Structure of 80058-84-0
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CAS No. : | 80058-84-0 |
Formula : | C12H18BrN |
M.W : | 256.18 |
SMILES Code : | NC1=C(C(C)C)C=C(Br)C=C1C(C)C |
MDL No. : | MFCD09743895 |
Boiling Point : | No data available |
InChI Key : | QAQRHTYPYQPBSX-UHFFFAOYSA-N |
Pubchem ID : | 11780114 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319 |
Precautionary Statements: | P501-P261-P270-P271-P264-P280-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330-P302+P352+P312-P304+P340+P312 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 67.71 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.03 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.29 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.0 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.79 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.86 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.25 |
Solubility | 0.0145 mg/ml ; 0.0000566 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.44 |
Solubility | 0.0094 mg/ml ; 0.0000367 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.54 |
Solubility | 0.00739 mg/ml ; 0.0000288 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.89 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.71 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0 - 5℃; for 0.333333h;Inert atmosphere; | A solution of NBS (24.59 g, 137 mmol) in DMF (160 mL) was added slowly to a solution of 2,6-diisopropylaniline (25 g, 137 mmol) in DMF (300 mL) at 0-5C under a nitrogen atmosphere over a period of 20 minutes. The reaction mixture was stirred at 0-5C. After the reaction was complete, water was added and the oil suspension was stirred at rt. The aqueous layer was decanted out and the remaining oil was dissolved in ethyl acetate. The organic layer was separated, washed water and brine.Evaporation gave light brown oil (35.1 g, 100% yield). |
99% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0℃; for 2h; | To a stirred solution of 2,6-diisopropylaniline (14 g, 78.97 mmol, 1.00 equiv) in N,N-dimethylformamide (200 mL) at 0 C. was added a solution of NBS (14 g, 78.65 mmol, 1.00 equiv) in N,N-dimethylformamide (100 mL) dropwise in 60 min. The reaction was stirred for another hour at 0 C. then water (900 mL) was added. The resulting mixture was extracted with 300 mL of ethyl acetate. The combined organic layers was washed with 3*100 mL of saturated NH4Cl solution and 1*100 mL of water then dried over anhydrous sodium sulfate and concentrated under vacuum to give 20.05 g (99%) of 4-bromo-2,6-diisopropylaniline as a red oil. 1H NMR (400 MHz, DMSO-d6): delta 6.95 (s, 2H), 4.77 (s, 2H), 5.47-5.39 (m, 1H), 3.04-2.98 (m, 1H), 1.13 (d, J=6.8 Hz, 12H) ppm. |
97% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0 - 20℃; for 48h; | Synthesis of 4-bromo-2,6-diisopropylaniline (0199) A three neck round bottom flask was charged with 2,6-diisopropylaniline (22.96 g, 130 mmol) and DMF (Volume: 250 ml). A solution of 1-bromopyrrolidine-2,5-dione (23.05 g, 130 mmol) in 100 ml DMF was added into reaction mixture drop wise at 0 C. After addition was over; reaction mixture was stirred for 2 days at room temperature. The reaction mixture was poured into 500 ml deionized water and extracted with 3×150 ml ether. The combined extracts were washed with 150 ml deionized water, 150 ml 10% lithium chloride, dried over MgSO4 and evaporated to dryness. The residue was purified by vacuum distillation to yield 4-bromo-2,6-diisopropylaniline (32.3 g; 97%). |
95% | With tetra-N-butylammonium tribromide; In tetrahydrofuran; at 0℃; | 40.8 g (85 mmol) of tetra-n-butylammonium tribromide are added, at 0 C. and portionwise, to a solution of 15 g (85 mmol) of 2,6-diisopropylphenyl-amine in 200 ml of tetrahydrofuran. The medium is stirred for 2 h. It is then poured into a saturated aqueous solution of sodium thiosulphate and extracted with ethyl acetate. The organic phases are combined and washed with water. They are dried over sodium sulphate. The residue is purified by silica gel chromatography (80/20 heptane/ethyl acetate). 20.6 g of 4-bromo-2,6-diisopropylphenylamine are obtained in the form of a yellow oil (yield=95%). |
88% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0℃; for 1h; | To a stirred solution of 2,6-diisopropylaniline (5.05 g, 28.4 mmol, 1.00 equiv) inN,Ndimethylformamide (70 mL) at 00 C was added a solution of NBS (5.05 g, 28.4 mmol, 1.00 equiv) in N,N-dimethylformamide (30 mL) dropwise over 60 mm. The reaction was stirred foranother hour at 0 C, at which time water (300 mL) was added. The resulting mixture was extracted with ethyl acetate (2 x 300 mL), and the combined organic layers were washed with saturated NH4C1 solution (3 x 100 mL) followed by water (100 mL) and dried over anhydrous sodium sulfate. Concentration of the solution under vacuum afforded 4-bromo-2,6- diisopropylaniline (6.5 g, 88% yield). LCMS (Method A): 256.1 [M+H], retention time 2.97mm. |
82% | With tetra-N-butylammonium tribromide; In tetrahydrofuran; at 20℃; | Preparative Example P16Step 1 : 4-Bromo-2,6-diisopropylaniline (PI 6a)To a solution of 2,6-diisopropylaniline (12.5 g, 70.6 mmol) in THF was added (C4H9)4NBr3 (47 g, 85 mmol) at rt and stirred overnight. Then sat. NaHS03 solution (30 mL) was added and the mixture was extracted with Et20 (3 x 250 mL). The organic layer was washed with brine, dried over Na2S04 and concentrated to give compound P16a (19 g, 82%). |
79% | With bromine; In methanol; at 20℃; | A solution of 2, [6-DIISOPROPYLANILINE] (2.0 mL, 11 mmol) in methanol (80 mL) was treated dropwise with bromine (543 muL, 10.6 mmol). The solution was stirred at room temperature for 15 min. Chloroform and 0.1 N [NAOH] were added and the organic layer was dried (Na2SO4), filtered and concentrated to an orange liquid. Kugelrohr distillation [(110 C &COMMAT; ] 0.06 Torr) afforded a colorless liquid (2.22 g 79%): 1H NMR (400 MHz) 8 1.25 (d, J= 6.4 Hz, 12H), 2. 88 (m, 2H), 3.70 (brs, 2H), 7.11 (s, 2H) [; 13C NMR 8] 22.1, 27.9, 111.0, 125.6, 134.5, 139.3 ; Anal calcd for [C12HIGBRN] : C, 56.26 ; H, 7. 08 ; Br, 31.19 ; Found, C, 56.24 ; H, 7.07 ; Br, 30.98 |
72% | With bromine; In methanol; dichloromethane; at 20℃; for 24h; | A solution of Br2(2.1 ml, 41.0 mmol, 1.05 eq.) in CH2Cl2/MeOH (100 ml, 1:1 v/v)was added to a stirring solution of 2,6-diisopropylaniline (7.4 ml,39.0 mmol, 1.0 eq.) in CH2Cl2/MeOH (200 ml, 1:1 v/v) at r.t. over2 h. The orange-red solution was stirred for 1 day. The solvents were evaporated and the resultant pink solid was washed with PE and further recristallized from CH2Cl2/PE to give the title compound as light orange-red solid (7.8 g, 28.1 mmol, 72%).1H-NMR (300 MHz,CDCl3) [ppm]: 10.08 (s, 2H), 7.36 (s, 2H), 3.80-3.62 (m, 2H), 1.29(d, J = 6.7 Hz, 12H). The analytical data are in accordance with theliterature. |
65.7% | With N-Bromosuccinimide; In acetonitrile; at 20℃; | Into a 500-mL round-bottom flask, was placed 2,6-bis(propan-2-yl)aniline (10 g, 56.4 mmol) in ACN (200 mL), to the stirred solution was added NBS (11.0 g, 62.0 mmol). The resulting solution was stirred overnight at RT. The resulting mixture was concentrated undervacuum. The residue was eluted from silica gel with petroleum ether. This resulted in 9.5 g (65.7%) of the title compound as brown oil. MS-ESI: 256/258 [M+1]. |
48.8 g (42%) | With potassium hydroxide; bromine; In water; acetic acid; | 4-Bromo-2,6-diisopropylaniline To a solution of 80.0 g (0.452 mol) of 2,6-diisopropylaniline in 2000 cm3 of glacial acetic acid, 23.3 ml (72.3 g, 0.452 mol) of bromine were added dropwise, while vigorously stirring, over 20 minutes. This mixture was stirred additionally for 2 hours at 40 C. The white precipitate that formed was filtered off, washed with 100 ml of acetic acid, and dried in air. The resulting white solid was added to a solution of 150 g of potassium hydroxide in 600 ml of water. This mixture was stirred for 30 minutes. The product was extracted with 3*100 ml of methyl-tert-butyl ether. The combined organic fractions were washed with Na2SO4 and evaporated to dryness. Fractional distillation gave a yellowish oil, b.p. 112-115 C./1 mm Hg. Yield 48.8 g (42%). Anal. calc. for Cl2H18BrN: C, 56.26; H, 7.08. Found: C, 56.11; H, 7.13. 1H NMR (CDCl3): delta 7.10 (s, 2H, 3,5-H), 3.69 (br.s, 2H, NH2), 2.86 (sept, J=6.8 Hz, 2H, CHMe2), 1.23 (d, J=6.8 Hz, 12H, CHMe2). 13C{1H}NMR (CDCl3): delta 139.3, 134.5, 125.6, 111.0, 27.9, 22.1. |
Reference Example 4 4-bromo-2,6-diisopropyl-N,N-dimethylaniline To a solution of 2,6-diisopropylaniline (25 g, 0.141 moL) in toluene (25 mL) was added dimethyl sulfoxide (12.1 g, 1.1 equivalents), and the mixture was heated to 90C. 48% Aqueous hydrobromic acid solution (26.1 g, 1.1 equivalents) was added dropwise to the mixture at the same temperature over 30 min. Then, the mixture was stirred at 86C for 3 hr and at 100C for 2 hr. Water (20 mL) was added to the mixture at 0C, and 1M aqueous sodium hydroxide solution (30 mL) was added dropwise to the mixture. The mixture was partitioned, and the organic layer was washed with 1M aqueous sodium hydroxide solution (50 mL). The organic layer was dried over anhydrous magnesium sulfate and filtered naturally, and the filtrate was concentrated under reduced pressure. The residue was distilled under reduced pressure to give 4-bromo-2,6-diisopropylaniline (29.4 g, pale-yellow liquid). | ||
540 g | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0 - 20℃; for 18h; | Apparatus set-up:A 10 L 3-necked round-bottomed flask, equipped with a mechanical overhead stirrer, nitrogen inlet and exhaust.Experimental Procedure:1. 2, 6-Diisopropyl aniline (500 g, 2.8202 mol) was dissolved in dry N, N-dimethyl formamide.It was cooled to 0 C using an ice bath.2. N-Bromosuccinimide (501.9 g, 2.8202 mol) was added slowly portion wise.3. The reaction mixture was stirred at the room temperature for 18 h.4. After 18 h, TLC showed complete conversion of starting material.5. To the mixture, 10% NaHCO3 solution (4 L) was added and extracted with ethyl acetate (3 x2L).6. The combined organic phase was washed with water (1 L), brine (1 L), dried over sodium sulphate and concentrated.7. The crude product was purified by silica column chromatography using 8 % ethyl acetate in hexane as an eluent to get 540 g with 95.75 % HPLC purity. 1H-NMR (300 MHz, CDCl3): delta[ppm] 1.26 (d, J = 6.78 Hz, 12H), 2.84 - 2.93 (m, 2H), 3.72 (br, s, 2H), 7.12 (s, 2H). |
With bromine; In methanol; at 20℃; | 49 ml (152 g, 954 mmol) ofbromine was slowly (for 2 h) added to a stirred solutionof 169.7 g (957 mmol) of2,6-diisopropylaniline in 1500 ml of methanol. Theresulting dark-red solution was stirred overnight at room temperature, then most ofmethanol was removed under reduced pressure, and 1000 ml of dichloromethane was added to the residue. This solution was shaken with a cold solution of 140 g (2.5mol) of potassium hydroxide in 1100 ml of water. The organic layer was separated,and the aqueous one was extracted with 200 ml of dichloromethane. The combinedorganic extract was dried over K2C03, passed through a short layer of silica gel 60( 40-63 )liD), and evaporated in vacuum to give crude 4-bromo-2,6-diisopropylaniline (purity ca. 90%) as dark-red oil which was further used without an additionalpurification.1H NMR (CDCh): b 7.15 (s, 2H), 3.82 (br.s, 2H), 2.90 (sept, J = 6.9 Hz, 2H), 1.28(d, J = 6.9 Hz, 12H). 13CeH} NMR (CDCh,): b 139.15, 134.55, 125.65, 111.08,27.92, 22.16. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | Dry nitrogen gas was bubbled into a mixture of <strong>[80058-84-0]4-bromo-2,6-diisopropylaniline</strong> (35.1 g, 137 mmol), potassium phosphate tribasic monohydrate (126 g, 548 mmol) and 2-dicyclo-hexylphosphino-2',6'-dimethoxybiphenyl [S-Phos] (2.250 g, 5.48 mmol) in toluene:water (10: 1, 1400 mL) at room temperature for a period of 40 minutes. Pd2(dba)3 (1.255 g, 1.370 mmol) was then added to the mixture above. The reaction was refluxed under a nitrogen atmosphere and monitored by GC-MS. The reaction was complete after overnight refluxing. The reaction mixture was cooled down and the organic layer was separated, washed with water (3X) and filtered through a bed of Celite.(R).. Toluene was removed in vacuum to give a crude oil which was purified by silica gel column chromatography using hexane/AcOEt: 9/1 to 85/15 as eluants. Pure fractions were distilled to afford the title compound as an oil (17.43 g, 50percent yield). | |
163 g | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 110℃; for 36h; | Apparatus set-up:A 5 L 3-necked round-bottomed flask, equipped with a mechanical overhead stirrer, nitrogen inlet and exhaust.Experimental Procedure:1. Intermediate 7 (250 g, 0.9758 mol), phenyl boronic acid (178.4 g, 1.4637 mol), potassium phosphate (827.9 g, 3.903 mol) were taken in toluene (2.5 L).2. The mixture was degassed for 30 mm.3. Pd(dba) (26.38 g, 0.0292 mol) and 5-Phos (12 g, 0.0292 mol) were added to the reaction mixture and heated to 110 °C for 36 h.4. After 36 h, TLC monitoring showed complete conversion of starting material.5. The reaction mixture was filtered through celite and the organic phase was washed with water (1 L), brine (1 L), dried over sodium sulphate and concentrated.6. The crude product (310 g) was purified thrice by flash column chromatography using7 to 10 percent ethyl acetate in hexane as an eluent to get 163 g of intermediate-8. 1H-NMR (300 MHz, CDCl3): delta [ppm] 1.34 (d, J = 6.81 Hz, 12H), 3.03 (m, 2H), 7.23-7.32 (m, 3H), 7.40 ? 7.45 (m, 2H), 7.58-7.6 1 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.53% | With propionic acid; for 17h;Heating / reflux; | 5. N,N'-Bis(4-bromo-2,6-diisopropylphenyl)-1,6,7,12-tetrachloro-3,4,9,10-tetracarboxylic acid diimide 10 g (0.019 mol) of 1,6,7,12-tetrachloroperylene-3,4,9,10-tetracarboxylic dianhydride, 24.16 g (0.094 mol) of <strong>[80058-84-0]4-bromo-2,6-diisopropylaniline</strong> and 250 ml of propionic acid are refluxed for 17 hours under argon in a 500 ml one-necked flask and cooled to room temperature, and the solid formed is subsequently filtered off via a D3 glass frit. The residue is washed in portions with 1 1 of water/methanol (1:3) and dried overnight at 75° C. in a vacuum drying oven. Yield: 15.4 g (80.53percent) of orange-red solid Melting point: >300° C. 1H-NMR spectrum (250 MHz, C2D2Cl4, 25° C.): delta (ppm)=8.68 (s, 4H, H-1), 7.28 (s, 4H, H-2), 2.61 (h, 3J=6.4 Hz, 4H, H-3), 1.18 (d, 3J=4.6 Hz, 24 H, H-4) 13C-NMR spectrum (spin echo experiment, 62.5 MHz, THF-d8, 25° C.): delta (ppm)=162.89 (C=O), 149.59 (arom. q), 136.17 (arom q), 133.80 (arom. CH), 132.72 (arom. q), 130.80 (arom. q), 129.60 (arom. q), 128.27 (arom. CH), 125.34 (arom. q), 124.63 (arom. q), 110.21 (arom. q), 30.09 (CHisopropyl) 24.03 (CH3 isopropyl) FD mass spectrum: m/e (u e0-1)=1001.4 (100percent, M+) (calc.: 1001.98) UV spectrum (CHCl3): lambdamax (epsilon)=427 (11078), 488 (33922), 522 nm (49517 1 mol-1 cm-1) IR spectrum: nu=1704 (nuC=O), 1663 (nuC=O), 1585, 1401, 1356, 1301, 1201, 852 cm-1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | To a mixture of 4-bromo-2,6-bis(propan-2-yl)aniline (20.5 g, 80.02 mmol, 1.00 equiv) in 2N hydrochloric acid (210 mL) at -5° C. was added NaNO2 (13.8 g, 200.00 mmol, 2.50 equiv) in portions. The reaction was allowed stir at -5° C. for 10 min. Hypophosphorous acid (90 mL) was then added at -5° C. The reaction was warmed to room temperature and then stirred for 12 h. The resulting solution was extracted with 300 mL of ethyl acetate. The organic layer was concentrated under vacuum. The residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether (1:100) to give 12 g (62percent) of 1-bromo-3,5-bis(propan-2-yl)benzene as a light brown oil. 1H NMR (300 MHz, CDCl3): delta 7.18 (s, 2H), 6.98 (s, 1H), 2.89-2.80 (m, 2H), 1.23 (d, J=6.9 Hz, 12H) ppm. | |
52% | 138 ml (2.59 mol) of96percent sulfuric acid was added dropwise to a solution of <strong>[80058-84-0]4-bromo-2,6-diisopropylaniline</strong> (as prepared above, purity ca. 90percent) in 2000 ml of95percent ethanol cooled to -1 ooc at such a rate to keep the reaction temperature below 7°C. After the addition was complete, the formed solution was stirred at roomtemperature for 1 h. Then, the reaction mixture was cooled in an ice-bath, and asolution of 103.1 g (1.49 mol) of sodium nitrite in 215 ml of water was addeddropwise over ca. 1 h. The formed solution was stirred at the same temperature for30 min. Further on, the cooling bath was removed, and 18 g of copper powder was added. Upon completion of the rapid evolution of nitrogen additional portions (ca. 5g each, ca. 70 gin total) of copper powder were added with 10 min intervals untilgas evolution ceased completely. The reaction mixture was stirred at roomtemperature overnight, then filtered through glass frit (G3), diluted with two-foldvolume of water, and crude product was extracted with 4 x 200 ml of dichloromethane. The combined extract was dried over K2C03, evaporated todryness, and then distilled in vacuum (b.p. up to 120°C/5 mm Hg) to give ayellowish liquid. This product was additionally purified by flash-chromatography onsilica gel 60 ( 40-63 )lm; eluent: hexane) and distilled once again (b.p. 85-99°C/5mm Hg) to give 120.0 g (52percent) of 1-bromo-3,5-diisopropylbenzene as a colorless liquid.1H NMR (CDCh): b 7.19 (d, J = 1.2 Hz, 2H), 6.99 (br.t, 1H), 2.86 (sept, J = 6.9 Hz,2H), 1.24 (d, J= 6.9 Hz, 12H). 13CeH} NMR (CDCh): b 151.04, 126.85, 123.70,122.34, 34.06, 23.87 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; In water; for 0.5h; | 2000 cm3 of glacial acetic acid, 23.3 ml (72.3 g, 0.452 mol) of bromine were added dropwise, while vigorously stirring, over 20 minutes. This mixture was stirred additionally for 2 hours at 4O0C. The white precipitate that formed was filtered off, washed with 100 ml of acetic acid, and dried in air. The resulting white solid was added to a solution of 150 g of potassium hydroxide in 600 ml of water. This mixture was stirred for 30 minutes. The product was extracted with 3 x 100 ml of methyl-tert-butyl ether. The combined organic fractions were washed with Na2SO4 and evaporated to dryness. Fractional distillation gave a yellowish oil, b.p. 112-115°C/1 mm Hg. Yield 48.8 g (42percent).Anal. calc. for C12H18BrN: C, 56.26; H, 7.08. Found: C, 56.11; H, 7.13.1H NMR (CDCl3): delta 7.10 (s, 2H, 3,5-H), 3.69 (br.s, 2H, NH2), 2.86 (sept, J= 6.8 Hz, 2H, CHMe2), 1.23 (d, J= 6.8 Hz, 12H, CHMe2).13C(1HI NMR (CDCl3): delta 139.3, 134.5, 125.6, 111.0, 27.9, 22.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With 1H-imidazole; zinc diacetate; In water; at 190℃; for 18h; | Following the procedure described by Langhals et [AL.,] (Feiler, L. et [AL.,] Liebigs Ann. 1995,1229-1244), samples of 3, 4,9, 10-perylenetetracarboxylic dianhydride (4.50 g, 11.5 mmol), <strong>[80058-84-0]2,6-diisopropyl-4-bromoaniline</strong> (1.61 g, 6.28 mmol), Zn (OAc) [2APOS;2H20] (1.64 g, 7.47 mmol), imidazole (23 g), and distilled water (9.8 mL) were placed into a heavy-walled reaction vessel. The vessel was sealed tightly with a Teflon screw cap and the flask was placed into a [190 °C] oil bath and stirred for 18 h. After cooling, the crude material was passed through a plug of alumina column using chloroform. The filtrate was washed with water, dried, and concentrated. Column chromatography (silica, CHC13, 8 x 30 cm) afforded a red solid (1.63 g, 46percent): mp [GT;300 °C ; LH] NMR 8 1.17 (d, [J=] 6.9 Hz, 12H), 2.73 (m, 2H), 7.45 (s, 2H), 7.67 (t, [J=] 7.8 Hz, 2H), 7.94 (d, J= 8.1 Hz, 2H), 8.49 (m, 4H), 8.66 (d, J= [8.] 1Hz, 2H); FAB-MS obsd 559.1133, calcd, 559.1147 [(C34H26BRNO2)] ; [? LAB,] 356,482, 509 nm ; rem (ex = 509 nm) 539,577 [NM.] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94 - 99% | With potassium carbonate;1-methyl-1H-imidazole; copper(l) chloride; In o-xylene; at 120 - 140℃; for 30h;Heating / reflux;Product distribution / selectivity; | To 32.4 g (0.234 mol) K2CO3, 0.58 g (5.8 mmol) CuCl, 13.2 g (0.14 mol) phenol, and 30 g (0.117 mol) 4-bromo-2,6-di-iso-propylaniline 2 in a 250 mL three-necked bulb with argon inlet, reflux condenser and stopper 4.7 mL (58 mmol) 1-methylimidazole and 100 mL o-xylene were added under argon atmosphere. The mixture was stirred and heated to 140° C., until thin layer chromatography (eluent toluene) showed no residual starting material 4-bromo-2,6-di-iso-propylaniline (ca. 30 h). After cooling, water and diethyl ether were added, the organic phase was washed with 10percent K2CO3 solution, water and brine and dried over Na2SO4. After evaporation of the solvents, an aliquot part of the dark oily material was filtered through a short silica gel plug with toluene as solvent to give, after removal of the solvent and drying in vacuum, a dark solid. The purity is determined to 95percent by gc, The calculated yield is 99percentMS (m/z, (intensity)): 269 (100), 254 (97), 146 (10), 134 (7), 77 (10).1H (CDCl3. 400 MHz, 300K): 7.27 (m, 2H); 6.99 (m, 1H); 6.92 (m, 2H); 6.77 (s, 2H); 3.62 (bs, 2H, NH2); 2.94 (hept., 2H, CH(CH3)2); 1.24 (d, 12H, CH(CH3)2). 13C (CDCl3. 100 MHz, 300K): 159.21; 148.30; 136.57; 134.32; 129.45; 121.61; 116.75; 115.08; 28.14; 22.39. |
With potassium hydroxide; potassium carbonate; In basic copper carbonate powder; N,N-dimethyl-formamide; toluene; | With stirring, 21 g (0.15 mol) of potassium carbonate are initially added to 141 g (1.5 mol) of phenol in 500 g of toluene, followed by the addition of 168 g (1.5 mol) of a 50percent aqueous solution of potassium hydroxide. The entire water of reaction is then separated under reflux, and then ca. 400 g of toluene are removed by distillation. The residue is dissolved in 700 g of dimethyl formamide. After addition of 6 g (0.05 mol) of copper carbonate, solvent is distilled off until the temperature of the reaction mixture is 140° C. Then 256 g (1 mol) of <strong>[80058-84-0]4-bromo-2,6-diisopropylaniline</strong> are added at 140° C. and the mixture is kept for 10 hours at 140° C. The dimethyl formamide is then removed by vacuum distillation, the residue is extracted with water, and the product is taken up in toluene. After stripping off the toluene, the crude product is purified by vacuum distillation, giving 215 g (80percent of theory) of 4-phenoxy-2,6-diisopropylaniline with a boiling point of 142°-145° C./0.04 mbar and a melting point of 69°-71° C., in the form of a bright red product. | |
With potassium hydroxide;copper chloride; In 5,5-dimethyl-1,3-cyclohexadiene; | (a) Production of 2,6-diisopropyl-4-phenoxyaniline 48.9 g of phenol are dissolved in 500 ml of xylene, and to this solution are added 30.2 g of pulverised potassium hydroxide in an atmosphere of nitrogen. The reaction mixture is stirred and heated to boiling point, while continuously distilling off the water that is formed. After addition of 0.6 g of copper chloride and 100 g of <strong>[80058-84-0]2,6-diisopropyl-4-bromoaniline</strong>, the mixture is stirred for 8 hours at 150°-155° C., then cooled, and filtered with suction. The filtrate is washed with 15percent sodium hydroxide solution (150 ml) and with two 150 ml portions of water. The organic phase is separated and dried over sodium sulfate. The solvent is removed by distillation and the product is distilled, affording the compound of the formula STR5 with a boiling point of 103°-104° C./0.01 torr and a melting point of 71°-72° C. (after recrystallisation from hexane). The following anilines are also obtained in analogous manner: STR6 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The following compounds of the invention are also of value:2,4,6-triiodoaniline;4-bromo-2,6-diisopropylaniline,2,3,6-tribromoaniline. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.2% | With sodium hydroxide; sodium formate; cetyltrimethylammonim bromide;5% palladium over charcoal; In water; for 4h;Heating / reflux; | A mixture containing <strong>[80058-84-0]4-bromo-2,6-diisopropylaniline</strong> (12.80 g, 50 mmol), CTAB (2.00 g, 5.5 mmol, 0.11 eq. ), 5percent palladium on charcoal (0.80 g, 50percent paste), sodium hydroxide (21.1 ml, 8.0M, 0.169 mol) and sodium formate (3.40 g, 50 mmol, 1 eq.) was mixed in water (30 ml) and heated to reflux for 4 hours. A further quantity of sodium formate (3.40 g, 50 mmol, 1 eq. ) was then added to the boiling solution and the reaction mixture stirred vigorously under reflux for a further 20 hours. The reaction mixture was cooled to room temperature, the solid filtered off and the residue washed with copious amounts of chloroform. The organic phase was separated from the aqueous layer and dried over magnesium sulfate. The organic phase was rapidly filtered through silica and the silica washed several times with chloroform. The filtrate was concentrated, distilled under reduced pressure at 150 °C (0.1 mmHg) to remove the remaining 2,6-disopropylaniline to give lb as a dark reddish solid (0.52 g, 5.2percent). Recystallisation of 16 was achieved from hexane. Compound 1b: ES mass spectrum, m/z 353 [M+H]+; IR (cm-1), 3401,3368 (N-H) ; 1H NMR (CDCl3), delta 1.25 (d, 24 H, 3J(HH) 7.2, CH(CH3)2, 2.92 (sept, 4H, CH(CH3)2), 3.70 (br, 4H, NH2), 7.11 (s, 4H, Ar-H) ; 13C NMR (CDC13, 1H gated decoupled), delta 21.5 (s, CH3), 27.1 (s, CH), 120.7 (s, Ar), 131.6 (s, Ar), 132.1 (s, Ar), 137.8 (s, Ar). Anal. (C25H38N2) calcd: C, 81.97; H, 10.38; N, 7.65. Found: C, 82.18; H, 10.09; N, 7.79percent. In addition, a single crystal X-ray diffraction study of 1b has confirmed the structural type. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With formic acid; In methanol; for 48h; | 4-bromo-2,6-diisopropyl aniline (7.2g, 28 mmol) and glyoxal (40percent solution, 1.58 ml (14 mmol)) were dissolved in methanol (30 ml), and formic acid (1 ml) was added thereto. The reaction mixture was stirred for 48 hours. The resultant solution was filtered and dried in vacuum to give a compound 3 as a yellow crystal (5.2g, yield: 70percent).1H NMR (CDCI3): 8.07 (s, 2 H), 7.32 (s, 4 H)1 2.87 (m, 4 H), 1.18 (d, 12 H, 6.9Hz), SUP>13C NMR(CDCI3) : 163.68, 147.26, 139.50, 126.90, 119.24, 90.57, 28.59, 23.63HRMS m/z calcd : 532.1088, obsd : 532.1089 |
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