4360-63-8

Usage

Uses

Used in Chemical Synthesis:
2-Bromomethyl-1,3-dioxolane is used as a synthetic intermediate for the preparation of α,β-unsaturated aldehydes and 1,4-two aldehyde monoacetals. Its reactivity and stability make it a valuable component in the synthesis of complex organic molecules.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 2-Bromomethyl-1,3-dioxolane is used as a key building block in the synthesis of 1,4-benzoxazepine (BZO) compounds. These BZO compounds have demonstrated potential applications in the development of new drugs, particularly in the treatment of various medical conditions.
Used in Material Science:
2-Bromomethyl-1,3-dioxolane's properties also make it suitable for use in the development of new materials, such as polymers and resins, due to its ability to form stable covalent bonds with other molecules.

InChI:InChI=1/C4H7BrO2/c5-3-4-6-1-2-7-4/h4H,1-3H2

Synthetic route

2-methyl-1,3-dioxolane (497-26-7) → 2-bromomethyl-1,3-dioxolane (4360-63-8)

Conditions	Yield
With bromine; di-tert-butyldicyclohexano-18-crown-18 In benzene at 20℃; for 0.166667h; Bromination;	96%
With 1,4-Dioxane Dibromide In tetrachloromethane at 29.9℃; Rate constant; Thermodynamic data; Mechanism; ΔH(excit.), ΔS(excit.), ΔG(excit.), lg A; further temp., kinetics;

1-bromo-2,2-dimethoxyethane (7252-83-7) + ethylene glycol (107-21-1) → 2-bromomethyl-1,3-dioxolane (4360-63-8)

Conditions	Yield
With Dowex 50(H+) at 120℃; for 1h;	94%
With Dowex-x8 (H+) resin	75%
With sulfuric acid
With potassium bisulfite; methoxybenzene at 140℃;	15 g
at 150℃;

ethylene glycol (107-21-1) + Bromoacetaldehyde diethyl acetal (2032-35-1) → 2-bromomethyl-1,3-dioxolane (4360-63-8)

Conditions	Yield
With toluene-4-sulfonic acid at 110℃; for 2h;	87%
With sulfuric acid
at 150℃;

ethylene glycol (107-21-1) + acetaldehyde (75-07-0) → 2-bromomethyl-1,3-dioxolane (4360-63-8)

Conditions	Yield
Stage #1: ethylene glycol; acetaldehyde at 20℃; for 0.5h; Large scale; Stage #2: With bromine at 0 - 3℃; for 3.5h; Temperature; Large scale;	79.2%

2-methyl-1,3-dioxolane (497-26-7) → 2-bromomethyl-1,3-dioxolane (4360-63-8) + bromoethyl acetate (927-68-4)

Conditions	Yield
With bromine In tetrachloromethane at 60 - 70℃;	A 45% B 45%
With N-Bromosuccinimide; di-tert-butylcyclohexano-18-crown-6 In benzene Ambient temperature;	A 32 % Chromat. B 68 % Chromat.

vinyl acetate (108-05-4) + ethylene glycol (107-21-1) → 2-bromomethyl-1,3-dioxolane (4360-63-8)

Conditions	Yield
With bromine

bis-(1,2-dibromo-ethyl) ether (6304-35-4) + ethylene glycol (107-21-1) → 2-bromomethyl-1,3-dioxolane (4360-63-8) + 2-bromoethanol (540-51-2)

ethylene glycol (107-21-1) + bromoacetaldehyde (17157-48-1) → 2-bromomethyl-1,3-dioxolane (4360-63-8)

Bromoacetaldehyde diethyl acetal (2032-35-1) → 2-bromomethyl-1,3-dioxolane (4360-63-8)

ethylene glycol (107-21-1) + ω.ω'-dibromo-paraldehyde → 2-bromomethyl-1,3-dioxolane (4360-63-8)

Conditions	Yield
With sulfuric acid

ethylene glycol (107-21-1) + tribromoparaldehyde → 2-bromomethyl-1,3-dioxolane (4360-63-8)

Conditions	Yield
With sulfuric acid at 100℃;

2-bromomethyl-1,3-dioxolane (4360-63-8) + tributylphosphine (998-40-3) → (1,3-dioxolan-2-ylmethyl)tributylphosphonium bromide (115754-62-6)

Conditions	Yield
at 90℃; for 96h;	100%
at 90℃; for 72h; Yield given;

2-bromomethyl-1,3-dioxolane (4360-63-8) → 2-(azidomethyl)-1,3-dioxolane

Conditions	Yield
With sodium azide In dimethyl sulfoxide at 100℃; for 0.5h;	100%
With sodium azide In dimethyl sulfoxide at 70℃;	93%
With sodium azide In dimethyl sulfoxide Inert atmosphere;	83%

2-bromomethyl-1,3-dioxolane (4360-63-8) → sodium S-((1,3-dioxolan-2-yl)methyl) thiosulfate

Conditions	Yield
With Sodium thiosulfate pentahydrate In methanol; water for 24h; Reflux;	100%

2-bromomethyl-1,3-dioxolane (4360-63-8) + triphenylphosphine (603-35-0) → (1,3-dioxolan-2-yl-methyl)triphenylphosphonium bromide (52509-14-5)

Conditions	Yield
In isopropyl alcohol at 60 - 65℃; for 3h; Inert atmosphere; Green chemistry;	99.1%
In toluene for 24h; Heating / reflux;	54%
at 120℃; for 24h;

2-bromomethyl-1,3-dioxolane (4360-63-8) + tris-n-propylphosphine (2234-97-1) → C13H28O2P(1+)*Br(1-)

Conditions	Yield
With sodium iodide In 1,4-dioxane for 24h; Heating;	97%

2-bromomethyl-1,3-dioxolane (4360-63-8) + 2-methoxy-phenol (90-05-1) → 2-[(2-methoxyphenoxy)methyl]-1,3-dioxolane (1160183-64-1)

Conditions	Yield
With potassium carbonate In 1-methyl-pyrrolidin-2-one at 135℃; for 10h; Product distribution / selectivity;	91.15%
With potassium carbonate In 2-methoxy-ethanol at 125 - 126℃; for 17h; Product distribution / selectivity;	88.59%
With potassium carbonate In ethylene glycol at 132℃; for 20h; Product distribution / selectivity;	80.6%

2-bromomethyl-1,3-dioxolane (4360-63-8) + dimethyl methylphosphonite (20278-51-7) → C6H13O4P

Conditions	Yield
at 120℃; for 5h; Inert atmosphere;	91.1%

2-bromomethyl-1,3-dioxolane (4360-63-8) + N,N-diethyl-2-propynylamine (4079-68-9) + 2-(vinyloxy)ethyl isothiocyanate (59565-09-2) → 5-[(1,3-dioxolan-2-ylmethyl)sulfanyl]-1-[2-(ethenyloxy)ethyl]-N,N-diethyl-1H-pyrrol-2-amine

Conditions	Yield
Stage #1: N,N-diethyl-2-propynylamine With n-butyllithium In tetrahydrofuran; hexane at -60℃; Inert atmosphere; Stage #2: 2-(vinyloxy)ethyl isothiocyanate In tetrahydrofuran; hexane at 0 - 45℃; for 0.0833333h; Inert atmosphere; Stage #3: 2-bromomethyl-1,3-dioxolane Further stages;	91%

2-bromomethyl-1,3-dioxolane (4360-63-8) + N-9-fluorenylisovaleraldehyde imine → N-(1-(1,3-dioxolan-2-yl)-4-methylpentan-2-yl)-9H-fluoren-9-imine

Conditions	Yield
Stage #1: 2-bromomethyl-1,3-dioxolane; N-9-fluorenylisovaleraldehyde imine With cobalt(II) bromide In diethyl ether at 25℃; for 0.166667h; Sealed tube; Stage #2: With lithium hexamethyldisilazane In diethyl ether at -20 - 25℃; for 2.16667h; Catalytic behavior; Reagent/catalyst; Solvent; Sealed tube; regioselective reaction;	91%

2-bromomethyl-1,3-dioxolane (4360-63-8) + epichlorohydrin (106-89-8) → (2R,2S)-(3,4-epoxy)butyl-1,3-dioxolane

Conditions	Yield
Stage #1: 2-bromomethyl-1,3-dioxolane With iodine; magnesium In tetrahydrofuran at 30 - 40℃; for 3h; Inert atmosphere; Stage #2: epichlorohydrin In tetrahydrofuran at 0 - 15℃; for 4h;	90.6%

2-bromomethyl-1,3-dioxolane (4360-63-8) + theophylline (58-55-9) → doxofylline (69975-86-6)

Conditions	Yield
With tetrabutylammomium bromide; sodium hydroxide In acetone for 6.3h; Reagent/catalyst; Solvent; Reflux; Large scale;	90%
With sodium carbonate In N,N-dimethyl-formamide at 120℃;	7 g
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide for 12h; Large scale;

2-bromomethyl-1,3-dioxolane (4360-63-8) + 5-methoxy-2-phenylindole (5883-96-5) → 8-methoxy-1H-benzocarbazole

Conditions	Yield
With bismuth(III) chloride In acetonitrile at 80℃; for 7h;	90%

2-bromomethyl-1,3-dioxolane (4360-63-8) + methyl 3-amino-3-iminopropanoate → 2-amino-3-pyrrolecarboxylate methyl ester

Conditions	Yield
Stage #1: 2-bromomethyl-1,3-dioxolane With hydrogenchloride In water; ethyl acetate at 10℃; for 0.333333h; Stage #2: methyl 3-amino-3-iminopropanoate In water; ethyl acetate at 100℃; for 3h;	89.3%

2-bromomethyl-1,3-dioxolane (4360-63-8) + ethyl-3-hydroxybenzoate (7781-98-8) → ethyl 3-((1,3-dioxolan-2-yl)methoxy)benzoate

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 120℃; for 18h;	89%
With potassium carbonate; sodium iodide In N,N-dimethyl-formamide at 120℃;	88%

2-bromomethyl-1,3-dioxolane (4360-63-8) + 5-[1-(4-chlorophenylsulfonyl)-3-piperidinyl]-1,3,4-oxadiazole-2-thiol → 5-[1-[(4-chlorophenyl)sulfonyl]-3-piperidinyl]-1,3,4-oxadiazole-2-yl 1,3-dioxolan-2-ylmethyl sulfide

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide	89%

2-bromomethyl-1,3-dioxolane (4360-63-8) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 1-(1,3-Dioxolan-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (141794-32-3)

Conditions	Yield
In acetonitrile for 1h; Heating;	88%

2-bromomethyl-1,3-dioxolane (4360-63-8) + 5-methoxylindole (1006-94-6) + acetoacetic acid methyl ester (105-45-3) → methyl 6-methoxy-1-methyl-9H-carbazole-2-carboxylate

Conditions	Yield
With bismuth(III) chloride In acetonitrile at 80℃; for 2h;	88%

2-bromomethyl-1,3-dioxolane (4360-63-8) → 2-(iodomethyl)-1,3-dioxolane (41031-93-0)

Conditions	Yield
With sodium iodide In acetone for 24h; Reflux;	87%
With sodium iodide In acetone at 25 - 120℃; for 8h; Inert atmosphere;	85%
With sodium iodide In various solvent(s) for 24h; Heating;	78%

2-bromomethyl-1,3-dioxolane (4360-63-8) + 5-Hydroxy-2-methylpyridine (1121-78-4) → 5-(1,3-dioxolan-2-ylmethoxy)-2-methylpyridine (494776-68-0)

Conditions	Yield
Stage #1: 5-Hydroxy-2-methylpyridine With sodium hydride In DMF (N,N-dimethyl-formamide) at 25℃; for 0.166667h; Stage #2: 2-bromomethyl-1,3-dioxolane In DMF (N,N-dimethyl-formamide) at 100℃; for 12h;	87%

Upstream product

• 108-05-4 vinyl acetate 
• 107-21-1 ethylene glycol 
• 7252-83-7 1-bromo-2,2-dimethoxyethane 
• 6304-35-4 bis-(1,2-dibromo-ethyl) ether 
• 2032-35-1 Bromoacetaldehyde diethyl acetal 
• 17157-48-1 bromoacetaldehyde 
• 497-26-7 2-methyl-1,3-dioxolane 
• 75-07-0 acetaldehyde 

Downstream Products

• 927-68-4 bromoethyl acetate 
• 4070-51-3 Bromessigsaeure-monoglykolester 
• 115754-62-6 (1,3-dioxolan-2-ylmethyl)tributylphosphonium bromide 
• 100157-42-4 1-cyano-1-<2-(1,1-ethylendioxyethyl)>diphenylmethane 
• 130220-08-5 2-(4-Chloro-2-methyl-phenylsulfanylmethyl)-[1,3]dioxolane 
• 107535-97-7 2-[2-Methylsulfanyl-2-(toluene-4-sulfonyl)-ethyl]-[1,3]dioxolane 
• 344439-21-0 N-(4-Bromo-phenyl)-N-[1,3]dioxolan-2-ylmethyl-methanesulfonamide 
• 117013-72-6 2-<(4-acetamido-3-nitro-phenoxy)-methyl>-1,3-dioxolane 
• 114614-55-0 4-Amino-5-chloro-N-(2-diethylamino-ethyl)-2-([1,3]dioxolan-2-ylmethoxy)-benzamide 
• 125228-46-8 (3R,8aR)-5-[1,3]Dioxolan-2-ylmethyl-3-phenyl-hexahydro-oxazolo[3,2-a]pyridine-5-carbonitrile 
• 71516-48-8 2-((benzyloxy)methyl)-1,3-dioxolane 
• 73785-78-1 allyl<2,2-(ethylenedioxy)ethyl>diphenylphosphonium bromide 
• 179669-44-4 dioxolanne de l'α-phenylthioacetaldehyde 
• 764-48-7 ethyleneglycol vinyl ether 

Relevant academic research and scientific papers

Electron Spin Resonance Spectra of Free Radicals. Part 2. Radicals formed by Hydrogen Abstraction from Cyclic and Acyclic Fluoro-acetals

Free radicals formed during the photolysis of solutions containing di-t-butyl peroxide and fluoro-acetals such as 1,1-diethoxy-2-fluoroethane and substituted 1,3-dioxolanes, have been studied by e.s.r. spectroscopy.Only the radicals formed initially by hydrogen abstraction were detected, although product analysis by g.c.-m.s. indicated that certain of the cyclic radicals rearranged to acyclic species.The e.s.r. parameters are discussed in relation to the preferred conformations of the radicals.

Kinetics and mechanism of bromination of cyclic acetals with 1,4-dioxane dibromide

It is shown that the reactivities of cyclic formals in the case of bromination with dioxane dibromide increase in the order 1,3-dioxepane > 1,3-dioxalane ? 1,3-dioxane, which is explained not only by steric factors but also by the ease of cleavage of the C4-O3 bond of the dioxacyclane ring. The bromination of cyclic acetals takes place through prior enolization of the cyclic acetal with subsequent electrophilic addition of bromine to the double bond.

Preparation method of doxofylline

The invention provides a preparation method of doxofylline and particularly relates to a synthetic method of bromoacetaldehyde ethylene acetal represented as the formula II and the doxofylline. The method includes the steps of preparing the side-chain bromoacetaldehyde ethylene acetal represented as the formula II through a one-pot reaction of acetaldehyde, ethylene glycol and bromine, and then carrying out a N-alkylation reaction to the compound represented as the formula II with theophylline to prepare the doxofylline. The synthetic method is carried out with easy-to-obtain raw materials, is low in cost, is high in yield, is simple in processes, is economical and environment-friendly, and is beneficial to industrial scale-up production of the drug.

Preparation methods of doxofylline

The invention discloses preparation methods of doxofylline. The preparation methods include the steps: under the action of an acid-binding agent, carrying out a condensation reaction of theophylline and halogenated acetaldehyde dimethyl acetal in a polar solvent, to obtain an intermediate 7-(2,2-dimethoxy ethyl)theophylline; and then, with soluble hydrosulfate as a catalyst, carrying out a condensation cyclization reaction of the intermediate 7-(2,2-dimethoxy ethyl)theophylline with ethylene glycol in a solvent, to obtain doxofylline; or, firstly, carrying out a condensation cyclization reaction of halogenated acetaldehyde dimethyl acetal and ethylene glycol to obtain halogenated acetaldehyde ethylene acetal, and carrying out a condensation reaction with theophylline, to obtain doxofylline. The soluble hydrosulfate is used as the catalyst and replaces conventional p-toluenesulfonic acid, moreover, and anisole and other solvents are used for replacing methylbenzene used in a conventional reaction route, so that under a condition of ensuring high yield of the product, the toxicity of the solution in the synthesis reaction is reduced, and the difficult problem that residual toxicity easily exists in the finished product is solved.

Catalytic Effect of Crown Ethers in the Bromination of 2-Alkyl-substituted 1,3-Dioxacyclanes

Bromination of 2-alkyl-1,3-dioxacyclanes with molecular bromine in the presence of crown ethers in benzene (chloroform) results, regardless of the acetal ring size, in exclusive formation of 2-(1-bromoalkyl)-1,3-dioxacyclanes in near-quantitative yields. The use of crown ethers allows the bromination to be accomplished at room temperature.

Effect of Crown Ethers on Bromination of 2-Methyl-1,3-dioxacycloalkanes with N-Bromosuccinimide

Crown ethers exert a pronounced catalytic effect on bromination of 2-methyl-1,3-dioxacycloalkanes with N-bromosuccinimide and increase the yield of 2-bromomethyl derivatives.

Bromination of 1,3-dioxolanes by molecular bromine

Bromination of alkyl-substituted 1,3-dioxolanes by molecular bromide in carbon tetrachloride occurs regioselectively with preservation of heterocycle and leads to formation of 2-(α-bromoalkyl)-1,3-dioxolane.

The mechanism of directed remote asymmetric reduction of carbonyl groups via homochiral boronate esters

In order to determine whether the remote asymmetric induction in the reduction of compounds such as 1 and 2 using borane is really controlled by intramolecular chelates of type 3, rather than dioxaborolane oxygenborane chelates of type 12, a study was undertaken to examine related reductions involving the corresponding homochiral acetal 30 and comparative reductions of the dioxaborolane 14 and the acetal 23b.While this study showed that reductions of the dioxaborolane 14 and the acetal 23b with borane and L-Selectride were virtually identical, this result did not necessarily indicate that dioxaborolane oxygens or acetal oxygens were directing borane reduction.However, that the more likely explanation for the remote asymmetric induction observed for 1 and 2 being mediated by complex 3 was confirmed by the fact that the acetal 30 gave no asymmetric induction with borane.A crystal structure of the phenylboronate ester 10 has been carried out.

Preparation of racemic and enantiomerically pure cyclic ketene acetals

Cyclic ketene acetals have been prepared from a-haloaldehyde dimethylacetals by transacetalization and subsequent elimination in PTC without solvent conditions. No racemization has been observed when an enantiomerically pure diol has been used. Stability and storage conditions have been studies.

Herbicidal composition containing dioxolane, dioxane, or dioxepane derivatives as antidote

The invention relates to a herbicidal composition which contains, besides binding, wetting, dispersing, emulsifying agents, solvents and/or surface-active substances, herbicides as active agent of thiocarbamate, carbamate, acid amide or urea type alone or in a combination, furthermore as antidote a compound of the general formula I STR1 wherein R1 and R2, independently of each other, are hydrogen, C1-6 alkyl, C2-6 alkenyl, C1-4 cyanoalkyl, C1-6 haloalkyl, phenyl-C1-4 -haloalkyl, phenyl, halogenphenyl, C1-4 -alkyl-phenyl, C1-4 -alkoxyphenyl, furfuryl; R3 and R4, independently of each other, are hydrogen, C1-18 -alkyl, C2-4 -haloalkyl, C2-4 -cyanoalkyl, C1-4 -alkoxy-C2-4 -alkyl, C5-6 -cycloalkyl, phenyl-C1-4 -alkyl, C3-4 -alkenyl, phenyl-C3-4 -alkenyl, di-C1-4 -alkylamino-C2-4 -alkyl, hydroxy-C2-6 -alkyl, furfuryl, tetrahydrofurfuryl, C1-4 -alkoxy-C2-4 -alkoxy-C2-4 -alkyl; R3 and R4, together, are C2-4 -alkylene, C4 -alkenylene, glucofuranosylene, acetoxy-C3 -alkylene, C1-4 -alkoxy-C3 -alkylene, hydroxy-C3 -alkylene, halogen-C3 -alkylene; wherein the quantity of the antidote lies between 0.01 and 15 parts by weight referred to 1 part by weight of herbicidal agent, furthermore the composition contains altogether 0.1 to 95 percent by weight of the herbicidal agents and the antidote.