal capital of Ipil is beautiful. And that is even an understatement.” That’s what Estan has to say about this well-kept secret. “The island is tear drop shaped as seen from above with a tadpole like profile. The apex fringed with a white sandy beach and gradually rising up to the top of the hill. On a beautiful morning, its ghost like when seen from Ipil’s port, about 20 minutes by speedboat.”
Curious? Here’s more information: Buluan Beach.


 
 

 

 
 

 
 
 

 
 







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3-Fluoro-1-H-1,5-benzodiazepine-2,4-dione

3-Fluoro-1-H-1,5-benzodiazepine-2,4-dione

 

 

 

o-Phenylenediamine (2.70 g, 25 mmol) was added to the solution of sodium (1.2 g, 53 mmol) in anhydrous ethanol (50 mL) and the mixture was heated to reflux. Diethyl 2-fluoromalonate (4.45 g, 25 mmol) was added dropwise over 10 minutes and the mixture was heated at reflux for 2 h. After cooling to room temperature, the solution was filtered, the residue was washed with ethanol (20 mL), dissolved in water (30 mL) and acidified with HCl to pH 1. The mixture was cooled in ice, filtered, washed with water (2 × 10mL) and dried in vacuo to afford 3-fluoro-1-H-1,5-benzodiazepine-2,4-dione (3.23 g, 68%) as a tan powder.

m.p.: >300 °C, ([M + H]⁺, 195.0567, C₉H₈FN₂O₂ requires: [M]⁺, 195.0570); 

IR (neat,cm⁻¹) 3084, 2951, 1727, 1681, 1500, 1159;  


δ_H (DMSO d₆, 400 MHz): 5.57 (1H, d, ²J_HF 46.4, CHF), 7.15–7.19 (2H, m, Ar–H), 7.22 (2H, dt, ³J_HH 6.6, ⁴J_HH 3.5, Ar–H), 10.81 (2H, bs N–H); δ_F (DMSO d₆, 376 MHz): – 207.99 (d, ²J_HF 46.4 C–F);

 δ_C (DMSO d₆, 100 MHz) 85.12 (d, ¹J_CF 184.5, C–F), 122.55, 125.52, 128.41, 163.36 (d, ²J_CF 23.2, CO), 164.59 (d, ²J_CF 13.4, CO); 

m/z (ASAP) 195 (100%, [M + H]⁺), 135 (23%, [M − COCHF]⁺)............   N. Ishikawa, A. Takaoka and M. K. Ibrahim, J. Fluorine Chem., 1984, 25, 203–212 CrossRef CAS.


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5-Fluorobarbituric acid

5-Fluorobarbituric acid

 

 

Urea (1.50 g, 25 mmol) was added to the solution of sodium (1.2 g, 53 mmol) in anhydrous ethanol (50 mL) and the mixture was heated to reflux. Diethyl 2-fluoromalonate (4.45 g, 25 mmol) was added dropwise over 10 minutes and the mixture was heated at reflux for 1 h. After cooling to room temperature, the solution was filtered, the residue was washed with ethanol (20 mL), dissolved in water (30 mL) and acidified with HCl to pH 1. The precipitated product was recrystallized from the liquor to afford 5-fluorobarbituric acid (1.87 g, 51%) as a tan powder.

m.p.: >300 °C; ([M + H]⁺, 147.0206, C₄H₄FN₂O₃ requires: [M]⁺, 147.0204);

IR (neat,cm⁻¹) 2926, 2828, 1578, 1383, 1241, 1128;

δ_F (D₂O + NaOD, 376 MHz): – 191.95 (s);  

δ_C (D₂O + NaOD, 100 MHz) 131.89 (d, ¹J_CF 214.4, C–F), 157.77 (d, ⁴J_CF 6.2, C–NH), 164.59 (d, ²J_CF 13.4, CO);  

m/z (ASAP) 147 (25%, [M + H]⁺).

1. (a) E. D. Bergmann, S. Cohen and I. Dharak, J. Chem. Soc., 1959, 3286–3289

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