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CAS No. : | 92-82-0 | MDL No. : | MFCD00005023 |
Formula : | C12H8N2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PCNDJXKNXGMECE-UHFFFAOYSA-N |
M.W : | 180.21 | Pubchem ID : | 4757 |
Synonyms : |
|
Num. heavy atoms : | 14 |
Num. arom. heavy atoms : | 14 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 57.04 |
TPSA : | 25.78 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -5.38 cm/s |
Log Po/w (iLOGP) : | 2.19 |
Log Po/w (XLOGP3) : | 2.84 |
Log Po/w (WLOGP) : | 2.78 |
Log Po/w (MLOGP) : | 2.4 |
Log Po/w (SILICOS-IT) : | 2.99 |
Consensus Log Po/w : | 2.64 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.49 |
Solubility : | 0.0588 mg/ml ; 0.000326 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.04 |
Solubility : | 0.164 mg/ml ; 0.000913 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -5.0 |
Solubility : | 0.00179 mg/ml ; 0.00000995 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.43 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
98% | With sodium dihydrosulfite; lithium hydroxide monohydrate In ethanol for 2.5h; Ambient temperature; | |
98% | With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate at 20℃; for 4h; Inert atmosphere; | Intermediate 1-1. Preparation of 5,10-dihydrophenazine Under a nitrogen atmosphere 14g (77.7 mmol) of phenazine and it was dissolved in 400ml of ethanol. added 28.0g (136.6 mmol) of sodiumdithionite (Na2S204) and it was dissolved in 400ml water for 1 h and the mixture was stirred in at a room temperature for 3hours. After the reaction was completed, the generated deposit was filtered and water was removed to the phosphorus pentoxide (P4O10) it was dried in a vacuum and the compound (13.9g) was obtained by yield 98%. |
97.5% | With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate at 85℃; for 0.5h; Inert atmosphere; | 1.2 (2) Phenazine (36.04 g, 200 mmol) was dissolved in 200 mL of ethanol and added to a 1000 mL reactor.The mixture was purged with nitrogen, heated to 85 ° C, and sodium dithionite (174.10 g, 1000 mmol) was dissolved in 400 mL of pure water and slowly added dropwise to the reactor using a dropping funnel.After the addition was completed, stir for 30 min and cool to room temperature.The precipitated solid is washed with water, filtered, and dried.50.37 g of intermediate b 5,10-dihydrophenazine can be obtained in a yield of 97.5%; |
96% | With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate at 20℃; for 18h; Heating; Schlenk technique; | |
96% | With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate for 3h; | |
95% | With sodium dihydrosulfite In ethanol at 20℃; Inert atmosphere; | 1.1 Synthesis of 5,10-Dihydrophenazine Under a protection of N 2, a phenazine (0.5 6 g, 3.108 mmol) was added to a 2 0 0 m 1 three-necked flask equipped with an electromagnetic stirrer,Dissolved in 20 ml of boiling ethanol, 1 h of sodium dithionite (2.24g, 10.92mmol) in 80ml of aqueous solution was added to the above solution of phenazine in ethanol solution, the drop was completed at room temperature stirring reaction 2.5 ~ 5h, the end of the reaction The reaction mixture was filtered and the filter cake was washed with water and dried to give 0.54 g of 5,10-dihydrophenazine. The yield was 95%. |
94% | With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate for 0.166667h; Reflux; | |
93.6% | With sodium hydrosulfite In ethanol; lithium hydroxide monohydrate at 80℃; for 1h; Inert atmosphere; | |
92% | With sodium dihydrosulfite In ethanol for 4h; Reflux; | 1 5,10-dihydrophenazine Phenazine 20 g (110 mmol)It is suspended in 600 ml of ethanol under protective gas. The reaction mixture is heated to reflux.600 ml of degassed waterSodium dithionite dissolved in38.3 g (220 mmol) is subsequently added dropwise, and the mixture is heated under reflux for a further 4 hours.After cooling, the precipitated yellow solid is filtered off under protective gas and vacuum dried.The purity is 92.0%. Yield: 19 g(107 mmol) 96% of theory. |
91% | With hydrogen In lithium hydroxide monohydrate at 20℃; for 24h; regioselective reaction; | |
88% | With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate for 4h; Inert atmosphere; Reflux; | |
88% | With sodium dihydrosulfite; lithium hydroxide monohydrate In ethanol for 4h; Inert atmosphere; Reflux; | 1 9, 10-Dihydrophenazine Ethanol and DI water were degassed by sparging with nitrogen for 30 min. 400 mL of water and 100 mL of ethanol were added to a 1 L round bottom. Phenazine (4.00 g, 22.2 mmol, 1 equiv) and sodium dithionite (46.6 g, 268 mmol, 12 equiv) were added and the solution was magnetically stirred. The reaction was heated to reflux and allowed to proceed for 4 hrs. Reaction is complete when no solid blue particulate remains. The reaction was allowed to cool, filtered quickly, washed with deoxygenated water, yielding (3.57 g, 88 % yield) light green powder. Product was dried and stored under vacuum until use. |
85% | With Na2S2O3 In ethanol; lithium hydroxide monohydrate at 80℃; for 1h; | |
83% | With 3-Benzylthiazolium bromide; benzaldehyde; triethylamine In methanol for 20h; Ambient temperature; | |
82% | With sodium hydrogen sulphate In ethanol; lithium hydroxide monohydrate Reflux; | 31 Synthesis of TZ16-91 Approximately 180 mg (1.0 mmol) of phenazine was placed in a 100 mL round bottom flask and 5.0 mL of ethanol was added and the solution was heated to boiling. Sodium hydrosulfate (1.7 g, 10.0 mmol) in 20 mL water was added to the above boiling solution. The solid formation was observed immediately. The solid formed was collected by filtration and dried under vacuum to give 151 mg (0.82 mmol, 82%) of TZ16-91 as white solid. 1HNMR (CDCl3): δ 8.30-8.24 (m, 4H), 7.90-7.80 (m, 4H). |
67% | With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate for 3h; Reflux; Inert atmosphere; | e 5,10-dihydrophenazine A 500 mL round bottom flask was charged with a mixture of H2O (200 mL), EtOH (50 mL), and a stir bar. The mixture was sparged with nitrogen for 30 minutes and then phenazine (2.00 g, 27.8 mmol, 1.00 eq.) and Na2S2O4 (23.3 g, 278 mmol, 10.0 eq.) were then added. This mixture was subsequently heated at reflux under nitrogen atmosphere for 3 h. After cooling to RT, the product was isolated as a precipitate via cannula filtration, washed with excess deoxygenated H2O, and dried under reduced pressure to yield a light green powder (1.35 g, 7.42 mmol, 67%). The product was stored under nitrogen until further use. |
41% | With [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-κN1,κN1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC]iridium hexafluorophosphate; N-methylamine hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25℃; Irradiation; | |
With hydrogen sulfide; ammonia | ||
With sodium hydroxide; sodium dihydrosulfite | ||
With pyridine; platinum Hydrogenation; | ||
With ethanol; palladium(0) Hydrogenation; | ||
With lithium aluminium hydride; diethyl ether | ||
With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate Heating; | ||
at 30℃; for 120h; microbial reduction by Pseudomonas cepacia IFO 15124 in growing culture at low oxygen tensions; pH 6.1-7.1; Yield given; | ||
With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate for 3h; Reflux; | ||
With sodium dihydrosulfite In ethanol | 1 5,10-Dihydrophenazine Example 1 5,10-Dihydrophenazine 20 g (110 mmol) of phenazine are suspended in 600 ml of ethanol under protective gas. The reaction mixture is heated under reflux. 38.3 g (220 mmol) of sodium dithionite dissolved in 600 ml of degassed water are subsequently added dropwise, and the mixture is heated under reflux for a further 4 h. After cooling, the precipitated yellow solid is filtered off under protective gas and dried in vacuo. The purity is 92.0%. Yield: 19 g (107 mmol) 96% of theory. | |
> 99 %Spectr. | With hydrogen In dichloromethane at 20℃; for 12h; | |
With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate Reflux; | ||
1.62 g | With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate for 2h; Reflux; | |
With sodium dihydrosulfite; lithium hydroxide monohydrate In ethanol at 95℃; for 3h; Inert atmosphere; | 1.1 Example 1 Step 1. Add 2.7 g of phenazine to the reaction flask, and add another reaction flask to add 26.1 g.Sodium dithionite was vacuumed and drummed three times, respectively.73mL of ethanol was injected into the phenazine system under nitrogen protection.100 mL of distillation was injected into the sodium dithionite system.After fully dissolving, the aqueous solution of sodium dithionite is injected into the phenazine alcohol solution.Shading treatment, heating to 95 ° C under nitrogen protection, condensation and reflux for 3 h.After the reaction is completed, it is cooled to room temperature, and the floc is filtered off with suction and washed with distilled water.Drying gave the 5,10-dihydrophenazine intermediate without further purification. | |
2.7 g | With sodium metabisulfate In ethanol; lithium hydroxide monohydrate Reflux; | Synthesis of 5,10-dihydrophenazine (1) The 5,10-dihydrophenazine (1) was prepared following reported procedures.57Phenazine (3 g, 16.6 mmol) was dissolved in ethanol (75 mL), and the solution washeated to boiling. An aqueous solution (300 mL) containing Na2S2O4 (30 g, 0.17mol) was added to the boiling solution. The solution turned purple immediately aftermixing; then, a greenish white precipitate formed. The precipitated solid wascollected by filtration, washed with water, and dried in vacuo to afford 2.7 g of agreenish white solid. Because of its instability in air, the solid was stored under nitrogenwithout further purification and characterized. |
With cobalt phosphide; hydrogen In [D3]acetonitrile at 20℃; for 24h; | ||
With anhydrous sodium sulphite In ethanol; lithium hydroxide monohydrate at 80 - 100℃; for 3h; Inert atmosphere; | Preparation of TPBP: Phenazine (170 mg, 0.944 mmol) was dissolvedin 5 mL ethanol in a three-neck flask and heated to 80 Cunder N2 atmosphere. Then, a solution of sodium dithionite(1.6 g, 9.190 mmol) in 40 mL water was added and a pale greenprecipitate appeared. After stirred at 100 C for 3 h under nitrogenprotection, the mixture was isolated via vacuum filtration andacquired 5,10-dihydrophenazine as a pale green solid. A roundbottomflask was charged with 5, 10-dihydrophenazine, TBT(305 mg, 0.562 mmol), potassium carbonate (1.3 g, 9.406 mmol),and toluene (50 mL). The mixture was heated to 80 C under anatmosphere of nitrogen. After that, palladium(II) acetate(26.3 mg, 0.117 mmol) and tri-tert-butylphosphine (1 mL) wereadded into the reaction mixture, and the solution was stirred at120 C for 48 h. After the mixture was cooled to room temperature,the brown precipitate was then filtered and washed with distilledwater and methanol. The precipitate was further Soxhlet extractionwith boiling methanol, dichloromethane, and acetone toremove unreacted monomers or catalysts. The collected solidwas dried at 80 C under vacuum (Scheme 1). | |
With sodium dihydrosulfite In ethanol | ||
With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate | ||
With C8H18N2O23V6(2-)*2C16H36N(1+) In acetonitrile at 25℃; Inert atmosphere; Schlenk technique; | ||
With sodium dihydrosulfite | 1 Example 1 Example 1 Synthesis of BMEPZ 2 g of phenazine and 20 g of sodium hydrosulfite (Na2S2O4) were dissolved in a mixture of 50 mL of ethanol and 200 mL of distilled water, stirred at 75° C., for 10 minutes, and then purified, and thus 1.8 g of 5,10-dihydrophenazine was obtained. | |
With sodium dihydrosulfite; lithium hydroxide monohydrate In ethanol Inert atmosphere; Reflux; | ||
1.8 g | With sodium dihydrosulfite In ethanol; lithium hydroxide monohydrate at 75℃; for 0.166667h; | 1 Example 1: Synthesis of BMEPZ 2 g of phenazine and 20 g of sodium hydrosulfite (Na2S2O4) were dissolved in a mixture of 50 mL of ethanol and 200 mL of distilled water, stirred at 75° C., for 10 minutes, and then purified, and thus 1.8 g of 5,10-dihydrophenazine was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 41% 2: 28% | With XNO2 | |
30% | With sulfuric acid; nitric acid at 75℃; for 8h; | |
With sulfuric acid; nitric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74.8% | With hydrogenchloride In methanol; chloroform; water | Preparation of the guest PheH+ Phenazine (200 mg, 1.1 mmol) was added into a mixture of CHCl3 (1 mL) and CH3OH (10 mL). The solution was acidified with concentrated hydrochloric acid (36-38%) (2 mL). The solution was evaporated, and then the residue was washed by hexane to produce a yellow solid, which was dried in vacuum, with a yield of 74.8%, 180 mg. |
74.8% | With hydrogenchloride In methanol; chloroform | |
With hydrogenchloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With HOF* CH3CN In chloroform at 0℃; for 0.666667h; | |
86% | With dihydrogen peroxide In acetonitrile at 80℃; for 6h; | |
80% | With phthalic anhydride; urea-hydrogen peroxide In acetonitrile for 24h; Ambient temperature; |
70% | With 3-chloro-benzenecarboperoxoic acid In dichloromethane | |
With dihydrogen peroxide; acetic acid substance of mp: 204 degree; | ||
With Perbenzoic acid; chloroform substance of mp: 191 degree; | ||
With Perbenzoic acid; chloroform substance of mp: 204 degree; | ||
With dihydrogen peroxide; acetic acid substance of mp: 191 degree; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 52% 2: 397 mg | With magnesium monoperoxyphthalate hexahydrate In acetic acid at 85℃; for 1h; | |
With dihydrogen peroxide; acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With oxygen; anhydrous silver carbonate at 100℃; for 0.0833333h; | |
durch Sublimieren; | ||
With ethanol |
With silver(I) nitrate | ||
With oxygen Explosionsgefahr; | ||
With superoxide ion In N,N-dimethyl-formamide at 20℃; | ||
With pyridine; 4-nitro-benzoyl chloride Yield given; | ||
beim Sublimieren; | ||
Multi-step reaction with 2 steps 1: 74 percent / 4-(dimethylamino)pyridine / pyridine / 3 h / Heating | ||
Multi-step reaction with 2 steps 1: 74 percent / 4-(dimethylamino)pyridine / pyridine / 3 h / Heating 2: n-butylamine | ||
With dicyclohexyl({2’,6’-dimethoxy-[1,1‘-biphenyl]-2-yl})phosphane; palladium diacetate; Cs2CO3 In toluene at 110℃; Inert atmosphere; | ||
With air In methanol for 0.166667h; | ||
Stage #1: 9,10-dihydrophenazine With cobalt phosphide In [D3]acetonitrile at 20℃; for 24h; Stage #2: With picoline In [D3]acetonitrile | ||
Multi-step reaction with 2 steps 1: n-butyllithium / tetrahydrofuran; hexane / -80 °C / Inert atmosphere 2: 1,1,2,2,3,3,4,4-octafluoro-1,4-diiodobutane; N,N,N,N,-tetramethylethylenediamine; rose bengal disodium salt / 12 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With Methyl phenyldiazoacetate; copper(II) bis(trifluoromethanesulfonate) In 1,2-dichloro-ethane at 60℃; for 12h; Inert atmosphere; Sealed tube; Molecular sieve; | |
With diammonium sulfide; ethanol Behandeln des Reaktionsprodukts mit wss. HCl und wss. HNO3; | ||
With palladium on activated charcoal; ethanol; hydrazine hydrate |
at 260 - 280℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triphenylphosphine for 0.0583333h; Microwave irradiation; | |
38% | With triphenylphosphine In toluene at 250℃; for 0.166667h; Sealed tube; | |
With potassium hydroxide; aniline; xylene |
With potassium hydroxide; aniline; toluene | ||
With iron(III) chloride | ||
With iron | ||
Multi-step reaction with 2 steps 1: alcohol; tin dichloride; fuming hydrochloric acid 2: sodium acetate / beim Erhitzen bis zum Sieden | ||
Multi-step reaction with 2 steps 1: aqueous acetic acid; iron / Hydrogenation 2: PbO | ||
With iron |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; acetic acid; tin(ll) chloride durch Oxydation, z. B. mit Wasserstoffperoxyd; | ||
Multi-step reaction with 2 steps 1: acetic acid; zinc 2: aqueous HCl; FeCl3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In water at 210℃; for 0.25h; Microwave irradiation; | 4 Example 4: Synthesis of Phenazine and 2,3-Dihvdroxyphenazine 1,2-Dihydoxybenzene (0.3 g, 2.8 mmol) and 1 ,2-phenylenediamine (0.3 g, 2.8 mmol) were heated in a microwave vial to 210 °C for 15 minutes. The melt solidified, was cooled to room temperature and washed several times with water. The insoluble product (0.2 g) contained phenazine and 2,3- dihydroxyphenazine according to HPLC and absorption spectroscopy. Washing the product mixture with 2 M aqueous sodium hydroxide yielded the desired phenazine. |
at 200℃; | ||
at 200 - 210℃; in geschlossenen Rohr; |
With potassium dichromate; acetic acid for 24h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Leiten durch ein gluehendes Rohr; | ||
With lead(II) oxide | ||
With sodium hydroxide; nitrobenzene at 140℃; |
Multi-step reaction with 2 steps 1: nitrobenzene; sodium hydroxide / 120 - 125 °C 2: 260 - 280 °C | ||
Multi-step reaction with 3 steps 1: sodium acetate / 215 °C 2: alcohol; tin dichloride; fuming hydrochloric acid 3: sodium acetate / beim Erhitzen bis zum Sieden | ||
Multi-step reaction with 2 steps 1: oxone||potassium monopersulfate triple salt / dichloromethane; water / 20 °C / Inert atmosphere 2: dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; silver hexafluoroantimonate; zinc trifluoromethanesulfonate; acetic acid / 1,2-dichloro-ethane / 24 h / 140 °C / Inert atmosphere; Schlenk technique; Sealed tube | ||
Multi-step reaction with 2 steps 1: water / 2.5 h / 120 °C / Sealed tube; Microwave irradiation 2: triphenylphosphine / toluene / 0.17 h / 250 °C / Sealed tube | ||
Multi-step reaction with 4 steps 1: copper(I) bromide; pyridine / toluene / 20 h / 60 °C / 760.05 Torr 2: N-Bromosuccinimide; palladium diacetate; toluene-4-sulfonic acid / acetonitrile / 20 h / 20 °C 3: tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; 1,1'-bis-(diphenylphosphino)ferrocene / toluene; water / 20 h / 80 °C 4: trifluoroacetic acid / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With calcium oxide at 600℃; for 0.666667h; | |
With lead(II) oxide bei der Destillation; | ||
With lead(II) oxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With hydrogenchloride In acetic acid at 20℃; for 144h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | In diethyl ether; o-xylene; cyclohexane at 20℃; for 3.5h; | 68 Synthesis Example 68. Synthesis of Compound A 66.3.6 g of 0.02 mol of phenazine, 1.6 g of 0.02 mol of phenyllithium in 10 ml of diethyl ether,In a mixed solution of 10 ml of o-xylene and 5 ml of cyclohexane, T=20 ° C, stirring for 3.5 h, the solution was spun dry, dissolved with ethyl acetate, added to silica gel, dried, and then subjected to column chromatography to give intermediate A66. -1, work-up gave 2.6 g of a white solid, yield 50%. |
In diethyl ether; o-xylene; cyclohexane at 20℃; for 3.5h; | ||
In diethyl ether; o-xylene at 20℃; |
Stage #1: Phenazin; phenyllithium In o-xylene at 20℃; for 2h; Stage #2: With methanol In o-xylene at 0℃; for 1h; | First, 2.01 g of phenazine and 15.4 ml (1.07 M, 1.3 eq) of phenyl lithium were stirred in an o-xylene solvent at room temperature for 2 hours. Then, 5.0 ml of methanol was added and stirred at 0° C. for 1 hour to prepare 10-phenyl-5-hydrophenazine. Into 10-phenyl-5-hydrophenazine, 2.42 g (0.75 eq) of 4-bromoiodobenzene, 2.71 g (1.5 eq) of sodium-tert-butoxide, 0.03 g (0.015 eq) of tri-tert-butylphosphine, and 0.05 g (0.02 eq) of palladium acetate were added, and stirred in a xylene solvent at 120° C. for 1.5 hours to obtain Compound A with the yield of 75%. Into 1.50 g of Compound A, 1.13 g (1.3 eq) of 9,9-dimethyl-N-(4-phenylphenyl)fluorene-2-amine, 0.52 g (1.5 eq) of sodium-tert-butoxide, 0.01 g (0.015 eq) of tri-tert-butylphosphine, and 0.08 g (0.02 eq) of bis(dibenzylideneacetone)palladium were added and stirred in a toluene solvent at 80° C. for 4 hours to obtain Compound 2 with the yield of 71%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 19% 2: 11% 3: 32% 4: 4% | With sodium hydroxide; Aminoiminomethanesulfinic acid at 85 - 90℃; for 1h; | |
1: 19% 2: 32% 3: 4% 4: 11% | With sodium hydroxide; thiourea dioxide at 85 - 90℃; for 1h; | |
1: 11% 2: 32% 3: 4% 4: 19% | With sodium hydroxide; thiourea dioxide In ethanol at 85 - 90℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 7% 2: 8% 3: 57% | at 750℃; for 2h; | |
1: 57% 2: 7% 3: 8% | at 750℃; for 2h; | |
1: 21% 2: 7% 3: 15% | at 750℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 86.9% 2: 8.5% 3: 3.7% 4: 0.7% | In water at 70 - 75℃; for 3.5h; | 18 Example 18 Influence of different molar ratios of organic and inorganic hydroxides to betaine on the condensation of aniline with nitrobenzene and, simultaneously, influence of betaine and tetramethylammonium hydroxide (TMAH) on aniline methylation to N-methylaniline (N-MAn) is obvious from the results in Table 10. Example 18 Influence of different molar ratios of organic and inorganic hydroxides to betaine on the condensation of aniline with nitrobenzene and, simultaneously, influence of betaine and tetramethylammonium hydroxide (TMAH) on aniline methylation to N-methylaniline (N-MAn) is obvious from the results in Table 10. Seven-fold molar excess of aniline was added to a prepared aqueous solution of individual components of the reaction system, consisting of TMAH, betaine and potassium hydroxide. After azeotropic distilling off the water, 0.95 mol of nitrobenzene were added to the reaction mixture at 70° C. and at a pressure of 7.3 kPa during 1.5 h. The reaction was completed after further 2 h. Yield (Table 10) of the components in the reaction product has been calculated in relation to the introduced nitrobenzene. N-methylaniline (N-MAn) was expressed in mole per cent, related to the introduced TMAH. |
1: 65% 2: 13.2% 3: 15.7% 4: 1.3% | at 80℃; for 6h; | 12 Example 12 Influence of a Crown Ether as the Phase Transfer Agent on the Conversion and Yield of the Reaction. Example 12 Influence of a Crown Ether as the Phase Transfer Agent on the Conversion and Yield of the Reaction. Experimental Conditions: Mole ratio of aniline: nitrobenzene: betaine-KOH: 18 dibenzocrown-6-ether=7:1:1.1:0.1; the reaction took place in an inert atmosphere at 80° C. and at a pressure of 7.3 kPa during the overall reaction time of 6 h (Table 6). |
1: 65.8% 2: 7.1% 3: 17.2% 4: 1.3% | In water; isopropyl alcohol at 80℃; for 6h; | 15 Example 15 Influence of Polarity of Auxiliary Solvents, Forming Azeotropic Mixtures with Water, on the Course of the Reaction of Nitrobenzene with Aniline Under Anaerobic Conditions. Example 15 Influence of Polarity of Auxiliary Solvents, Forming Azeotropic Mixtures with Water, on the Course of the Reaction of Nitrobenzene with Aniline Under Anaerobic Conditions. 0.078 mol of nitrobenzene were dosed into a reaction mixture, consisting of 0.09 mol of KOH (84.0% concentration), 0.09 mol of betaine hydrate, 4 ml of water, 0.51 mol of aniline and 15 ml of an auxiliary solvent, at 80° C. during 1.5 h. Completing the reaction required further 4.5 h, while water was continuously removed from the reaction medium as an azeotrope with the auxiliary solvent. In an experiment with 2-propanol, the azeotrope was distilled off through a short column under an atmospheric pressure. In an experiment with pyridine, the azeotrope distilled at a reduced pressure of 13.3 to 9.3 kPa. In an experiment with cyclohexane water was continuously removed as an azeotrope by means of an azeotropic attachment. The results are given in the following Table 7. |
1: 62.2% 2: 21.9% 3: 14% 4: 1.9% | In pyridine; water at 80℃; for 6h; | 15 Example 15 Influence of Polarity of Auxiliary Solvents, Forming Azeotropic Mixtures with Water, on the Course of the Reaction of Nitrobenzene with Aniline Under Anaerobic Conditions. Example 15 Influence of Polarity of Auxiliary Solvents, Forming Azeotropic Mixtures with Water, on the Course of the Reaction of Nitrobenzene with Aniline Under Anaerobic Conditions. 0.078 mol of nitrobenzene were dosed into a reaction mixture, consisting of 0.09 mol of KOH (84.0% concentration), 0.09 mol of betaine hydrate, 4 ml of water, 0.51 mol of aniline and 15 ml of an auxiliary solvent, at 80° C. during 1.5 h. Completing the reaction required further 4.5 h, while water was continuously removed from the reaction medium as an azeotrope with the auxiliary solvent. In an experiment with 2-propanol, the azeotrope was distilled off through a short column under an atmospheric pressure. In an experiment with pyridine, the azeotrope distilled at a reduced pressure of 13.3 to 9.3 kPa. In an experiment with cyclohexane water was continuously removed as an azeotrope by means of an azeotropic attachment. The results are given in the following Table 7. |
1: 56.9% 2: 8.1% 3: 1% 4: 0.13% | In water at 70 - 75℃; for 3.5h; | 18 Example 18 Influence of different molar ratios of organic and inorganic hydroxides to betaine on the condensation of aniline with nitrobenzene and, simultaneously, influence of betaine and tetramethylammonium hydroxide (TMAH) on aniline methylation to N-methylaniline (N-MAn) is obvious from the results in Table 10. Example 18 Influence of different molar ratios of organic and inorganic hydroxides to betaine on the condensation of aniline with nitrobenzene and, simultaneously, influence of betaine and tetramethylammonium hydroxide (TMAH) on aniline methylation to N-methylaniline (N-MAn) is obvious from the results in Table 10. Seven-fold molar excess of aniline was added to a prepared aqueous solution of individual components of the reaction system, consisting of TMAH, betaine and potassium hydroxide. After azeotropic distilling off the water, 0.95 mol of nitrobenzene were added to the reaction mixture at 70° C. and at a pressure of 7.3 kPa during 1.5 h. The reaction was completed after further 2 h. Yield (Table 10) of the components in the reaction product has been calculated in relation to the introduced nitrobenzene. N-methylaniline (N-MAn) was expressed in mole per cent, related to the introduced TMAH. |
1: 53% 2: 24% 3: 11.4% 4: 1% | In cyclohexane; water at 80℃; for 6h; | 15 Example 15 Influence of Polarity of Auxiliary Solvents, Forming Azeotropic Mixtures with Water, on the Course of the Reaction of Nitrobenzene with Aniline Under Anaerobic Conditions. Example 15 Influence of Polarity of Auxiliary Solvents, Forming Azeotropic Mixtures with Water, on the Course of the Reaction of Nitrobenzene with Aniline Under Anaerobic Conditions. 0.078 mol of nitrobenzene were dosed into a reaction mixture, consisting of 0.09 mol of KOH (84.0% concentration), 0.09 mol of betaine hydrate, 4 ml of water, 0.51 mol of aniline and 15 ml of an auxiliary solvent, at 80° C. during 1.5 h. Completing the reaction required further 4.5 h, while water was continuously removed from the reaction medium as an azeotrope with the auxiliary solvent. In an experiment with 2-propanol, the azeotrope was distilled off through a short column under an atmospheric pressure. In an experiment with pyridine, the azeotrope distilled at a reduced pressure of 13.3 to 9.3 kPa. In an experiment with cyclohexane water was continuously removed as an azeotrope by means of an azeotropic attachment. The results are given in the following Table 7. |
1: 46% 2: 8.8% 3: 11.5% 4: 0.7% | In water at 50 - 80℃; for 3.5 - 6h; | 7,17,18 Example 7 Reaction of Aniline with Nitrobenzene Under the Conditions, where Water (reaction water and water, introduced as a solvent) is Continually Removed from the Reaction Medium, Particularly by Distillation in the Form of an Azeotrope Water-aniline, while Vacuum in the System is Gradually Decreased. Example 7 Reaction of Aniline with Nitrobenzene Under the Conditions, where Water (reaction water and water, introduced as a solvent) is Continually Removed from the Reaction Medium, Particularly by Distillation in the Form of an Azeotrope Water-aniline, while Vacuum in the System is Gradually Decreased. 114.0 g (0.131 mol) of 20% solution of an equimolar amount of betaine and potassium hydroxide were introduced into a 500 ml three-neck flask, and after heating up to 50° C. water was distilled off under vacuum, until crystalline slurry remained in the flask. 72.3 g of aniline (0.776 mol) were added, and 13.5 g (0.1097 mol) of nitrobenzene were dosed to the reaction mixture during 1.5 h at 80° C. in nitrogen atmosphere under intensive stirring. In the course of aniline adding a pressure of 26 kPa was maintained in the flask, while an azeotrope water-aniline distilled. During the final stage of the reaction in which the reaction mixture was stirred for further 4.5 h, the pressure in the apparatus was gradually reduced from the starting 26 kPa down to 4 kPa at the end of the reaction. After cooling down the reaction mixture was analyzed. A 100% conversion of nitrobenzene was achieved with the following yields (in %) of individual reaction components (calculated in relation to the introduced nitrobenzene): 4-NODFA 82.1%; 4-NO2DFA 11.7%; azobenzene 11.6%; phenazine 1.4%. Example 17 Effect of Water Content on the Reaction of Aniline with Nitrobenzene. A reaction mixture, consisting of aniline, nitrobenzene, potassium hydroxide, betaine and water with mutual molar ratios, given in Table 9, was let to react under intensive stirring at 80° C. at an atmospheric pressure under nitrogen during 6 h. After cooling down and diluting with methanol the obtained solution was analyzed, and the results were expressed in nitrobenzene conversion and yields, related to the charged nitrobenzene. Water in the reaction mixture is a sum of the reaction water, dissolving water and water, introduced by raw material, and it is expressed in mol per 1 mol of nitrobenzene. Example 18 Influence of different molar ratios of organic and inorganic hydroxides to betaine on the condensation of aniline with nitrobenzene and, simultaneously, influence of betaine and tetramethylammonium hydroxide (TMAH) on aniline methylation to N-methylaniline (N-MAn) is obvious from the results in Table 10. Seven-fold molar excess of aniline was added to a prepared aqueous solution of individual components of the reaction system, consisting of TMAH, betaine and potassium hydroxide. After azeotropic distilling off the water, 0.95 mol of nitrobenzene were added to the reaction mixture at 70° C. and at a pressure of 7.3 kPa during 1.5 h. The reaction was completed after further 2 h. Yield (Table 10) of the components in the reaction product has been calculated in relation to the introduced nitrobenzene. N-methylaniline (N-MAn) was expressed in mole per cent, related to the introduced TMAH. |
1: 39.1% 2: 17.6% 3: 10.8% 4: 9.8% | at 70℃; | 2 Example 2 Results of the Reaction of Aniline with Nitrobenzene, when Using Lithium, sodium, Potassium and Cesium Hydroxide in a Reaction System, Containing Betaine-hydroxide. Example 2 Results of the Reaction of Aniline with Nitrobenzene, when Using Lithium, sodium, Potassium and Cesium Hydroxide in a Reaction System, Containing Betaine-hydroxide. The reaction systems were prepared by the reaction of betaine monohydrate with alkali hydroxides. According to the procedure, described in Example 1, 3 identical reactions were performed at a temperature of 70° C. with various cations of alkali metals, given in Table 2. |
1: 24.7% 2: 31.1% 3: 31.6% 4: 10.9% | at 70℃; | 2 Example 2 Results of the Reaction of Aniline with Nitrobenzene, when Using Lithium, sodium, Potassium and Cesium Hydroxide in a Reaction System, Containing Betaine-hydroxide. Example 2 Results of the Reaction of Aniline with Nitrobenzene, when Using Lithium, sodium, Potassium and Cesium Hydroxide in a Reaction System, Containing Betaine-hydroxide. The reaction systems were prepared by the reaction of betaine monohydrate with alkali hydroxides. According to the procedure, described in Example 1, 3 identical reactions were performed at a temperature of 70° C. with various cations of alkali metals, given in Table 2. |
1: 89 % Chromat. 2: 4 % Chromat. 3: 3.5 % Chromat. 4: 3.5 % Chromat. | With tetramethyl ammoniumhydroxide at 50℃; | |
1: 22.2 - 40.3 %Chromat. 2: 18.7 - 23.1 %Chromat. 3: 7.3 - 44.1 %Chromat. 4: 1.4 - 9.3 %Chromat. | In methanol at 50 - 130℃; for 4.5h; | 1 Example 1 Results of the Reaction of Aniline with Nitrobenzene Under Anaerobic Conditions, when the Reaction System is a Solution of Betaine and Potassium Hydroxide in Methanol at Different Temperatures in the Range of 55 to 130° C. Example 1 Results of the Reaction of Aniline with Nitrobenzene Under Anaerobic Conditions, when the Reaction System is a Solution of Betaine and Potassium Hydroxide in Methanol at Different Temperatures in the Range of 55 to 130° C. For the reaction an apparatus was used which consisted of a 100 ml 3-neck flask with a magnetic stirrer, a thermometer, a dropping funnel and an azeotropic attachment, and was joined with a water-jet pump. 3,5 g (84.02%) of potassium hydroxide (0.052 mol) were dissolved in 6 g of methanol. 6.1 g of betaine (0.052 mol) were added and, after heating up to 50° C., 37.0 g of aniline (0.49 mol) were added. Air in the apparatus was replaced by nitrogen and after heating up to the reaction temperature at first methanol was distilled off at a pressure of 5.2 kPa, and then nitrobenzene, 6.4 g (0.052 mol) on the whole, was dosed under intensive stirring during 1.5 h. The reaction mixture was left to react for further 3 hours, then it was cooled down, diluted by methanol, and analyzed by the method of highly effective liquid chromatography. The yield of reaction components was calculated relative to the amount of nitrobenzene, introduced into the reaction. Further reaction conditions and results achieved are given in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With titanium tetrachloride; tin(ll) chloride In benzene for 0.5h; Ambient temperature; | |
96% | With titanium In tetrahydrofuran for 0.25h; Ambient temperature; | |
91% | With ammonium formate; silica gel; zinc In methanol at 20℃; for 0.333333h; chemoselective reaction; |
90% | With titanium tetrachloride; sodium iodide In acetonitrile at 30℃; for 0.166667h; | |
76% | With sodium hydroxide; thiourea S,S-dioxide In ethanol at 80 - 85℃; for 3h; | |
62% | With ammonium formate; zinc In methanol for 7h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 87.9% 2: 6.9% 3: 6% 4: 1% 5: 1% | In water at 70 - 75℃; for 3.5h; | 18 Example 18 Influence of different molar ratios of organic and inorganic hydroxides to betaine on the condensation of aniline with nitrobenzene and, simultaneously, influence of betaine and tetramethylammonium hydroxide (TMAH) on aniline methylation to N-methylaniline (N-MAn) is obvious from the results in Table 10. Example 18 Influence of different molar ratios of organic and inorganic hydroxides to betaine on the condensation of aniline with nitrobenzene and, simultaneously, influence of betaine and tetramethylammonium hydroxide (TMAH) on aniline methylation to N-methylaniline (N-MAn) is obvious from the results in Table 10. Seven-fold molar excess of aniline was added to a prepared aqueous solution of individual components of the reaction system, consisting of TMAH, betaine and potassium hydroxide. After azeotropic distilling off the water, 0.95 mol of nitrobenzene were added to the reaction mixture at 70° C. and at a pressure of 7.3 kPa during 1.5 h. The reaction was completed after further 2 h. Yield (Table 10) of the components in the reaction product has been calculated in relation to the introduced nitrobenzene. N-methylaniline (N-MAn) was expressed in mole per cent, related to the introduced TMAH. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 36% 2: 9% | With naphthalene; cyclohexa-1,4-diene In tetrahydrofuran at 168℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: Phenazin; dimethyl sulfate In nitrobenzene at 100℃; for 0.116667h; Stage #2: With sodium dithionite In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium hydroxide; potassium permanganate for 2h; Heating; | |
55% | With potassium permanganate In water | |
With potassium permanganate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 30 percent / nitric acid; sulfuric acid / 8 h / 75 °C 2: 68 percent / H2 / Pd/C / trifluoroacetic acid / 2 h | ||
Multi-step reaction with 2 steps 1: H2SO4; HNO3 2: palladium/charcoal; acetone / Hydrogenation | ||
Multi-step reaction with 2 steps 1: H2SO4; HNO3 2: zinc-powder; acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: fuming H2SO4; HNO3 / 0.5 h / Heating 2: 35 percent / Zn; aq. AcOH / 0.08 h / Heating 3: 89 percent / Et3N; DMAP / CHCl3 / 20 °C 4: 99 percent / aq. NaOH / methanol / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: fuming H2SO4; HNO3 / 0.5 h / Heating 2.1: 35 percent / Zn; aq. AcOH / 0.08 h / Heating 3.1: 89 percent / Et3N; DMAP / CHCl3 / 20 °C 4.1: 99 percent / aq. NaOH / methanol / 20 °C 5.1: pyridine / 20 °C 5.2: aq. HCl / CHCl3 / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: fuming H2SO4; HNO3 / 0.5 h / Heating 2: 35 percent / Zn; aq. AcOH / 0.08 h / Heating 3: 89 percent / Et3N; DMAP / CHCl3 / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With palladium on activated carbon; ammonium formate; sodium formate; lithium hydroxide In m-xylene at 170℃; for 66h; Schlenk technique; Inert atmosphere; | |
Multi-step reaction with 2 steps 2: oxygen / Explosionsgefahr | ||
Multi-step reaction with 2 steps 1: 200 - 210 °C / im Rohr 2: ammoniacal silver nitrate solution |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.1% | With hydrogen In methanol; water at 180℃; for 0.116667h; | 19,20 Example 19 Example 19 Reaction mixture, obtained by the procedure of Example 7, was diluted by addition of 30% by weight of methanol, the catalyst Raney Ni was added in an amount of 30% by weight in water (related to the amount of nitrobenzene, charged to the reaction). The reaction took place at 60° C. and at a starting pressure of 5 MPa for 7 minutes. A sample of the reaction mixture, taken away, was analyzed for content of 4-ADFA. The overall yield, related to the starting content of 4-NODFA, 4-NO2DFA and 4-FADFA, was 99.1%. The yield of 4-ADFA, related to the reacted nitrobenzene, was 88.5%.Example 20 Batch Solution of the Reaction with Subsequent Processing of the Condensation Mixture, and Isolation of the 4-ADFA Product. For the reaction of aniline with nitrobenzene by the action of the reaction system of a solution of trimethylammonio-acetate with potassium hydroxide a device was used, consisting of a reactor with a volume of 250 l, provided with a rapid agitator, a tempering jacket which was heated by warm water to regulate the temperature in the reactor, a nitrogen inlet under the surface of the reaction mixture, a condensator for condensation of vapours from the reactor, and a receiver for condensate collection which was used as a phase separator, and it was provided with an overflow for recycling the aniline phase with a content of nitrobenzene back to the reactor, while the separated aqueous phase of the condensate was permanently removed from the phase separator. The reactor was further provided with a thermometer and a pressure regulator. 19.1 l of distilled water, 12.8 kg of solid KOH, containing 86.5% of KOH, were inserted into an auxiliary vessel having the volume of 50 l, and after it had dissolved, 26.6 kg of betaine hydrate were added. After dissolving of all components the reaction system in the form of an aqueous solution was prepared to be used in the reaction. 111.8 kg (1.2 kmol) of aniline were inserted into the reactor, and 58.5 kg of the above given solution were added. The reactor was closed and was purged by nitrogen once, while the mixture was stirred. After termination of the reactor purging by nitrogen an absolute pressure of 20 kPa was set in the reactor, and the reactor content was gradually heated up to a temperature of 80° C. After reaching the temperature 21.1 kg of nitrobenzene (0.17 kmol) were started to be dosed into the reactor at such a rate that all nitrobenzene was fed within 1.5 h. The azeotrope aniline-water which was distilled off the reactor was collected in the receiver, where aqueous and aniline phase were separated. The aniline phase contained a certain amount of nitrobenzene and, therefore, it was periodically recycled to the condensation reactor during the whole experiment. After completing the dosing of nitrobenzene pressure in the reactor was gradually reduced to a value of 14 kPa, and the reaction mixture reacted at this pressure and at a temperature of 80° C. for 1.5 h. Then the pressure was gradually reduced to 8 kPa, and at this pressure the reaction mixture reacted for 1.5 h. Finally, pressure in the reactor was reduced to the value 4 kPa, and the reaction mixture was let to complete the reaction within 1.5 h. Finally it was cooled down to 40° C., approximately 15% of methanol were added, it was discharged from the reactor and weighed. An analysis of the reaction mixture has shown that 100% conversion of nitrobenzene took place with the following yield (in %) of individual reaction components (calculated in relation to the introduced nitrobenzene): 4-NODFA 77.0%; 4-NO2DFA 14.3%; 4-phenylazodiphenylamine 0.21%; azobenzene 9.6%; phenazine 1.3%. Note: Content of N-methylaniline was less than 0.05%, related to the introduced betaine. Reaction mixture from the condensation was diluted by methanol in such a way that its content in the diluted condensation mixture was 30% by weight, and it was hydrogenated under conditions, given |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 73.5% 2: 13.5% 3: 9.6% 4: 1.2% 5: 0.17% | In methanol; water at 40 - 80℃; for 6h; | 20,21 xample 20 Batch Solution of the Reaction with Subsequent Processing of the Condensation Mixture, and Isolation of the 4-ADFA Product. Example 20 Batch Solution of the Reaction with Subsequent Processing of the Condensation Mixture, and Isolation of the 4-ADFA Product. For the reaction of aniline with nitrobenzene by the action of the reaction system of a solution of trimethylammonio-acetate with potassium hydroxide a device was used, consisting of a reactor with a volume of 250 l, provided with a rapid agitator, a tempering jacket which was heated by warm water to regulate the temperature in the reactor, a nitrogen inlet under the surface of the reaction mixture, a condensator for condensation of vapours from the reactor, and a receiver for condensate collection which was used as a phase separator, and it was provided with an overflow for recycling the aniline phase with a content of nitrobenzene back to the reactor, while the separated aqueous phase of the condensate was permanently removed from the phase separator. The reactor was further provided with a thermometer and a pressure regulator. 19.1 l of distilled water, 12.8 kg of solid KOH, containing 86.5% of KOH, were inserted into an auxiliary vessel having the volume of 50 l, and after it had dissolved, 26.6 kg of betaine hydrate were added. After dissolving of all components the reaction system in the form of an aqueous solution was prepared to be used in the reaction. 111.8 kg (1.2 kmol) of aniline were inserted into the reactor, and 58.5 kg of the above given solution were added. The reactor was closed and was purged by nitrogen once, while the mixture was stirred. After termination of the reactor purging by nitrogen an absolute pressure of 20 kPa was set in the reactor, and the reactor content was gradually heated up to a temperature of 80° C. After reaching the temperature 21.1 kg of nitrobenzene (0.17 kmol) were started to be dosed into the reactor at such a rate that all nitrobenzene was fed within 1.5 h. The azeotrope aniline-water which was distilled off the reactor was collected in the receiver, where aqueous and aniline phase were separated. The aniline phase contained a certain amount of nitrobenzene and, therefore, it was periodically recycled to the condensation reactor during the whole experiment. After completing the dosing of nitrobenzene pressure in the reactor was gradually reduced to a value of 14 kPa, and the reaction mixture reacted at this pressure and at a temperature of 80° C. for 1.5 h. Then the pressure was gradually reduced to 8 kPa, and at this pressure the reaction mixture reacted for 1.5 h. Finally, pressure in the reactor was reduced to the value 4 kPa, and the reaction mixture was let to complete the reaction within 1.5 h. Finally it was cooled down to 40° C., approximately 15% of methanol were added, it was discharged from the reactor and weighed. An analysis of the reaction mixture has shown that 100% conversion of nitrobenzene took place with the following yield (in %) of individual reaction components (calculated in relation to the introduced nitrobenzene): 4-NODFA 77.0%; 4-NO2DFA 14.3%; 4-phenylazodiphenylamine 0.21%; azobenzene 9.6%; phenazine 1.3%. Note: Content of N-methylaniline was less than 0.05%, related to the introduced betaine. Reaction mixture from the condensation was diluted by methanol in such a way that its content in the diluted condensation mixture was 30% by weight, and it was hydrogenated under conditions, given in Example 19. A withdrawn sample of the reaction mixture was analyzed for the content of 4-ADFA. The overall yield of 4-ADFA, related to the starting content of 4-NODFA, 4-NO2DFA and 4-FADFA, was 99.2%. The yield of 4-ADFA in the hydrogenate, related to the nitrobenzene reacted, was 89.9%. After completing the hydrogenation the catalyst Raney Ni was filterred off, and it was washed by methanol and distilled water. The washing solutions were added to the hydrogenate. Methanol was distilled off the diluted hydrogenate at an absolute pressure of 35 kPa and at a temperature of 60 to 70° |
1: 58.6% 2: 12.8% 3: 13.2% 4: 0.2% 5: 1.1% | In methanol | 6 Example 6 Effect of the Molar ratio Betaine-potassium Hydroxide to Nitrobenzene on the Course of the Reaction. Example 6 Effect of the Molar ratio Betaine-potassium Hydroxide to Nitrobenzene on the Course of the Reaction. By the procedure, given in Example 1, reactions of aniline with nitrobenzene with the molar ratio of 7:1 were performed with the difference that the molar ratio of the reaction System to nitrobenzene was changing from 1:1 to 1.5:1. The reaction system was formed by betaine hydrate and potassium hydroxide with the molar ratio of 1:1 in a methanol solution. Results of the experiments, given in Table 3, have shown the effect of the increasing amount of the reaction system on the yields of the reaction and conversion of nitrobenzene. |
1: 35.7 %Chromat. 2: 17.8 %Chromat. 3: 10.9 %Chromat. 4: 0.12 %Chromat. 5: 1.25 %Chromat. | In water at 80℃; for 5h; | 4 Example 4 Modified Procedure in which all Reaction Components were Introduced into the Reaction at the Beginning. Example 4 Modified Procedure in which all Reaction Components were Introduced into the Reaction at the Beginning. In a flask, 2.66 g (83.0%) of potassium hydroxide were dissolved in 5.0 ml of water, 5.31 g of betaine hydrate, 24.1 g of aniline and 4.83 g of nitrobenzene were added. The reaction mixture was intensively stirred at 80° C. in nitrogen atmosphere for 5 h. Within this time interval pressure in the apparatus was gradually reduced from 53 kPa down to 2.6 kPa. Finally, the reaction mixture was dissolved in methanol and analyzed by the method of highly effective liquid chromatography. Conversion of nitrobenzene was 75.6%, and the yields (in %) of individual products, calculated relative to the introduced nitrobenzene, were as follows: 4-NODFA 35.7%; 4-NO2DFA 17.8%; 4-FADFA 0.12%; azobenzene 10.9%; phenazine 1.25%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 16.9% 2: 1.2% | In water at 80℃; for 4.75h; | 13 Example 13 A procedure was Tested at Which a Solution of Betaine and Potassium Hydroxide was Dosed into the Reaction Mixture of Reagents Under Aerobic Conditions. Example 13 A procedure was Tested at Which a Solution of Betaine and Potassium Hydroxide was Dosed into the Reaction Mixture of Reagents Under Aerobic Conditions. A solution, consisting of 6.0 g of potassium hydroxide (KOH concentration of 84%), 12.1 g of betaine and 10.5 ml of water, was dosed into a mixture of 9.6 g of nitrobenzene and 48.0 g of aniline under intensive stirring at 80° C. and a pressure of 8 kPa during 2 h. Stirring continued further 2 h and 45 minutes under azeotrope distillation. After cooling down the reaction mixture was dissolved in methanol, and it was analyzed. With 94.7% nitrobenzene conversion following yields (in %), related to nitrobenzene, introduced into the reaction, were achieved: 4-ADFA intermediates 76.6%; azobenzene 16.9%; phenazine 1.2%. Content of M-methylaniline was less than 0.05% (related to the introduced betaine). |
1: 11% 2: 4.2% | In methanol at 75℃; for 5h; | 9 Example 9 Reaction of Aniline with Nitrobenzene in the Presence of the Reaction System Betaine-potassium Hydroxide in Methanol Under Anaerobic Conditions. Example 9 Reaction of Aniline with Nitrobenzene in the Presence of the Reaction System Betaine-potassium Hydroxide in Methanol Under Anaerobic Conditions. 48.2 g of aniline (7-fold molar excess, related to nitrobenzene) were added to a solution of 5.8 g of potassium hydroxide and 11.9 g of betaine hydrate (10% molar excess, related to nitrobenzene), and the reaction mixture was heated up to 75° C., air in the apparatus was replaced by nitrogen, and nitrobenzene was dosed under intensive stirring at a starting pressure of 26 kPa during 2 h. The reaction was continuing for further 3 h, while pressure was gradually reduced down to 6 kPa. The reaction was terminated by cooling down and dissolving the reaction mixture in methanol. 96.7% conversion of nitrobenzene and following yields (in %), related to the introduced nitrobenzene, were achieved: 4-ADFA intermediates 80.5%; azobenzene 11.0%; phenazine 4.2%. |
1: 7.2% 2: 0.5% | In water at 80℃; for 4.5h; | 10 Example 10 Reaction of Aniline with Nitrobenzene in the Presence of a Reaction System of Trimethylammonio-propane Sulfonate and Potassium Hydroxide in an Aqueous Solution. Example 10 Reaction of Aniline with Nitrobenzene in the Presence of a Reaction System of Trimethylammonio-propane Sulfonate and Potassium Hydroxide in an Aqueous Solution. 0.517 mol of aniline were added at 80° C. to a solution of a catalyst, consisting of 0.0858 mol of trimethylammonio-propane sulfonate and 0.0858 mol of potassium Hydroxide in 6.6 ml of water. A part of water was distilled off at a reduced pressure (21 kPa) as azeotrope, then nitrobenzene was dosed into the reaction mixture under intensive stirring at 80° C. and a pressure of 26 kPa during 1.5 h. A viscous mixture arose which was stirred for further 3 hours. Then it was diluted by methanol, and it was analyzed. Nitrobenzene conversion reached 71.1%. The yield of the reaction products, related to nitrobenzene, charged to the reaction, has achieved (in %): 4-ADFA intermediates 28.6%; azobenzene 7.2%; phenazine 0.5%. |
1: 5.5% 2: 1.8% | In methanol at 75 - 80℃; for 4h; Heating / reflux; | 14 Example 14 Reaction of Aniline with Nitrobenzene in the Presence of a Reaction System According to this Invention Under Normal Pressure, without Distilling off the Solvent from the Reaction Mixture Under Anaerobic Conditions. Example 14 Reaction of Aniline with Nitrobenzene in the Presence of a Reaction System According to this Invention Under Normal Pressure, without Distilling off the Solvent from the Reaction Mixture Under Anaerobic Conditions. Nitrobenzene (4.7 g) was dosed into a reaction mixture, consisting of 24.0 g of aniline, 2.68 g of 84% potassium hydroxide, 5.5 g of betaine hydrate and 3 g of methanol, at 75° C. and normal pressure in nitrogen atmosphere during 2 h. Then the reaction mixture was stirred for further 2 hours at 80° C. under reflux. After cooling down and diluting with methanol the mixture was analyzed. Nitrobenzene conversion achieved 75.1%. The yields (in %), related to the introduced nitrobenzene: 4-ADFA intermediates 57.0%; azobenzene 5.5%; phenazine 1.8%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetramethyl ammoniumhydroxide; dihydrogen peroxide In water at 66 - 91℃; | 1-15 EXAMPLE 1 [0045] This example provides reference information, for discussion of the effect of using hydrogen peroxide during the coupling reaction in the other examples. The procedure for Runs 1-3 is similar to that of Example 2, except using plant recycle TMAH (26.8 wt. %) and plant recycle aniline, with base concentration and drying at 62 torr and reaction at 60 torr. The procedure for Runs 4-6 is to charge 145.28 g of fresh aniline (1.56 moles) and 87.36 g of aqueous pre-concentrated fresh TMAH solution (36.0 wt. %, 0.345 moles TMAH) to a 500-mL round bottom flask equipped with a thermocouple, heating mantle, subsurface feed tubes for nitrobenzene and peroxide or water and a Teflon paddle stirrer. With pressure at 70 torr, the mixture is heated to remove 18 mL of water, along with aniline, (?30 minutes) and then nitrobenzene feed (36.93 g, 0.30 moles) is started. Temperature rises from about 66-67 C. to 80 C. during the reaction period, while water and aniline are boiled off. Table 1 gives the times for nitrobenzene feed and reaction hold for all six runs. Water and aniline are boiled off during the hold. Batches for Runs 4-6 are quenched with 20 mL of water after the hold period. The hydrogen peroxide charge is 20.40 g (0.03 moles) of a 5 wt. % aqueous solution concurrent with nitrobenzene. Since water can affect selectivity by protecting TMAH from degradation and by shifting reaction equilibriums, water is fed concurrently with nitrobenzene for direct comparison with peroxide. [0046] The example illustrates that both shorter nitrobenzene feed time and the addition of water can increase selectivity, although water is not very effective for the longer feed time. However, peroxide gave the highest selectivity, 1.9% greater than water addition. More importantly, for a commercial process that involves recycles and waste disposal, aqueous peroxide greatly reduced the levels of two key by-products compared to water alone, viz. azobenzene (by 39%) and phenazine (by 36%). Replicate baseline runs by a slightly different procedure gave selectivities of 92.7% and 92.6%, indicating that the experimental results reported herein are very reproducible. Moreover, the replicates indicate that the small selectivity differences, such as 1.9% higher for peroxide vs. water, are indeed significant. EXAMPLE 2 [0047] Some of the runs in the following examples had relatively low conversions, because the procedure used a fixed nitrobenzene feed time plus hold time rather than holding the batches to reaction completion. This example shows the effect of an extended hold period on selectivity. [0048] The procedure is to charge 432.85 g of plant recycle base (24.4 wt. % TMAH, 1.16 moles) to a 1-L water/glycol jacketed reactor. Begin agitation at 150 rpm and boil off 92 mL water at constant pressure of 65 torr, with the water bath temperature starting at 72 C. and increasing by 1 C. per 10 mL of water removed. Then charge 301.50 g (3.24 moles) of fresh aniline via vacuum. Continue to remove water plus aniline at 65 torr, by raising the bath temperature 1 C. per 9 mL of water removed, while continuously charging 120 mL of aniline from a sidearm pressure-vented dropping funnel. When 72 mL of water has been removed (164 mL total), begin co-feeding 123.11 g of nitrobenzene (1.00 moles) and 27.20 g hydrogen peroxide (10 wt. % aqueous solution, 0.08 moles) subsurface via peristaltic pumps over a period of 80 minutes. Continuously add 60 mL of aniline during the reaction step, while holding pressure at 65 torr and boiling off water plus aniline. Gradually increase bath temperature in 0.5 C. increments to achieve 91 C. in the bath and 80-82 C. in the reactor by the end of the reaction step. Initiate the hold period by reducing pressure to 60 torr and increasing the bath and reactor temperatures by another 1 C. Continue removing water plus aniline during an extended hold. [0049] This example shows that holding a low conversion batch to essentially complete conversion had only a minimum impact on selectivity. In the examples following this one, conversion ranged from 73.4% to 100%. These results show that driving conversion from 89.3% to 99.8% reduced selectivity by only 0.5% and going from 96% to 99.8% conversion reduced selectivity by only 0.2%. Therefore, low conversion for some runs in the following examples does not affect the conclusions. EXAMPLE 3 [0050] A 3-factor, 8-run Design of Experiments (DOE) with pressure, nitrobenzene feed rate, and peroxide as variables was executed. Concentration of peroxide (5 wt. % aqueous solution) and H2O2/NB (0.1 molar ratio) were arbitrarily selected for the four runs using peroxide. To a 500-mL round bottom flask equipped with a heating mantle, thermocouple, subsurface feed tubes for nitrobenzene and peroxide and a Teflon paddle stirrer was charged 130.02 g of recycle base (24.4 wt. %), which was then concentrated to 31 wt. % by boiling off 28 mL of water at the pressure indicated in Table 3. Then 145.28 g of aniline was added and another 16 mL of water was removed, along with aniline (44 mL total water). Then nitrobenzene feed of 36.93 g was started, with continued boil off of water and aniline. When peroxide was used, the 20.40 g of 5 wt. % peroxide solution was co-fed with nitrobenzene at an appropriate feed rate to finish with nitrobenzene. Batches were held as described below, then quenched with 20 mL of water. Reactions were run at 80 C. and either 65 or 95 torr (specified in the design) on a 0.3 mole scale. Hold periods were fixed at 20 minutes for the 110 minute nitrobenzene feed and 45 minutes for the 70 minute nitrobenzene feed, both with continued boil off of water and aniline. [0051] Results in Table 3 show that selectivity is consistently higher when peroxide is used at a low level and the range is much smaller (96.1 to 96.6% with vs. 89.8 to 94.8% without) for variations of reaction pressure and nitrobenzene feed rate. Also, with peroxide more 4-NDPA was made relative to azobenzene, whereas without, nearly equimolar amounts were generated. Less 4-NDPA (by 30-40%) was made with peroxide at the longer nitrobenzene feed time and in all runs, much less azobenzene and phenazine were made with peroxide. Example 1 showed that nitrobenzene feed rate can affect selectivity without peroxide and this example shows that peroxide reduces the effect of both nitrobenzene feed rate and reaction pressure, which is unexpected. EXAMPLE 4 [0052] A refining DOE was completed to assess both 1) amount of peroxide and 2) peroxide concentration for the coupling reaction. The procedure was the same as for Example 3, except for the mole ratios and peroxide concentrations listed in Table 4 and a nitrobenzene feed time of about 70 minutes with a 30 minute hold. Table 4 shows that with a fast nitrobenzene feed rate, selectivity is relatively independent of peroxide concentration, especially at the lower molar ratio. This is surprising, because Example 1 showed that adding water can increase selectivity and the runs with 5 wt. % peroxide had 6.33 times the amount of water as 25 wt. % peroxide. The results also show that selectivity can be affected by the amount of oxidant. A comparison of Runs with equal peroxide concentration in Table 4 shows that the higher mole ratio gave lower selectivity in each case. Again, this is surprising, since twice the amount of water was added at the higher mole ratio. So the benefits of water and peroxide are not additive, as the effect of peroxide predominates. EXAMPLE 5 [0053] This example further illustrates the effect of pressure on selectivity when peroxide is used. The batches were made by a procedure similar to Example 2, with a nitrobenzene feed time of 110 minutes, a hold time of 20 minutes, a different sample of plant recycle base (26.8 wt. %) and plant recycle aniline instead of fresh. The results in Table 5 show that pressure does not have an impact on selectivity when 30 wt. % peroxide is used, just as in Example 3 with 5 wt. % peroxide. This is additional evidence that peroxide mitigates the effect of other reaction variables. EXAMPLE 6 [0054] Example 1 showed that shorter nitrobenzene feed time (80 minutes) alone, or with water, or with aqueous peroxide, can increase selectivity. Example 3 showed that for a fixed peroxide concentration and molar ratio, nitrobenzene feed time (about 75 minutes vs. about 110 minutes) had little effect on selectivity. Example 4 showed that with a short nitrobenzene feed time (about 70 minutes), selectivity is relatively independent of peroxide concentration, especially at the lower mole ratio. [0055] This example explores the effect of peroxide concentration on selectivity for a longer nitrobenzene feed time. A series of batches were made by a procedure similar to that of Example 5. Also, peroxide feed for the 0.064 mole ratio runs was via a piston pump (see Example 14). Peroxide concentration was varied from 5 wt. % to 35 wt. %, with H2O2/NB=0.1 and 0.064. The results in Table 6 show that also for a longer nitrobenzene feed time, selectivity is essentially independent of peroxide concentration. Moreover, phenazine level increases only slightly as significantly less water is charged with the peroxide, which is consistent with Example 4. With a longer nitrobenzene feed time, the rate of removal of water relative to the rate of nitrobenzene charge is greater than for a shorter nitrobenzene feed time. So as less water is charged with the peroxide, the batches become even drier. However, even the lowest water charge in Table 6 has significantly higher selectivity than for water alone with a 110 minute nitrobenzene feed in Table 1. This illustrates that although water and peroxide can both play a role in increasing selectivity, the effect of peroxide is more important. Furthermore, since water can influence the rate of formation of the Meisenheimer complex and the rate of its oxidation by nitrobenzene, it should be possible to improve selectivity with peroxide by tuning H2O2/NB to match the Meisenheimer concentration in the batch. EXAMPLE 7 [0056] A series of coupling reactions were done with a fixed peroxide concentration of 5 wt. % to determine the effect of temperature on selectivity. The procedure was as follows: Charge 130.02 g recycle base (24.4 wt. % TMAH) to 500-mL scale coupler and boil off 28 mL of water. Add 145.28 g aniline and remove another 16 mL of water, along with aniline (44 mL total water). Feed 36.93 g nitrobenzene concurrently with 5 wt. % aqueous peroxide solution at H2O2/NB=0.08 molar, both subsurface, while boiling off water and aniline. Complete the co-feed in 100-110 minutes at the temperatures indicated in Table 7 and at a constant pressure of 65 torr. Hold for 30 minutes, while boiling off water and aniline, and then quench with 20 mL of water. [0057] The results in Table 7 illustrate the effect that the rates of formation and intramolecular oxidation of the Meisenheimer complex have on selectivity with peroxide. As temperature is increased, selectivity reaches a maximum at about 80 C. At lower temperatures, the rate of Meisenheimer formation is too low for the rate of peroxide addition, so that oxidation of aniline to azobenzene by peroxide increases. At higher temperatures, the higher rate of intramolecular Meisenheimer oxidation to p-NDPA reduces the amount of Meisenheimer available for reaction with peroxide, so that again oxidation of aniline to azobenzene by peroxide increases. Also, the selectivity at 70 C. is higher than that obtained without peroxide at otherwise comparable reaction conditions. Therefore, the effective range for this example can be extended down to about 65 C. [0058] Thus, 80 C. is an apparent optimum that is dependent on the reaction procedure. Any procedure change that will change the rate of Meisenheimer formation, such as changing the rate of water removal, will affect selectivity with peroxide. This could shift the optimum selectivity to a different temperature. Moreover, selectivity can be increased at lower and higher temperatures simply by adjusting the molar ratio of H2O2/NB to match the rate of formation or rate of intramolecular oxidation of the Meisenheimer. Thus selectivity is highest at 80 C. for this particular reaction procedure with H2O2/NB=0.08 molar. However, the optimum temperature will vary with other variables, such as water level in the reactor and H2O2/NB mole ratio. Furthermore, varying temperature will require a different mole ratio of H2O2/NB for maximum selectivity. Therefore, the effective ranges given in other examples are not absolute. EXAMPLE 8 [0059] Two sets of coupling reactions were done with fixed peroxide concentrations to determine the effective mole ratio range that would give increased selectivity. The procedure for 5 wt. % peroxide was basically the same as for Example 3. Peroxide and nitrobenzene were fed over 105-110 minutes, with a 20 minute hold period for reaction at 80 C. and 65 torr. The procedure for 30 wt. % was similar to Example 5. [0060] FIG. 1 and Table 8 show that the effective range for 5 wt. % peroxide is about H2O2/NB=0.01-0.20, the preferred range is about H2O2/NB=0.03-0.16 and the most preferred range is about H2O2/NB=0.06-0.12. The optimum molar ratio with 5 wt. % peroxide was H2O2/NB=0.07-0.09 for this procedure, which is about the same as the mole % of 4-NDPA that was made from nitrobenzene. So peroxide reacts in high selectivity to make 4-NDPA with minimum formation of azobenzene. This is a surprising result, due to the very large molar excess of aniline that is available to be oxidized to azobenzene. [0061] The effective mole ratio range for 30 wt. % peroxide is about 0.01-0.25. An optimum cannot be derived from the data, but it appears to be within 0.06-0.21, which is shifted higher than for 5 wt. % peroxide. A more preferred range appears to be within 0.08-0.17. So the effective mole ratio range, preferred range and most preferred range for peroxide are expected to vary with some process variables, such as peroxide concentration, impurity levels in recycle streams, reaction temperature, water removal rate and nitrobenzene feed rate. Therefore, these ranges are not absolute for peroxide, but rather representative. It is envisaged that the effective range could extend to H2O2/NB=0.01-0.4 with recycle base or perhaps even somewhat wider. EXAMPLE 9 [0062] An optimization study was done for fresh base with peroxide to examine the effect of base quality. The procedure was similar to Example 3 for 5 and 20 wt. %, with a 126.89 g charge of 25 wt. % base, and to Example 10 for 35 wt. %. As seen in FIG. 2 and Table 9, fresh base gave flatter and wider optimization curves vs. recycle base. Moreover, the optimum mole ratio and effective range varied with concentration, the maximum selectivity was lower vs. recycle base and selectivity increased after the initial optimum was passed. The upturns are due to the higher water charge as mole ratio increased, which did not occur with 35 wt. % peroxide, for which the least water was added. Selectivity rose because water inhibits oxidation of Meisenheimer by nitrobenzene, so that more is oxidized by peroxide. The results show that at the conditions used for Examples 8 and 9, peroxide is more effective with recycle base. Moreover, the salts in recycle base must moderate the effect of water, since the selectivity upturn did not occur with it. Even so, the selectivity increase with fresh base is substantial. The effective range for 35 wt. % peroxide is about 0.01-0.33 and if water was removed faster with 20 wt. % peroxide, the curve tracks to an effective range of about 0.01-0.46. Since nitrobenzene feed rate can extend well beyond 110 minutes for a commercial process, the effective range could wellEXAMPLE 10 [0063] This example further illustrates the effect | |
With potassium hydroxide; dihydrogen peroxide; tetramethlyammonium chloride In water at 60℃; for 1h; | 2 COMPARATIVE EXAMPLE 2 [0072] This example examines the effect of peroxide with a strong inorganic base and phase transfer catalyst (PTC), by the following procedure. Aniline (99%, 22.58 g, 240 mmoles), nitrobenzene (99%, 4.97 g, 40 mmoles), hydrogen peroxide (50 wt. % aqueous, molar amount indicated below in FIG. 5), water (water is added such that the total water is kept constant at 2.16 g), potassium hydroxide (86% ground powder, 7.83 g, 120 mmoles) and tetramethylammonium chloride (97%, 4.52 g, 40 mmoles) was charged to a 50-mL round bottom flask equipped with a magnetic stirrer. Peroxide was charged to the reaction mixture before adding KOH & TMACI. Then the flask was quickly stoppered and the reaction was allowed to proceed for 1 hour at 60 C. In this example, azoxybenzene and 2-NDPA were obtained as reaction by-products that were not obtained with TMAH. So these by-products were included in the calculation of selectivity. [0073] FIG. 5 shows that with a strong inorganic base and a phase transfer catalyst, selectivity increases steadily as the mole ratio of peroxide/NB is increased from 0 to unity. However, with a strong organic base, i.e. TMAH, there were optimum mole ratios with both fresh and recycle base. It is unexpected that there is an optimum mole ratio with a strong organic base, but not with a strong inorganic base and PTC that generate the same strong organic base in situ. Moreover, the inorganic system gave 2-NDPA+azoxybenzene levels of 1.1% to 2.4%, whereas none was formed with TMAH. Again, it is surprising that these by-products are formed with a strong inorganic base, but not with a strong organic base. |
Yield | Reaction Conditions | Operation in experiment |
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With sodium hydroxide In dimethyl sulfoxide at 80℃; for 3h; | 6 Example 6 The changes in the amounts of 4-NODPA and 4-NDPA, so generated, were observed from this Example, when various types of base were added. A mixture of 1.0g of carbanilide (4.7mmole), 5.8g of nitrobenzene (47mmole), 4.4g of aniline (47mmole) and base (28mmole) was added to 5ml DMSO in a 100ml three-necked flask equipped with a cooler and an agitator, and reacted under the atmosphere of oxygen at 80°C for 3 hours. After the reacting solution was extracted with ethylac'etate, the extract was analyzed on gas chromatography. The results were shown in the following Table 7. From the above Table 7, it was revealed that when sodium hydroxide, potassium hydroxide or sodium hydride as a base was employed, the selectivity or yield of final product was high. | |
With sodium hydride In dimethyl sulfoxide at 80℃; for 3h; | 6 Example 6 The changes in the amounts of 4-NODPA and 4-NDPA, so generated, were observed from this Example, when various types of base were added. A mixture of 1.0g of carbanilide (4.7mmole), 5.8g of nitrobenzene (47mmole), 4.4g of aniline (47mmole) and base (28mmole) was added to 5ml DMSO in a 100ml three-necked flask equipped with a cooler and an agitator, and reacted under the atmosphere of oxygen at 80°C for 3 hours. After the reacting solution was extracted with ethylac'etate, the extract was analyzed on gas chromatography. The results were shown in the following Table 7. From the above Table 7, it was revealed that when sodium hydroxide, potassium hydroxide or sodium hydride as a base was employed, the selectivity or yield of final product was high. | |
With potassium <i>tert</i>-butylate In dimethyl sulfoxide at 80℃; for 3h; | 6 Example 6 The changes in the amounts of 4-NODPA and 4-NDPA, so generated, were observed from this Example, when various types of base were added. A mixture of 1.0g of carbanilide (4.7mmole), 5.8g of nitrobenzene (47mmole), 4.4g of aniline (47mmole) and base (28mmole) was added to 5ml DMSO in a 100ml three-necked flask equipped with a cooler and an agitator, and reacted under the atmosphere of oxygen at 80°C for 3 hours. After the reacting solution was extracted with ethylac'etate, the extract was analyzed on gas chromatography. The results were shown in the following Table 7. From the above Table 7, it was revealed that when sodium hydroxide, potassium hydroxide or sodium hydride as a base was employed, the selectivity or yield of final product was high. |
Yield | Reaction Conditions | Operation in experiment |
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95.1% | Stage #1: nitrobenzene; aniline With sodium hydroxide; tetramethyl ammoniumhydroxide; tetramethylammonium carbonate In ethanol at 75℃; for 5h; Stage #2: With hydrogen In ethanol at 75 - 80℃; for 5h; | 3; 4 Example 3 A. Condensation Under vacuum condition, feeding pumps for the above complex base catalyst, aniline and nitrobenzene were simultaneously switched on and adjusted to such flow rate as aniline 150 kg/h, nitrobenzene 30 kg/h and the complex base catalyst 200 kg/h. The aniline, nitrobenzene and complex base catalyst were continuously fed into a falling film reactor to be heated and allowed to condense. Condensation liquid in the falling film reactor was discharged from the bottom into a first reactor to proceed with condensing. Part of condensation liquid from the bottom of the first reactor was conveyed back to the falling film reactor via a circulating pump, forming a local circulating system. Ethanol vapor at 78-90° C. was used as the heat medium of the falling film reactor. Reaction temperature was controlled as 75° C., pressure was controlled as 0.008 MPa (absolute pressure) and flow rate of the circulating liquid was controlled as 1 m3/h. The reactants overflowed from the first reactor into a second reactor. The process conditions of the second reactor, such as operational temperature and pressure, were identical with that of the first reactor. The total residence time of the reactants in the falling film reactor, first reactor and second reactor was controlled as 5 h. Once the condensation reaction became stable, the complex base catalyst recovered according to the procedure as described below could be used, with only a minor amount of fresh complex base catalyst prepared according to example 1 being replenished, and the molar ratio of hydroxide ion to nitrobenzene in the reaction mixture was controlled not less than 1:1. The effluent of the second reactor was found to contain not larger than 0.1 wt.-% of nitrobenzene, 24.9 wt.-% of water and 16.1 wt.-% of 4-nitrosodiphenylamine and 4-nitrodiphenylamine. B. Separation I Thus obtained condensation liquid was continuously fed into the separation I process stage. To the condensation liquid subjected to filtering were introduced carbon dioxide and water until pH of the solution reaches about 8. The layers of system were separated, then calcium hydroxide was added at a rate of 25 kg/h to the obtained aqueous phase. After filtering, the obtained complex base catalyst was concentrated to its initial concentration, then conveyed back to the condensation process. The obtained organic phase contained 4-nitrodiphenylamine and 4-nitrosodiphenylamine. C. Hydrogenation The organic phase containing 4-nitrodiphenylamine and 4-nitrosodiphenylamine obtained by filtration in the separation I was fed to a first-stage hydrogenation reactor equipped with a sealed magnetic stirrer and a cooling and heating system. Hydrogen gas was used to replace the atmosphere of the system and pressurize to 1.3 MPa. A hydrogen gas circulator was switched on and flow rate of circulating hydrogen gas was maintained at 1 Nm3/h. The circulating hydrogen gas was bubbled into the hydrogenation reactors to improve the gas-liquid mass transfer effect during reaction. The flow rate of the organic phase containing 4-nitrodiphenylamine and 4-nitrosodiphenylamine was controlled as 180 kg/h, and the flow rate of methanol was controlled as 48 kg/h. The powdery composite catalyst above-prepared was added simultaneously to the reactor so that the solid-liquid ratio by weight was 6:100. Hydrogenation-reduced liquid overflowed from the first-stage reactor into a second-stage reactor, then into a third-stage reactor, finally into a settler. The reaction temperature was 75-80° C., pressure was 1.3 MPa and total residence time was 5 h. The powdery composite catalyst was recovered as much as possible under the action of a magnetic separator. Solid-liquid mixture containing higher concentration of solid catalyst at the bottom of the settler was returned to the first-stage hydrogenation reactor via a Venturi type solid-liquid conveying device using the power of feeding stocks. The activity of the catalyst in the hydrogenation reaction was judged by monitoring the endpoint of reducing reaction, and thus it could be determined whether powdery composite catalyst for hydrogenation reaction was replenished. The hydrogenation liquid was measured by high performance liquid chromatograph (HPLC) and was found not containing 4-nitrodiphenylamine and 4-nitrosodiphenylamine. D. Separation II The above hydrogenation liquid was conveyed to separation II process stage. The hydrogenation liquid was subjected to filtration to recover a minor amount of the powdery composite catalyst entrained in the hydrogenation liquid. The powdery composite catalyst recovered by filtration was recycled back to the hydrogenation process after regeneration. The filtrate was fed at a flow rate of 228 kg/h to a methanol column, where methanol was obtained from column top and could be reused in the hydrogenation process. The bottoms was fed to an aniline column, where aniline was obtained from the column top and recycled back to the condensation process stage, and crude 4-aminodiphenylamine was obtained from column bottom. The aniline column was operated at a pressure of 0.005 MPa (absolute pressure), a column bottom temperature of 150 to 160° C., and a gas phase temperature of 115 to 125° C. E. Refining The crude 4-aminodiphenylamine from multiple sets of separation II equipment enters one set of refining equipment. The crude product of 4-aminodiphenylamine (containing 78.1 percent of 4-aminodiphenylamine, 21.75 percent of aniline, 0.05 percent of azobenzene and 0.1 percent of phenazine) was continuously fed to rectification column 1 at a flow rate of 120 kg/h via a gear pump. The temperature of still was controlled as 270° C., the temperature of column top was controlled as 110° C., vacuum degree was controlled as 0.094 MPa and reflux ratio was controlled as 5:1. Light components, i.e. aniline, azobenzene and phenazine, were taken out from the column top at a flow rate of about 26.2 kg/h, and conveyed to rectification column 3. The rectification column 3 was operated at conditions of still temperature of 150° C., column top temperature of 90° C., vacuum degree of 0.094 MPa and reflux ratio of 1:1. Aniline was distilled off from column top at a flow rate of 24 kg/h, and azobenzene and phenazine were left in column bottom. Bottoms of the rectification column 1 were conveyed to rectification column 2. The rectification column 2 was operated at conditions of still temperature of 280° C., column top temperature of 170° C., vacuum degree of 0.097 MPa and reflux ratio of 1:1. The finished 4-aminodiphenylamine was obtained at the column top of the rectification column 2. Bottoms of the rectification column 2 were conveyed to batch still. The batch still was operated at conditions of kettle temperature of 285-320° C., vacuum degree of 0.094 MPa and top temperature of 235-250° C., to distill off the residual 4-aminodiphenylamine, which was recycled back to the rectification column 2 to be further distilled. The whole refining process of 4-aminodiphenylamine was continuously carried out. The finished 4-aminodiphenylamine product obtained had a purity of 99.1%, a melting point of 72° C. and a solidifying point of 72.4° C. The yield of the process in industrial scale production was 95.1%. Example 4 4-Aminodiphenylamine was prepared according to the same procedure as described in Example 3 except that condensation was carried out as follows: Under vacuum condition, feeding pumps for the complex base catalyst, aniline and nitrobenzene were simultaneously switched on and adjusted to such flow rate as aniline 150 kg/h, nitrobenzene 30 kg/h and the complex base catalyst 200 kg/h. The aniline, nitrobenzene and complex base catalyst were continuously fed into a falling film reactor to be heated and allowed to condense. Condensation liquid in the falling film reactor was discharged from the bottom into a first reactor to proceed with condensing. Part of condensation liquid from the bottom of the first reactor was conveyed back to the falling film reactor via a circulating pump, forming a local circulating system. Ethanol vapor at 78-90° C. was used as the heat medium of the falling film reactor. Reaction temperature was controlled as 75° C., pressure was controlled as 0.008 MPa (absolute pressure) and flow rate of the circulating liquid was controlled as 1 m3/h. The reactants overflowed from the first reactor into a second reactor. The process conditions of the second reactor, such as operational temperature and pressure, were identical with that of the first reactor. The total residence time of the reactants in the falling film reactor, first reactor and second reactor was controlled as 5 h. Once the condensation reaction became stable; the complex base catalyst recovered was used, with sodium hydroxide and tetraalkyl ammonium salt (i.e. tetramethylammnium carbonate according to Example 1) in a molar ratio of 1:1 being replenished, and the molar ratio of hydroxide ion to nitrobenzene in the reaction mixture was controlled not less than 1:1. The effluent of the second reactor was found to contain not larger than 0.1 wt.-% of nitrobenzene, 15.6 wt.-% of water and 17.6 wt.-% of 4-nitrosodiphenylamine and 4-nitrodiphenylamine. |
Yield | Reaction Conditions | Operation in experiment |
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With sodium; potassium In 1,2-dimethoxyethane | 8 Synthesis of 5,10-diisopropyl-5,10-dihydrophenazine EXAMPLE 8 Synthesis of 5,10-diisopropyl-5,10-dihydrophenazine Phenazine, 9.0 grams, was stirred with 6.5 grams a finely divided metal alloy of 10:1 potassium to sodium, in 150 milliliters of 1,2-dimethoxyethane, at 40° C., until a brick red slurry was formed: approximately 24 hours. 2-bromopropane, 14.1 milliliters, was added and the reaction was allowed to stir for 2 hours at which time the reaction mixture was filtered, the filtrate was rotovaped to dryness and the product loaded as a solid onto a silica gel column. The column was prepared with and eluted with 8:2 hexane/ethylacetate. Removal of solvent from the target compound fractions gave a white solid which was recrystallized from methanol to give 2.1 grams of white needles, m.p. 80-81° C. A mass of 306 was confirmed by mass spectrometry. | |
Stage #1: Phenazin With sodium; potassium at 40℃; for 24h; Stage #2: isopropyl bromide for 2h; | 1.2.1 (1) 9.0 g (51.1 mmol) of phenazine of formula (2c) and 6.5 g of a mixture of metallic potassium and metallic potassium (metallic potassium: metallic sodium = 10: 1) were dissolved in 150 ml of 1,2 _ Dimethyl ethane, stirred at 40 ° C for 24h; then added 14.1ml of bromine isopropane, stirred for 2h, the product was filtered and evaporated to dryness 2, separated by a silica gel column; |
Yield | Reaction Conditions | Operation in experiment |
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1: 37% 2: 8% 3: 3% 4: 4% 5: 12% | With tetramethyl ammoniumhydroxide In water at 70 - 100℃; for 3h; | 1; 2; 3; 4 Experimental Example 1[43] 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. After heating the flask to 80 0C, 23.9 g (132 mmole) of TMA(OH) -5H O was added.Reaction was performed for 3 hours while keeping the degree of vacuum at about90-50 mmHg and distilling water. [44] 500 mg of pyrene was added as internal standard at the early step of the reaction(This procedure was applied to all experimental examples and examples). [45] Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. [46] Conversion ratio of carbanilide was 99 %. Production yield was 90 mole%4-NDPA and 8 mole% 4-NODPA, based on carbanilide. Byproducts were 8 mole% phenazine, 9 mole% azobenzene and 27 mole% azoxybenzene, based on carbanilide.; [47] Experimental Example 2[48] Production yield of 4-NDPA and 4-NODPA was compared for various nitrobenzene contents. [49] 12.7 g (60 mmole) of carbanilide and 4-10 molar equivalents of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer.After heating the flask to 80 0C, 21.7 g (120 mmole) of TMA(0H)-5H O was added.Reaction was performed for 3 hours while keeping the degree of vacuum at about90-50 mmHg and distilling water. [50] Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. [51] The result is given in Table 1.; [53] Experimental Example 3[54] Production yield of 4-NDPA and 4-NODPA was compared for various base contents. [55] 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. After heating the flask to 80 0C, 21.7 g (120 mmole) of TMA(OH) -5H O was added.Reaction was performed for 3 hours while keeping the degree of vacuum at about90-50 rnrnHg and distilling water. [56] Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. [57] Conversion ratio of carbanilide was 92 %. Production yield was 84 mole% 4-NDPA and 8 mole% 4-NODPA, based on carbanilide. Byproducts were 4 mole% phenazine, 7 mole% azobenzene and 25 mole% azoxybenzene, based on carbanilide.; [58] Experimental Example 4[59] Production yield of 4-NDPA and 4-NODPA was compared for various reaction temperatures. [60] 6.4 g (30mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. Varying temperature, 10.9 g (60 mmole) of TMA(OH)-5H O was added. Reaction was performed for 3 hours while keeping the degree of vacuum at about 90-50 mmHg and distilling water. [61] Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. [62] The result is given in Table 2. |
1: 29 - 90 %Chromat. 2: 3 - 9 %Chromat. 3: 0 - 8 %Chromat. 4: 0 - 10 %Chromat. 5: 0 - 27 %Chromat. | Stage #1: nitrobenzene; bis(diphenyl)urea With tetramethyl ammoniumhydroxide In water at 70 - 100℃; for 3h; Stage #2: With acetic acid In water; ethyl acetate | 1; 2; 3; 4; 6 EXAMPLES Experimental Example 1 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. After heating the flask to 80° C., 23.9 g (132 mmole) of TMA(OH).5H2O was added. Reaction was performed for 3 hours while keeping the degree of vacuum at about 90-50 mmHg and distilling water. 500 mg of pyrene was added as internal standard at the early step of the reaction (This procedure was applied to all experimental examples and examples). Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. The conversion ratio of carbanilide was 99%. The production yield was 90 mole % 4-NDPA and 8 mole % 4-NODPA, based on carbanilide. By-products included 8 mole % phenazine, 9 mole % azobenzene and 27 mole % azoxybenzene, based on carbanilide. Experimental Example 2 Production yield of 4-NDPA and 4-NODPA was compared for various nitrobenzene contents. 12.7 g (60 mmole) of carbanilide and 4 to 10 molar equivalents of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. After heating the flask to 80° C., 21.7 g (120 mmole) of TMA(OH).5H2O was added. Reaction was performed for 3 hours while keeping the degree of vacuum at about 90-50 mmHg and distilling water. Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. The results are shown in Table 1. TABLE 1 Nitrobenzene content* (molar Products (mole %)** equivalents) 4-NDPA 4-NODPA Phenazine Azobenzene Azoxybenzene 4 76 9 4 7 24 5 84 8 4 7 25 10 88 4 7 4 12 *Molar equivalents of nitrobenzene per initial carbanilide. **Production yield per initial carbanilide (mole %). Experimental Example 3 Production yield of 4-NDPA and 4-NODPA was compared for various base contents. 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. After heating the flask to 80° C., 21.7 g (120 mmole) of TMA(OH).5H2O was added. Reaction was performed for 3 hours while keeping the degree of vacuum at about 90-50 mmHg and distilling water. Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. The conversion ratio of carbanilide was 92%. The production yield was 84 mole % 4-NDPA and 8 mole % 4-NODPA, based on carbanilide. By-products included 4 mole % phenazine, 7 mole % azobenzene and 25 mole % azoxybenzene, based on carbanilide. Experimental Example 4 Production yield of 4-NDPA and 4-NODPA was compared for various reaction temperatures. 6.4 g (30 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. At varying temperatures, as shown below in Table 2, 10.9 g (60 mmole) of TMA(OH).5H2O was added. Reaction was performed for 3 hours while keeping the degree of vacuum at about 90-50 mmHg and distilling water. Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. The results are shown in Table 2. TABLE 2 Re- action Products (mole %)* temp. 4- 4- (° C.) NDPA NODPA Phenazine Azobenzene Azoxybenzene 100 37 4 3 10 17 80 84 8 4 7 25 70 79 4 3 7 21 *Production yield per initial carbanilide (mole %).; Experimental Example 6 Production yield of 4-NDPA and 4-NODPA was compared for various solvents. 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. 64 mL of reaction solvent was added to the flask. After heating the flask to 80° C., 21.7 g (120 mmole) of TMA(OH).5H2O was added. Reaction was performed for 3 hours while varying reaction conditions, as shown in Table 4, below. Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. The results are shown in Table 4. TABLE 4 Reaction Products (mole %)* condition 4- 4- Solvents (mmHg) NDPA NODPA Phenazine Azoxybenzene Toluene 300 35 9 2 - Toluene 760 10 7 - - THF 760 9 3 - - DMSO 760 50 4 - 15 Benzene 760 24 10 2 5 Nitro- 760 29 3 - - benzene *Production yield per initial carbanilide (mole %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 35% 2: 9% 3: 2% | With tetramethyl ammoniumhydroxide In water; toluene at 80℃; for 3h; | 6 Experimental Example 6; [71] Production yield of 4-NDPA and 4-NODPA was compared for various solvents. [72] 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. 64 mL of reaction solvent was added to the flask. After heating the flask to 80 0C, 21.7 g (120 mmole) of TMA(OH)-5H O was added. Reaction was performed for 3 hours while varying reaction conditions.[73] Ethyl acetate was added to the reaction solution. The solution was neutralized with EPO water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC.[74] The result is given in Table 4. |
1: 10 - 35 %Chromat. 2: 7 - 9 %Chromat. 3: 0 - 2 %Chromat. | Stage #1: nitrobenzene; bis(diphenyl)urea With tetramethyl ammoniumhydroxide In water; toluene at 80℃; for 3h; Stage #2: With acetic acid In water; ethyl acetate; toluene | 6 Experimental Example 6 Production yield of 4-NDPA and 4-NODPA was compared for various solvents. 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. 64 mL of reaction solvent was added to the flask. After heating the flask to 80° C., 21.7 g (120 mmole) of TMA(OH).5H2O was added. Reaction was performed for 3 hours while varying reaction conditions, as shown in Table 4, below. Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. The results are shown in Table 4. TABLE 4 Reaction Products (mole %)* condition 4- 4- Solvents (mmHg) NDPA NODPA Phenazine Azoxybenzene Toluene 300 35 9 2 - Toluene 760 10 7 - - THF 760 9 3 - - DMSO 760 50 4 - 15 Benzene 760 24 10 2 5 Nitro- 760 29 3 - - benzene *Production yield per initial carbanilide (mole %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 24% 2: 10% 3: 5% 4: 2% | With tetramethyl ammoniumhydroxide In water; benzene at 80℃; for 3h; | 6 Experimental Example 6; [71] Production yield of 4-NDPA and 4-NODPA was compared for various solvents. [72] 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. 64 mL of reaction solvent was added to the flask. After heating the flask to 80 0C, 21.7 g (120 mmole) of TMA(OH)-5H O was added. Reaction was performed for 3 hours while varying reaction conditions.[73] Ethyl acetate was added to the reaction solution. The solution was neutralized with EPO water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC.[74] The result is given in Table 4. |
1: 24 %Chromat. 2: 10 %Chromat. 3: 2 %Chromat. 4: 5 %Chromat. | Stage #1: nitrobenzene; bis(diphenyl)urea With tetramethyl ammoniumhydroxide In water; benzene at 80℃; for 3h; Stage #2: With acetic acid In water; ethyl acetate; benzene | 5 Experimental Example 6 Production yield of 4-NDPA and 4-NODPA was compared for various solvents. 12.7 g (60 mmole) of carbanilide and 36.9 g (300 mmole) of nitrobenzene were put in a 200 mL, 3-necked round bottom flask equipped with a cooler and a stirrer. 64 mL of reaction solvent was added to the flask. After heating the flask to 80° C., 21.7 g (120 mmole) of TMA(OH).5H2O was added. Reaction was performed for 3 hours while varying reaction conditions, as shown in Table 4, below. Ethyl acetate was added to the reaction solution. The solution was neutralized with water and acetic acid. The ethyl acetate layer was separated and analyzed by HPLC. The results are shown in Table 4. TABLE 4 Reaction Products (mole %)* condition 4- 4- Solvents (mmHg) NDPA NODPA Phenazine Azoxybenzene Toluene 300 35 9 2 - Toluene 760 10 7 - - THF 760 9 3 - - DMSO 760 50 4 - 15 Benzene 760 24 10 2 5 Nitro- 760 29 3 - - benzene *Production yield per initial carbanilide (mole %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium dichromate; acetic acid In ethanol; water | 85 EXAMPLE 85 EXAMPLE 85 A mixture of 22 parts of phenyl-β-naphthylamine and 24.5 parts of the sodium salt of 3-sulpho-4-diethylaminoaniline in 250 parts of ethyl alcohol and 250 parts of water is stirred and refluxed. 45 Parts of acetic acid are added, followed by a solution of 31 parts of sodium dichromate in 50 parts of water. The mixture is stirred and refluxed for 15 minutes, cooled to 20°C and diluted with 100 parts of water. The precipitated phenazine of formula: SPC19 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In acetone shaking (room temp., 5 min), NMR monitoring; solvent removal (dry N2), drying (vac.); elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In dichloromethane-d2 shaking (25°C); solvent removal (N2, vac.); elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In dichloromethane-d2 shaking (25°C); solvent removal (N2, vac.); elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In dichloromethane-d2 shaking (25°C); solvent removal (N2, vac.); elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In tetrahydrofuran byproducts: N2, THF; (N2); stirring lanthanum compd. and phenazine in THF overnight; evapn., 1H NMR; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | In benzene byproducts: 5,10-dihydrophenazine; (Ar, Schlenk) a mixt. of complex and phenazine (1:1) in benzene was heated at 80°C for 4 h; volatiles were removed in vac., extd. into benzene, filtered, liophilized by freezing the benzene-soln. in liquid N2, allowed to reach ambient temp., the residue was washed with pentane, dried in vac.; elem. anal.; | |
In benzene-d6 (Ar, Schlenk) a mixt. of complex and phenazine (1:1) in C6D6 was heated at 80°C; not isolated, detected by NMR spectra; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | In benzene (Ar, Schlenk) a mixt. of complex and 2 equiv of phenazine in benzene washeated at 95°C for 4 days; crystals were washed with pentane and dried in vac.; elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | In Cyclohexane-d12 byproducts: 5,10-dihydrophenazine; (Ar, Schlenk) a mixt. of complex and 0.5 equiv of phenazine in cyclohexane-d12 was heated at 140°C for 5 h; volatiles were removed in vac., the residue was washed with benzene and with pentane, the benzene-soln. was lyophilized, crystd. by slow evapn. pentane-soln. at -18°C; elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | Stage #1: Phenazin; phenyllithium In dibutyl ether; toluene at 20℃; for 12h; Stage #2: 1,3,5-trichloro-2,4,6-triazine In tetrahydrofuran; dibutyl ether; toluene for 6h; Heating / reflux; | 1.2 In a nitrogen atmosphere, phenyllithium (2.0 M dibuthylether solution, 53.0 mmol) was dropped in a dried toluene solution (180 mL) of phenazine (10.1 g, 56.0 mmol) at room temperature. After drying at room temperature for 12 hours, a dried THF solution (50 mL) of cyanuric chloride (2.40 g, 13.2 mmol) was dropped. After holding the reaction mixture at reflux by heating for 6 hours, water was added to the reaction solution, and extraction was performed with toluene. Further, insoluble matter precipitated during the extraction was removed by filtration. The toluene layer was washed with a saturated salt solution, and then, dried, filtered, and condensed with magnesium sulfate. About 300 mL of ether was added to the obtained solid, and ether insoluble matter was obtained by filtration. This solid was purified by recrystallization (twice) with chloroform/ethanol to obtain light brown compound (yield: 45%). Measurement of the obtained compound by NMR (Nuclear Magnetic Resonance) could confirm that the compound was a material represented by a structure formula (72) (2,4,6-tris(10-phenyl-dihydrophenazine-5-yl)-1,3,5-triazine). NMR (Nuclear Magnetic Resonance) spectrum data is shown below. 1H NMR (300 MHz, CDCl3) δ 6.25 (dd, 6H, J=1.5, 8.4 Hz), 6.77-6.86 (m, 12H), 7.36-7.58 (m, 21H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.8% | With water-d2; aluminium at 200℃; for 3h; Microwave irradiation; | 1 Example 1 1.8 g of phenazine, 0.2 g of platinum-activated carbon (5%), and 0.2 g of aluminum powder were added to 50 ml of heavy water, and the resulting mixture was subjected to microwave irradiation at 200° C. for 180 minutes. The pressure applied during the reaction was 1.7 to 1.9 MPa. After being left to stand for cooling, the reaction mixture was extracted with dichloromethane, followed by the 1H-NMR measurements (using deuterochloroform (hereafter, abbreviated as CDCl3)) and GC-MS measurements (main peak (measured value); 188.00). As a result, the isolated yield of the deuterated compound was 87.8%, and the deuteration ratio was 98.9% (on average). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With dirhodium tetraacetate; 1,3-bis(mesityl)imidazolium chloride; sodium t-butanolate In toluene at 95℃; for 24h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 53 %Spectr. 2: 15 %Spectr. | at 700℃; flash vacuum pyrolysis; |
Yield | Reaction Conditions | Operation in experiment |
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79% | With 2Na(1+)*CuC6H4(NCHC6H3OO3S)2(2-)=CuC6H4(NCHC6H3ONaO3S)2; tetrabutylammonium bromide; potassium carbonate In water monomer at 120℃; for 30h; | 3. General procedure for Synthesis of phenazines General procedure: 2-iodoaniline (0.5 mmol) or 2-bromoaniline (0.5 mmol), complex 1 (0.05mmol), K2CO3 (1 mmol), (n-Bu)4NBr (0.1 mmol) and water (10 mL) were added to a sealed tube. The reaction mixture was stirred at 120oC for 30 h, then cooled to room temperature and then extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and the solvent was then removed under reduced pressure. The product was finally obtained by column chromatography on silica gel. |
79% | With ferric(III) chloride; tetrabutylammonium bromide; L-proline lithium salt; sodium hydroxide In water monomer at 100℃; for 0.5h; Microwave irradiation; Green chemistry; | 1 Example 1: Phenazine 1mmol of 2-iodoaniline was added to the reaction vessel, 0.1 mmol of ferric chloride, 1 ml of proline lithium, 3 mmol of sodium hydroxide, 4-butyl bromide Ammonium (fcBu) 4NBr) 0.1 mmol, water 3 mL. Placed in a microwave reactor at 150 W power to 100 ° C continuous reaction for 30 min. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. The product was purified by column chromatography to give a yellow solid in 79% yield. |
With copper(I) tetrakis(acetonitrile)tetrafluoroborate; caesium hydroxide; 2-(1H-pyrazol-1-yl)-N-(pyridine-2-ylmethyl)ethan-1-amine In dimethylsulfoxide-d6; water monomer at 120℃; for 15h; |
Multi-step reaction with 4 steps 1.1: pyridine / 5 h / 20 °C 2.1: caesium fluoride / acetonitrile / 24 h / 20 °C 3.1: glacial acetic acid; 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) / acetonitrile / 24 h / 20 °C 3.2: 2 h / 0 - 80 °C 4.1: Caswell No. 744A; triphenylphosphine / water monomer; N,N-dimethyl acetamide / 0.5 h / 120 °C 4.2: 48 h / 120 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 48% 2: 26% 3: 70% | With 2Na(1+)*CuC6H4(NCHC6H3OO3S)2(2-)=CuC6H4(NCHC6H3ONaO3S)2; tetrabutylammomium bromide; potassium carbonate In water at 120℃; for 30h; | 4. Synthesis of 1,3-dimethylphenazine General procedure: 2-iodoaniline (0.1 mmol), 2-iodo-4,6-dimethylbenzenamine (0.5 mmol), complex 1 (0.01 mmol), K2CO3 (0.2 mmol), (n-Bu)4NBr (0.02 mmol) and water (10 mL) were added to a sealed tube. The reaction mixture was stirred at 120oC for 30 h , then cooled to room temperature and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and the solvent was then removed under reduced pressure. The product was finally obtained by column chromatography on silica gel. |
1: 38% 2: 42% 3: 44% | With 2Na(1+)*CuC6H4(NCHC6H3OO3S)2(2-)=CuC6H4(NCHC6H3ONaO3S)2; tetrabutylammomium bromide; potassium carbonate In water at 120℃; for 30h; | 4. Synthesis of 1,3-dimethylphenazine General procedure: 2-iodoaniline (0.1 mmol), 2-iodo-4,6-dimethylbenzenamine (0.5 mmol), complex 1 (0.01 mmol), K2CO3 (0.2 mmol), (n-Bu)4NBr (0.02 mmol) and water (10 mL) were added to a sealed tube. The reaction mixture was stirred at 120oC for 30 h , then cooled to room temperature and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and the solvent was then removed under reduced pressure. The product was finally obtained by column chromatography on silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With 2Na(1+)*CuC6H4(NCHC6H3OO3S)2(2-)=CuC6H4(NCHC6H3ONaO3S)2; tetrabutylammomium bromide; potassium carbonate In water at 120℃; for 30h; | 3. General procedure for Synthesis of phenazines General procedure: 2-iodoaniline (0.5 mmol) or 2-bromoaniline (0.5 mmol), complex 1 (0.05mmol), K2CO3 (1 mmol), (n-Bu)4NBr (0.1 mmol) and water (10 mL) were added to a sealed tube. The reaction mixture was stirred at 120oC for 30 h, then cooled to room temperature and then extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and the solvent was then removed under reduced pressure. The product was finally obtained by column chromatography on silica gel. |
71% | With iron(III) chloride; tetrabutylammomium bromide; L-proline lithium salt; sodium hydroxide In water at 100℃; for 0.5h; Microwave irradiation; | 13 Example 13: Phenazine: 1mmol of 2-bromoaniline was added to the reaction vessel, 0.1 mmol of ferric chloride, 0.1 ml of proline lithium, 3 mmol of sodium hydroxide, 4-butylammonium bromide fcBu) 4NBr) 0.1 mmol, water 3 mL. Was heated to 150 ° C in a microwave reactor at 30 ° C for 30 min. After completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. The product was purified by column chromatography to give a yellow solid in 71% yield. |
Multi-step reaction with 3 steps 1.1: sodium nitrite; hydrogenchloride / water / 0.42 h / 0 °C 1.2: 20 h / 0 - 20 °C 2.1: tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; 1,1'-bis-(diphenylphosphino)ferrocene / toluene; water / 20 h / 80 °C 3.1: trifluoroacetic acid / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | In toluene at -35℃; for 24h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: 1,4-bis(diisopropylphenyl)-aza-1,4-butadienenickel dibromide With potassium In diethyl ether at 20℃; for 48h; Inert atmosphere; Stage #2: Phenazin In diethyl ether for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In dichloromethane at 20℃; for 48h; | Reactivity of MoCl5 with phenazine (C12H8N2). Synthesis of MoCl5(C12H8N2), 4 General procedure: MoCl5 (0.230g, 0.842mmol) in CH2Cl2 (15mL) was treated with phenazine (0.153g, 0.849mmol). The resulting mixture was stirred for 48h at room temperature and then filtered in order to remove some solid. The filtrated, clean dark-green solution was concentrated up to ca. 2mL and added of hexane (20mL). A dark-green solid was recovered, washed with pentane (2×15mL), and then dried under vacuo. Yield: 0.285g (75%) Anal. Calc. for C12H8Cl5MoN2: C, 31.79; H, 1.78; N, 6.18; Cl, 39.10. Found: C, 31.96; H, 1.85; N, 6.28; Cl, 38.90%. IR (solid state): ν=3230w, 3078w, 3005w, 1616s, 1518m, 1468m, 1448w, 1417s, 1345m, 1324w-m, 1287w, 1261m, 1224w, 1170w, 1133s, 992m-s, 876m, 854m, 823m, 804w, 738vs cm-1. Magnetic measurement: χMcorr=9.94·10-4cgsu, μeff=1.55BM. 1H NMR (CD3CN): δ=9.2-8.3ppm (m-br). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.34 g | In dichloromethane for 18h; | Synthesis of Mo(O)Cl3[κ1(N)-C12H8N2], 5 Compound 5 was prepared in good yield by the following procedure. MoCl5 (1.20mmol) in CH2Cl2 (10mL) was treated with tetrahydrofuran (1.15mmol). The mixture was stirred for 72h, then it was dried under vacuo, and the resulting dark-brown precipitate was washed repeatedly with hexane. Afterwards, CH2Cl2 (10mL) and phenazine (1.20mmol) were added in the order given, and the obtained mixture was stirred for 18h. Hence the green solution was concentrated (up to 3mL) and layered with hexane. Compound 5 was obtained as bright-green microcrystalline solid upon storing the CH2Cl2/hexane mixture for 3days at -30°C. Yield: 0.340g (71%). Anal. Calc. for C12H8Cl3MoN2O: C, 36.17; H, 2.02; N, 7.03; Cl, 26.69. Found: C, 36.01; H, 2.19; N, 6.85; Cl, 26.32%. IR (solid state): ν=2963w, 1612w, 1506w, 1471w, 1447w, 1417w, 1347w, 1259m, 1072vs, 1014vs, 842m, 793vs, 742s cm-1. Magnetic measurement: χMcorr=1.04×10-3cgsu, μeff=1.58BM. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; caesium carbonate In toluene at 110℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; caesium carbonate In toluene at 110℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | In benzene for 168h; Schlenk technique; Inert atmosphere; Glovebox; | Preparation of 1 A solution of [Ru2(4-F-2-OMePhCO2)4(THF)2] (41 mg, 0.04 mmol) in CH2Cl2 (10 ml) was separated into five portions and placed in narrow-diameter glass tubes (Φ 8 mm) (bottom layer). Then, a mixed solvent of CH2Cl2/benzene 1:1 v/v (1 ml) was placed on the bottom layer to slow the rate of diffusion (middle layer). Finally, a solution (2 ml) of phz (28 mg, 0.16 mmol) in benzene (10 ml) was carefully placed on the middle layer of each bath (top layer). The glass tubes were left undisturbed for one week to obtain needle-type brown crystals of 1 (yield 39%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | In benzene for 168h; Schlenk technique; Inert atmosphere; Glovebox; | Preparation of 1 General procedure: A solution of [Ru2(4-F-2-OMePhCO2)4(THF)2] (41 mg, 0.04 mmol) in CH2Cl2 (10 ml) was separated into five portions and placed in narrow-diameter glass tubes (Φ 8 mm) (bottom layer). Then, a mixed solvent of CH2Cl2/benzene 1:1 v/v (1 ml) was placed on the bottom layer to slow the rate of diffusion (middle layer). Finally, a solution (2 ml) of phz (28 mg, 0.16 mmol) in benzene (10 ml) was carefully placed on the middle layer of each bath (top layer). The glass tubes were left undisturbed for one week to obtain needle-type brown crystals of 1 (yield 39%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With dipotassium peroxodisulfate; D-Glucose In water at 40℃; for 6h; | |
70% | With dipotassium peroxodisulfate In acetonitrile at 90℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With dipotassium peroxodisulfate In acetonitrile at 90℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | In ethanol; water | 2.2 Synthesis of [AuCl3(phz)] (1) and [AuCl3(qx)] (2) General procedure: The solution of 0.5 mmol of the corresponding heterocyclic ligand, 90.1 mg of phenazine (phz) and 65.1 mg of quinoxaline (qx) in 1.0 mL of ethanol was added slowly under stirring to the solution containing an equimolar amount of K[AuCl4] (188.9 mg) in 5.0 mL of water. The yellow precipitate, formed immediately after addition of the heterocyclic ligand, was filtered off, washed with water, and recrystallized in dichloromethane to form yellow crystals of 1 and 2. The crystals of the corresponding gold(III) complexes were collected from the solution and dried in the dark at ambient temperature. The yield was 43% for 1 (104.0 mg) and 65% for 2 (140.9 mg). |
43% | In ethanol; water | 2.2 Synthesis of [AuCl3(phz)] (1) and [AuCl3(qx)] (2) General procedure: The solution of 0.5 mmol of the corresponding heterocyclic ligand, 90.1mg of phenazine (phz) and 65.1 mg of quinoxaline (qx) in 1.0 mL of ethanol was added slowly under stirring to the solution containing an equimolar amount of K[AuCl4] (188.9mg) in 5.0mL of water. The yellow precipitate, formed immediately after addition of the heterocyclic ligand, was filtered off, washed with water, and recrystallized in dichloromethane to form yellow crystals of 1 and 2. The crystals of the corresponding gold(III) complexes were collected from the solution and dried in the dark at ambient temperature. The yield was 43% for 1 (104.0 mg) and 65% for 2 (140.9 mg). Anal. Calc. for 1=C12H8AuCl3N2 (Mr=483.52): C, 29.81; H, 1.67; N, 5.79. Found: C, 30.27; H, 1.88; N, 6.00%. Anal. Calc. for 2=C8H6AuCl3N2 (Mr=433.46): C, 22.17; H, 1.40; N, 6.46. Found: C, 22.41; H, 1.51; N, 6.48%. |
In ethanol; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 28% 2: 16% 3: 10% | With potassium phosphate; 1,1'-bis(di-tertbutylphosphino)ferrocene; palladium diacetate In N,N-dimethyl-formamide at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With 2,6-dichloro-4,4’-bipyridine In cyclohexane at 60℃; for 16h; Glovebox; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 18% 2: 21% 3: 11% | In m-xylene at 139℃; for 18h; Inert atmosphere; Schlenk technique; | Reaction of Os3(CO)12 with phenazine A 1,3-xylene solution (30 mL) of Os3(CO)12 (0.10 g, 0.11 mmol) and phenazine (20 mg, 0.11 mmol) was heated at reflux for 18 h, during which time the solution color changed from yellow to dark red. The solvent was removed under reduced pressure and the residue chromatographed by TLC on silica gel. Elution with cyclohexane/dichloromethane (4:1, v/v) developed six bands. The third and the fourth bands gave Os3(CO)9(μ3,η2-C12H7N2)(μ-H) (1) (20 mg, 18 %), Os3(CO)9(μ3,η2-C12H6N2)(μ-H)2 (2) (23 mg, 21 %), respectively, as dark red crystals after recrystallization from CHCl3/hexane at room temperature. The first band afforded unreacted Os3(CO)12 (5mg), the second band gave Os6(CO)18 (10 mg, 11 %), and the sixth band was unreacted phenazine. Spectral data for 1: Anal. Calcd for C21H8N2O9Os3: C, 25.15; H, 0.80; N, 2.79. Found: C, 25.42; H, 0.95; N, 2.94%. IR (νCO, CH2Cl2): 2080 (s), 2052 (vs), 2024 (s), 1995 (vs), 1959 (s), 1945 (w) cm-1; 1H NMR (CDCl3): δ 8.67 (d, J 10.0Hz, 1H), 8.17 (d, J 10.0Hz, 1H), 8.10 (t, J 10.0Hz, 1H), 8.01 (d, J 10.0Hz, 1H), 7.84 (t, J 10.0Hz, 1H), 7.24 (t, J 10.0Hz, 1H), 7.08 (d, J 10.0Hz, 1H),-14.46 (s, 1H). Spectral data for 2: Anal. Calcd for C21H8N2O9Os3: C, 25.15; H, 0.80; N, 2.79. Found: C, 25.38; H, 0.98; N, 2.88%. IR (νCO, CH2Cl2): 2110 (s), 2082 (vs), 2058 (vs), 2029 (s), 2007 (s), 1980 (w) cm-1; 1H NMR (CDCl3): δ 8.20 (m, 1H), 8.16 (m, 1H), 8.02 (d, J 10.0Hz, 1H), 7.82 (m, 2H), 7.48 (d, J 10.0Hz,1H),-21.12 (b, 1H),-17.24 (b, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 85% 2: 10% | With toluene-4-sulfonic acid In water at 200℃; for 2h; | |
1: 85% 2: 10% | With toluene-4-sulfonic acid at 200℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium dithionite; sodium carbonate; methyl tributylammonium chloride In water; acetonitrile at 80℃; for 24h; Overall yield = 7.7 g; | 13 [0065] Example 13. Synthesis of bis-5,10-(4-(bromobutyl)-5,10-dihydrophenazine and a butyl bridged bis(phenazine): [0066] Phenazine (95.0 g), sodium dithionite (6.0 g), sodium carbonate (6.5 g), 1,4- dibromobutane, (100 ml), tributylmethyl ammonium chloride (2 ml), water (2 ml), and acetonitrile (100 ml) are combined in a 250 ml flask. The reaction mixture was heated to 80 °C for 24 hours. The reaction was then quenched with water (lOOml). Filtered the solid to give 7.7 g of mixture 60% desired and 40% butyl bridged bis(phenazine). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | In benzene at 80℃; for 3h; Inert atmosphere; | Reaction of Fe3(CO)12 with phenazine A benzene solution (25 mL) containing Fe3(CO)12 (0.20 g, 0.40 mmol) and phenazine (71 mg, 0.39 mmol) was heated to reflux for 3 h. The solvent was removed under reduced pressure and the residue chromatographed by TLC on silica gel. Elution with cyclohexane/CH2Cl2 (2:3, v/v) developed four bands. The slowest moving band afforded Fe(CO)3(η4-C12N2H8) (1a) (0.18 g, 47%) as orange crystals after recrystallization from dichloromethane/hexane at 4 °C. The first and second bands were too small for complete characterization, while the third band afforded unreacted phenazine. Spectral data for 1a: IR (νCO, CH2Cl2): 2064 vs, 2005 vs, 1997 sh cm-1. 1H NMR (CD2Cl2): δ 3.87 (AA', diene, J = 5.4, 3.5 Hz, 2H), 6.53 (XX', diene, J = 5.4, 3.5 Hz, 2H), 7.38 (AA', aryl, J = 6.5, 3.0 Hz, 2H), 7.51 (BB', J = 6.5, 3.0 Hz, 2H). 13C NMR (CD2Cl2): δ 62.14 (CH), 88.03 (CH), 127.55 (CH), 128.18 (CH), 139.46 (C), 156.98 (C), 207.25 (Fe-CO). Anal. Calcd. for C15H8FeN2O3: C, 56.29; H, 2.52; N, 8.75. Found: C, 56.55; H, 2.72; N, 8.83%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | In benzene at 80℃; for 3h; Inert atmosphere; | Reaction of Fe3(CO)12 with phenazine A benzene solution (25 mL) containing Fe3(CO)12 (0.20 g, 0.40 mmol) and phenazine (71 mg, 0.39 mmol) was heated to reflux for 3 h. The solvent was removed under reduced pressure and the residue chromatographed by TLC on silica gel. Elution with cyclohexane/CH2Cl2 (2:3, v/v) developed four bands. The slowest moving band afforded Fe(CO)3(η4-C12N2H8) (1a) (0.18 g, 47%) as orange crystals after recrystallization from dichloromethane/hexane at 4 °C. The first and second bands were too small for complete characterization, while the third band afforded unreacted phenazine. Spectral data for 1a: IR (νCO, CH2Cl2): 2064 vs, 2005 vs, 1997 sh cm-1. 1H NMR (CD2Cl2): δ 3.87 (AA', diene, J = 5.4, 3.5 Hz, 2H), 6.53 (XX', diene, J = 5.4, 3.5 Hz, 2H), 7.38 (AA', aryl, J = 6.5, 3.0 Hz, 2H), 7.51 (BB', J = 6.5, 3.0 Hz, 2H). 13C NMR (CD2Cl2): δ 62.14 (CH), 88.03 (CH), 127.55 (CH), 128.18 (CH), 139.46 (C), 156.98 (C), 207.25 (Fe-CO). Anal. Calcd. for C15H8FeN2O3: C, 56.29; H, 2.52; N, 8.75. Found: C, 56.55; H, 2.72; N, 8.83%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | In benzene at 80℃; for 3h; Inert atmosphere; | Reaction of Fe3(CO)12 with phenazine A benzene solution (25 mL) containing Fe3(CO)12 (0.20 g, 0.40 mmol) and phenazine (71 mg, 0.39 mmol) was heated to reflux for 3 h. The solvent was removed under reduced pressure and the residue chromatographed by TLC on silica gel. Elution with cyclohexane/CH2Cl2 (2:3, v/v) developed four bands. The slowest moving band afforded Fe(CO)3(η4-C12N2H8) (1a) (0.18 g, 47%) as orange crystals after recrystallization from dichloromethane/hexane at 4 °C. The first and second bands were too small for complete characterization, while the third band afforded unreacted phenazine. Spectral data for 1a: IR (νCO, CH2Cl2): 2064 vs, 2005 vs, 1997 sh cm-1. 1H NMR (CD2Cl2): δ 3.87 (AA', diene, J = 5.4, 3.5 Hz, 2H), 6.53 (XX', diene, J = 5.4, 3.5 Hz, 2H), 7.38 (AA', aryl, J = 6.5, 3.0 Hz, 2H), 7.51 (BB', J = 6.5, 3.0 Hz, 2H). 13C NMR (CD2Cl2): δ 62.14 (CH), 88.03 (CH), 127.55 (CH), 128.18 (CH), 139.46 (C), 156.98 (C), 207.25 (Fe-CO). Anal. Calcd. for C15H8FeN2O3: C, 56.29; H, 2.52; N, 8.75. Found: C, 56.55; H, 2.72; N, 8.83%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | Stage #1: 4-bromo-1,1'-biphenyl With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: Phenazin In tetrahydrofuran at -78 - 20℃; for 12h; Inert atmosphere; | Into the 4-bromobiphenyl 10g (42.9mmol) in a round bottom flask it was dissolved in 143mL anhydrous tetrahydro furan under nitrogen atmosphere. The solution was cooled to 78° C , is stirred and slowly 1.6M n-butyl lithium solution 27mL(42.9mmol) and this was the reaction at -78° C for 1 hour. Phenazine placed 8.5g (47.2mmol) in a round bottom flask was dissolved in 143mL anhydrous tetrahydro furan under nitrogen atmosphere. The solution cooled to -78° C , stirred and heated to room temperature was added to 4-phenyl lithium solution was slowly added to the reaction here was for 12 hours. After then distilled water was added to terminate the reaction and the reaction solution was concentrated under reduced pressure to remove the tetrahydrofuran and extracted with toluene / distilled water, and the organic layer was dried with sodium sulphate, filtered and the filtrate was concentrated under reduced pressure. The toluene under nitrogen and the product / intermediate M-14 by the objective compound was purified by recrystallization in ethanol to give the 7.2g (50% yield). The product was stored under nitrogen cooling. |
50% | Stage #1: 4-bromo-1,1'-biphenyl With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: Phenazin In tetrahydrofuran; hexane at -78 - 20℃; for 12h; Inert atmosphere; | Synthesis of Intermediate M-14 10 g (42.9 mmol) of 4-bromobiphenyl was dissolved in 143 ml of anhydrous tetrahydrofuran in a round-bottomed flask under a nitrogen atmosphere. The solution was cooled down to -78° C. and agitated, 27 ml (42.9 mmol) of a 1.6 M n-butyl lithium hexane solution was slowly added thereto, and the mixture was reacted at -78° C. for 1 hour. 8.5 g (47.2 mmol) of phenazine was dissolved in 143 ml of anhydrous tetrahydrofuran in a round-bottomed flask under a nitrogen atmosphere. The solution was cooled down to -78° C. and agitated, a 4-biphenyl lithium solution was slowly added thereto, and the mixture was heated up to room temperature and reacted for 12 hours. Then, distilled water was added to the resultant to complete the reaction, the reaction solution was concentrated under a reduced pressure to remove tetrahydrofuran and then extracted with toluene/distilled water, an organic layer obtained therefrom was dried with sodium sulfate and filtered, and the filtered solution was concentrated under a reduced pressure. The concentrated product was recrystallized under nitrogen and then purified with toluene/ethanol, obtaining 7.2 g of a desired compound, an intermediate M-14 (50% of a yield). The obtained product was refrigerated under nitrogen. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol | 2.1. Preparation of molecular complexes, 1a-1h and 1c' General procedure: In a typical experiment, 110 mg (0.5 mmol) of iodophenol,1 and 78 mg (0.5 mmol) of 4,4'-bipyridine, (a) were dissolved in about 15 mL CH3OH, by gently boiling the solution and allowed for slow evaporation.Good quality crystals are obtained within 72 h, which are utilized for single crystal diffraction studies. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol | Cocrystals preparation method General procedure: HCT and cocrystal former in a definite stoichiometric ratio were subjected to grinding using an agate mortar and pestle for about 6-8 min with the addition of few drops of methanol. The Liquid Assisted Grinding (LAG) was used because it is expected to increase cocrystallization kinetics and for polymorph control [29]. After grinding, the mixture was dissolved in ethanol (or methanol) and the suspension was heated until a clear solution was obtained. Then the solution was filtered to remove any undissolved particles into a fresh conical flask and the filtrate was left to evaporate slowly at ambient conditions. The single crystals suitable for X-ray diffraction studies were obtained in 4-6 days. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sodium dithionite; sodium carbonate monohydrate; methyl tributylammonium chloride In acetonitrile for 48h; Inert atmosphere; Reflux; | 1 Example 1. To a 2 liter round bottom flask under nitrogen was charged400 mL acetonitrile, phenazine (45.0 g; 250 mmol), sodium dithionite (52.2 g; 300 mmol),sodium carbonate monohydrate (62.0 g; 500 mmol), methyl 3-bromopropionate (167 g;1,000 mmol), and tributylmethylammonium chloride (11.3 g; 37.5 mmol) and mixed atreflux. After 48 hours of mixing at reflux, H20 (40 mL; 18 MQ-cm reverse osmosisdeoionized) was added to the mixture over 1 hour. 72 hours following completion of theH20 addition, the mixture was vacuum filtered, washed with chilled ethanol, andrecrystallized from an acetane/ethanol mixture to provide 1 as a white crystalline solid in85% yield. |
Tags: 92-82-0 synthesis path| 92-82-0 SDS| 92-82-0 COA| 92-82-0 purity| 92-82-0 application| 92-82-0 NMR| 92-82-0 COA| 92-82-0 structure
[ 536753-86-3 ]
2-Methyldibenzo[f,h]quinoxaline
Similarity: 0.82
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Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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