132178-78-0|1,5-Dibromonaphthalene-2,6-diol| Ambeed

CAS No. :	132178-78-0
Formula :	C₁₀H₆Br₂O₂
M.W :	317.96
SMILES Code :	OC1=C(Br)C2=C(C=C1)C(Br)=C(O)C=C2
MDL No. :	MFCD16251539
InChI Key :	COJNHIANORGBGY-UHFFFAOYSA-N
Pubchem ID :	14896989

Safety of [ 132178-78-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 132178-78-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	14
Num. arom. heavy atoms	10
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	2.0
Molar Refractivity	63.39
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	40.46 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.25
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.84
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.78
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	3.26
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	3.3
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.29

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-4.76
Solubility	0.00554 mg/ml ; 0.0000174 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-4.39
Solubility	0.0131 mg/ml ; 0.0000412 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-4.61
Solubility	0.00786 mg/ml ; 0.0000247 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	Yes
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	Yes
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.51 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.76

Application In Synthesis of [ 132178-78-0 ]

* 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.

Downstream synthetic route of [ 132178-78-0 ]

[ 132178-78-0 ] Synthesis Path-Downstream 1~54

1
[ 581-43-1 ]
[ 132178-78-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	With N-Bromosuccinimide; In tetrahydrofuran; at 0 - 60℃; for 3h;	In a more detailed embodiment, the method begins by taking a solution of 2,6-naphthalene diol (10.16 g, 63.43 mmol) in tetrahydrofuran (110 mL) and cooling the solution to about 0 C., then treated slowly with N-bromosuccinimide (22.58 g, 0.13 mol). The flask was then topped with a water condenser and heated to around 60 C. for around 3 hours, then cooled to room temperature. This reaction mixture A was diluted with a saturated aqueous Na2S2O3 solution (250 mL) and water (1.5 L), and the resulting solid was collected by filtration, and then left under vacuum for around 18 hours. The desired product, (0082) (19.5 g, 0.061 mol, 97% yield), was obtained as a tan solid. The 1H NMR spectrum of (0083) is shown in FIG. 2.
97%	With N-Bromosuccinimide; In tetrahydrofuran; at 0 - 60℃; for 3h;	In a more detailed embodiment of producing al,2,5,6-naphthalenediimide monomer, the method can begin by taking a solution of 2,6-naphthalene diol (10.16 g, 63.43 mmol) in tetrahydrofuran (110 mL) and cooling the solution to about 0 C, then treated slowly with N- bromosuccinimide (22.58 g, 0.13 mol). The flask was then topped with a water condenser and heated to around 60C for around 3 hours, then cooled to room temperature. This reaction mixture A was diluted with a saturated aqueous Na2S203 solution (-250 mL) and water (-1.5 L), and the resulting solid was collected by filtration, and then left under vacuum for around 18 hours. The desired product, mol, 97% yield), was obtained as a tan solid. The 1H NMR spectrum of is shown in Figure 2.
90%	With N-Bromosuccinimide; In tetrahydrofuran;Reflux;	Example 1 - l,5-dibromonaphthalene-2,6-diol [00123] To a solution of naphthalene -2, 6-diol (1) (5.1 g) in 50 mL of Tetrahydrofuran (THF), was added N-Bromosuccinimide (NBS, 1 1.4 g). The mixture was re fluxing and monitored by GCMS. The reaction was quenched with saturated sodium thiosulfate, and filtered. The solid was washed by water to afford 1 ,5- dibromonaphthalene-2,6-diol (90%). LRMS (ESI): Calcd. for Ci0H6Br2O2: 317.8714, Found: 317.9.

With bromine; In acetic acid; at 120 - 125℃;

Synthesis of 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene2,6-dihydroxynaphthalene (2 g, 12.5 mol) was dissolved in acetic acid (60 ml). The acetic acid was used as a solvent. Bromine (2.6 ml. 50.7 mol) was dripped in the solution, and reaction was carried out under a reflux temperature (120 C. to 125 C.).As is explained in the embodiment for carrying out the present invention, in this stage, first and fifth hydrogen atoms with a high reactivity among hydrogen atoms contained in 2,6-dihydroxynaphthalene were substituted by bromine atoms, and 1,5-dibromo-2,6-dihydroxynaphthalene was merely produced. In order to obtain naphthodithiophene having a linear structure at last, it was further necessary to substitute the third and seventh hydrogen atoms with bromine.Next, bromine (2.6 ml) was further dripped into the reaction solution by five times at total, and iron powders (50 mg, 1.3 mol) as a catalyst were added thereto, and reaction was caused for 76 hours.Next, the reaction solution was cooled to a room temperature, and pure water (50 ml) was added thereto. A precipitated solid was separated and collected by filtering. This solid substance was rinsed by acetone, dried under a reduced pressure condition, thereby obtaining a rough product.The obtained rough product was caused to be recrystallized using 1,4-dioxane as a solvent, and purified. Accordingly, 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene (3.0 g, yield: 51%) with colorless needle crystals was obtained.As explained above, by dripping bromine several times and by adding iron powders as a catalyst, 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene was synthesized at a high yield.The reaction formula of the above-explained reaction is as follow. Various spectrum data of the obtained 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene are indicated below.1H-NMR (270 MHz, CDCl3) delta6.18 (s, 2H, OH), 8.31 (s, 2H, ArH); EIMS (70 eV) m/z=476 (M+)

References: [1]Patent: US10174043,2019,B1 .Location in patent: Page/Page column 15.
[2]Patent: WO2019/23022,2019,A1 .Location in patent: Paragraph 0034.
[3]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.
[4]Patent: WO2013/149001,2013,A2 .Location in patent: Paragraph 00123.
[5]Journal of the Chemical Society,1937,p. 1859,1861.
[6]Patent: US2011/224445,2011,A1 .Location in patent: Page/Page column 8.

2
[ 132178-78-0 ]
[ 132178-77-9 ]

References: [1]Chemische Berichte,1943,vol. 76,p. 924,928,936.

3
[ 132178-78-0 ]
[ 77-78-1 ]
[ 25315-06-4 ]

References: [1]Journal of the Chemical Society,1937,p. 1859,1861.

4
[ 132178-78-0 ]
[ 133546-47-1 ]

References: [1]Bulletin of the Chemical Society of Japan,1991,vol. 64,p. 68 - 73.

5
[ 132178-78-0 ]
[ 90947-23-2 ]

References: [1]Journal fur praktische Chemie (Leipzig 1954),1962,vol. 18,p. 219 - 224.

6
[ 132178-78-0 ]
[ 135-19-3 ]
6'-(2-Hydroxy-naphthalen-1-yloxy)-[1,1';5',1'']ternaphthalene-2,2',2''-triol [ No CAS ]
[1,1';5',1'';5'',1''']Quaternaphthalene-2,2',6',2'',6'',2'''-hexaol [ No CAS ]
[1,1';5',1'']Ternaphthalene-2,2',6',2''-tetraol [ No CAS ]

References: [1]Tetrahedron,1996,vol. 52,p. 11013 - 11024.
[2]Tetrahedron,1996,vol. 52,p. 11013 - 11024.

7
[ 132178-78-0 ]
[ 135-19-3 ]
[1,1';5',1'']Ternaphthalene-2,2',6',2''-tetraol [ No CAS ]

References: [1]Tetrahedron,1996,vol. 52,p. 11013 - 11024.
[2]Tetrahedron,1996,vol. 52,p. 11013 - 11024.

8
[ 132178-78-0 ]
[ 42075-32-1 ]
(2R,4S)-4-[1,5-Dibromo-6-((1S,3R)-3-hydroxy-1-methyl-butoxy)-naphthalen-2-yloxy]-pentan-2-ol [ No CAS ]

References: [1]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.

9
[ 132178-78-0 ]
[ 89012-59-9 ]
C₃₄H₃₄Br₂O₆ [ No CAS ]

References: [1]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.

10
[ 132178-78-0 ]
[ 108-24-7 ]
[ 213268-47-4 ]

References: [1]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.
[2]Chemical Communications,2012,vol. 48,p. 5671 - 5673.

11
[ 132178-78-0 ]
[ 107-30-2 ]
[ 245093-97-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0℃; for 18.0833h;	To a solution of <strong>[132178-78-0]1,5-dibromonaphthalene-2,6-diol</strong> (5.0 g, 15.73 mmol) in dichloromethane (100 mL) was added diisopropylethylamine (16.43 mL) and the reaction was cooled at 0 C. in water/ice bath. To the reaction mixture was added chloromethyl methyl ether (7.17 mL) via a syringe and dropwise over 5 minutes. The reaction was left to stir for 18 hours. After this time the reaction was diluted with water (100 mL) and dichloromethane (100 mL). The organic was separated and the aqueous re-extracted with dichloromethane (100 mL). The combined organics were washed with brine (150 mL), filtered through a phase separator and reduced to dryness to give brown gum. The gum was triturated with heptane to give a pale brown solid which was filtered to give 1,5-dibromo-2,6-bis(methoxymethoxy)naphthalene as yellow solid (5.79, 91%). 1H NMR (396 MHz, DMSO-d6): delta 8.12 (d, 2H), 7.63 (d, 2H), 5.38 (s, 4H), 3.42 (s, 6H).
90%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 22℃; for 22h;	Example 2 - l,5-Dibromo-2,6-bis(methoxymethoxy)naphthalene [00124] To a solution of l ,5-dibromonaphthalene-2, 6-diol (2) (77.15 g) in dichloromethane (500 mL), diisoprorylethylamine (255 mL) and chloro(methoxy)methane (MOMCl, 98.6 g) were added at 0C. After stirring for 22 h at room temperature, the reaction was quenched by adding water. The crude products were extracted with ethyl acetate and the combined organic extracts were washed with brine, dried over sodium sulfate (Na2S04), and concentrated in vacuum. The solid residue was stirred in n-hexanes to afford analytically pure l ,5-dibromo-2,6- bis(methoxymethoxy)naphthalene (90%). LRMS (ESI): Calcd. for Ci4Hi4Br204: 405.9238, Found: 406.0.

References: [1]Angewandte Chemie - International Edition,2009,vol. 48,p. 5638 - 5641.
Angew. Chem., Int. Ed.,2009,vol. 121,p. 5748 - 5751.
[2]Patent: US2020/16151,2020,A1 .Location in patent: Paragraph 0775; 0850-0852.
[3]Patent: WO2013/149001,2013,A2 .Location in patent: Paragraph 00124.
[4]Journal of Organic Chemistry,2016,vol. 81,p. 2911 - 2919.
[5]Chemistry Letters,1999,p. 833 - 834.

12
[ 111-83-1 ]
[ 132178-78-0 ]
1,5-dibromo-2,6-dioctyloxynaphthalene [ No CAS ]

References: [1]Macromolecules,2005,vol. 38,p. 687 - 694.

13
[ 132178-78-0 ]
[ 79044-35-2 ]
[ 928160-26-3 ]
7,7''-bis-allyloxy-[1,1';5',1'']ternaphthalene-2,2',6',2''-tetraol [ No CAS ]

References: [1]Tetrahedron,2007,vol. 63,p. 1762 - 1769.

14
[ 132178-78-0 ]
[ 190434-39-0 ]
7,7''-diisopropoxy-[1,1';5',1'']ternaphthalene-2,2',6',2''-tetraol [ No CAS ]
7,7''-diisopropoxy-[1,1';5',1'']ternaphthalene-2,2',6',2''-tetraol [ No CAS ]

References: [1]Tetrahedron,2007,vol. 63,p. 1762 - 1769.

15
[ 132178-78-0 ]
[ 760179-65-5 ]
7,7''-diisopropyl-[1,1';5',1'']ternaphthalene-2,2',6',2''-tetraol [ No CAS ]
7,7''-diisopropyl-[1,1';5',1'']ternaphthalene-2,2',6',2''-tetraol [ No CAS ]

References: [1]Tetrahedron,2007,vol. 63,p. 1762 - 1769.

16
[ 132178-78-0 ]
[ 846605-90-1 ]

References: [1]Macromolecules,2005,vol. 38,p. 687 - 694.

17
[ 132178-78-0 ]
1,5-bis-(3,5-di-<i>tert</i>-butyl-phenyl)-naphthalene-2,6-dione [ No CAS ]

References: [1]Chemistry Letters,1999,p. 833 - 834.

18
[ 132178-78-0 ]
[ 245093-99-6 ]

References: [1]Chemistry Letters,1999,p. 833 - 834.

19
[ 132178-78-0 ]
[ 245093-98-5 ]

References: [1]Chemistry Letters,1999,p. 833 - 834.

20
[ 132178-78-0 ]
[1,1';5',1'']Ternaphthalene-2,2',6',2''-tetraol [ No CAS ]

References: [1]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.

21
[ 132178-78-0 ]
[ 213268-45-2 ]

References: [1]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.

22
[ 132178-78-0 ]
[ 213268-48-5 ]

References: [1]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.

23
[ 132178-78-0 ]
Acetic acid 1,5-dibromo-6-methoxymethoxy-naphthalen-2-yl ester [ No CAS ]

References: [1]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.

24
[ 132178-78-0 ]
[ 213268-46-3 ]

References: [1]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.

25
[ 132178-78-0 ]
[ 244015-06-3 ]

References: [1]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.

26
[ 132178-78-0 ]
[ 213268-42-9 ]

References: [1]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.

27
[ 132178-78-0 ]
C₄₀H₃₆O₄ [ No CAS ]

References: [1]Tetrahedron Letters,1998,vol. 39,p. 6487 - 6490.

28
[ 132178-78-0 ]
[ 22428-34-8 ]

References: [1]Journal fur praktische Chemie (Leipzig 1954),1962,vol. 18,p. 219 - 224.

29
[ 83-56-7 ]
[ 132178-78-0 ]

References: [1]Tetrahedron Letters,2009,vol. 50,p. 4781 - 4784.

30
[ 132178-78-0 ]
[ 98-59-9 ]
[ 1178529-76-4 ]

References: [1]Tetrahedron Letters,2009,vol. 50,p. 4781 - 4784.

31
[ 132178-78-0 ]
[ 98-59-9 ]
[ 85337-31-1 ]

References: [1]Tetrahedron Letters,2009,vol. 50,p. 4781 - 4784.

32
[ 132178-78-0 ]
[ 133546-43-7 ]

Yield	Reaction Conditions	Operation in experiment
51%	With bromine;iron; In acetic acid; for 76h;	Synthesis of 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene2,6-dihydroxynaphthalene (2 g, 12.5 mol) was dissolved in acetic acid (60 ml). The acetic acid was used as a solvent. Bromine (2.6 ml. 50.7 mol) was dripped in the solution, and reaction was carried out under a reflux temperature (120 C. to 125 C.).As is explained in the embodiment for carrying out the present invention, in this stage, first and fifth hydrogen atoms with a high reactivity among hydrogen atoms contained in 2,6-dihydroxynaphthalene were substituted by bromine atoms, and <strong>[132178-78-0]1,5-dibromo-2,6-dihydroxynaphthalene</strong> was merely produced. In order to obtain naphthodithiophene having a linear structure at last, it was further necessary to substitute the third and seventh hydrogen atoms with bromine.Next, bromine (2.6 ml) was further dripped into the reaction solution by five times at total, and iron powders (50 mg, 1.3 mol) as a catalyst were added thereto, and reaction was caused for 76 hours.Next, the reaction solution was cooled to a room temperature, and pure water (50 ml) was added thereto. A precipitated solid was separated and collected by filtering. This solid substance was rinsed by acetone, dried under a reduced pressure condition, thereby obtaining a rough product.The obtained rough product was caused to be recrystallized using 1,4-dioxane as a solvent, and purified. Accordingly, 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene (3.0 g, yield: 51%) with colorless needle crystals was obtained.As explained above, by dripping bromine several times and by adding iron powders as a catalyst, 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene was synthesized at a high yield.The reaction formula of the above-explained reaction is as follow. Various spectrum data of the obtained 1,3,5,7-tetrabromo-2,6-dihydroxynaphthalene are indicated below.1H-NMR (270 MHz, CDCl3) delta6.18 (s, 2H, OH), 8.31 (s, 2H, ArH); EIMS (70 eV) m/z=476 (M+)

References: [1]Patent: US2011/224445,2011,A1 .Location in patent: Page/Page column 8.

33
[ 132178-78-0 ]
[ 1227743-83-0 ]

References: [1]Patent: US2011/224445,2011,A1 .

34
[ 132178-78-0 ]
[ 883553-07-9 ]

References: [1]Patent: US2011/224445,2011,A1 .

35
[ 132178-78-0 ]
[ 1227744-09-3 ]

References: [1]Patent: US2011/224445,2011,A1 .

36
[ 132178-78-0 ]
[ 1227744-11-7 ]

References: [1]Patent: US2011/224445,2011,A1 .

37
[ 132178-78-0 ]
[ 1227744-15-1 ]

References: [1]Patent: US2011/224445,2011,A1 .

38
[ 132178-78-0 ]
[ 1280178-74-6 ]

References: [1]Patent: US2011/224445,2011,A1 .

39
[ 132178-78-0 ]
[ 1227743-44-3 ]

References: [1]Patent: US2011/224445,2011,A1 .

40
[ 132178-78-0 ]
[ 1227743-48-7 ]

References: [1]Patent: US2011/224445,2011,A1 .

41
[ 132178-78-0 ]
2,7-dibromonaphtho[2,3-b:6,7-b']dithiophene [ No CAS ]

References: [1]Patent: US2011/224445,2011,A1 .

42
[ 132178-78-0 ]
[ 1379765-29-3 ]

References: [1]Chemical Communications,2012,vol. 48,p. 5671 - 5673.

43
[ 358-23-6 ]
[ 132178-78-0 ]
1,5-dibromonaphthalene-2,6-diyl bis(trifluoromethanesulfonate) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With pyridine; In dichloromethane; at 0 - 20℃; for 18h;Schlenk technique; Inert atmosphere;	The next reaction in the method involves charging (0085) in a Schlenk flask. A hot, oven-dried Schlenk flask was evacuated for about 30 min, refilled with argon, then charged with (0086) (10 g, 31.45 mmol) and evacuated for about 1 hour. The flask was refilled with argon and dry dichloromethane (300 mL) was added. The resulting suspension was cooled to about 0 C. for about 15 min, then triflic anhydride (11.62 mL, 0.069 mol) was added dropwise, followed by the dropwise addition of pyridine (15.2 mL, 0.189 mol). The reaction was then gradually warmed to room temperature and stirred for about 18 hours. The reaction mixture was diluted with dichloromethane and water, then transferred to a separatory funnel. The aqueous layer was acidified with hydrochloric acid, then extracted with dichloromethane. The combined organic extracts were dried (MgSO4), filtered, and concentrated into reaction mixture B. Reaction mixture B was then diluted with a mixture of dichloromethane and acetone, applied to the top of a 4?×6? column, and eluted with dichloromethane. All fractions containing (0087) were concentrated. The material was then dissolved in dichloromethane, adsorbed onto silica gel and purified on a 340 g Biotage silica gel cartridge with a 10-30% dichloromethane/hexanes gradient. Fractions containing pure product (0088) were concentrated (15.2 g, 0.026 mol, 83% yield) and was a white, crystalline solid. The 1H NMR spectrum of (0089) is shown in FIG. 3.
83%	With pyridine; In dichloromethane; at 0 - 20℃; for 18h;Schlenk technique; Inert atmosphere;	The next reaction in the method involves ch in a Schlenk flask. A hot, oven-dried Schlenk flask was evacuated for about 30 min, refilled with argon, then charged with (io g, 31.45 mmol) and evacuated for about 1 hour. The flask was refilled with argon and dry dichloromethane (300 mL) was added. The resulting suspension was cooled to about 0 C for about 15 min, then triflic anhydride (11.62 mL, 0.069 mol) was added dropwise, followed by the dropwise addition of pyridine (15.2 mL, 0.189 mol). The reaction was then gradually warmed to room temperature and stirred for about 18 hours. The reaction mixture was diluted with dichloromethane and water, then transferred to a separatory funnel. The aqueous layer was acidified with hydrochloric acid, then extracted with dichloromethane. The combined organic extracts were dried (MgSCn), filtered, and concentrated into reaction mixture B. Reaction mixture B was then diluted with a mixture of dichloromethane and acetone, applied to the top of a 4" x 6" column, and eluted with dichloromethane. All fractions containing concentrated. The material was then dissolved in dichloromethane, adsorbed onto silica gel and purified on a 340 g Biotage silica gel cartridge with -30% dichloromethane/hexanes gradient. Fractions containing pure product concentrated (15.2 g, 0.026 mol, 83% yield) and was a white, crystalline solid. The 1H NMR spectrum of is shown in Figure 3.
50%	With pyridine; In dichloromethane; at 0 - 20℃; for 8h;	Example 13 - l,5-dibromonaphthalene-2,6-diyl bis(trifluoromethanesulfonate) [00135] To a suspension of l ,5-dibromonaphthalene-2,6-diol (10.1 g), pyridine (15.3 mL) in dichloro methane (305 mL) was slowly added trifluoromethanesulfonic anhydride (12.2 mL) at 0C. After the mixture was stirred for 8 h at room temperature, water and hydrochloric acid (1 M) were added. The resulting mixture was extracted with dichloro methane and combined organic layer was dried (MgS04) and concentrated in vacuo. The residue was purified by column chromatography to give 1 ,5- dibromonaphthalene-2,6-diyl bis(trifluoromethanesulfonate) (50%) LRMS (ESI): Calcd. For Ci2H4Br2F606S2: 581.7700, Found: 581.8.

50%

With pyridine; In dichloromethane; at 20℃; for 30h;Inert atmosphere; Schlenk technique; Cooling with ice;

Under a nitrogen atmosphere, 5.17 g (16.2 mmol) of <strong>[132178-78-0]1,5-dibromo-2,6-dihydroxynaphthalene</strong> (Tokyo Kasei Kogyo), 150 ml of dichloromethane (dehydrated grade), and 7.8 ml of pyridine were added to a 300 ml Schlenk reaction vessel. did. After cooling this mixture with ice, 10.4 g (36.8 mmol) of trifluoromethanesulfonic anhydride (Tokyo Kasei Kogyo) was added. This mixture was reacted at room temperature for 30 hours. 20 ml of water and 20 ml of 1M hydrochloric acid were added to the obtained reaction mixture to quench the reaction. The mixture was extracted twice with dichloromethane. After phase separation, the organic phase was dried over anhydrous sodium sulfate. The organic phase was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (solvent; hexane / toluene = 10/1 to 1/1). 4.76 g of a white solid of 1,5-dibromo-2,6-bis (trifluoromethanesulfonyloxy) naphthalene was obtained (yield: 50%).

References: [1]Patent: US10174043,2019,B1 .Location in patent: Page/Page column 16.
[2]Patent: WO2019/23022,2019,A1 .Location in patent: Paragraph 0035.
[3]Journal of Organic Chemistry,2016,vol. 81,p. 5595 - 5605.
[4]Patent: WO2013/149001,2013,A2 .Location in patent: Paragraph 00135.
[5]Patent: JP2020/29450,2020,A .Location in patent: Paragraph 0138-0139.

44
[ 132178-78-0 ]
3,7-dibromo-2,6-bis(methoxymethoxy)-1,5-dimethylnaphthalene [ No CAS ]