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 2927-34-6 * Storage: {[proInfo.prStorage]}
* 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 xenon difluoride; boron trifluoride diethyl etherate In acetonitrile at -25 - 22℃;
General procedure: A glass reactor equipped with a Teflon-lined magnetic stir bar and connected to a gas-washing bottle was charged with C6H5R (0.95–1.14 mmol), MeCN (1–2.5 mL per mmol of C6H5R), and BF3 · Et2O (1.3–1.6 mmol per mmol of C6H5R). The solution was stirred for 10–15 min at –25°C, and XeF2 (1.2–1.3 mmol per mmol of C6H5R) was added in portions. The mixture was allowed to warm up to 22°C over a period of 1 h and stirred for 40–60 min more, hexafluorobenzene (internal standard) was added, and a sample was withdrawn for 19F NMR analysis (procedure B). The mixture was treated with a saturated aqueous solution of NaHCO3 and extracted with methylene chloride (1–2 mL). The extract was dried over MgSO4 and analyzed by 19F and GC/MS (procedure C). The main products are given in table, and the others are listed below (GC/MS data).
Reference:
[1] Russian Journal of Organic Chemistry, 2016, vol. 52, # 10, p. 1400 - 1407[2] Zh. Org. Khim., 2016, vol. 52, # 10, p. 1412 - 1419,8
2
[ 108-88-3 ]
[ 352-32-9 ]
[ 95-52-3 ]
[ 352-70-5 ]
[ 452-76-6 ]
[ 452-67-5 ]
[ 2927-34-6 ]
Yield
Reaction Conditions
Operation in experiment
0.3 mmol
With xenon difluoride; boron trifluoride diethyl etherate In acetonitrile at -25 - 22℃;
General procedure: A glass reactor equipped with a Teflon-lined magnetic stir bar and connected to a gas-washing bottle was charged with C6H5R (0.95–1.14 mmol), MeCN (1–2.5 mL per mmol of C6H5R), and BF3 · Et2O (1.3–1.6 mmol per mmol of C6H5R). The solution was stirred for 10–15 min at –25°C, and XeF2 (1.2–1.3 mmol per mmol of C6H5R) was added in portions. The mixture was allowed to warm up to 22°C over a period of 1 h and stirred for 40–60 min more, hexafluorobenzene (internal standard) was added, and a sample was withdrawn for 19F NMR analysis (procedure B). The mixture was treated with a saturated aqueous solution of NaHCO3 and extracted with methylene chloride (1–2 mL). The extract was dried over MgSO4 and analyzed by 19F and GC/MS (procedure C). The main products are given in table, and the others are listed below (GC/MS data).
Reference:
[1] Russian Journal of Organic Chemistry, 2016, vol. 52, # 10, p. 1400 - 1407[2] Zh. Org. Khim., 2016, vol. 52, # 10, p. 1412 - 1419,8
3
[ 108-88-3 ]
[ 352-32-9 ]
[ 95-52-3 ]
[ 352-70-5 ]
[ 452-76-6 ]
[ 452-67-5 ]
[ 2927-34-6 ]
Yield
Reaction Conditions
Operation in experiment
0.3 mmol
With xenon difluoride; boron trifluoride diethyl etherate In acetonitrile at -25 - 22℃;
General procedure: A glass reactor equipped with a Teflon-lined magnetic stir bar and connected to a gas-washing bottle was charged with C6H5R (0.95–1.14 mmol), MeCN (1–2.5 mL per mmol of C6H5R), and BF3 · Et2O (1.3–1.6 mmol per mmol of C6H5R). The solution was stirred for 10–15 min at –25°C, and XeF2 (1.2–1.3 mmol per mmol of C6H5R) was added in portions. The mixture was allowed to warm up to 22°C over a period of 1 h and stirred for 40–60 min more, hexafluorobenzene (internal standard) was added, and a sample was withdrawn for 19F NMR analysis (procedure B). The mixture was treated with a saturated aqueous solution of NaHCO3 and extracted with methylene chloride (1–2 mL). The extract was dried over MgSO4 and analyzed by 19F and GC/MS (procedure C). The main products are given in table, and the others are listed below (GC/MS data).
Reference:
[1] Russian Journal of Organic Chemistry, 2016, vol. 52, # 10, p. 1400 - 1407[2] Zh. Org. Khim., 2016, vol. 52, # 10, p. 1412 - 1419,8
4
[ 2927-34-6 ]
[ 455-86-7 ]
Yield
Reaction Conditions
Operation in experiment
98%
at 16℃; for 1 h;
Example 5: 3,4-Difluorobenzoic Acid In a 100 ml jacketed vessel, 200 ml of acetic acid, 0.05 g of manganese(II) acetate, 1.91 g of sulfuric acid and 14.1 g of 3,4-difluorotoluene were initially charged. The mixture was cooled to 16° C. and 4.0 g of ozone were introduced within a period of 60 minutes. After completion of ozonolysis, the ozone present in the solvent was blown out using nitrogen. Analysis of the reaction mixture by means of HPLC or GC gave the following results: 3,4-difluorotoluene: >0.1percent; 3,4-difluorobenzoic acid: 98percent
6.06 g of cobalt acetate and 6.06 g of sodium molybdate were dissolved in 200 ml3,4-difluorotoluene and 200 mlAcetic acid to form a mixed solution,At this time η (cobalt acetate):Η (3,4-difluorotoluene) = 0.015:1, 6.06 g of sodium bromide was dissolved in 15percentH202formH202- acetic acid solution,At this time η (sodium bromide):Η (3,4-difluorotoluene) = 0.015: 1,3,4-difluorotoluene-acetic acid solutionWith H22-acetic acid solution at 8.33 ml / min and 16.67 ml / min, respectivelyOf the flow rate through the constant flow into the continuous heat exchanger tube reactor,At this time η (H2 2): η (3,4-difluoromethyl = 2: 1,The reaction temperature was controlled Using Figure 2 microchannel reactor,Control the reaction temperature65 ° C, residence time 200s. Export material 0 ° C cooling,The reaction was quenched with difluoromethane.After GC analysis,The conversion of 3,4-difluorotoluene was 42.0percent and the yield of 3,4-difluorobenzaldehyde was 30.7percent.
Reference:
[1] Patent: US5998477, 1999, A,
[2] Patent: US6028116, 2000, A,
[3] Patent: US5401774, 1995, A,
[4] Patent: US5776962, 1998, A,
[5] Patent: US5696159, 1997, A,
7
[ 108-88-3 ]
[ 352-32-9 ]
[ 95-52-3 ]
[ 352-70-5 ]
[ 452-76-6 ]
[ 452-67-5 ]
[ 2927-34-6 ]
Yield
Reaction Conditions
Operation in experiment
0.3 mmol
With xenon difluoride; boron trifluoride diethyl etherate In acetonitrile at -25 - 22℃;
General procedure: A glass reactor equipped with a Teflon-lined magnetic stir bar and connected to a gas-washing bottle was charged with C6H5R (0.95–1.14 mmol), MeCN (1–2.5 mL per mmol of C6H5R), and BF3 · Et2O (1.3–1.6 mmol per mmol of C6H5R). The solution was stirred for 10–15 min at –25°C, and XeF2 (1.2–1.3 mmol per mmol of C6H5R) was added in portions. The mixture was allowed to warm up to 22°C over a period of 1 h and stirred for 40–60 min more, hexafluorobenzene (internal standard) was added, and a sample was withdrawn for 19F NMR analysis (procedure B). The mixture was treated with a saturated aqueous solution of NaHCO3 and extracted with methylene chloride (1–2 mL). The extract was dried over MgSO4 and analyzed by 19F and GC/MS (procedure C). The main products are given in table, and the others are listed below (GC/MS data).
Reference:
[1] Russian Journal of Organic Chemistry, 2016, vol. 52, # 10, p. 1400 - 1407[2] Zh. Org. Khim., 2016, vol. 52, # 10, p. 1412 - 1419,8
8
[ 2927-34-6 ]
[ 127371-50-0 ]
Reference:
[1] Patent: EP342849, 1990, A3,
9
[ 2927-34-6 ]
[ 875664-38-3 ]
Yield
Reaction Conditions
Operation in experiment
83%
for 12 h; Cooling with ice
Step 1: l-Bromo-4,5-difluoro-2-methylbenzene (16). To a ice cooled flask containing 3,4-difluorotoluene 15 (27 g, 210 mmol) and iron powder (600 mg, 10 mmol) was added dropwise Br2 (40 g, 250 mmol). The reaction was stirred for 12 h while it was slowly warmed to RT. Water was added and the resulting mixture was extracted with diethyl ether. The ether layer was washed with sodium thiosulfate solution, brine and dried over Na2S04. Removal of ether gave the desired bromotoluene 16 (36 g, 83percent). -NMR (400MHz, DMSO-d6):D D 8 7.78 (t, 1H), 7.52 (t, 1H), 2.29 (s, 3H).
With N-Bromosuccinimide;zirconium(IV) chloride; In dichloromethane; at 0℃; for 6h;Conversion of starting material;
The reaction of NBS and toluene in the presence of 5 mole % ZrCI4 did not give the ring substituted product, but rather benzyl bromide almost exclusively. Table 5 shows some additional examples. The reaction also proceeds smoothly in the presence of FeCk or AICI3 with almost the same reactivity as that of ZrCU. Without wishing to be bound by any theory of interpretation, it is believed that this reaction may proceed by a radical mechanism. In fact, the reaction does not proceed at all in the presence of a radical inhibitor. EPO <DP n="30"/>Table 5 ZrCI4 Catalyzed Radical Bromination of Aromatic Compound by NBSa(5 mol %), CH2CI2 (4 c See spectroscopic data for characterization.
With sulfuric acid; ozone; acetic acid;manganese(II) acetate; at 16℃; for 1h;
Example 5: 3,4-Difluorobenzoic Acid In a 100 ml jacketed vessel, 200 ml of acetic acid, 0.05 g of manganese(II) acetate, 1.91 g of sulfuric acid and 14.1 g of <strong>[2927-34-6]3,4-difluorotoluene</strong> were initially charged. The mixture was cooled to 16 C. and 4.0 g of ozone were introduced within a period of 60 minutes. After completion of ozonolysis, the ozone present in the solvent was blown out using nitrogen. Analysis of the reaction mixture by means of HPLC or GC gave the following results: <strong>[2927-34-6]3,4-difluorotoluene</strong>: >0.1%; 3,4-difluorobenzoic acid: 98%
5-chloro-1-methyl-4,4,5-trifluorocyclohexene[ No CAS ]
4-chloro-1-methyl-4,5,5-trifluorocyclohexene[ No CAS ]
[ 2927-34-6 ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; calcium chloride;
Example 15 Preparation of 3,4-difluorotoluene To a stirred mixture of 4-chloro-1-methyl-4,5,5-trifluorocyclohexene and 5-chloro-1-methyl-4,4,5-trifluorocyclohexene (1.20 kg) prepared in Example 1 was added 42 g of benzyltriethylammonium chloride, and then the reaction mixture was heated to 85 C. followed by slowly adding 2.15 kg of 50% aqueous sodium hydroxide solution over 4.5 hours. The reaction mixture was stirred for an additional 1.5 hours at 90 C. and then the resultant was purified by steam distillation followed by separating the aqueous layer. The organic layer was dried with 32 g of calcium chloride, and then 0.64 kg of the desired product was collected by fractional distillation at temperature range of 112 C. as a colorless liquid. 1 H-NMR (CDCl3) delta (ppm): 2.30 (3H, s), 6.8-7.1 (3H, m) 19 F-NMR (CDCl3) delta (ppm, CFCl3): 138.7 (1F), 143.0 (1F)
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; calcium chloride;
Example 15 Preparation of 3,4-difluorotoluene To a stirred mixture of 4-chloro-1-methyl-4,5,5-trifluorocyclohexene and 5-chloro-1-methyl-4,4,5-triflurocyclohexene (1.20 kg) prepared in Example 1 was added 42 g of benzyltriethylammonium chloride, and then the reaction mixture was heated to 85 C followed by slowly adding 2.15 kg of 50% aqueous sodium hydroxide solution over 4.5 hours. The reaction mixture was stirred for an additional 1.5 hours at 90 C, and then the resultant was purified by steam distillation followed by separating the aqueous layer. The organic layer was dried with 32 g of calcium chloride, and then 0.64 kg of the desired product was collected by fractional distillation at temperature range of 112 C as a colorless liquid. 1H-NMR (CDCl3) delta (ppm): 2.30 (3H, s), 6.8-7.1 (3H, m) 19F-NMR (CDCl3) delta (ppm, CFCl3): 138.7 (1F), 143.0 (1F)
With bromine; calcium carbonate; In dichloromethane;
(A) 3,4-difluorobenzaldehyde. In a 250 ml three-necked flask equipped with a magnetic stirrer, thermometer, condenser, and dropping funnel is placed 25.6 g (0.2 mol) of <strong>[2927-34-6]3,4 difluorotoluene</strong>. The liquid is heated to 105 C. and illuminated as 67 g (0.42 mol) of bromine is added slowly. The temperature is kept between 105-110 C. while the first half of the bromine is added over a period of one hour. The rest of the bromine is added over approximately a 2-hour period and the temperature is raised to 150 C. and kept there for 5 minutes. The reaction mixture is cooled and transferred to a 1 liter 3-necked flask with a motor driven stirrer and condenser. 120 ml H2 O and 90 g of calcium carbonate are added, and the mixture is refluxed for 20 hours with good stirring. The reaction mixture is steam distilled until no further oil is collected. The oil is taken up in methylene chloride and dried over MgSO4. Evaporation of the solvent yields 3,4-difluorobenzaldehyde which is used without further purification.
With bromine; calcium carbonate; In dichloromethane;
(A) 3,4-Difluorobenzaldehyde <strong>[2927-34-6]3,4-difluorotoluene</strong> (25.6 g, 0.2 mol) is heated to 105 C. in a 250 ml 3-necked flask equipped with a magnetic stirrer, thermometer, condenser, and dropping funnel, and is illuminated as bromine (67 g, 0.42 mol) is added slowly. The temperature is kept between 105-110 C. while the first half of the bromine is added over a period of one hour. The rest of the bromine is added over approximately a two-hour period, and the temperature is raised to 150 C., and is kept there for 5 minutes. The reaction mixture is cooled and is transferred to a 1 liter 3-necked flask with a motor-driven stirrer and condenser. H2 O (120 ml) and calcium carbonate (90 g) are added, and the mixture is refluxed for 20 hours with good stirring. The reaction mixture is steam distilled until no further oil is collected. The oil is taken up in methylene chloride and dried over MgSO4. Evaporation of the solvent yields 3,4-difluorobenzaldehyde that is used without further purification.
With bromine; calcium carbonate; In dichloromethane;
(A) 3,4-difluorobenzaldehyde. In a 250 ml. three-necked flask equipped with a magnetic stirrer, thermometer, condenser, and dropping funnel is placed 25.6 g (0.2 mole) of <strong>[2927-34-6]3,4 difluorotoluene</strong>. The liquid is heated to 105 and illuminated as 67 g. (0.42 mole) of bromine is added slowly. The temperature is kept between 105-110 while the first half of the bromine is added over a period of one hour. The rest of the bromine is added over approximately a 2 hour period and the temperature is raised to 150 and kept there for 5 minutes. The reaction mixture is cooled and transferred to a 1 liter 3-necked flask with a motor driven stirrer and condenser. 120 ml. H2 O and 90 g. of calcium carbonate are added, and the mixture is refluxed for 20 hours with good stirring. The reaction mixture is steam distilled until no further oil is collected. The oil is taken up in methylene chloride and dried over MgSO4. Evaporation of the solvent yields 3,4-difluorobenzaldehyde which is used without further purification.
With bromine; calcium carbonate; In dichloromethane;
(A) 3,4-difluorobenzaldehyde In a 250 ml three-necked flask equipped with a magnetic stirrer, thermometer, condenser, and dropping funnel is placed 25.6 g (0.2 mol) of <strong>[2927-34-6]3,4-difluorotoluene</strong>. The liquid is heated to 105 and illuminated as 67 g (0.42 mol) of bromine is added slowly. The temperature is kept between 105-110 C. while the first half of the bromine is added over a period of one hour. The rest of the bromine is added over approx. a 2 hour period, and the temperature is raised to 150 and kept there for 5 minutes. The reaction mixture is cooled and transferred to a 1 liter 3-necked flask with a motor driven stirrer and condenser. 120 ml H2 O and 90 g of calcium carbonate are added, and the mixture is refluxed for 20 h with good stirring. The reaction mixture is steam distilled until no further oil is collected. The oil is taken up in methylene chloride and dried over MgSO4. Evaporation of the solvent yields 3,4-difluorobenzaldehyde which is used without further purification.
aluminium trichloride; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; 1,2-dichloro-ethane;
Referential Preparation Example 1 Synthesis of 3,4-difluoro-6-methylacetophenone (1) 5.5ml (2.0eq., 77mmol) of acetyl chloride was added to a solution of 10.0 g (1.9 eq., 75 mmol) of aluminum chloride in 20 ml of 1,2-dichloroethane, and then 5.0 g (39 mmol) of <strong>[2927-34-6]3,4-difluorotoluene</strong> was dropwise added with cooling with ice. After the completion of the addition, the mixture was stirred at room temperature for 5 hours. The reaction mixture was cooled and then gradually added to 100 ml of ice water to separate the reaction mixture to two layers. An organic layer was concentrated. An aqueous layer was extracted with methylene chloride, and the extract was added to the organic layer. The resultant mixture was washed with 5 % hydrochloric acid once, with a sodium hydrogencarbonate aqueous solution twice and with a saturated sodium chloride aqueous solution once, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give 6.77 g (yield 100 %) of a crude product of 3,4-difluoro-6-methylacetophenone. NMR (ppm, solvent: deutero chloroform, internal standard: tetramethylsilane): 2.49(3H,s), 2.55(3H,s), 7.04(1H,dd, J = 7.7, 11.1), 7.55(1H,dd, J = 8.2)
With sodium molybdate; dihydrogen peroxide; cobalt(II) acetate; acetic acid; sodium bromide; at 65℃;
6.06 g of cobalt acetate and 6.06 g of sodium molybdate were dissolved in 200 ml<strong>[2927-34-6]3,4-difluorotoluene</strong> and 200 mlAcetic acid to form a mixed solution,At this time eta (cobalt acetate):Eta (<strong>[2927-34-6]3,4-difluorotoluene</strong>) = 0.015:1, 6.06 g of sodium bromide was dissolved in 15%H202formH202- acetic acid solution,At this time eta (sodium bromide):Eta (<strong>[2927-34-6]3,4-difluorotoluene</strong>) = 0.015: 1,<strong>[2927-34-6]3,4-difluorotoluene</strong>-acetic acid solutionWith H22-acetic acid solution at 8.33 ml / min and 16.67 ml / min, respectivelyOf the flow rate through the constant flow into the continuous heat exchanger tube reactor,At this time eta (H2 2): eta (3,4-difluoromethyl = 2: 1,The reaction temperature was controlled Using Figure 2 microchannel reactor,Control the reaction temperature65 C, residence time 200s. Export material 0 C cooling,The reaction was quenched with difluoromethane.After GC analysis,The conversion of <strong>[2927-34-6]3,4-difluorotoluene</strong> was 42.0% and the yield of 3,4-difluorobenzaldehyde was 30.7%.
With bromine; calcium carbonate; In dichloromethane;
(A) 3,4-difluorobenzaldehyde. In a 250 ml. three-necked flask equipped with a magnetic stirrer, thermometer, condenser, and dropping funnel is placed 25.6 g (0.2 mole) of <strong>[2927-34-6]3,4 difluorotoluene</strong>. The liquid is heated to 105 and illuminated as 67 g. (0.42 mole) of bromine is added slowly. The temperature is kept between 105-110 while the first half of the bromine is added over a period of one hour. The rest of the bromine is added over approximately a 2 hour period and the temperature is raised to 150 and kept there for 5 minutes. The reaction mixture is cooled and transferred to a 1 liter 3-necked flask with a motor driven stirrer and condenser. 120 ml. H20 and 90 g. of calcium carbonate are added, and the mixture is refluxed for 20 hours with good stirring. The reaction mixture is steam distilled until no further oil is collected. The oil is taken up in methylene chloride and dried over MgSO4. Evaporation of the solvent yields 3,4-difluorobenzaldehyde which is used without further purification.
With bromine; calcium carbonate; In dichloromethane; water;
(A) 3,4-difluorobenzaldehyde In a 250 ml. three-necked flask equipped with a magnetic stirrer, thermometer, condenser, and dropping funnel is placed 25.6 g (0.2 mole) of <strong>[2927-34-6]3,4 difluorotoluene</strong>. The liquid is heated to 105 and illuminated as 67 g. (0.42 mole) of bromine is added slowly. The temperature is kept between 105-110 while the first half of the bromine is added over a period of one hour. The rest of the bromine is added over approximately a 2-hour period and the temperature is raised to 150 and kept there for 5 minutes. The reaction mixture is cooled and transferred to a 1 liter 3-necked flask with a motor driven stirrer and condenser. 120 ml. H2O and 90 g. of calcium carbonate are added, and the mixture is refluxed for 20 hours with good stirring. The reaction mixture is steam distilled until no further oil is collected. The oil is taken up in methylene chloride and dried over MgSO4. Evaporation of the solvent yields 3,4-difluorobenzaldehyde which is used without further purification.
With sulfuric acid; nitric acid; acetic acid; In dichloromethane;
EXAMPLE 18 4,5-Difluoro-2-nitrotoluene To a stirring solution of <strong>[2927-34-6]3,4-difluorotoluene</strong> (1.34 g, 10.5 mmol) in a mixture of concentrated sulfuric acid (1.7 ml) and acetic acid (1 ml) at 0C was added dropwise a chilled mixture of concentrated nitric acid (1.6 ml) and concentrated sulfuric acid (3.4 ml). After stirring for 10 minutes at 0C, ice (20 g) and dichloromethane (30 ml) were added. The layers were then separated and the organic phase was washed with water (20 ml) and brine (20 ml), and was dried (MgSO4) and filtered. The solvent was removed from the organic layer with a rotary evaporator, affording 1.73 g (95%) of the title compound as a light yellow oil 1H NMR (CDCl3): 7.91 (1H, dd, J = 8, 10), 7.14 (1H, dd, J = 8, 10), 2.57 (3H, s).
4-fluoro-toluene-3-diazonium ; tetrafluoroborate[ No CAS ]
[ 2927-34-6 ]
Yield
Reaction Conditions
Operation in experiment
EXAMPLE 17 3,4-Difluorotoluene The diazonium salt prepared in Example 16 was placed in a 250 ml round-bottom flask topped with a reflux condenser in a fume hood. The condenser was equipped with a gas inlet tube connected to a length of tubing running to the back of the fume hood. The surface of the flask was heated with a heat gun, and the solid was gradually converted to a refluxing liquid. When all of the solid was liquified, the glassware was rinsed with dichloromethane, and the resulting crude mixture was fractionally distilled at atmospheric pressure, affording 1.76 g (69%) of the title compound as a colorless liquid, b.p. 124-128.
To a solution of diisopropylamine (20.2 g, 0.2 mol) in THF (500 mL) cooled with an ice-water bath was added a solution of n-BuLi in hexane (2.5 M, 8OmL) dropwise for over 30 min. The mixture was stirred in the ice bath for 30 min then cooled to -78 C. A solution of l,2-difluoro-4-methylbenzene (12.8 g, 0.1 mol) in THF (80 mL) was added dropwise, after 20-30 min, a solution of TMSCl (21.6 g, 0.2 mol) in THF (20 mL) was added dropwise. The mixture was stirred at -78 C for 2-3 h. Sat. NH4Cl (300 mL) was added to the mixture, diluted with water (200 mL) and extracted with ether. The ether layer was washed with brine and dried over Na2Stheta4, the solvent <n="164"/>was removed to give (2,3-difluoro-5-methylphenyl) trimethylsilane (26 g, 100%), which was used for the next step without purification. 1H NMR (CDCl3) delta 6.90 (m, 2H), 2.40 (s, 3H), 0.33 (s, 9H).
Step 1: l-Bromo-4,5-difluoro-2-methylbenzene (16). To a ice cooled flask containing <strong>[2927-34-6]3,4-difluorotoluene</strong> 15 (27 g, 210 mmol) and iron powder (600 mg, 10 mmol) was added dropwise Br2 (40 g, 250 mmol). The reaction was stirred for 12 h while it was slowly warmed to RT. Water was added and the resulting mixture was extracted with diethyl ether. The ether layer was washed with sodium thiosulfate solution, brine and dried over Na2S04. Removal of ether gave the desired bromotoluene 16 (36 g, 83%). -NMR (400MHz, DMSO-d6):D D 8 7.78 (t, 1H), 7.52 (t, 1H), 2.29 (s, 3H).
With bromine; iron; In dichloromethane; at 20℃; for 66.5h;Cooling with ice;
4',5'-Difluoro-2'-methyl-biphenyl-4-ol To a stirred solution of <strong>[2927-34-6]3,4-difluorotoluene</strong> (30 g, 234.1 mmol) and iron powder (0.784 g, 14.05 mmol) in methylene chloride (140 mL) in an ice bath was added bromine (12 mL, 155 mmol) slowly over 6.5 hrs. The reaction mixture was warmed to RT and stirred for an additional 60 hrs. The mixture was washed with water (200 mL), 10% Na2SO3 (3*150 mL), saturated (NaHCO3 (100 mL) and saturated NaCl. The organic layer was dried over MgSO4, filtered and concentrated in vacuo to give 40 g of crude 1-bromo-4,5-difluoro-2-methyl-benzene. Bromo-4,5-difluoro-2-methyl-benzene (30 g, 145 mmol) and 4-hydroxyphenyl-boronic acid (20.99 g, 152.2 mmol) were suspended in 725 ml of dioxane. The mixture was degassed with argon. Potassium carbonate (23.17 g, 166 mmol) in 72.5 ml water solution was added and after stirring for 10 minutes, bis(tricyclohexylphosphine)palladium(0) (2.4 g, 3.62 mmol) was added. The reaction was stirred at 80-85 C. for 19 hrs and concentrated. The mixture was diluted with ethyl acetate and water. The organic layer was washed with brine, dried and solvents were evaporated. The crude product was purified by flash chromatography, eluting with 0-7% ethyl acetate in hexanes to obtain the crude product which was further recrystallized from hexane to afford 4',5'-difluoro-2'-methyl-biphenyl-4-ol (23.76 g, 74.5%). LR-MS (ES) calculated for C13H10F2O, 220.22. found m/z 219 [M-H].
With xenon difluoride; boron trifluoride diethyl etherate; In acetonitrile; at -25 - 22℃;
General procedure: A glass reactor equipped with a Teflon-lined magnetic stir bar and connected to a gas-washing bottle was charged with C6H5R (0.95-1.14 mmol), MeCN (1-2.5 mL per mmol of C6H5R), and BF3 · Et2O (1.3-1.6 mmol per mmol of C6H5R). The solution was stirred for 10-15 min at -25C, and XeF2 (1.2-1.3 mmol per mmol of C6H5R) was added in portions. The mixture was allowed to warm up to 22C over a period of 1 h and stirred for 40-60 min more, hexafluorobenzene (internal standard) was added, and a sample was withdrawn for 19F NMR analysis (procedure B). The mixture was treated with a saturated aqueous solution of NaHCO3 and extracted with methylene chloride (1-2 mL). The extract was dried over MgSO4 and analyzed by 19F and GC/MS (procedure C). The main products are given in table, and the others are listed below (GC/MS data).
A suspension of <strong>[2927-34-6]1,2-difluoro-4-methylbenzene</strong> (4 mL, 35 mmol)in THF (75 mL) and tert-butyl methyl ether (25 mL) was cooledto -78 C under N2. Then, n-BuLi (16.8 mL, 42 mmol, 2.4 M in THF)was added dropwise at -78 C, and after the mixturewas stirred for1 h, I2 (13.34 g, 52.5 mmol) dissolved in THF was added dropwiseat -78 C. After another 1 h, the mixture was stirred at roomtemperature for another 1 h. After the reaction was complete, thesolvent was removed under reduced pressure. The residue wasdissolved inwater, saturated Na2S2O4 solutionwas added, and thenthe aqueous solution was extracted with ethyl acetate (50 mL 2).The combined organic layers were washed with brine, dried overanhydrous sodium sulfate, and concentrated to give the crudeproduct, which was purified by column chromatography to give1,2-difluoro-3-iodo-5-methylbenzene (7) (6.2 g, 70% yield) as awhite liquid. 1H NMR (400 MHz, CDCl3) delta: 7.31 (m, 1H), 6.98-6.90(m, 1H), 2.29 (s, 3H).
With sodium hydroxide; ammonium nitrate; trifluoroacetic acid;
EXAMPLE 152 [2-(5,6-Difluoro-1H-indol-3-yl)-cyclopropylmethyl]-dimethyl-amine <strong>[2927-34-6]3,4-Difluorotoluene</strong> (9.00 g, 70.3 mmol), ammonium nitrate (6.75 g, 84.3 mmol) and trifluoroacetic acid (25 ml) were stirred at ambient temperature for 18 h. The resulting solution was made basic to pH>10 with 5 N sodium hydroxide and, after cooling to ambient temperature, extracted with diethyl ether (3*40 ml). The combined organic layers were washed with brine (40 ml) and dried over anhydrous sodium sulfate. The filtrate was concentrated in vacuo. The crude product was purified by silica gel column chromatography, eluding with hexanes/ethyl acetate (9:1), to afford 3,4-difluoro-5-nitrotoluene (4.63 g, 40%) as a light yellow oil. 1H-NMR delta(400 MHz, CDCl3) 7.94 (1 H, dd, J=9.9, 7.3 Hz), 7.17 (1 H, dd, J=10.3, 7.6 Hz), 2.61 (3 H, s).
4-chloro-4,5,5-trifluoro-1-methylcyclohex-1-ene[ No CAS ]
[ 5527-94-6 ]
[ 2927-34-6 ]
Yield
Reaction Conditions
Operation in experiment
8.5%; 83%
With N-benzyl-N,N,N-triethylammonium chloride; potassium hydroxide; In water; at 75 - 95℃; for 4.5h;
General procedure: A 50% aqueous KOH (392.0 g, 3.50 mol) was added to a mixture of cyclohexene 3a (170.5 g, 1.0 mol) and TEBAC (7.0 g)at 75-85 C (oil bath) with stirring over 90 min, then the mixture was stirred for 3 h at 85-95 C. Steam distillation of the resulting mixture gave a mixture of organic products, which was driedwith CaCl2. The dried mixture of product (110.8 g) contained 86.1% of 1,2-difluorobenzene (4a) and 9.2% of 2-chloro-1-fluorobenzene (8a). Distillation of this mixture afforded 94.91 g (83%) of 1,2-difluorobenzene (4a), b.p. 92-92.5 C, and 9.22 g (7%) of chlorofluorobenzene 8a, b.p. 137-138 C.
5-chloro-4,4,5-trifluoro-1-methylcyclohex-1-en[ No CAS ]
[ 1513-25-3 ]
[ 2927-34-6 ]
Yield
Reaction Conditions
Operation in experiment
9.1%; 82%
With N-benzyl-N,N,N-triethylammonium chloride; potassium hydroxide; In water; at 75 - 95℃; for 4.5h;
General procedure: A 50% aqueous KOH (392.0 g, 3.50 mol) was added to a mixture of cyclohexene 3a (170.5 g, 1.0 mol) and TEBAC (7.0 g)at 75-85 C (oil bath) with stirring over 90 min, then the mixture was stirred for 3 h at 85-95 C. Steam distillation of the resulting mixture gave a mixture of organic products, which was driedwith CaCl2. The dried mixture of product (110.8 g) contained 86.1% of 1,2-difluorobenzene (4a) and 9.2% of 2-chloro-1-fluorobenzene (8a). Distillation of this mixture afforded 94.91 g (83%) of 1,2-difluorobenzene (4a), b.p. 92-92.5 C, and 9.22 g (7%) of chlorofluorobenzene 8a, b.p. 137-138 C.