5394-63-8

Basic information

• Product Name: 2,2,6-Trimethyl-4H-1,3-dioxin-4-one
• Synonyms: DIKETENE ACETONE ADDUCT;DIKETE ACETONE ADDUCT;2,6,6-TRIMETHYL-1,3-DIOXIN-4-ONE;2,2,6-TRIMETHYL-1,3-DIOXEN-4-ONE;2,2,6-TRIMETHYL-1,3-DIOXIN-4-ONE;2,2,6-TRIMETHYL-4H-1,3-DIOXIN-4-ONE;2,2,4-TRIMETHYL-6-KETO-1,3-DIOXIN;2,2,6-trimethyl-1,3-dioxine-4H-one
• CAS NO: 5394-63-8
• Molecular Formula: C₇H₁₀O₃
• Molecular Weight: 142.15
• EINECS: 226-403-3
• Mol File: 5394-63-8.mol

Chemical Properties

• Melting Point: 12-13 °C(lit.)
• Boiling Point: ~275 °C(lit.)
• Flash Point: 67 °F
• Appearance: Dark brown/Liquid
• Density: 1.07 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.119mmHg at 25°C
• Refractive Index: n20/D 1.460(lit.)
• Storage Temp.: 2-8°C
• Solubility: water: insoluble
• Water Solubility: practically insoluble
• BRN: 2408
• CAS DataBase Reference: 2,2,6-Trimethyl-4H-1,3-dioxin-4-one(CAS DataBase Reference)
• NIST Chemistry Reference: 2,2,6-Trimethyl-4H-1,3-dioxin-4-one(5394-63-8)
• EPA Substance Registry System: 2,2,6-Trimethyl-4H-1,3-dioxin-4-one(5394-63-8)

Safety Data

• Hazard Codes: F,Xi
• Statements: 11-36/37/38-36
• Safety Statements: 16-26-27-36/37/39-9-33
• RIDADR: UN 1993 3/PG 2
• WGK Germany: 3
• HazardClass: 3
• PackingGroup: II
• Hazardous Substances Data: 5394-63-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Synthesis:
2,2,6-Trimethyl-4H-1,3-dioxin-4-one is used as a key intermediate in the synthesis of dihydropyrimidinones, which serve as picomolar sodium iodide symporter inhibitors. It is also utilized in the synthesis of resorcinol amide Hsp90 Inhibitor AT13387, a compound with potential applications in the pharmaceutical industry.
Used in Chemical Synthesis:
2,2,6-Trimethyl-4H-1,3-dioxin-4-one is used as a starting material to produce N-alkenyl acetoacetamides through reaction with imines. It can also be involved in the preparation of acetoacetamide derivatives, leading to the formation of pyrrole amides via the oxime of the acetoacetamides. Additionally, 2,2,6-Trimethyl-4H-1,3-dioxin-4-one may be introduced to promote the acetoacetylation of O-(hydroxypropyl)cellulose for generating O-(acetoxypropyl)cellulose.
Used in the Synthesis of β-Keto Esters and β-Ketoamides:
2,2,6-Trimethyl-4H-1,3-dioxin-4-one can be used to yield β-keto esters and β-ketoamides through the reaction with secondary or tertiary alcohols (including chiral ones) or primary or secondary amines.
Used in the Preparation of Acetylketene:
2,2,6-Trimethyl-4H-1,3-dioxin-4-one generates unstable acetylketene along with acetone when heated above 120 ℃. Subsequent condensation with isocyanates, arylcyanates, or substituted cyanamides provides access to a wide range of 1,3-oxazine derivatives.
Used as a Transportable Form of Diketene:
Diketene-Acetone Adduct, which includes 2,2,6-Trimethyl-4H-1,3-dioxin-4-one, can be used in place of diketene in many reactions. As a transportable form of diketene, it is especially important in countries where the transportation of diketene is not allowed or at least not desired.
Used in the Synthesis of Various Compounds:
Diketene-Acetone Adduct, which contains 2,2,6-Trimethyl-4H-1,3-dioxin-4-one, can also be used for the preparation of a variety of compounds that are not accessible from diketene alone.

Reference

Dannibale, A.; Pesce, A.; Resta, S.; Trogolo, C., Reaction of 2,2,6-trimethyl-4H-1,3-dioxin-4-one with imines: An easy route to enamides. Tetrahedron Lett. 1996, 37, 7429-7432. Huggins, M.; Barber, P.; Florian, D.; Howton, W., Short, Efficient Syntheses of Pyrrole -Amides. Synth. Commun. 2008, 38, 4226-4239. Pawlowski, W. P.; Gilbert, R. D.; Fornes, R. E.; Purrington, S. T., ACETOACETYLATION OF O-(HYDROXYPROPYL)CELLULOSE BY 2,2,6-TRIMETHYL-4H-1,3-DIOXIN-4-ONE. Carbohydr. Res. 1986, 156, 232-235. Sridharan, V.; Ruiz, M.; Menendez, J. C., Mild and High-Yielding Synthesis of beta-Keto Esters and beta-Ketoamides. Synthesis 2010, 1053-1057.

Chemical Reactivity

Diketene – acetone adduct (2,2,6-Trimethyl-4H-1,3-dioxin-4-one) can be regarded as a stabilized form of diketene. It can be safely transported and may conveniently be used instead of diketene in many reactions. For example, it reacts with alcohols and amines to yield acetoacetates and acetoacetamides, respectively. Diketene – acetone adduct generates unstable acetylketene together with acetone when heated above 120 ?C. Subsequent condensation with isocyanates, arylcyanates, or substituted cyanamides gives access to a wide range of 1,3-oxazine derivatives. Furthermore, diketene – acetone adduct can also be used for the preparation of a variety of compounds that are not accessible from diketene.

InChI:InChI=1/C7H10O3/c1-5-4-6(8)10-7(2,3)9-5/h4H,1-3H3

Synthetic route

tert-butyl acetoacetate (1694-31-1) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

Conditions	Yield
With sulfuric acid; acetic anhydride In acetone at 0 - 20℃; for 5h;	100%

tert-butyl acetoacetate (1694-31-1) + acetone (67-64-1) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

Conditions	Yield
With sulfuric acid; acetic anhydride at 0 - 20℃; for 5h;	98%

4-methyleneoxetan-2-one (674-82-8) + acetone (67-64-1) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

Conditions	Yield
With Aliquat 336 In toluene at 70℃; for 6h;	95%
toluene-4-sulfonic acid

acetylketene (691-45-2) + acetone (67-64-1) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

Conditions	Yield
	83%

5-(1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (85920-63-4) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

Conditions	Yield
In acetone; toluene at 111℃; for 2h;	80%

4-methyleneoxetan-2-one (674-82-8) + toluene-4-sulfonic acid (104-15-4) + acetone (67-64-1) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

4-methyleneoxetan-2-one (674-82-8) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

Conditions	Yield
With pyridine; acetone; zinc(II) sulfate
With toluene-4-sulfonic acid; acetone

Ketene (463-51-4) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

Conditions	Yield
With diethyl ether; acetone; zinc(II) chloride

isopropenyl acetoacetate (93304-66-6) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

Conditions	Yield
With toluene-4-sulfonic acid In (2)H8-toluene at 70 - 90℃; for 1h;
With acetone In xylene at 91.7℃; for 1h;	100 % Chromat.

isopropenyl acetoacetate (93304-66-6) → 2,6-dimethylpyrone (1004-36-0) + 3-acetyl-4-hydroxy-6-methyl-2H-pyran-2-one (771-03-9) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + 4-methyl-1,5-dioxaspiro[5.5]undec-3-en-2-one (4412-03-7) + 1,3-diacetyl acetone (626-53-9)

Conditions	Yield
In xylene at 91.7℃; for 0.75h; Product distribution;	A n/a B n/a C 15 % Chromat. D 14 % Chromat. E n/a

2,2,6-trimethyl-4H-1,3-dioxin-4-one (42490-66-4) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + 5-bromo-2,2,6-trimethyl-1,3-diox-5-in-4-one (104687-80-1)

Conditions	Yield
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); potassium carbonate 1) -78 deg C, 2) -78 to 0 deg C, 2) 0 deg C; Yield given. Multistep reaction. Yields of byproduct given;

2-methyl-5-norbornen-2-yl exo-acetoacetate (93304-64-4) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 48 percent / 600 °C / 0.1 - 1 Torr 2: p-TsOH / toluene-d8 / 1 h / 70 - 90 °C View Scheme

2-methyl-5-norbornen-2-yl endo-acetoacetate (93304-65-5) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 48 percent / 600 °C / 0.1 - 1 Torr 2: p-TsOH / toluene-d8 / 1 h / 70 - 90 °C View Scheme

cycl-isopropylidene malonate (2033-24-1) → 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / dichloromethane / 2 h / 0 - 20 °C 2: acetone; toluene / 2 h / 111 °C View Scheme

2-methyl-but-2-ene (513-35-9) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) → (1S,6R)-1,3,3,7,7,8-Hexamethyl-2,4-dioxa-bicyclo[4.2.0]octan-5-one

Conditions	Yield
In hexane for 24h; Irradiation;	100%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + (R,S)-2,2-dimethyl-1,3-dioxolane-4-methanol (100-79-8) → (2,2-dimethyl-1,3-dioxolan-4-yl)methyl 3-oxobutanoate (85513-98-0)

Conditions	Yield
In toluene at 20 - 130℃; for 3.5h; Inert atmosphere;	100%
In xylene for 1h; Heating;

pyrrolidine (123-75-1) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) → 1-(pyrrolidin-1-yl)butane-1,3-dione (41153-96-2)

Conditions	Yield
In toluene at 20℃; for 12.25h; Reflux;	100%
for 0.0333333h; microwave irradiation;	87%
In toluene for 3h; Reflux;
In toluene for 3h; Reflux;

N-benzyloxyglycine ethyl ester (70771-89-0) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) → acetoacetamido-N-benzyloxyglycine ethyl ester (136942-58-0)

Conditions	Yield
In toluene at 110℃; for 4h;	100%

piperidine (110-89-4) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) → 1-(piperidin-1-yl)-butane-1,3-dione (1128-87-6)

Conditions	Yield
In toluene at 20℃; for 12.25h; Reflux;	100%
With sodium acetate In tetrahydrofuran for 24h; Reflux;	99%
In 5,5-dimethyl-1,3-cyclohexadiene at 150℃; for 0.5h;	95%
In toluene for 2h; Reflux; Inert atmosphere;	93%
In toluene for 2h; Inert atmosphere; Reflux;	93%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + N,N-diethylethylenediamine (100-36-7) → N-(2-(diethylamino)ethyl)-3-oxobutanamide (590424-03-6)

Conditions	Yield
at 130℃; for 0.0833333h; Microwave irradiation; Green chemistry;	100%
at 110 - 115℃; Product distribution / selectivity;

3-Hydroxy-3-methyl-2-butanone (115-22-0) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) → 3-Acetyl-4,5,5-trimethyl-Δ3-butenolide (13156-10-0)

Conditions	Yield
With triethylamine In toluene at 110℃; for 3h; Reagent/catalyst; Concentration; Molecular sieve; Inert atmosphere;	100%
With triethylamine In toluene for 3h; Reflux;	86%
With triethylamine for 3h; Reflux;

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + ethylenediamine (107-15-3) → 7-methyl-3,4-dihydro-1H-1,4-diazepin-5(2H)-one (89600-61-3)

Conditions	Yield
at 130℃; for 0.0833333h; Microwave irradiation; Green chemistry;	100%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + 1,4-diaminobutane (110-60-1) → (Z)-4-methyl-6,7,8,9-tetrahydro-1H-1,5-diazonin-2(5H)-one

Conditions	Yield
at 130℃; for 0.0833333h; Microwave irradiation; Green chemistry;	100%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + 1,2-diamino-benzene (95-54-5) → 4-methyl-1H-benzo[b][1,4]diazepin-2(5H)-one (60568-46-9)

Conditions	Yield
at 130℃; for 0.0833333h; Microwave irradiation; Green chemistry;	100%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + L-Tryptophan (73-22-3) → (3-oxobutanoyl)-L-tryptophan

Conditions	Yield
With potassium carbonate In water for 2h; Reflux;	100%

L-leucine (61-90-5) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) → (3-oxobutanoyl)-L-leucine (1803-64-1)

Conditions	Yield
With potassium carbonate In water for 2h; Reflux;	100%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + L-tryptophan methyl ester (4299-70-1) → methyl (3-oxobutanoyl)-L-tryptophanate

Conditions	Yield
With potassium carbonate In water for 2h; Reflux;	100%

Benzophenone-3 (131-57-7) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) → 3-acetyl-7-methoxy-4-phenylcoumarin (93655-48-2)

Conditions	Yield
In decalin for 12h; Solvent; Reflux;	100%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + diphenylamine (122-39-4) → N,N-diphenylacetoacetamide (2540-31-0)

Conditions	Yield
In toluene at 20℃; for 12.25h; Reflux;	100%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (582-52-5) → 3-Oxo-butyric acid (5R,6S)-5-(2,2-dimethyl-[1,3]dioxolan-4-yl)-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxol-6-yl ester (66888-11-7)

Conditions	Yield
In xylene at 150℃; for 0.5h;	99%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + (-)-8-phenylmenthol (65253-04-5) → (+)-(1R,2S,5R)-8-phenylmenthyl 3-oxobutanoate (90358-31-9)

Conditions	Yield
With sodium acetate In tetrahydrofuran for 24h; Reflux;	99%
In xylene at 160℃; for 0.5h; preheated bath;

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + (2S,3S,4R,5S,6R)-3,4,5-Tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-ol (96553-53-6) → 3-Oxo-butyric acid (2R,3S,4R,5S,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl ester (96453-23-5)

Conditions	Yield
In xylene at 150℃; for 0.5h;	99%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + cyclohexanol (108-93-0) → cyclohexyl 3-oxobutanoate (6947-02-0)

Conditions	Yield
With sodium acetate In tetrahydrofuran for 24h; Reflux;	99%
In xylene for 0.5h; Heating;	80%
In 5,5-dimethyl-1,3-cyclohexadiene at 150℃; for 2h;	76%
Esterification;	35%
Condensation;

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + tert-butyl alcohol (75-65-0) → tert-butyl acetoacetate (1694-31-1)

Conditions	Yield
With sodium acetate In tetrahydrofuran for 24h; Reflux;	99%
Esterification;	92%
for 0.1h; microwave irradiation;	70%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + N-tert-butylbenzylamine (3378-72-1) → N-tert-butyl-N-benzylacetoacetamide (151813-55-7)

Conditions	Yield
In 5,5-dimethyl-1,3-cyclohexadiene at 120℃; for 5h; Dean-Stark; Inert atmosphere;	99%
In m-xylene at 120 - 150℃;

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + (+/-)-1-(N-tert-Butoxycarbonylamino)propan-2-one (170384-29-9) → C12H19NO5

Conditions	Yield
In 5,5-dimethyl-1,3-cyclohexadiene at 150℃; for 0.166667h; Inert atmosphere;	99%

(R,E)-7-hydroxy-7-methyl-3-(prop-1-en-1-yl)-6H-isochromene-6,8(7H)-dione (915789-19-4) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) → (S)-trichoflectin

Conditions	Yield
With triethylamine In toluene at 110℃; for 1h; Molecular sieve; Inert atmosphere; Schlenk technique;	99%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + (S,E)-7-hydroxy-7-methyl-3-(prop-1-en-1-yl)-6H-isochromene-6,8(7H)-dione → (R)-trichoflectin

Conditions	Yield
With triethylamine In toluene at 110℃; for 1h; Molecular sieve; Inert atmosphere; Schlenk technique;	99%

6-chloro-1,2,3,4-tetrahydroquinoline (49716-18-9) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) → C13H14ClNO2

Conditions	Yield
In toluene at 110℃; for 1.5h; Microwave irradiation;	99%

alpha-D-glucopyranose (492-62-6) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) → D-(+)-glucose pentaacetoacetate (96481-26-4)

Conditions	Yield
In xylene at 150℃; for 0.5h;	98.5%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + 3-Hydroxypropionitrile (109-78-4) → 2-cyanoethylacetoacetate (65193-87-5)

Conditions	Yield
In o-xylene at 141℃; for 2h;	98.3%
In 5,5-dimethyl-1,3-cyclohexadiene at 140 - 145℃; for 1h;	90%
In xylene at 140 - 145℃; for 1h;	81.6%

dimethyl (S)-malate (617-55-0) + 2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) → (1'S)-1',2'-bis(methoxycarbonyl)ethyl 3-oxobutanoate (50595-57-8)

Conditions	Yield
In toluene for 1h; Heating;	98%

2,2,6-trimethyl-4H-1,3-dioxin-4-one (5394-63-8) + aniline (62-53-3) → N-phenylacetoacetamide (102-01-2)

Conditions	Yield
With sodium acetate In tetrahydrofuran for 24h; Reflux;	98%
In water for 2.5h; Reflux; Green chemistry;	94%
In 5,5-dimethyl-1,3-cyclohexadiene Reflux;	82%

Upstream product

• 674-82-8 4-methyleneoxetan-2-one 
• 104-15-4 toluene-4-sulfonic acid 
• 67-64-1 acetone 
• 463-51-4 Ketene 
• 93304-66-6 isopropenyl acetoacetate 
• 42490-66-4 2,2,6-trimethyl-4H-1,3-dioxin-4-one 
• 691-45-2 acetylketene 
• 1694-31-1 tert-butyl acetoacetate 
• 2033-24-1 cycl-isopropylidene malonate 
• 85920-63-4 5-(1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 93304-65-5 2-methyl-5-norbornen-2-yl endo-acetoacetate 
• 93304-64-4 2-methyl-5-norbornen-2-yl exo-acetoacetate 

Downstream Products

• 520-45-6 Dehydracetic acid 
• 67-64-1 acetone 
• 61386-84-3 6-methyl-3-phenethyl-[1,3]oxazine-2,4-dione 
• 40352-03-2 6-methyl-3-m-tolyl-[1,3]oxazine-2,4-dione 
• 30645-78-4 3-(4-chloro-phenyl)-6-methyl-[1,3]oxazine-2,4-dione 
• 34132-56-4 3-phenyl-3,4-dihydro-6-methyl-2H-1,3-oxazine-2,4-dione 
• 43066-09-7 3-(4-fluoro-phenyl)-6-methyl-[1,3]oxazine-2,4-dione 
• 34132-66-6 3-(4-methoxy-phenyl)-6-methyl-[1,3]oxazine-2,4-dione 
• 34132-62-2 3-(3-difluoromethyl-phenyl)-6-methyl-[1,3]oxazine-2,4-dione 
• 40459-18-5 3-(4-chloro-3-difluoromethyl-phenyl)-6-methyl-[1,3]oxazine-2,4-dione 
• 61386-74-1 3-(3-chloro-4-trifluoromethoxy-phenyl)-6-methyl-[1,3]oxazine-2,4-dione 
• 61387-27-7 6-methyl-2-phenoxy-[1,3]oxazin-4-one 
• 34132-69-9 3-cyclohexyl-6-methyl-[1,3]oxazine-2,4-dione 
• 61387-28-8 6-methyl-2-(4-nitro-phenoxy)-[1,3]oxazin-4-one 

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The present invention relates to derivatives of the 1H-pyrano[4,3-b]benzofuran-1-one structure and their nitrogen analogues which possess powerful antioxidant properties combined with a highly effective UV absorbing functionality in one molecule. These compounds are especially useful in cosmetical and dermatological formulations.

Sodium carbonate as a solid-phase reagent for the generation of acetylketene

Reaction of a toluene solution of 3-oxobutanoyl chloride (14) with Na2CO3 in the presence of a catalytic amount of triethylamine at -78 °C generates a solution of acetylketene (2), the dimer of which was isolated. Acetylketene (2) was trapped with 2-propanone, 2-propanol, and ethyl vinyl ether.

Ester and process for producing the same

6-Alkoxycarbonylmethyl-4H-1,3-dioxin-4-one derivatives are produced by reacting a 6-halomethyl-4H-1,3-dioxin-4-one derivative with carbon monoxide and an alcohol or water, and 3-oxopentanedicarboxylic acid esters are further produced by reacting the above derivatives with an alcohol or water. Such a process can produce 3-oxopentanedicarboxylic acid esters in an easy and simple and efficient manner.

Bromination of 2,2,6-Trialkyl-1,3-dioxan-4-ones. Application of the Deuterium Isotope Effect to the Synthesis of a Chiral Trialkyldioxinone

Free-radical bromination (2 equiv of NBS) of 2-tert-butyl-2,6-dimethyl-1,3-dioxan-4-one (6a) gives the 2-bromomethyl product 7a.By contrast, bromination of 2-tert-butyl-2-methyl-1,3-dioxan-4-one (1) is reported to occur at the 6-position.Deuterium-labeling experiments established that 7a is formed by direct substitution at the 2-methyl group of 6a and not by abstraction of H-6 followed by hydrogen atom transfer from the 2-methyl group and bromination of the resultant primary radical 12.When 2-tert-butyl-6-methyl-2-(methyl-d3)-1,3-dioxan-4-one (13) is reacted with 4 equiv of NBS, the course of the reaction is altered dramatically and the major product formed in high yield is dioxinone 16.Thus, a trideuteriomethyl group directs bromination away from the 2-methyl site to H-6.Bromination at the 6-position followed by the loss of HBr, addition of Br2, and loss of a second HBr gives 16.Dioxinone 14, a valuable substrate for asymmetric induction studies, is formed in high yield by reductive debromination of 16.When (R)-3-hydroxybutyric acid is used in the preparation of 13, optically pure (-)-14 is obtained using the sequence described.

Kinetic and Spectroscopic Studies on the Thermal Decomposition of 2,2,6-Trimethyl-4H-1,3-dioxin-4-one: Generation of Acetylketene

Acetylketene is shown to be a reactive intermediate in thermolytic reactions of 2,2,6-trimethyl-4H-1,3-dioxin-4-one (the diketene-acetone adduct) via a series of kinetic studies.The uncatalyzed acetoacetylations of phenol, 1-butanol, and di-n-butylamine with the title dioxinone at 82-107 deg C are first-order reactions in which the rate-limiting step is the formation of acetylketene and acetone, presumably via a retro-Diels-Alder reaction.Isopropenyl acetoacetate is not an intermediate in the aforementioned reactions but also provides acetylketene when heated.Acetylketene was observed by FT-IR spectroscopy in an argon matrix.

Isopropenyl Acetoacetate and the Reaction of Diketene with Acetone

The acid-catalyzed reaction of diketene with acetone to form 2,2,6-trimethyl-4H-1,3-dioxin-4-one, when conducted by using acetone-d6, yields a product with a high degree of deuterium scrambling.This scrambling is inconsistent with the intermediacy of either acetylketene or a 1,4-dipolar form of diketene in the reaction.Pathways involving isopropenyl acetoacetate or its protonated form are judged more compatible with the labeling results.Authentic isopropenyl acetoacetate was synthesized by using a retro-Diels-Alder route and was found to be converted to the title dioxinone under the diketene-acetone reaction conditions.

Onium Salt-Catalyzed Reactions between Carbonyl Compounds and Diketene

4-Oxo-1,3-dioxins (plus dehydracetic acid) are obtained in high yields on refluxing the title compounds in toluene in the presence of catalytic amounts of quaternary ammonium chlorides.