57280-22-5

Basic information

• Product Name: 4,4-Dimethyl-3,5,8-trioxabic-yclo[5,1,0]Octane
• Synonyms: 4,4-Dimethyl-3,5,8-trioxabic-yclo[5,1,0]Octane;3,5,8-Trioxabicyclo[5.1.0]octane, 4,4-diMethyl-;4,4-diMethyl-3,5,8-trioxabicyclo[5.1.0]octane(EP2)
• CAS NO: 57280-22-5
• Molecular Formula: C₇H₁₂O₃
• Molecular Weight: 144.17
• EINECS: 421-750-9
• Mol File: 57280-22-5.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 179℃
• Flash Point: 56℃
• Appearance: /
• Density: 1.071
• Refractive Index: 1.4560 to 1.4600
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• CAS DataBase Reference: 4,4-Dimethyl-3,5,8-trioxabic-yclo[5,1,0]Octane(CAS DataBase Reference)
• NIST Chemistry Reference: 4,4-Dimethyl-3,5,8-trioxabic-yclo[5,1,0]Octane(57280-22-5)
• EPA Substance Registry System: 4,4-Dimethyl-3,5,8-trioxabic-yclo[5,1,0]Octane(57280-22-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36-43
• Safety Statements: 26-36/37-24/25
• Hazardous Substances Data: 57280-22-5(Hazardous Substances Data)

Usage

Chemical Properties

Clear colorless to yellow liquid

Uses

4,4-Dimethyl-3,5,8-trioxabicyclo[5.1.0]octane is used in the CO2-mediated formation of chiral carbamates from meso-epoxides via polycarbonate intermediates and amine nucleophiles, which opens up a wide a wide range of CO2-based carbamate scaffolds with excellent yields and 99% enantiomeric excess.

Synthetic route

2,2-dimethyl-4,7-dihydro-1,3-dioxepin (1003-83-4) → 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5)

Conditions	Yield
With disodium hydrogenphosphate; dihydrogen peroxide; sodium hydroxide In methanol; water; acetonitrile at 60 - 80℃; pH=7 - 9.5; Large scale; Green chemistry;	85.2%
With disodium hydrogenphosphate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 18h; Inert atmosphere;	85%
With disodium hydrogenphosphate; dihydrogen peroxide; Hexafluoroacetone In 1,2-dichloro-ethane for 24h; Heating;	83%

2,2-dimethoxy-propane (77-76-9) → 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / dichloromethane / 3 h / 20 °C / Inert atmosphere 2: 3-chloro-benzenecarboperoxoic acid; disodium hydrogenphosphate / dichloromethane / 18 h / 20 °C / Inert atmosphere View Scheme

C7H13BrO3 → 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5)

Conditions	Yield
With potassium carbonate In methanol at 20℃; for 16h;	19 g

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + Trimethylenediamine (109-76-2) → C17H34N2O6

Conditions	Yield
In ethanol epoxide:amine=2:1;	100%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + benzylamine (100-46-9) → trans-6-benzylamino-2,2'-dimethyl-1,3-dioxocycloheptan-5-ol (1036765-71-5)

Conditions	Yield
Stage #1: benzylamine With titanium(IV) isopropylate; (R)-1,1'-Bi-2-naphthol; (R)-6,6'-dibromo-1,1'-binaphth-2-ol In toluene at 20℃; for 0.5h; Stage #2: 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane With water In toluene at 40℃; for 12h; optical yield given as %ee;	99%
With titanium(IV) isopropylate; (R)-1,1'-Bi-2-naphthol In toluene enantioselective reaction;	78%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + benzylamine (100-46-9) → (5R,6S)-6-(benzylamino)-2,2-dimethyl-1,3-dioxepan-5-ol

Conditions	Yield
With C92H72N2O6*2Ti*2O In water; toluene at 40℃; for 18h; Reagent/catalyst; Inert atmosphere; Green chemistry;	99%
Stage #1: benzylamine With titanium(IV) isopropylate; C20H24O2; (R)-3,3'-diiodo-2,2'-dihydroxy-1,1'-binaphthyl In toluene at 20℃; for 0.5h; Stage #2: 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane With water In toluene at 40℃; for 12h; optical yield given as %ee;	27%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + 1,4,7-tris-tert-butoxycarbonylmethyl-1,4,7,10-tetraazacyclododecane (122555-91-3) → 1,4,7-tris(tert-butoxycarbonylmethyl)10-(6-hydroxy-2,2-dimethyl-1,3-dioxepane-5yl)-1,4,7,10-tetraazacyclododecane

Conditions	Yield
With potassium carbonate In isopropyl alcohol at 60℃; for 12h; Reagent/catalyst; Temperature;	99%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + ethylenediamine (107-15-3) → 6-(2-Amino-ethylamino)-2,2-dimethyl-[1,3]dioxepan-5-ol

Conditions	Yield
In ethanol epoxide:amine=1:1; addition of epoxide to amine dropwise over 1 h;	98%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + thiophenol (108-98-5) → (2R*,3R*)-1,4-di-O-isopropylidene-3-phenylthio-1,2,4-butanetriol

Conditions	Yield
With sodium hydride In tetrahydrofuran 0 deg C, 30 min, reflux, 1 h;	96.9%

bis(3-aminopropyl)amine (56-18-8) + 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) → 6-[3-(3-Amino-propylamino)-propylamino]-2,2-dimethyl-[1,3]dioxepan-5-ol

Conditions	Yield
In ethanol epoxide:amine=1:1; addition of epoxide to amine dropwise over 1 h;	92%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + isopropylamine (75-31-0) → 6-(isopropylamino)-2,2-dimethyl-1,3-dioxepan-5-ol (1036765-73-7)

Conditions	Yield
Stage #1: isopropylamine With titanium(IV) isopropylate; (R)-1,1'-Bi-2-naphthol In toluene at 20℃; Stage #2: 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane With water In toluene at 40℃; for 12h; optical yield given as %ee;	91%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) → (5S,6S)-6-Iodo-2,2-dimethyl-[1,3]dioxepan-5-ol

Conditions	Yield
With lithium iodide for 15h; Ambient temperature;	90%
With silica gel; lithium iodide for 0.25h; Ambient temperature;	90%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) → trans-2,2-Dimethyl-6-hydroxy-5-amino-1,3-dioxepane (188923-20-8)

Conditions	Yield
With ammonia In water	87%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + tert-butylamine (75-64-9) → 6-(tert-butylamino)-2,2-dimethyl-1,3-dioxepan-5-ol (1036765-74-8)

Conditions	Yield
Stage #1: tert-butylamine With titanium(IV) isopropylate; (R)-1,1'-Bi-2-naphthol In toluene at 20℃; Stage #2: 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane With water In toluene at 40℃; for 48h; optical yield given as %ee;	85%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + 1,4,7-tris(tert-butyloxycarbonyl)-1,4,7,10-tetraazacyclododecane (175854-39-4) → C12H28N4O3

Conditions	Yield
Stage #1: 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane; 1,4,7-tris(tert-butyloxycarbonyl)-1,4,7,10-tetraazacyclododecane With lithium chloride In isopropyl alcohol for 20h; Reflux; Stage #2: With hydrogenchloride In water; isopropyl alcohol at 60℃; for 2h;	85%

bromobenzene (108-86-1) + 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) → (5S,6R)-2,2-dimethyl-6-phenyl-1,3-dioxepan-5-ol

Conditions	Yield
With [2,2]bipyridinyl; manganese; (1,2-dimethoxyethane)dichloronickel(II); bis(η5((1R,2S,5R)-5-methyl-2-[prop-2-yl]-cyclohex-1-yl)cyclopentadienyl)-titanium dichloride; triethylamine hydrochloride at 20℃; for 12h; Inert atmosphere; Glovebox; Autoclave; enantioselective reaction;	82%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) → (5S,6S)-6-Bromo-2,2-dimethyl-[1,3]dioxepan-5-ol

Conditions	Yield
With lithium bromide for 8h; Ambient temperature;	80%
With silica gel; lithium bromide for 8h; Ambient temperature;	80%

1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid trisodium salt + 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) → 2,2',2"-(10-(1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (138168-36-2)

Conditions	Yield
Stage #1: 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid trisodium salt; 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane In isopropyl alcohol for 10h; Inert atmosphere; Reflux; Industrial scale; Stage #2: With hydrogenchloride In water for 1h; Solvent; Industrial scale;	80%

1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid trisodium salt + gadolinium(III) chloride + 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) → gadolinium complex of 10-[2,3-dihydroxy-1-(hydroxymethyl)propyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid

Conditions	Yield
Stage #1: 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid trisodium salt; 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane With hydrogenchloride In water at 40 - 80℃; for 12h; Stage #2: gadolinium(III) chloride In water at 50℃; for 1h; Stage #3: With hydrogenchloride; sodium hydroxide more than 3 stages;	79.1%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + lithium cyanide (2408-36-8) → (+/-)-trans-6-hydroxy-2,2-dimethyl-1,3-dioxepane-5-carbonitrile (141077-78-3)

Conditions	Yield
In tetrahydrofuran for 3h; Heating;	79%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + trimethylsilan (993-07-7) + carbon monoxide (201230-82-2) → 2,2-Dimethyl-5-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-[1,3]dioxepane

Conditions	Yield
dicobalt octacarbonyl In toluene at 25℃; under 760 Torr; for 20h;	77%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) → (5S,6S)-6-Chloro-2,2-dimethyl-[1,3]dioxepan-5-ol

Conditions	Yield
With water; silica gel; lithium chloride for 96h; Ambient temperature;	76%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 3-(1,4,7,10-tetraazacyclododecane-1-yl)butane-1,2,4-triol tetrahydrochloride

Conditions	Yield
Stage #1: 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane; 1,4,7,10-tetraazacyclododecan With lithium chloride In isopropyl alcohol at 85 - 95℃; Large scale; Stage #2: With hydrogenchloride In methanol for 3h; Reflux; Large scale;	73.4%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) → 4,4-dimethyl-3,5-dioxacycloheptanol (141509-49-1)

Conditions	Yield
With lithium aluminium tetrahydride In diethyl ether for 24h; Ambient temperature;	68%

4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]-octane (57280-22-5) + 1,5-diamino-3-azapentane (111-40-0) → 6-[2-(2-Amino-ethylamino)-ethylamino]-2,2-dimethyl-[1,3]dioxepan-5-ol

Conditions	Yield
In ethanol epoxide:amine=1:1; addition of epoxide to amine dropwise over 1 h;	67%

Upstream product

• 77-76-9 2,2-dimethoxy-propane 
• 1003-83-4 2,2-dimethyl-4,7-dihydro-1,3-dioxepin 

Downstream Products

• 1010701-95-7 (2R)-2-benzyloxycarbonylamino-2-[(4S)-2,2-dimethyl-1,3-dioxolane-4-yl]ethanol 
• 72791-82-3 4-Hydroxy-3-(3-methoxy-2-methoxymethoxy-5-methyl-phenyl)-butan-2-one 
• 72791-81-2 3-Hydroxy-4-(3-methoxy-2-methoxymethoxy-5-methyl-phenyl)-butan-2-one 
• 72791-80-1 2-(3-Methoxy-2-methoxymethoxy-5-methyl-phenyl)-propan-2-ol 

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