29668-44-8

Basic information

• Product Name: 1,4-BENZODIOXAN-6-CARBOXALDEHYDE
• Synonyms: 1,4-Benzodioxin-6-carboxaldehyde, 2,3-dihydro-;7-Formyl-1,4-benzodioxane;1,4-BENZODIOXAN-6-CARBALDEHYDE;1,4-BENZODIOXAN-6-CARBOXALDEHYDE;1,4-BENZODIOXAN-6-CARBOXYALDEHYDE;1,4-BENZODIOXANE-6-CARBOXALDEHYDE;2,3-DIHYDRO-BENZO[1,4]DIOXINE-6-CARBALDEHYDE;2,3-DIHYDRO-1,4-BENZODIOXINE-6-CARBOXALDEHYDE
• CAS NO: 29668-44-8
• Molecular Formula: C₉H₈O₃
• Molecular Weight: 164.16
• EINECS: 249-763-3
• Product Categories: Aromatic Aldehydes & Derivatives (substituted);Aldehydes;BenzodioxanesCarbonyl Compounds;Building Blocks;C9;Heterocyclic Building Blocks;Benzodioxanes;Building Blocks;Carbonyl Compounds;Chemical Synthesis;Heterocyclic Building Blocks;Organic Building Blocks;Benzodioxan Series
• Mol File: 29668-44-8.mol
• Article Data: 40

Chemical Properties

• Melting Point: 50-52 °C(lit.)
• Boiling Point: 105 °C15 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Yellow-beige/Chunks and Powder
• Density: 1.2132 (rough estimate)
• Vapor Pressure: 0.000238mmHg at 25°C
• Refractive Index: 1.5380 (estimate)
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: Solubility in methanol is almost transparent.
• CAS DataBase Reference: 1,4-BENZODIOXAN-6-CARBOXALDEHYDE(CAS DataBase Reference)
• NIST Chemistry Reference: 1,4-BENZODIOXAN-6-CARBOXALDEHYDE(29668-44-8)
• EPA Substance Registry System: 1,4-BENZODIOXAN-6-CARBOXALDEHYDE(29668-44-8)

Safety Data

• Hazard Codes: Xi
• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 29668-44-8(Hazardous Substances Data)

Usage

Description

1,4-benodioxan-6-carboxaldehyde is a kind of aldehyde derivative. It is a useful intermediate in organic synthesis. It can be used as the building bock of the manufacturing tetrahydroisoquinoliones and benzofuran analog (a inhibitor of cAMP-specific phosphodiesterase type IV). It can also be used as an intermediate during the manufacturing of some novel Dopamine D3 and D4 receptor antagonists. It can also be used as the initial material for the manufacturing of some novel chalcone analogues that exhibit strong anti-tumor activity and low toxic side effects.

Chemical Properties

Yellowish-beige powder and chunks

Uses

Different sources of media describe the Uses of 29668-44-8 differently. You can refer to the following data:
1. 1,4-Benzodioxane-6-carboxaldehyde was screened as a fragment for inhibitors of PDEA using enthalpy arrays and X-ray crystallography. 1,4-Benzodioxane-6-carboxaldehyde have also been used as an interme diate in the synthesis of a new class of Dopamine D3 and D4 receptor antagonists.
2. 1,4-Benzodioxan-6-carboxaldehyde finds its uses as building block in the synthesis of tetrahydroisoquinolinones, in the preparation of benzofuran analog, a potential inhibitor of CAMP-specific phosphodiesterase type IV, in the synthesis of (5Z)-5-(2,3-dihydro-1,4-benzodioxan-6-ylmethylene)-1-methyl-2-thioxoimidazolidin-4-one. It was screened as a fragment for inhibitors of PDEA using enthalpy arrays and X-ray crystallography. 1,4-Benzodioxane-6-carboxaldehyde have also been used as an intermediate in the synthesis of a new class of Dopamine D3 and D4 receptor antagonists.

References

https://www.alfa.com/zh-cn/catalog/A18696/ Jiang, Ji Miao, et al. "Study on the synthesis and anti-tumor activity of novel chalcone analogues." Chemical Research & Application 22.11(2010): 1405-1408.

InChI:InChI=1/C9H8O3/c10-4-7-1-2-9-8(3-7)5-11-6-12-9/h1-4H,5-6H2

Synthetic route

ethylene dibromide (106-93-4) + 3,4-dihydroxybenzaldehyde (139-85-5) → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 70℃; for 16h;	97%
With caesium carbonate In DMF (N,N-dimethyl-formamide) at 70℃; for 16h;	97%
With sodium hydroxide; tetrabutylammomium bromide In water	90%

1,2-dichloro-ethane (107-06-2) + 3,4-dihydroxybenzaldehyde (139-85-5) → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 105℃; for 4h;	90%
With potassium carbonate In acetone at 50 - 60℃; for 29h;

9-methyl-9H-fluorene-9-carbonyl chloride (82102-37-2) + 6-bromo-1,4-benzodioxane (52287-51-1) → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
With dichloro(1,5-cyclooctadiene)palladium(II); N-Methyldicyclohexylamine; potassium formate; tetra-(n-butyl)ammonium iodide; tricyclohexylphosphine tetrafluoroborate; bis(dibenzylideneacetone)-palladium(0); tri tert-butylphosphoniumtetrafluoroborate at 100℃; for 18h; Reagent/catalyst; Solvent; Sealed tube; Glovebox; Inert atmosphere;	81%

benzo-1,4-dioxane (493-09-4) + hexamethylenetetramine (100-97-0) → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
In trifluoroacetic acid at 90 - 95℃; for 24h;	72%

benzo-1,4-dioxane (493-09-4) + hydrogen cyanide (74-90-8) → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
With hydrogenchloride; aluminium trichloride Zersetzung des Reaktionsprodukts durch Erhitzen mit verd. Salzsaeure;

benzo-1,4-dioxane (493-09-4) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
With N-Bromosuccinimide; n-butyllithium 1) MeOH, 2) THF, -78 deg C; Multistep reaction;

2,3-dihydro-benzo<1,4>dioxin in benzene → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
With zinc(II) cyanide; hydrogenchloride; aluminium trichloride anschliessendes Behandeln mit wss. Salzsaeure;

ethylene dibromide (106-93-4) + disodium compound of protocatechualdehyde → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
With ethanol

3,4-dihydroxybenzaldehyde (139-85-5) + ethylene dihalide → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide

1-benzoyl-1-<2-(hydroxy)phenoxy>ethane (78490-09-2) → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1) AlCl3, 2) 10percent HCl / 1) benzene, temp ,40 deg C, 2) benzene, 1 h, 50 deg C 2: 48percent HBr / 15 h / Ambient temperature 3: 48 percent / NaOMe / methanol / 24 h / Heating View Scheme

Conditions	Yield
Multi-step reaction with 4 steps 1: 78 percent / NaOEt / dimethylformamide / 0.5 h / Ambient temperature 2: 1) AlCl3, 2) 10percent HCl / 1) benzene, temp ,40 deg C, 2) benzene, 1 h, 50 deg C 3: 48percent HBr / 15 h / Ambient temperature 4: 48 percent / NaOMe / methanol / 24 h / Heating View Scheme

1-benzoil-1-<(2-idrossi-5-formil)fenossi>etano → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 48percent HBr / 15 h / Ambient temperature 2: 48 percent / NaOMe / methanol / 24 h / Heating View Scheme

benzene-1,2-diol (120-80-9) + 1,2-bis<2-(-p-toluenesulfonyloxy)ethoxy>amine → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide; water / 100 °C 2: hydrogen chloride; aluminium chloride / Zersetzung des Reaktionsprodukts durch Erhitzen mit verd. Salzsaeure View Scheme

6-iodo-1,4-benzodioxane (57744-67-9) → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium formate; palladium diacetate; 1,2-bis-(diphenylphosphino)ethane / dimethyl sulfoxide / Inert atmosphere; Sealed tube 2: water View Scheme

C13H17NO2 → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
With water

3,4-dibromobenzaldehyde (74003-55-7) + ethylene glycol (107-21-1) → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
With potassium carbonate; triethylamine In N,N-dimethyl-formamide at 80℃; Inert atmosphere;

vanillin (121-33-5) → 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride; pyridine / dichloromethane / 24 h / Reflux 2: potassium carbonate / N,N-dimethyl-formamide / 100 - 110 °C View Scheme

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + ethyl acetoacetate (141-97-9) → α-acetyl-(2,3-dihydro-1,4-benzodioxin-6-yl)propenoic acid ethyl ester

Conditions	Yield
With piperidine; acetic acid In benzene for 15h; Heating;	100%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + 1-phenyl-3-trimethylsilylmethyl-3,4-pentadien-1-ol (312298-12-7) → 6-((2S,6S)-3,4-Dimethylene-6-phenyl-tetrahydro-pyran-2-yl)-2,3-dihydro-benzo[1,4]dioxine

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate In diethyl ether at -78℃; for 4h;	100%

trimethylsulphonium iodide (2181-42-2) + 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → 6-Oxiranyl-2,3-dihydro-benzo[1,4]dioxine (389124-25-8)

Conditions	Yield
With potassium hydroxide; water In acetonitrile at 60℃; for 1.5h;	100%

diethoxyphosphoryl-acetic acid ethyl ester (867-13-0) + 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → (E)-ethyl 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylate (84959-25-1)

Conditions	Yield
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With lithium chloride In tetrahydrofuran at 20℃; for 0.25h; Horner-Wadsworth-Emmons Olefination; Inert atmosphere; Stage #2: 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran Horner-Wadsworth-Emmons Olefination; Inert atmosphere;	100%
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde In tetrahydrofuran at 20℃; for 17h; Inert atmosphere;	93%

nitromethane (75-52-5) + 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → (E)-6-(2-nitrovinyl)-2,3-dihydro[1,4]benzodioxine (10554-65-1)

Conditions	Yield
With ammonium acetate at 100℃; Inert atmosphere;	99%
With ethanol; methylamine hydrochloride; sodium carbonate
With sodium hydroxide at 15℃;
Henry reaction;

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → 2,3-dihydro-1,4-benzodioxin-6-carboxylic acid (4442-54-0)

Conditions	Yield
With sodium chlorite; sodium dihydrogen phosphate; 2-methyl-but-2-ene In water; tert-butyl alcohol at 20℃; for 45h;	99%
With urea hydrogen peroxide adduct; sodium hydroxide In methanol; water for 1.5h; Reflux;	81%
With potassium permanganate at 70 - 80℃; for 0.666667h;	76%

1-(4-fluorophenyl)-1H-indazole-5-amine (934601-20-4) + 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-(1-(4-fluorophenyl)-1H-indazol-5-yl)methanimine

Conditions	Yield
With magnesium sulfate In dichloromethane at 20℃; for 48h;	99%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → 2,3-dihydro-1,4-benzodioxin-6-carboxaldehyde-α-d1

Conditions	Yield
With 1,3-bis[2,6-bis(1-methylethyl)phenyl]-4,5-dihydro-1H-imidazolium bromide; water-d2; potassium carbonate In toluene at 40℃; for 12h;	99%
With 1,3,5-triscyano-2,4,6-tris(N-carbazolyl)benzene; water-d2; sodium carbonate; triisopropylsilanethiol In ethyl acetate at 20℃; for 36h; Inert atmosphere; Sealed tube; Irradiation;	91%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + malononitrile (109-77-3) → 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)malononitrile

Conditions	Yield
With nickel(II) ferrite In ethanol at 20℃; for 32h; Knoevenagel Condensation; Green chemistry;	98.9%
With triethylamine In methanol Reflux;
With piperidine In ethanol at 20℃; for 2h;

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → dihydrobenzo[1,4]dioxin-6-ol (10288-72-9)

Conditions	Yield
With potassium fluoride; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; Cooling with ice;	98%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 50℃; for 16h;	94%
Stage #1: 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 50℃; for 16h; Stage #2: With sodium hydroxide In methanol; water for 2h;	94%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → 2,3-dihydrobenzo[b][1,4]dioxin-6-carbaldoxime (31127-39-6)

Conditions	Yield
With hydroxylamine hydrochloride; sodium hydroxide In ethanol at 80℃; for 4h; Inert atmosphere;	98%
With hydroxylamine hydrochloride; sodium acetate In ethanol for 12h;
With hydroxylamine hydrochloride; sodium carbonate In ethanol; water at 60℃; for 1h;

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + dimethyl 2-((tertbutyldiphenylsilyl)methyl)cyclopropane-1,1-dicarboxylate (362610-79-5) → 5-[(tert-butyl-diphenyl-silanyl)-methyl]-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-dihydro-furan-3,3-dicarboxylic acid dimethyl ester

Conditions	Yield
With scandium tris(trifluoromethanesulfonate) In dichloromethane at 30 - 32℃; for 6h;	98%

1-methyl-2-thioxoimidazolidin-4-one (29181-65-5) + 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → (5Z)-5-(2,3-dihydro-1,4-benzodioxan-6-ylmethylene)-1-methyl-2-thioxoimidazolidin-4-one (1334337-84-6)

Conditions	Yield
With propylamine at 80℃; for 1h; Knoevenagel condensation; Microwave irradiation;	98%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → 2,3-dihydrobenzo[b][1,4]dioxine-6-carbonitrile (19102-07-9)

Conditions	Yield
With HCl·DMPU; hydroxylamine hydrochloride In acetonitrile at 60℃;	98%
With oxygen; acetonitrile; copper(l) chloride In N,N-dimethyl acetamide at 130℃; for 24h; Schlenk technique;	87%
With ammonia; oxygen In tert-Amyl alcohol at 40℃; under 750.075 Torr; for 24h; Green chemistry;	85%
With hydroxylamine hydrochloride; sodium sulfate In N,N-dimethyl-formamide at 170℃; for 4h;	81%
Multi-step reaction with 2 steps 1.1: hydroxylamine hydrochloride / methanol; water / 0.5 h / 20 °C 1.2: 20 °C 2.1: acetic anhydride / Reflux View Scheme

4-chloro-2-hydroxy acetophenone (6921-66-0) + 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → (E)-1-(4-chloro-2-hydroxyphenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)prop-2-en-1-one (96755-02-1)

Conditions	Yield
With sodium hydroxide In ethanol for 40h; Ambient temperature;	97%
With potassium hydroxide In ethanol Ambient temperature;	97%
With sodium hydroxide In methanol at 20℃;	37.89%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → (2,3-dihydro-benzo[1,4]dioxin-6-yl)-methanol (39270-39-8)

Conditions	Yield
Stage #1: 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde With sodium tetrahydroborate In ethanol at 0 - 20℃; for 1h; Stage #2: With water In ethanol	97%
With methanol; sodium tetrahydroborate at 0℃; for 0.5h;	95%
With sodium tetrahydroborate In methanol at 25℃; for 2h;	93%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + (trifluoromethyl)trimethylsilane (81290-20-2) → 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2,2,2-trifluoroethanol (923170-94-9)

Conditions	Yield
Stage #1: 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde; (trifluoromethyl)trimethylsilane With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 4h; Stage #2: With water In N,N-dimethyl-formamide for 4h; Acidic conditions;	97%

5-Bromo-2-hydroxyacetophenone (1450-75-5) + 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → (E)-1-(5-bromo-2-hydroxyphenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)prop-2-en-1-one (96755-06-5)

Conditions	Yield
With sodium hydroxide In ethanol for 40h; Ambient temperature;	96%
With potassium hydroxide In ethanol Ambient temperature;	96%
With sodium hydroxide In methanol at 20℃;	58.33%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + 1-(2-benzyloxy-5-fluorophenyl)-ethanone (1799-18-4) → 1-(2-benzyloxy-5-fluorophenyl)-3-(6-benzodioxan-1,4-yl)propenone (96755-16-7)

Conditions	Yield
With sodium hydroxide In ethanol for 40h; Ambient temperature;	96%
With potassium hydroxide In ethanol Ambient temperature;	96%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + 1-(2-(benzyloxy)-5-bromophenyl)ethanone (69822-20-4) → 1-(2-benzyloxy-5-bromophenyl)-3-(6-benzodioxan-1,4-yl)propenone (96755-14-5)

Conditions	Yield
With sodium hydroxide In ethanol for 40h; Ambient temperature;	96%
With potassium hydroxide In ethanol Ambient temperature;	96%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + 4-methoxy-aniline (104-94-9) + Dimethyl phosphite (868-85-9) → dimethyl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(4-methoxyphenylamino)methylphosphonate (1582309-56-5)

Conditions	Yield
With titanium(IV) oxide In neat (no solvent) at 50℃; for 0.166667h; Green chemistry;	96%

hydrogen cyanide (74-90-8) + 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-hydroxyacetonitrile

Conditions	Yield
With Prunus communis hydroxynitrile lyase 5 L331A mutant In tert-butyl methyl ether at 10℃; for 12h; pH=3.5; Catalytic behavior; Reagent/catalyst; Enzymatic reaction; enantioselective reaction;	96%
With hydroxynitrile lyase isozyme 5 from Prunus communis In tert-butyl methyl ether at 25℃; for 7h; pH=5; Enzymatic reaction;	84%
With (R)-oxynitrilase In di-isopropyl ether Enzymatic reaction;

1-<5-chloro-2-(phenylmethoxy)phenyl>ethanone (42972-62-3) + 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) → 1-(2-benzyloxy-5-chlorophenyl)-3-(6-benzodioxan-1,4-yl)propenone (96755-15-6)

Conditions	Yield
With sodium hydroxide In ethanol; water for 40h; Ambient temperature;	95%
With potassium hydroxide In ethanol Ambient temperature;	95%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + 2-benzyloxy-4,5-dimethylacetophenone (69822-19-1) → 1-(2-benzyloxy-4,5-dimethylphenyl)-3-(6-benzodioxan-1,4-yl)propenone (96755-18-9)

Conditions	Yield
With sodium hydroxide In ethanol for 40h; Ambient temperature;	95%
With potassium hydroxide In ethanol Ambient temperature;	95%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + malonic acid dimethyl ester (108-59-8) → C14H14O6 (1267658-51-4)

Conditions	Yield
With piperidine; acetic acid In benzene Knoevenagel condensation;	95%
With piperidine; acetic acid In benzene Dean-Stark; Reflux;

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + p-toluidine (106-49-0) + Dimethyl phosphite (868-85-9) → dimethyl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(p-tolylamino)methylphosphonate (1582309-57-6)

Conditions	Yield
With titanium(IV) oxide In neat (no solvent) at 50℃; for 0.2h; Green chemistry;	95%

2-aminofluorene (153-78-6) + 2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + Dimethyl phosphite (868-85-9) → dimethyl (((9H-fluoren-2-yl)amino)(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)phosphonate (1618086-78-4)

Conditions	Yield
With polystyrene-supported p-toluenesulfonic acid In neat (no solvent) at 70℃; for 0.0833333h; Kabachnik-Fields Reaction; Microwave irradiation; Green chemistry;	95%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + 4-amino-1-phenylpiperazine (14340-32-0) → (E)-N-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-4-phenylpiperazin-1-amine

Conditions	Yield
In toluene at 100℃;	95%

2,3-dihydro-benzo[1,4]dioxin-6-carbaldehyde (29668-44-8) + acrylic acid methyl ester (292638-85-8) → methyl 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(hydroxy)methyl)acrylate

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane at 30 - 40℃; Morita-Baylis-Hillman Alkylation; Sonication;	95%
With 1,4-diaza-bicyclo[2.2.2]octane In methanol at 20℃; Morita-Baylis-Hillman Alkylation;

Upstream product

• 106-93-4 ethylene dibromide 
• 139-85-5 3,4-dihydroxybenzaldehyde 
• 121-33-5 vanillin 
• 107-06-2 1,2-dichloro-ethane 
• 74003-55-7 3,4-dibromobenzaldehyde 
• 107-21-1 ethylene glycol 
• 57744-67-9 6-iodo-1,4-benzodioxane 
• 82102-37-2 9-methyl-9H-fluorene-9-carbonyl chloride 
• 52287-51-1 6-bromo-1,4-benzodioxane 
• 120-80-9 benzene-1,2-diol 
• 86301-73-7 1-benzoil-1-<(2-idrossi-5-formil)fenossi>etano 
• 78490-09-2 1-benzoyl-1-<2-(hydroxy)phenoxy>ethane 
• 493-09-4 benzo-1,4-dioxane 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 106584-16-1 1-(2-hydroxy-5-methoxyphenyl)-3-(6-benzodioxan-1,4-yl)propenone 
• 96755-09-8 (E)-1-(4-Benzyloxy-2-hydroxy-phenyl)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-propenone 
• 96755-05-4 1-(2-hydroxy-4-methoxyphenyl)-3-(6-benzodioxan-1,4-yl)propenone 
• 106584-17-2 1-(2-hydroxy-5-methylphenyl)-3-(6-benzodioxan-1,4-yl)propenone 
• 96755-07-6 (E)-1-(5-chloro-2-hydroxyphenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)prop-2-en-1-one 
• 128126-69-2 7-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-2-(4-methoxy-phenyl)-4-methyl-6,7-dihydro-thiopyrano[2,3-d]pyrimidin-5-one 
• 96755-04-3 1-(2-hydroxy-4-methylphenyl)-3-(6-benzodioxan-1,4-yl)propenone 
• 106584-18-3 1-(3,5-dichloro-2-hydroxyphenyl)-3-(6-benzodioxan-1,4-yl)propenone 
• 138621-63-3 3-amino-3-(2,3-dihydrobenzo[b] [1,4]dioxin-6-yl)propanoic acid 
• 96755-10-1 1-(2-hydroxy-4,5-dimethylphenyl)-3-(6-benzodioxan-1,4-yl)propenone 
• 96755-01-0 1-(3-chloro-2-hydroxyphenyl)-3-(6-benzodioxan-1,4-yl)propenone 
• 96755-11-2 1-(2-benzyloxyphenyl)-3-(6-benzodioxan-1,4-yl)propenone 
• 96755-20-3 1-(2-benzyloxy-5-methylphenyl)-3-(6-benzodioxan-1,4-yl)propenone 
• 96755-15-6 1-(2-benzyloxy-5-chlorophenyl)-3-(6-benzodioxan-1,4-yl)propenone 

Relevant articles and documents

Synthesis of phenylpiperazine derivatives of 1,4-benzodioxan as selective COX-2 inhibitors and anti-inflammatory agents

1-((2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-4-substituted-phenylpiperazine moiety was prepared and has been found to be a new and selective ligand for the enzyme cyclooxygenase-2 (COX-2). The biological activity of compound 3k as anti-inflammatory agent was further investigated both in vitro and in vivo. Notably, compound 3k exhibited the best anti-inflammatory activity among the eleven designed compounds with no toxicity, as determined by the ulcerogenic activity. Computational docking studies also showed that compound 3k has interaction with COX-2 key residues in the active site. Compound 3k maybe a new anti-inflammatory lead-candidate as powerful and novel non-ulcerogenic.

CONDENSED HETEROCYCLIC COMPOUND HAVING 1,4-BENZO DIOXANE RING OR SALT THEREOF, AND ANTI-JUVENILE HORMONE AGENT COMPOSED OF THE COMPOUND

PROBLEM TO BE SOLVED: To provide a pest control agent containing a practical juvenile hormone antagonist activity compound as an active ingredient. SOLUTION: By using a reporter gene assay system that uses a juvenile hormone sequence, a heterocyclic compound having an antagonist activity is discovered, and a pest control agent containing the compound as an active ingredient is provided. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2020,JPOandINPIT

Synthesis, characterization, and docking studies of novel cyanopyridone analogs with serotonin 5-HT1B receptor agonists

The medications in use for treating migraine are directed either towards inhibiting the characteristic migraine pain or towards preventing it from occurring. In this pursuit, ergotamine and sumatriptan class of 5-HT1B receptor agonists have been proved to be extremely effective. Further research into this field led us to design cyanopyridone derivatives that were synthesized through cyclization of 2-cyano-N-phenylacetamides with malonitrile and 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde. The synthesized cyanopyridones analogs, when docked with active site of 5-HT1B receptor, showed better binding affinity compared to standard antimigraine medications. Additionally, in silico ADME prediction for drug-likeness and pharmacokinetics revealed that all compounds are safer and can be used as antimigraine medicine. The structure of the synthesized compounds has been elucidated on the basis of spectral analysis.