Category: bromides-buliding-blocks

Electric Literature of 21120-91-2,Some common heterocyclic compound, 21120-91-2, name is 7-Bromobicyclo[4.2.0]octa-1,3,5-triene, molecular formula is C8H7Br, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

In a 250 ml rbf with magnetic stir bar was added aminophenol (1 g, 1 eq), THF (15 ml) and KOtBu (1.23 g, 1.2 eq). The mixture was allowed to stir for 1 hour at room temperature. Bromo BCB (1.68 g, 1 eq) was added in THF (15 ml). The reaction was capped and allowed to stir for 12 h at room temperature. Water (100 ml) was then added. Ethyl acetate (3×100 ml) was used to extract the product from the aqueous phase. The combined organics were dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was subjected to a column of silica gel using heptanes and ethyl acetate (9:1) as eluent to give product (892 mg, 46%) as a dark oil. (0077) 1H NMR (500 MHz, Chloroform-d) delta 7.32 (dt, J=6.6, 4.3 Hz, 1H), 7.28-7.23 (m, 2H), 7.18 (d, J=7.4 Hz, 1H), 6.86 (d, J=9.0 Hz, 2H), 6.69 (d, J=9.0 Hz, 2H), 5.59 (dd, J=4.3, 2.1 Hz, 1H), 3.66 (dd, J=14.1, 4.3 Hz, 1H), 3.46 (br s, 2H), 3.28 (d, J=14.1 Hz, 1H). 13C NMR (126 MHz, Chloroform-d) delta 151.04, 145.18, 142.64, 140.49, 129.73, 127.29, 123.47, 123.00, 116.48, 116.36, 74.89, 39.47. DSC Showed an exotherm peak temperature at 179 C at a scan rate of 10 C/min.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 7-Bromobicyclo[4.2.0]octa-1,3,5-triene, its application will become more common.

Reference:
Patent; Rohm and Haas Electronic Materials LLC; Hayes, Colin; Gallagher, Michael K.; Riener, Michelle; (10 pag.)US2019/169327; (2019); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 444-14-4,Some common heterocyclic compound, 444-14-4, name is 2-Bromo-4,6-difluoroaniline, molecular formula is C6H4BrF2N, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Dissolve 2-bromo-4,6-difluoroaniline (40 g, 192 mmol) in methyldisulfide (250 mL) and heat to 75 C under nitrogen. Add isoamyl nitrite (67 mL, 500 mmol) dropwise via an addition funnel trough a reflux condenser (-1 drop/sec). Large exotherm may occur if addition is too fast. After addition is complete, heat the reaction to 95 C for 1 hour and cool to room temperature and concentrate in vacuo. Purify dark brown residue via silica gel chromatography eluting with hexanes to yield 30.3 g of 1-bromo-3, 5- difluoro-2-methylsulfanyl-benzene (66%). Charge a flask with isopropyl magnesium chloride (145 mL, 2M in THF, 290 mmol) and dilute with tetrahydrofuran (150 mL) and heat to 40 C under nitrogen. Add 1-bromo-3, 5-difluoro-2-methylsulfanyl-benzene (28 g, 117 mmol) slowly over 5 minutes. After 30 minutes, cool the reaction to 0 C and add trimethylborate (46 mL, 410 mmol) diluted with tetrahydrofuran (100 mL) via an addition funnel over 5 minutes. Partition the resulting gelatinous mixture between methylene chloride and 1N HC1. Acidify the aqueous layer to pH-1 (if needed) and vigorously stir the biphasic mixture until all solids are dissolved. the organic layer. Dry over sodium sulfate, filter and concentrate. Triturate with hexanes and filter to yield 14.7 g (61 %) of the title compound.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-4,6-difluoroaniline, its application will become more common.

Reference:
Patent; ELI LILLY AND COMPANY; WO2005/73204; (2005); A1;,
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bromide – Wiktionary

Synthetic Route of 22385-77-9,Some common heterocyclic compound, 22385-77-9, name is 1-Bromo-3,5-di-tert-butylbenzene, molecular formula is C14H21Br, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

2,6-Bis(aniline)pyridine (500 mg, 1.914 mmol), 3,5-di-t-butyl-bromobenzene (1.26 g, 4.688 mmol), Pd2(dba)3 (87.6 mg, 95.7 mumol), BINAP (128.7 mg, 229.5 mumol) and sodium t-butoxide (552 mg, 5.744 mmol) were dissolved in 15 mL of toluene. The mixture was stirred for 48 h at 90 0C before cooling it to room temperature and quenching the reaction with 20 mL of water. After separation with dichloromethane, the volatiles were removed in vacuo from the organic extract. The obtained orange oil was passed through a silica gel column by a 20:1 mixture of dichloromethane and ethyl acetate and then was triturated from cold methanol and collected by filtration. 854 mg of pale-yellow solid 6a were obtained after a single wash (70 percent yield). 1H NMR (CDCl3) delta: 1.22 (s, 36eta, C(CH3)3), 6.93 (td, 2eta), 6.99 (t, 2H tBu-Ph-H), 7.05 (d, 4eta, tBu-Ph-H), 7.30 (td, 2eta), 7.54 (dd, 2H), 7.66 (d, 4H, Ph-H, Py-H), 7.90 (t, 1eta, Py-H), 9.8 (s, 2eta,NH). 1H-NMR (C6D6) delta: 1.22 (s, 36H, C(CH3)3), 6.86 (td, 2eta, Ph-H), 7.14 (t, 2eta), 7.1-7.2 (d+t, 3H, Py-H), 7.24 (td, 2eta, Ph-H), 7.32 (d, 4eta), 7.52 (dd, 2H, Ph-H), 7.85 (dd, 2eta, Ph-H), 10.14 (s, 2eta,NH). 13C NMR (CDCl3) delta: 31.6 (CH3), 35.0 (C(CH3)3), 114.6, 115.8, 116.1, 118.9, 120.5, 124.7, 130.0, 130.5, 138.5, 141.5, 143.2, 151.9, 157.3.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Bromo-3,5-di-tert-butylbenzene, its application will become more common.

Reference:
Patent; CALIFORNIA INSTITUTE OF TECHNOLOGY; AGAPIE, Theodor; GOLISZ, Suzanne; TOFAN, Daniel; BERCAW, John, E.; WO2008/36882; (2008); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 22034-13-5 as follows. Quality Control of 4-Bromobenzo[c][1,2,5]thiadiazole

General procedure: To a solution of 4-bromobenzo[c] [1,2,5]thiadiazole (107 mg,0.50 mmol) and N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (124 mg, 0.50 mmol) in toluene-ethanol(30 mL/10 mL), Pd(PPh3)4 (57 mg, 0.05 mmol) and anhydrous K2CO3 (207 mg, 1.5 mmol) were added under an argon flow at room temperature. The mixturewas then heated to 80 °C for12 h. The mixture was quenched with water after cooling back to room temperature and extracted with dichloromethane. The combined extract was dried with anhydrous Na2SO4 and concentrated by rotary evaporation. The residue was purified by column chromatography on silica gel with CH2Cl2/petroleum (1:1) to afford NBT as an orange solid.

According to the analysis of related databases, 22034-13-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Jiang, Di; Chen, Songhua; Xue, Zheng; Li, Yongjun; Liu, Huibiao; Yang, Wensheng; Li, Yuliang; Dyes and Pigments; vol. 125; (2016); p. 100 – 105;,
Bromide – Wikipedia,
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Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 40422-70-6, name is 1-Bromo-3-(2-bromoethyl)benzene, A new synthetic method of this compound is introduced below., Computed Properties of C8H8Br2

A mixture of 2,4,6-trimethyl-N-((3′-(methylsulfonyl)-[l, r-biphenyl]-4- yl)methyl)benzenesulfonamide (0.443 g, 1 mmol), K2CO3 (0.276 g, 2 mmol), and l-bromo-3-(2-bromoethyl)benzene (0.792 g, 3 mmol) in anhydrous acetonitrile (5 ml) was heated to 85 C for 2 h under microwave irradiation. The white powder was filtered off, the solvent was evaporated and the mixture was dissolved in ethyl acetate and extracted with brine. The organic phase was separated, dried over anhydrous MgS04, filtered and concentrated in vacuo. The remaining crude residue was purified by flash chromatography on silica gel (ethyl acetate/hexanes) to obtain the title compound as white sharp needles (88% based on recovery of the starting materials); FontWeight=”Bold” FontSize=”10″ H NMR (400 MHz, Chloroform-Patent; THE SCRIPPS RESEARCH INSTITUTE; KAMENECKA, Theodore, Mark; BURRIS, Thomas; WO2014/85453; (2014); A2;,
Bromide – Wikipedia,
bromide – Wiktionary

Adding a certain compound to certain chemical reactions, such as: 827-08-7, name is 1,2-Dibromo-3,4,5,6-tetrafluorobenzene, belongs to bromides-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 827-08-7, name: 1,2-Dibromo-3,4,5,6-tetrafluorobenzene

By the following method,A compound represented by the formula (1m) (1,2-bis (2-methyl-5-phenyl-3-thienyl) tetrafluorobenzene) was synthesized.3-Bromo-2-methyl-5-phenylthiophene in a three-necked flask under an argon atmosphere [Literature Description: M.M. Irie, T .; Lifka, S .; Kobatake, N .; Kato, J .; Am. Chem. Soc. , 122, 4871-4876 (2000)] 520 mg (2.1 mmol) was added and dissolved in 15 mL of anhydrous tetrahydrofuran (THF).. After cooling to -78 C., 1.3 mL (2.2 mmol) of 1.6 M n-butyllithium hexane solution was slowly added dropwise. After stirring for 2 hours,Tributyl borate 1.0 mL (3.7 mmol) was slowly added dropwise and stirred for 2 hours.Then return to room temperature,Quenched with water.The mixture was acidified with dilute hydrochloric acid and extracted with diethyl ether.Add sodium hydroxide aqueous solution to the organic layer,After basifying, extraction with diethyl ether was performed again.Add concentrated hydrochloric acid to the aqueous phase,The resulting white precipitate was obtained by filtration. It was dissolved in THF, 120 mg (0.40 mmol) of 1,2-dibromotetrafluorobenzene,2 mL of 20 wt% aqueous sodium carbonate solution and 50 mg (0.043 mmol) of Pd (PPh3) 4 were added and refluxed for 8 hours. The mixture was neutralized with dilute hydrochloric acid, extracted with diethyl ether, salted out, and dried over magnesium sulfate. The solvent was distilled off and the residue was purified by silica gel column chromatography using hexane as a developing solvent.Yield 81 mg, Yield 83%

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Osaka City University; Kobatake, Seiya; Kitagawa, Daichi; (28 pag.)JP2019/151596; (2019); A;,
Bromide – Wikipedia,
bromide – Wiktionary

These common heterocyclic compound, 1435-53-6, name is 2,4-Dibromo-1-fluorobenzene, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Application In Synthesis of 2,4-Dibromo-1-fluorobenzene

1,3-Dibromo-4-fluorobenzene (837 mg) was dissolved in a toluene-THF (10:1) mixture (15 ml). The mixture was cooled to -78 C. and n-butyllithium (2.64 M, 1.19 ml) was added dropwise. After stirring at the same temperature for one hour, a solution of (+/-)-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c]isoxazole obtained in Preparation Example 1-(2) (200 mg) in toluene-THF (10:1) (5.0 ml) and a boron trifluoride-diethyl ether complex (394 mul) were added dropwise at the same time. After stirring at the same temperature for three hours, the reaction was terminated with an ammonium chloride solution. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (365 mg).

The synthetic route of 2,4-Dibromo-1-fluorobenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; EISAI R&D MANAGEMENT CO., LTD.; US2010/93999; (2010); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Adding a certain compound to certain chemical reactions, such as: 69038-76-2, name is 4-Bromo-N1-methylbenzene-1,2-diamine, belongs to bromides-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 69038-76-2, HPLC of Formula: C7H9BrN2

After methyl dichloro(methoxy)acetate (2.5 ml) was added to a solution of 4-bromo-N1-methylbenzene-1,2-diamine (1.0 g), N,N-diisopropylethylamine (7.1 ml) in 1,2-dichloroethane (30 ml), the reaction mixture was stirred at room temperature for 1 hour, and then stirred at 60 C. for 3 days. After the reaction mixture was cooled to room temperature, a saturated aqueous sodium hydrogen carbonate solution was added thereto, and extraction was carried out using chloroform. After the organic layer was dried over anhydrous sodium sulfate, the desiccant was removed, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate), thereby obtaining methyl 5-bromo-1-methyl-1H-benzimidazole-2-carboxylate (820 mg) as a solid.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Bromo-N1-methylbenzene-1,2-diamine, and friends who are interested can also refer to it.

Reference:
Patent; ASTELLAS PHARMA INC.; Ohnuki, Kei; Azami, Hidenori; Sawada, Yuki; Shin, Takashi; Kuramoto, Kazuyuki; Kikuchi, Shigetoshi; Saito, Tomoyuki; Hamaguchi, Hisao; Nagashima, Takeyuki; US2015/266869; (2015); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 6320-40-7, These common heterocyclic compound, 6320-40-7, name is 1,3,5-Tribromo-2-methylbenzene, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Synthesizing of Intermediates A and B 3.3g (10 mmol) of 2,4,6-tribromotoluene was dissolved in 30 mL of diethylether. The resulting solution was cooled to -78 C and 4.4mL (11 mmol) of normalbutylithium (2.5M in Hexane) was slowly added thereto. The resulting solution was stirred at -78C for one hour and 1.48g (11 mmol) of cooper chloride (II) was added thereto at -78C. The reactant product was stirred for 5 hours and cleaned using distilled water and ethylacetate at room temperature. The cleaned ethylacetate layer was dried over MgSO4 and dried under a reduced pressure, thereby producing a crude-product. The pre-product was refined through a column chromatography and the refined result was recrylstallized in dichloromethane and hexane, thereby producing white solid intermediates A and B. Amounts of A and B were 622 mg (yield 25%) and 746 mg (yield: 30%), respectively. Intermediate A : 1H NMR (CDCl3, 400MHz) delta (ppm) 7.74 (d, 4H), 7.18 (d, 4H), 2.06 (s, 6H); 13C NMR (CDCl3, 100MHz) delta (ppm) 142.8, 134.9, 134.5, 131.1, 126.4, 119.4, 19.9 Intermediate B : 1H NMR (CDCl3, 400MHz) delta (ppm) 7.60 (s, 4H), 2.61 (s, 6H); 13C NMR (CDCl3, 100MHz) delta (ppm) 138.3, 137.2, 129,9, 125.8, 23.5

The synthetic route of 6320-40-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Samsung SDI Co., Ltd.; EP1752442; (2007); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Application of 176317-02-5, A common heterocyclic compound, 176317-02-5, name is 1-Bromo-2,3,4-trifluorobenzene, molecular formula is C6H2BrF3, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Step 1: 5-bromo-2,3,4-trifluorobenzoic acid To a solution of 1-bromo-2,3,4-trifluorobenzene (13.64 g, 64.6 mmol) in THF (120 mL) was added lithium diisopropylamide (2.0 M in THF, 33.9 mL, 67.8 mmol) at -78 C. under nitrogen atmosphere. After stirring for 1 h at -78 C., the mixture was transferred to a bottle with dry ice. The mixture was stirred overnight at room temperature. The reaction was quenched with 10% aqueous HCl (300 mL) and extracted with ethyl acetate (200 mL*3). The combined organic extracts were washed with 5% sodium hydroxide (300 mL). The aqueous layer was acidized to pH 1 and extracted with ethyl acetate (200 mL*3). The combined organic extract was dried over Na2SO4, filtered and concentrated under reduced pressure to afford the desired product (white solid, 13.51 g, 82% yield). 1H NMR (400 MHz, CDCl3): delta 13.94 (s, 1H), 7.95 (m, 1H).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; TIANJIN BINJIANG PHARMA, INC.; Tian, Hongqi; Ji, Conghui; Liu, Chunlei; Kong, Li; Cheng, Ying; Huang, Gongchao; US2014/371278; (2014); A1;,
Bromide – Wikipedia,
bromide – Wiktionary