2678-54-8

Basic information

• Product Name: KETENE DIETHYL ACETAL
• Synonyms: KETENE DIETHYL ACETAL;1,1-DIETHOXYETHENE;1,1-Diethoxyethene, stabilized;KETENE DIETHYL ACETAL STAB. WACKER &;1,1-diethoxyethylene;2-(1-ethoxypropoxy)ethen-1-one;Diethyl ketene acetal;Ethene, 1,1-diethoxy-
• CAS NO: 2678-54-8
• Molecular Formula: C₆H₁₂O₂
• Molecular Weight: 116.16
• Mol File: 2678-54-8.mol
• Article Data: 13

Chemical Properties

• Boiling Point: 49-50 °C(lit.)
• Flash Point: 27 °C
• Appearance: /
• Density: 0.880 g/mL at 20 °C(lit.)
• Vapor Pressure: 34.1mmHg at 25°C
• Refractive Index: n20/D 1.414
• Storage Temp.: 2-8°C
• CAS DataBase Reference: KETENE DIETHYL ACETAL(CAS DataBase Reference)
• NIST Chemistry Reference: KETENE DIETHYL ACETAL(2678-54-8)
• EPA Substance Registry System: KETENE DIETHYL ACETAL(2678-54-8)

Safety Data

• Statements: 10
• Safety Statements: 23
• RIDADR: UN 1993 3/PG 3
• WGK Germany: 3
• Hazardous Substances Data: 2678-54-8(Hazardous Substances Data)

Usage

Uses

1,1-diethoxyethylene can be used as organic synthesis intermediate and pharmaceutical intermediate, mainly used in laboratory research and development process and chemical production process.

Synthesis

Preparation of 1,1-diethoxyethene 610.4 g (4.0 mol) of chloroacetaldehyde diethyl acetal, 800 g (12.0 mol) of powdered technical grade potassium hydroxide, 32 g of polyethylene glycol 1000 dimethyl ether and 88 g (1.0 mol) of 2-methyl-2-butanol were heated to reflux in 1.2 l of tert.-butyl methyl ether while stirring. After six hours the reaction was stopped, the salts filtered off and the reaction mixture distilled at reduced pressure (5 kPa). 326 g (72.5% of theoretical) of 1,1-diethoxyethene (b.p. 49° C./5 kPa) were obtained.

InChI:InChI=1/C6H12O2/c1-4-7-6(3)8-5-2/h3-5H2,1-2H3

Synthetic route

Bromoacetaldehyde diethyl acetal (2032-35-1) → ketene diethyl acetal (2678-54-8)

Conditions	Yield
With potassium hydroxide In dimethyl sulfoxide at 130 - 140℃; under 100 Torr;	92%
With potassium tert-butylate for 0.1 - 0.183333h; Cooling with ice;	72%
With potassium tert-butylate at 20℃; Reflux; Inert atmosphere;	69.9%

XCH2CH(OCH2CH3)2 → ketene diethyl acetal (2678-54-8)

Conditions	Yield
With 18-crown-6 ether; potassium tert-butylate In tetrahydrofuran at 0℃; for 2h; Elimination;	70%

β-(1,1-diethoxy-ethoxy)-chalcone (855175-05-2) → ketene diethyl acetal (2678-54-8) + 1,3-diphenylpropanedione (120-46-7)

Conditions	Yield
at 140℃; under 38 Torr;

Triethyl orthoacetate (78-39-7) → ketene diethyl acetal (2678-54-8)

Conditions	Yield
With aluminium tert-butyl oleate at 180℃;

potassium tert-butylate (865-47-4) + 1,1-diethoxy-2-iodoethane (51806-20-3) → ketene diethyl acetal (2678-54-8)

1,1-diethoxy-2-iodoethane (51806-20-3) → ketene diethyl acetal (2678-54-8)

Conditions	Yield
With potassium tert-butylate
With potassium tert-butylate

1,1-Diethoxy-ethylamine; hydrochloride → ketene diethyl acetal (2678-54-8)

Conditions	Yield
With sodium methylate for 0.666667h; Ambient temperature; Yield given;

orthobromoacetic acid triethyl ester → ketene diethyl acetal (2678-54-8)

Conditions	Yield
With sodium; benzene

triethyl bromoorthoacetate (40070-39-1) + benzene (71-43-2) + sodium → ketene diethyl acetal (2678-54-8)

tert-Amyl alcohol (75-85-4) + tert-butyl methyl ether (1634-04-4) + ethylene glycol (107-21-1) + chloroacetaldehyde diethyl acetal (621-62-5) → ketene diethyl acetal (2678-54-8)

Conditions	Yield
With potassium hydroxide In Dimethyl ether

tert-Amyl alcohol (75-85-4) + ethylene glycol (107-21-1) + chloroacetaldehyde diethyl acetal (621-62-5) → ketene diethyl acetal (2678-54-8)

Conditions	Yield
With potassium hydroxide In Dimethyl ether; tert-butyl methyl ether

N-propylsulfonylchloralimine (127826-29-3) + ketene diethyl acetal (2678-54-8) → N-(1-trichloromethyl-3,3-diethoxy-2-propenyl)-1-propanesulfonamide

Conditions	Yield
In dichloromethane Ambient temperature;	100%

ketene diethyl acetal (2678-54-8) + 2-ethynyl-N-methyl-cyclohex-1-enecarboximidic acid methyl ester → 1-(2,2-diethoxy-cyclopropyl)-3-methoxy-2-methyl-4,5,6,7-tetrahydro-2H-isoindole

Conditions	Yield
dirhodium tetraacetate In dichloromethane at 20℃; for 2h;	100%

ketene diethyl acetal (2678-54-8) + (2-ethynylcyclohex-1-en-1-yl)(phenyl)methanone (436146-73-5) → 1-(2,2-diethoxy-cyclopropyl)-3-phenyl-4,5,6,7-tetrahydro-isobenzofuran

Conditions	Yield
chromium(0) hexacarbonyl In tetrahydrofuran at 20℃; for 2h;	99%
With pentacarbonyl(tetrahydrofuran)chromium(0) In tetrahydrofuran at 20℃; for 2h;	99%

ketene diethyl acetal (2678-54-8) + methyl 1,2,3-triazine-5-carboxylate → methyl 6-ethoxynicotinate (74357-22-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 60℃; for 0.5h; Diels-Alder reaction; Inert atmosphere; regioselective reaction;	99%

ketene diethyl acetal (2678-54-8) + benzaldehyde (100-52-7) → ethyl cinnamate (4192-77-2)

Conditions	Yield
With (2,4,5-trifluorophenyl)boronic acid In tert-butyl methyl ether at 50℃; for 14h;	98%

4-methyl-benzaldehyde (104-87-0) + ketene diethyl acetal (2678-54-8) → ethyl (E)-3-(4-methylphenyl)acrylate (97585-04-1, 20511-20-0, 24393-49-5)

Conditions	Yield
With (2,4,5-trifluorophenyl)boronic acid In tert-butyl methyl ether at 50℃; for 14h;	97%

ketene diethyl acetal (2678-54-8) + 4-bromo-benzaldehyde (1122-91-4) → ethyl (E)-3-(4-bromophenyl)-2-propenoate (24393-53-1, 136265-11-7, 15795-20-7)

Conditions	Yield
With (2,4,5-trifluorophenyl)boronic acid In tert-butyl methyl ether at 50℃; for 14h;	97%

(S)-5-methoxycarbonylmethyl-6,6-dimethyl-2-cyclohexen-1-one (70591-46-7) + ketene diethyl acetal (2678-54-8) → 4-carbomethoxymethyl-7,7-diethoxy-3,3-dimethylbicyclo<4.2.0>octan-2-one (70591-47-8, 82509-28-2, 82509-31-7)

Conditions	Yield
for 3h; Ambient temperature; Irradiation;	96%

ketene diethyl acetal (2678-54-8) + Hexafluoroacetone (684-16-2) → 4,4-diethoxy-1,1,1-trifluoro-2-trifluoromethyl-but-3-en-2-ol (63504-98-3)

Conditions	Yield
In methanol at 20℃;	95%

ketene diethyl acetal (2678-54-8) + 6-[(benzyloxycarbonyl)amino]-3-(methylthio)-1,2,4,5-tetrazine (213320-13-9) → 6-[(benzyloxycarbonyl)amino]-4-ethoxy-3-(methylthio)pyridazine

Conditions	Yield
In 1,4-dioxane at 100℃; for 2h; Diels-Alder reaction;	95%

ketene diethyl acetal (2678-54-8) + 5-phenyl-1,2,3-triazine (106636-96-8) → 2-ethoxy-5-phenylpyridine

Conditions	Yield
In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 24h; Diels-Alder reaction; regioselective reaction;	95%

3,6-dimethyl-o-quinone monoacetal (1270038-98-6) + ketene diethyl acetal (2678-54-8) → C16H24O5

Conditions	Yield
In toluene at 150℃; for 17h; Diels-Alder Cycloaddition; Inert atmosphere; regioselective reaction;	95%

1,1,3-trichloro-1,3,3-trifluoroacetone (79-52-7) + ketene diethyl acetal (2678-54-8) → 1,1-Diethoxy-4,4-difluoro-4-chloro-3-fluorodichloromethyl-1-buten-3-ol (138351-94-7)

Conditions	Yield
for 18h; Ambient temperature;	94%

ketene diethyl acetal (2678-54-8) + 4-methoxy-benzaldehyde (123-11-5) → ethyl (E)-3-(4-methoxyphenyl)prop-2-enoate (24393-56-4)

Conditions	Yield
With (2,4,5-trifluorophenyl)boronic acid In tert-butyl methyl ether at 50℃; for 14h;	94%

1-naphthaldehyde (66-77-3) + ketene diethyl acetal (2678-54-8) → (E)-ethyl 3-(naphthalen-1-yl)acrylate (98978-43-9)

Conditions	Yield
With (2,4,5-trifluorophenyl)boronic acid In tert-butyl methyl ether at 50℃; for 14h;	93%

1-(2-diazo-1,3-dioxobutyl)-2-pyrrolidinone (126685-93-6) + ketene diethyl acetal (2678-54-8) → 7-Acetyl-8,8-diethoxy-10-oxa-5-aza-tricyclo[5.2.1.01,5]decan-6-one

Conditions	Yield
dirhodium tetraacetate In benzene for 2h; Heating;	92%

5-(4-chlorophenyl)-2,3-dihydrofuran-2,3-dione (58303-62-1) + ketene diethyl acetal (2678-54-8) → [5-(4-Chloro-phenyl)-2-hydroxy-3-oxo-2,3-dihydro-furan-2-yl]-acetic acid ethyl ester (159107-87-6)

Conditions	Yield
In dichloromethane at 40℃; for 1h;	91%

ketene diethyl acetal (2678-54-8) + methyl 3-(1-oxo-2-cyclohexen-2-yl)acrylate → 3,3-diethoxy-8-oxo-2,3,4,4a,5,6,7,8-octahydro-naphthalene-2-carboxylic acid methyl ester

Conditions	Yield
In toluene for 1.5h; Heating;	91%

ketene diethyl acetal (2678-54-8) + 5-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>-2-cyclohexen-1-one (84011-69-8) → 4-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>-7,7-diethoxybicyclo<4.2.0>octane-2-one (84011-67-6)

Conditions	Yield
In benzene for 3.5h; Irradiation;	90%

ketene diethyl acetal (2678-54-8) + diethyl Fumarate (623-91-6) → trans-3,3-diethoxy-1,2-cyclobutanedicarboxylic acid diethyl ester (127696-10-0)

Conditions	Yield
With diisobutylaluminum chloride; N-ethyl-N,N-diisopropylamine In toluene at -40℃;	90%
In tert-butyl alcohol at 84℃; for 72h;	54%
In tert-butyl alcohol at 84℃; for 72h;	53%
Stage #1: ketene diethyl acetal With diethylaluminium chloride In toluene at -45℃; for 0.166667h; Inert atmosphere; Stage #2: With N-ethyl-N,N-diisopropylamine In toluene at -45℃; for 0.166667h; Inert atmosphere; Stage #3: diethyl Fumarate In toluene at -45℃; for 3h; Inert atmosphere;	42.3%

ketene diethyl acetal (2678-54-8) + 5-(4-bromo-phenyl)-furan-2,3-dione (55991-70-3) → [5-(4-Bromo-phenyl)-2-hydroxy-3-oxo-2,3-dihydro-furan-2-yl]-acetic acid ethyl ester (159107-86-5)

Conditions	Yield
In dichloromethane at 40℃; for 1h;	90%

N-[(4-methylbenzene-1-sulfonyl)(phenyl)methyl]formamide (37643-54-2) + ketene diethyl acetal (2678-54-8) → 3-formylamino-3-phenyl-propionic acid ethyl ester (850011-53-9)

Conditions	Yield
With caesium carbonate In dichloromethane for 24h; Heating;	90%
With caesium carbonate In dichloromethane for 24h; Product distribution / selectivity; Heating / reflux;	90%
With triethylamine In dichloromethane for 24h; Product distribution / selectivity; Heating / reflux;	80%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane for 24h; Product distribution / selectivity; Heating / reflux;	48%

ethyl acetoacetate (141-97-9) + ketene diethyl acetal (2678-54-8) → Ethyl 2-acetyl-3-ethoxybut-2-enoate (182916-87-6)

Conditions	Yield
With sodium ethanolate In ethanol at 22 - 90℃; for 8.5h;	89%

5-chloro-2,2-dimethyl-1,3-dioxin-4-one (904731-83-5) + ketene diethyl acetal (2678-54-8) → 5-chloro-2,2-diethoxy-2,3-dihydropyran-4-one (904731-84-6)

Conditions	Yield
In toluene for 0.666667h; Product distribution / selectivity; Heating / reflux;	89%

ketene diethyl acetal (2678-54-8) + cyclohexanecarbaldehyde (2043-61-0) → (E)-3-cyclohexyl-acrylic acid ethyl ester (17343-88-3)

Conditions	Yield
With (2,4,5-trifluorophenyl)boronic acid In tert-butyl methyl ether at 50℃; for 14h;	89%

C3H9B8F3O3S + ketene diethyl acetal (2678-54-8) → C11H30B16O2

Conditions	Yield
With lithium hexamethyldisilazane In cyclohexane at 20℃; for 0.0833333h; Inert atmosphere;	89%

nitropentafluoroacetone (3888-00-4) + ketene diethyl acetal (2678-54-8) → 4,4-diethoxy-1,1-difluoro-1-nitro-2-trifluoromethyl-but-3-en-2-ol (40657-28-1)

Conditions	Yield
at -30°C, then at 20°C 2 h;	88%
at -30°C, then at 20°C 2 h;	88%

ketene diethyl acetal (2678-54-8) + dicyano(7,7-dimethyl-2,5-di-p-tolyl-3,4-diaza-bicyclo[4.1.0]hepta-2,4-dien-3-ium-3-yl)methanide → 5,5-diethoxy-1,1-dimethyl-2,6a-di-p-tolyl-1,1a,5,6,6a,6b-hexahydro-cis-1a-transoid-6a,6b-3,3a-diaza-cyclopropa[e]indene-4,4-dicarbonitrile

Conditions	Yield
In acetonitrile at 20 - 50℃; for 19h; Cycloaddition;	87%

3-bromo-1-trifluoromethylbenzene (401-78-5) + ketene diethyl acetal (2678-54-8) → 1,1-diethoxy-6-(trifluoromethyl)benzocyclobutene (1017235-56-1)

Conditions	Yield
With sodium amide In tetrahydrofuran for 22h; Heating;	87%

Upstream product

• 78-39-7 Triethyl orthoacetate 
• 865-47-4 potassium tert-butylate 
• 51806-20-3 1,1-diethoxy-2-iodoethane 
• 40070-39-1 triethyl orthobromoacetate 
• 71-43-2 benzene 
• 75-85-4 tert-Amyl alcohol 
• 1634-04-4 tert-butyl methyl ether 
• 107-21-1 ethylene glycol 
• 621-62-5 chloroacetaldehyde diethyl acetal 
• 2032-35-1 Bromoacetaldehyde diethyl acetal 
• 855175-05-2 β-(1,1-diethoxy-ethoxy)-chalcone 

Downstream Products

• 78-39-7 Triethyl orthoacetate 
• 87874-45-1 2,2-diethoxy-1-phenylcyclopropane 
• 109506-43-6 5,5-diethoxy-3-phenyl-4,5-dihydro-isoxazole 
• 74-85-1 ethene 
• 105-39-5 chloroacetic acid ethyl ester 
• 74-96-4 ethyl bromide 
• 2021-28-5 ethyl dihydrocinnamate 
• 57772-73-3 ethyl 2-benzyl-3-phenylpropionate 
• 63473-79-0 1,1-diethoxy-3-phenylprop-1-ene 
• 141-78-6 ethyl acetate 
• 101115-54-2 3,3-diethoxy-acrylic acid o-anisidide 
• 100616-61-3 3,3-diethoxy-acrylic acid-(2-nitro-anilide) 
• 123-66-0 Ethyl hexanoate 
• 998-91-4 ethyl 3-ethoxy-2-butenoate 

Relevant articles and documents

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Photoinduced Cross-Coupling of Aryl Iodides with Alkenes

A protocol for photoinduced cross-coupling of aryl iodides having polar π-functional groups or elongated π-conjugation with alkenes has been developed. The radical cascade mechanism involving generation of aryl radicals via C-I bond homolysis of photoexcited aryl iodides and their subsequent addition to alkenes is proposed. The method enables iodide-selective cross-coupling over other halogen leaving groups with functional group compatibility on both arene and alkene motifs.

Design, Synthesis, and Evaluation of a Series of Novel Benzocyclobutene Derivatives as General Anesthetics

In the present work, a series of structurally novel benzocyclobutene derivatives were identified as general anesthetics through the loss of righting reflex (LORR) experiment on mice. Our initial efforts found compound 1a with a fused four-membered ring on the 2,3-position of the phenol ring could significantly improve the safety profile. Further SAR study revealed that small hydrogen bond acceptor (HBA) groups are optimal for good ED50 along with much broader therapeutic windows, such as compounds 16b and 17. Present work demonstrates the superiority of this novel benzocyclobutene scaffold.

Process for the synthesis of 3,4-dimethoxybicyclo[4.2.0]OCTA-1,3,5-triene-7-carbonitrile, and application in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid

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