82104-74-3

Basic information

• Product Name: 5-Cyanophthalide
• Synonyms: 5-CYANO-3H-ISOBENZOFURANONE;5-CYANOPHTHALIDE;1,3-DIHYDRO-1-OXO-5-ISOBENZOFURANCARBONITRILE;1,3-DIHYDRO-1-OXOISOBENZOFURAN-5-CARBONITRILE;1-OXO-1,3-DIHYDRO-2-BENZOFURAN-5-CARBONITRILE;5-Phthalidenitrile;5-CYANO- PHTHALIDE/1-(4-FLUOROPHENYL)-1,3-DIHYROSOBENZOFURAN-5-CARBONITRILE;5-Cyanophthaleine
• CAS NO: 82104-74-3
• Molecular Formula: C₉H₅NO₂
• Molecular Weight: 159.14
• EINECS: 279-900-2
• Product Categories: Phthalides;INTERMEDIATESOFCITALOPRAM;API intermediates;Aromatics Compounds;Aromatics;Miscellaneous Reagents
• Mol File: 82104-74-3.mol
• Article Data: 13

Chemical Properties

• Melting Point: 201-205 °C(lit.)
• Boiling Point: 407.5 °C at 760 mmHg
• Flash Point: 199.3 °C
• Appearance: White to light yellow/Crystalline Powder
• Density: 1.36 g/cm³
• Vapor Pressure: 7.53E-07mmHg at 25°C
• Refractive Index: 1.606
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Acetone (Slightly), Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: 5-Cyanophthalide(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Cyanophthalide(82104-74-3)
• EPA Substance Registry System: 5-Cyanophthalide(82104-74-3)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 20/21/22-36/37/38
• Safety Statements: 36/37-36-26
• RIDADR: 3439
• WGK Germany: 3
• Hazardous Substances Data: 82104-74-3(Hazardous Substances Data)

Usage

Uses

5-Cyanophthalide is a useful synthetic intermediate.

InChI:InChI=1/C9H5NO2/c10-4-6-1-2-8-7(3-6)5-12-9(8)11/h1-3H,5H2

Synthetic route

5-hydroxamyl phthalide (934473-85-5) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
With thionyl chloride at 80℃; for 6h; Product distribution / selectivity; Heating / reflux;	91%

5-carboxyphtalide (4792-29-4) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
Stage #1: 5-carboxyphtalide With ethyl phosphate; ammonium carbonate In acetonitrile at 0 - 25℃; for 6h; Stage #2: at 90 - 95℃; for 12h;	89.5%
With thionyl chloride; SULFAMIDE In sulfolane; water
With thionyl chloride; SULFAMIDE In sulfolane; water

potassium cyanide + 5-bromophthalide (64169-34-2) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
Stage #1: potassium cyanide With acetic acid In ethylene glycol at 20℃; Sealed tube; Stage #2: 5-bromophthalide With P(t-Bu)3 Palladacycle Gen. 3; potassium acetate In 1,4-dioxane; water at 60℃; for 16h; Sealed tube;	84%

5-bromophthalide (64169-34-2) + 2-methyl-2-phenylmalononitrile (86164-70-7) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
With C10H8Br2N2Ni*(x)H2O; zinc In N,N-dimethyl acetamide at 80℃; for 16h; Inert atmosphere; Sealed tube;	57%

4-cyanopyridine N-oxide (14906-59-3) + 5-bromophthalide (64169-34-2) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
With potassium fluoride; 4,4'-dimethyl-2,2'-bipyridines; trifluoroacetic acid; sodium iodide; nickel dichloride; zinc In N,N-dimethyl acetamide at 60℃; for 36h;	38%

1-oxo-3-hydroxy-1,3-dihydro-N-phenylisoindole-5-carbonitrile (389613-68-7) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
Stage #1: 1-oxo-3-hydroxy-1,3-dihydro-N-phenylisoindole-5-carbonitrile With sodium tetrahydroborate In methanol at 20℃; for 24h; Stage #2: With hydrogenchloride In methanol at 20℃; for 48h; pH=1;	35%

5-amino-3H-isobenzofuran-1-one (65399-05-5) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
With potassium cyanide; copper(II) sulfate ueber eine wss. Diazoniumsalz-Loesung;

4-cyanobenzanilide (17922-96-2) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: BuLi / hexamethylphosphoric acid triamide; tetrahydrofuran / 0.67 h / -20 - 20 °C 1.2: 68 percent / tetrahydrofuran; hexamethylphosphoric acid triamide / -78 - 20 °C 2.1: NaBH4 / methanol / 24 h / 20 °C 2.2: 35 percent / aq. HCl / methanol / 48 h / 20 °C / pH 1 View Scheme

4-cyanobenzoyl chlorIde (6068-72-0) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 92 percent / pyridine / CH2Cl2 / 20 h 2.1: BuLi / hexamethylphosphoric acid triamide; tetrahydrofuran / 0.67 h / -20 - 20 °C 2.2: 68 percent / tetrahydrofuran; hexamethylphosphoric acid triamide / -78 - 20 °C 3.1: NaBH4 / methanol / 24 h / 20 °C 3.2: 35 percent / aq. HCl / methanol / 48 h / 20 °C / pH 1 View Scheme

(E,Z)-1-oxo-1,3-dihydroisobenzofuran-5-carbaldehyde oxime (452978-39-1) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
Stage #1: (E,Z)-1-oxo-1,3-dihydroisobenzofuran-5-carbaldehyde oxime With triethylamine; trifluoroacetic acid In tetrahydrofuran at 0 - 20℃; for 1h; Stage #2: With sodium hydrogencarbonate In tetrahydrofuran; water

4,4-dimethyl-2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)oxazoline (265137-37-9) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
In thionyl chloride; water; N,N-dimethyl-formamide; toluene	11.9 g (75%)

thionyl chloride (7719-09-7) + 1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
In N,N-dimethyl-formamide; toluene

5-bromophthalide (64169-34-2) + Cu(CN)2 → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
In water

5-bromophthalide (64169-34-2) + Zn(CN)2 → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
tetrakis(triphenylphosphine)palladium (0) In N,N-dimethyl-formamide
With NaCN; tetrakis(triphenylphosphine)palladium (0) In N,N-dimethyl-formamide

5-iodoisobenzofuran-1(3H)-one (41284-92-8) + Zn(CN)2 → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
tetrakis(triphenylphosphine)palladium (0) In N,N-dimethyl-formamide

5-chloro-3H-isobenzofuran-1-one (54109-03-4) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
With NaCN; triphenylphosphine; nickel dichloride In tetrahydrofuran; water; acetonitrile

(1-oxo-1,3-dihydroisobenzofuran-5-yl)carbonyl chloride (227954-90-7) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
With SULFAMIDE In sulfolane; water

3,4-bis(hydroxymethyl)benzonitrile (1446757-51-2) → 6-cyanoisobenzofuran-1(3H)-one (89877-62-3) + 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
With Oxone; 2-iodo-3,4,5,6-tetramethylbenzoic acid In water; acetonitrile at 30℃; for 8h; Green chemistry; Overall yield = 56 %;

methanol (67-56-1) + 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) → methyl 2-(chloromethyl)-4-cyanobenzoate

Conditions	Yield
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile With thionyl chloride; boron trifluoride diethyl etherate; N-benzyl-N,N,N-triethylammonium chloride at 90℃; for 72h; Stage #2: methanol With N-ethyl-N,N-diisopropylamine In ethanol; dichloromethane pH=8;	99%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + 4-dimethylamino-benzaldehyde (100-10-7) → 5-cyano-2-(p-dimethylaminophenyl)indan-1,3-dione

Conditions	Yield
With sodium methylate In ethyl acetate for 0.166667h; Heating;	98%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) → sodium 4-cyano-2-(hydroxymethyl)benzoate

Conditions	Yield
With sodium hydroxide In water for 2h; Reflux;	97%
With sodium hydroxide In tetrahydrofuran; water at 20℃; for 2h;

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) → potassium 4-cyano-2-(hydroxymethyl)benzoate

Conditions	Yield
With potassium hydroxide In water; isopropyl alcohol at 35 - 40℃; for 2h;	97%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) → (1-oxo-1,3-dihydroisobenzofuran-5-yl)methanaminium chloride

Conditions	Yield
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile With ammonia; hydrogen In water; isopropyl alcohol at 80℃; under 15001.5 Torr; for 24h; Autoclave; Stage #2: With hydrogenchloride In methanol; ethyl acetate Cooling with ice;	95%
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile With ammonium hydroxide; hydrogen In water; isopropyl alcohol under 37503.8 Torr; for 4h; Autoclave; Heating; Stage #2: With hydrogenchloride In methanol	90%
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile With borane-ammonia complex; C17H16BrMnN2O3S In hexane at 60℃; for 12h; Stage #2: With hydrogenchloride In diethyl ether; water	50%
Multi-step reaction with 2 steps 1: palladium 10% on activated carbon / 1,4-dioxane; water / 16 h / 80 °C 2: hydrogenchloride / water / 100 °C View Scheme

3-(N,N-dimethylamino)propylmagnesium chloride (19070-16-7) + 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + 4-flourophenylmagnesium bromide (352-13-6) → 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile (103146-25-4)

Conditions	Yield
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile; 4-flourophenylmagnesium bromide With diethylene glycol dimethyl ether; tetrabutyl-ammonium chloride In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #2: 3-(N,N-dimethylamino)propylmagnesium chloride In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	90%
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile; 4-flourophenylmagnesium bromide In tetrahydrofuran at 0 - 20℃; for 3.5h; Grignard reaction; Stage #2: 3-(N,N-dimethylamino)propylmagnesium chloride In tetrahydrofuran at 0 - 20℃; Grignard reaction;	79%
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile; 4-flourophenylmagnesium bromide In tetrahydrofuran at -5℃; for 0.25h; Stage #2: 3-(N,N-dimethylamino)propylmagnesium chloride In tetrahydrofuran at -5℃;
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile; 4-flourophenylmagnesium bromide In tetrahydrofuran at -5℃; for 0.25h; Stage #2: 3-(N,N-dimethylamino)propylmagnesium chloride In tetrahydrofuran at -5 - 20℃; for 0.5h; Stage #3: With hydrogenchloride; water In tetrahydrofuran pH=2; Product distribution / selectivity;
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile; 4-flourophenylmagnesium bromide In tetrahydrofuran at 5 - 15℃; for 4h; Inert atmosphere; Stage #2: 3-(N,N-dimethylamino)propylmagnesium chloride In tetrahydrofuran at 0 - 15℃; for 4h;	98.8 g

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) → 4-cyano-2-hydroxymethylbenzoic acid (1378843-02-7)

Conditions	Yield
With lithium hydroxide In methanol; water for 5h; Solvent; Reagent/catalyst;	87.3%
With sodium hydroxide In tetrahydrofuran; water at 20℃; for 0.25h;

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + pivaloyl chloride (3282-30-2) + 4-flourophenylmagnesium bromide (352-13-6) → 5-cyano-2-(4-fluorobenzoyl)benzyl pivalate

Conditions	Yield
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile; 4-flourophenylmagnesium bromide In tetrahydrofuran; dichloromethane at 0 - 25℃; for 18h; Stage #2: pivaloyl chloride In tetrahydrofuran; dichloromethane at 60℃; for 2h;	87%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + methylmagnesium bromide (75-16-1) → 3-(hydroxymethyl)-4-(1-hydroxy-1-methylethyl)benzonitrile (1109262-40-9)

Conditions	Yield
In tetrahydrofuran at -30℃; for 1h;	87%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) → 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (64169-67-1)

Conditions	Yield
In tetrahydrofuran; chloroform	86.5%
In tetrahydrofuran; 1,2-dichloro-ethane	85%
In tetrahydrofuran; chlorobenzene	78%
In tetrahydrofuran; benzene	78%
In tetrahydrofuran; toluene	70%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + 4-flourophenylmagnesium bromide (352-13-6) → 4-(4-fluorobenzoyl)-3-(hydroxymethyl)benzonitrile (260371-16-2)

Conditions	Yield
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile; 4-flourophenylmagnesium bromide In tetrahydrofuran; 1,2-dimethoxyethane at -10℃; for 3.5h; Stage #2: With water; ammonium chloride In tetrahydrofuran; 1,2-dimethoxyethane at 20℃; for 0.0833333h;	86.2%
In tetrahydrofuran at 0 - 5℃; for 5h; Solvent; Temperature;	85%
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile; 4-flourophenylmagnesium bromide In tetrahydrofuran; dichloromethane at -6 - -2℃; Stage #2: With water; ammonium chloride In tetrahydrofuran; dichloromethane
In tetrahydrofuran; toluene at -4 - -2℃; Product distribution / selectivity;

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) → N'-hydroxy-1-oxo-1,3-dihydroisobenzofuran-5-carboximidamide (1146973-38-7)

Conditions	Yield
With hydroxylamine In ethanol; water at 20℃; for 63h; Heating / reflux;	86.2%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + magnesium (7439-95-4) + 1-Bromo-4-fluorobenzene (460-00-4) → 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (64169-67-1)

Conditions	Yield
Stage #1: magnesium; 1-Bromo-4-fluorobenzene; iodine In tetrahydrofuran Stage #2: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile In tetrahydrofuran; dichloromethane at -6 - -2℃;	86%
Stage #1: magnesium; 1-Bromo-4-fluorobenzene; iodine In tetrahydrofuran Stage #2: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile In tetrahydrofuran; toluene at -6 - -2℃;

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + 4-flourophenylmagnesium bromide (352-13-6) → 4-(bis(4-fluorophenyl)hydroxymethyl)-3-(hydroxymethyl)benzonitrile (762266-07-9)

Conditions	Yield
In toluene at 0 - 80℃; for 10h; Temperature; Solvent;	84%
In tetrahydrofuran at 0 - 20℃; for 17h; Inert atmosphere;	64.18%
In tetrahydrofuran at 25 - 35℃;

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + 2-Methyl-1-phenyl-2-propanol (100-86-7) → 5-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)isobenzofuran-1(3H)-one

Conditions	Yield
With sulfuric acid In toluene at 0 - 20℃;	82%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) → 3,4-bis(hydroxymethyl)benzonitrile (1446757-51-2)

Conditions	Yield
With phenylsilane; potassium hydroxide In tetrahydrofuran at 66℃; for 6h;	75%
With phenylsilane; potassium hydroxide In tetrahydrofuran for 4h; Schlenk technique; Inert atmosphere; Reflux;	68%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + C16H25N → C24H29NO2

Conditions	Yield
With tris[2-phenylpyridinato-C2,N]iridium(III); sodium acetate In N,N-dimethyl acetamide at 20℃; for 2h; Inert atmosphere; Glovebox; Irradiation; diastereoselective reaction;	73%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + 1-(tert-butoxycarbonyl)-L-proline (15761-39-4) → tert-butyl 2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)pyrrolidine-1-carboxylate (1588517-25-2)

Conditions	Yield
With Ir[p-F(tert-butyl)2-phenylpyridine]3; cesium fluoride In dimethyl sulfoxide at 20℃; for 48h; Inert atmosphere; Irradiation;	70%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + N-carbobenzyloxyproline (1148-11-4) → benzyl 2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)pyrrolidine-1-carboxylate

Conditions	Yield
With 1-(4-(9H-carbazol-9-yl)phenyl)-3-amino-9H-fluorene-2,4-dicarbonitrile; cesium fluoride In dimethyl sulfoxide at 20℃; for 24h; Inert atmosphere; Irradiation;	69%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + 1-Bromo-4-fluorobenzene (460-00-4) → 4-(4-fluorobenzoyl)-3-(hydroxymethyl)benzonitrile (260371-16-2)

Conditions	Yield
Stage #1: 1-Bromo-4-fluorobenzene With magnesium In tetrahydrofuran Reflux; Inert atmosphere; Stage #2: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere;	63%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + ethyl hexa-2,3-dienoate (131431-64-6, 113644-17-0) → 3-ethyl-9-hydroxy-1-oxo-1,3-dihydronaphtho[2,3-c]furan-6-carbonitrile

Conditions	Yield
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.75h; Inert atmosphere; Stage #2: ethyl hexa-2,3-dienoate In tetrahydrofuran; hexane at -78℃; for 0.25h; Inert atmosphere; regioselective reaction;	60%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + di-tert-butyl dicarbonate (24424-99-5) → tert-butyl ((1-oxo-1,3-dihydroisobenzofuran-5-yl)methyl)carbamate

Conditions	Yield
With 1-methyl-pyrrolidin-2-one; sodium tetrahydroborate; nickel(II) chloride hexahydrate at 0 - 20℃; for 12h; Inert atmosphere;	56%

formic acid (64-18-6) + 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) → N-((1-oxo-1,3-dihydroisobenzofuran-5-yl)methyl)formamide

Conditions	Yield
With palladium 10% on activated carbon In 1,4-dioxane; water at 80℃; for 16h;	55%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + (E)-1-phenyl-N-(piperidin-1-yl)methanimine (1885-87-6) → 1-[(E)-benzylideneamino]piperidine-2-carbonitrile + 5-[1-[(E)-benzylideneamino]-2-piperidyl]-3H-isobensofuran-1-one

Conditions	Yield
With tris[2-phenylpyridinato-C2,N]iridium(III); lithium acetate In dimethyl sulfoxide at 40℃; for 0.166667h; Inert atmosphere; Irradiation;	A 15% B 50%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + Methyltriphenylphosphonium bromide (1779-49-3) + 4-flourophenylmagnesium bromide (352-13-6) → 4-(1-(4-fluorophenyl)vinyl)-3-(hydroxymethyl)benzonitrile

Conditions	Yield
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile; 4-flourophenylmagnesium bromide Stage #2: Methyltriphenylphosphonium bromide With potassium tert-butylate	47%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) + ethyl 4-phenylbuta-2,3-dienoate (91962-64-0) → 9-hydroxy-1-oxo-3-phenyl-1,3-dihydronaphtho[2,3-c]furan-6-carbonitrile

Conditions	Yield
Stage #1: 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.75h; Inert atmosphere; Stage #2: ethyl 4-phenylbuta-2,3-dienoate In tetrahydrofuran; hexane at -78℃; for 0.25h; Inert atmosphere; regioselective reaction;	45%

Upstream product

• 14906-59-3 4-cyanopyridine N-oxide 
• 64169-34-2 5-bromophthalide 
• 1975-53-7 4-Cyano-2-methylbenzoic acid 
• 86164-70-7 2-methyl-2-phenylmalononitrile 
• 1446757-51-2 3,4-bis(hydroxymethyl)benzonitrile 
• 227954-90-7 (1-oxo-1,3-dihydroisobenzofuran-5-yl)carbonyl chloride 
• 54109-03-4 5-chloro-3H-isobenzofuran-1-one 
• 41284-92-8 5-iodoisobenzofuran-1(3H)-one 
• 7719-09-7 thionyl chloride 
• 85118-25-8 1-oxo-1,3-dihydroisobenzofuran-5-carboxamide 
• 265137-37-9 4,4-dimethyl-2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)oxazoline 
• 452978-39-1 (E,Z)-1-oxo-1,3-dihydroisobenzofuran-5-carbaldehyde oxime 
• 4792-29-4 5-carboxyphtalide 
• 6068-72-0 4-cyanobenzoyl chlorIde 

Downstream Products

• 219861-08-2 escitalopram oxalate 
• 128196-01-0 escitalopram 
• 128173-53-5 4-(1S)-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile (+)-di-(p-toluoyl)tartaric acid 
• 103146-26-5 4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile hydrobromide 
• 1374150-56-7 ethyl 4-cyano-2-(hydroxymethyl)benzoate 

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Ni-Catalyzed Reductive Cyanation of Aryl Halides and Phenol Derivatives via Transnitrilation

Herein, we report a Ni-catalyzed reductive coupling for the synthesis of benzonitriles from aryl (pseudo)halides and an electrophilic cyanating reagent, 2-methyl-2-phenyl malononitrile (MPMN). MPMN is a bench-stable, carbon-bound electrophilic CN reagent that does not release cyanide under the reaction conditions. A variety of medicinally relevant benzonitriles can be made in good yields. Addition of NaBr to the reaction mixture allows for the use of more challenging aryl electrophiles such as aryl chlorides, tosylates, and triflates. Mechanistic investigations suggest that NaBr plays a role in facilitating oxidative addition with these substrates.

Facile organocatalytic domino oxidation of diols to lactones by in situ-generated TetMe-IBX

The domino oxidation of diols to lactones is an important transformation, and catalytic protocols that allow this conversion smoothly are scarce. Capitalizing on the established reactivity of tetramethyl-IBX (TetMe-IBX) and its in situ generation in the presence of a co-oxidant, such as oxone, we have shown that a variety of diols can be converted to the corresponding lactones in respectable yields by employing the precursor of TetMe-IBX, namely, tetramethyl-o-iodobenzoic acid (TetMe-IA), as a catalyst in 5 mol % in the presence of 2 equiv of oxone.