PROCESS FOR THE DI-O-ALKYLATION OF 1,3-DIOLS TO 1,3-DIETHERS

Abstract

The present invention relates to a process for the di-O-alkylation of a 1,3-diol according to Formula I (I), said process comprising reacting said 1,3-diol with dioxane, an aliphatic or aromatic hydrocarbon solvent, an alkali metal hydroxide, and dimethyl sulphate, in order to obtain a 1,3-diether according to Formula II (II), wherein R.sup.1 and R.sup.2 are each independently a hydrogen atom or a hydrocarbyl group selected from alkyl, alkenyl, aryl, aralkyl, or alkylaryl groups, and one or more combinations thereof. The process according to the invention is an improved process for preparing 1,3-diether, such as 9,9-bis(methoxymethyl)fluorene, in a high yield and/or having a high purity. 9,9-bis(methoxymethyl)fluorene is a compound that is used as an electron donor for Ziegler-Natta catalysts.

##STR00001##

Claims

1. A process for the di-O-alkylation of a 1,3-diol according to Formula I, ##STR00005## said process comprising reacting said 1,3-diol with dioxane, an aliphatic or aromatic hydrocarbon solvent, an alkali metal hydroxide, and dimethyl sulphate, in order to obtain a 1,3-diether according to Formula II, ##STR00006## wherein R.sup.1 and R.sup.2 are each independently a hydrogen atom or a hydrocarbyl group selected from an alkyl group, an alkenyl group, an aryl group, and aralkyl group, an alkylaryl groups, or one or more combinations thereof.

2. Process according to claim 1, wherein the 1,3-diol is 9,9-bis(hydroxymethyl)fluorene, and the 1,3-diether is 9,9-bis(methoxymethyl)fluorene.

3. Process according to claim 1, wherein the aliphatic or aromatic hydrocarbon solvent is a cyclic hydrocarbon.

4. Process according to claim 1, wherein the alkali metal hydroxide is in the form of a solid.

5. Process according to claim 1, wherein the reaction is carried out in a one phase system.

6. Process according to claim 1, wherein the alkali metal hydroxide is potassium hydroxide.

7. Process according to claim 1, wherein dimethyl sulfate is used in an amount of between 2.2 and 2.6 moles per mole of mono- or dialcohol used.

8. Process according to claim 1, comprising contacting a pre-mixture comprising the 1,3-diol, the dioxane, and a first portion of the hydrocarbon solvent with the alkali metal hydroxide, and subsequently adding dimethyl sulphate and a second portion of the hydrocarbon solvent.

9. Process according to claim 8, wherein the hydrocarbon solvent is miscible with the pre-mixture.

10. Process according to claim 8, wherein the ratio of dioxane and hydrocarbon solvent in the pre-mixture is between 1:2 and 2:1.

11. Process according to claim 1, comprising the steps of i) providing a pre-mixture comprising the 1,3-diol, the dioxane, and a first portion of the hydrocarbon solvent; ii) adding the hydroxide to the pre-mixture formed in step i) to form a mixture; iii) adding the dimethyl sulfate and a second portion of the hydrocarbon solvent to the mixture formed in step ii) to form a reaction mixture; iv) stirring the reaction mixture obtained in iii); v) adding water to the reaction mixture obtained in step iv) and mixing; vi) allowing the reaction mixture obtained in step v) to separate into an organic layer and a water layer; vii) separate the organic layer formed in step vi) from the water layer; viii) optionally washing the organic layer obtained in step vii) with water; ix) optionally extracting the water layer obtained in step vii) with an additional portion of the hydrocarbon solvent to provide an organic extract layer; x) evaporate the dioxane and the hydrocarbon solvent in the organic layer obtained in step viii) and optionally the organic extract layer obtained in step ix) to obtain crude 1,3-diether.

12. Process according to claim 11, wherein the crude 1,3-diether obtained in step x) is recrystallized to obtain 1,3-diether.

13. Process according to claim 11, wherein the stirring in step iv) is carried out for a period of between 6 and 8 hours.

14. Process according to claim 11, wherein step iii) and/or step iv) are carried out at a temperature of between 15 and 20° C.

15. Process according to claim 1, comprising the steps of i) providing a pre-mixture of 9,9-bis(hydroxymethyl)fluorene, dioxane in an amount of between 400 and 500 milliliter per mole of 9,9-bis(hydroxymethyl)fluorene used, and toluene in an amount of between 400 and 500 milliliter per mole of 9,9-bis(hydroxymethyl)fluorene used; ii) adding to the pre-mixture of step i) solid potassium hydroxide in an amount of between 4 and 10 mole per mole of 9,9-bis(hydroxymethyl)fluorene used to obtain a reaction mixture; iii) adding gradually, to the reaction mixture of step ii) a mixture of dimethyl sulfate in an amount of between 2.2 to 2.6 mole dimethyl sulfate per mole of 9,9-bis(hydroxymethyl)fluorene and toluene and between 400 and 500 milliliter toluene per mole of 9,9-bis(hydroxymethyl)fluorene used over a period of between 2 and 3 hours at a temperature of between 15 and 20° C.; iv) stirring the reaction mixture obtained in step iii) for a period of between 6 and 8 hours at a temperature of between 15 and 20° C.; v) adding water to the reaction mixture obtained in step iv) in an amount of between 600 and 800 milliliter per mole of 9,9-bis(hydroxymethyl)fluorene used and stirring for a period of time between 5 and 25 minutes at a temperature of between 15 and 20° C.; vi) allowing the reaction mixture obtained in step v) to separate in an organic layer and a water layer; vii) separate the organic layer formed in step iv) from the water layer; viii) washing the organic layer obtained in step vii) with water in an amount of between 400 and 500 milliliter water per mole of 9,9-bis(hydroxymethyl)fluorene used; ix) extracting the water layer obtained in step vii) with toluene in an amount of between 100 and 250 milliliter per mole of 9,9-bis(hydroxymethyl)fluorene used to obtain an organic extract layer; x) evaporating the dioxane and the toluene from the organic layer formed in step vii) and the organic extract layer obtained in step ix) to obtain crude 9,9-bis(methoxymethyl)fluorene; and xii) recrystallize the crude 9,9-bis(methoxymethyl)fluorene from between 1000 and 1200 milliliter of methanol per mole of 9,9-bis(hydroxymethyl)fluorene used and drying under vacuum to obtain 9,9-bis(methoxymethyl)fluorene.

Description

DESCRIPTION OF EMBODIMENTS

[0028] In an embodiment of the present invention, said hydrocarbyl group is be linear, branched or cyclic. Said hydrocarbyl group may be substituted or unsubstituted. Said hydrocarbyl group may contain one or more heteroatoms. Preferably, said hydrocarbyl group has from 1 to 10 carbon atoms, more preferably from 1 to 8 carbon atoms, even more preferably from 1 to 6 carbon atoms. Suitable examples of hydrocarbyl groups include alkyl-, cycloalkyl-, alkenyl-, alkadienyl-, cycloalkenyl-, cycloalkadienyl-, aryl-, aralkyl, alkylaryl, and alkynyl-groups.

[0029] In an embodiment of the present invention, the 1,3-diol is 9,9-bis(hydroxymethyl)fluorene, and the 1,3-diether is 9,9-bis(methoxymethyl)fluorene.

[0030] In an embodiment, the aliphatic or aromatic hydrocarbon solvent is a cyclic hydrocarbon. In an embodiment of this, the cyclic hydrocarbon is chosen from the group of toluene, benzene, cyclohexene and xylene. In a preferred embodiment, said solvent is toluene.

[0031] In an embodiment, the alkali metal hydroxide is in the form of a solid. In an embodiment, alkali metal hydroxide is in the form of a powder. Said alkali metal hydroxide in solid form can be in granulate form, for instance pellets or flakes, which can be ground to obtain a powder before addition.

[0032] In an embodiment, the reaction is carried out in a one phase system.

[0033] In an embodiment, as the alkali metal hydroxide, potassium hydroxide is used.

[0034] Potassium hydroxide is used to abstract proton more easily.

[0035] In case the reaction is diluted with water, the reaction will slow not or may not be completed.

[0036] However, with any alkyl halide, the reaction will not work with potassium hydroxide as it will hydrolyze.

[0037] In addition, dimethylsulphate decomposes slowly in alkali or alkaline solution.

[0038] However, potassium hydroxide with dimethylsulphate in presence of dioxane allow to obtain good reaction condition for dialkylation with high yield process is industrially viable and feasible.

[0039] In an embodiment of this, potassium hydroxide is used in an amount of between 4 and 10 moles per mole of mono- or dialcohol used.

[0040] In an embodiment, dimethyl sulfate is used in an amount of between 2.2 and 2.6 moles per mole of mono- or dialcohol used.

[0041] In an embodiment, the process comprises contacting a pre-mixture comprising the 1,3-diol, the dioxane, and a first portion of the hydrocarbon solvent with the alkali metal hydroxide, and subsequently adding dimethyl sulphate and a second portion of the hydrocarbon solvent. In embodiment of this, the hydrocarbon solvent is miscible with the pre-mixture. In another embodiment of this, the ratio of dioxane and hydrocarbon solvent in the pre-mixture is between 1:2 and 2:1, preferably between 1:1.5 and 1.5:1, more preferably between 1:1.1 and 1.1:1.

[0042] In an embodiment, the process comprises the steps of [0043] i) providing a pre-mixture comprising the 1,3-diol, the dioxane, and a first portion of the hydrocarbon solvent; [0044] ii) adding the hydroxide to the pre-mixture formed in step i) to form a mixture; [0045] iii) adding the dimethyl sulfate and a second portion of the hydrocarbon solvent to the mixture formed in step ii) to form a reaction mixture; [0046] iv) stirring the reaction mixture obtained in iii); [0047] v) adding water to the reaction mixture obtained in step iv) and mixing; [0048] vi) allowing the reaction mixture obtained in step v) to separate into an organic layer and a water layer; [0049] vii) separate the organic layer formed in step vi) from the water layer; [0050] viii) optionally washing the organic layer obtained in step vii) with water; [0051] ix) optionally extracting the water layer obtained in step vii) with an additional portion of the hydrocarbon solvent to provide an organic extract layer; [0052] x) evaporate the dioxane and the hydrocarbon solvent in the organic layer obtained in step viii) and optionally the organic extract layer obtained in step ix) to obtain crude 1,3-diether.

[0053] In an embodiment, mixing in step v) means stirring.

[0054] In an embodiment, in step iv) the reaction mixture is stirred until completion. With “until completion” in this context is meant that at most 10 wt. % of the starting material has remained in the reaction mixture, preferably at most 5 wt. %, more preferably at most 1 wt. %.

[0055] In an embodiment, step viii) entails the following: adding water to the organic layer obtained in step vii) and mixing; allowing the mixture to separate into an organic layer and a water layer; and separating said organic layer from the water layer.

[0056] In an embodiment, the crude 1,3-diether obtained in step x) is recrystallized to obtain 1,3-diether, preferably using an alcohol solvent, more preferably methanol. Recrystallization can for instance be performed with alcohol such as ethanol, isopropanol or methanol. Preferably, recrystallization is performed with methanol. In an embodiment, between 1000 and 1200 milliliter of methanol per mole of 9,9-bis(hydroxymethyl)fluorene used for the recrystallization.

[0057] In an embodiment, the stirring in step iv) is carried out for a period of between 6 and 8 hours.

[0058] In an embodiment, step iii) and/or step iv) are carried out at a temperature of between 15 and 20° C.

[0059] In an embodiment, in step i) and dioxane is used in an amount of between 400 and 500 milliliter per mole of the 1,3-diol used. In an embodiment, in step i) the hydrocarbon solvent is toluene, used in an amount of between 400 and 500 milliliter per mole the 1,3-diol used.

[0060] In an embodiment, in step ii) the hydroxide is solid potassium hydroxide, and this is added in an amount of between 4 and 10 mole per mole of the 1,3-diol used.

[0061] In an embodiment, in step iii) dimethyl sulfate is added in an amount of between 2.2 to 2.6 mole dimethyl sulfate per mole of the 1,3-diol. In an embodiment, the solvent is toluene, of which between 400 and 500 milliliter toluene per mole of the 1,3-diol used. In a specific embodiment, a mixture of dimethyl sulfate and toluene is added gradually, preferably dropwise, to the reaction mixture of step ii) over a period of between 2 and 3 hours at a temperature of between 15 and 20° C.

[0062] In an embodiment, in step iv) the reaction mixture is stirred for a period of between 6 and 8 hours at a temperature of between 15 and 20° C.

[0063] In an embodiment, in step v) water is added in an amount of between 600 and 800 milliliter per mole of the 1,3-diol used and stirred for a period of time between 5 and 25 minutes at a temperature of between 15 and 20° C.

[0064] In an embodiment, in step viii) the organic layer is washed with water in an amount of between 400 and 500 milliliter water per mole of the 1,3-diol used;

[0065] In an embodiment, in step ix) the hydrocarbon solvent is toluene, which is used in an amount of between 100 and 250 milliliter per mole of the 1,3-diol used.

[0066] In an embodiment of the present invention, the process comprises the steps of [0067] i) providing a pre-mixture of 9,9-bis(hydroxymethyl)fluorene, dioxane in an amount of between 400 and 500 milliliter per mole of 9,9-bis(hydroxymethyl)fluorene used, and toluene in an amount of between 400 and 500 milliliter per mole 9,9-bis(hydroxymethyl)fluorene used; [0068] ii) adding to the pre-mixture of step i) solid potassium hydroxide in an amount of between 4 and 10 mole per mole of 9,9-bis(hydroxymethyl)fluorene used to obtain a reaction mixture; [0069] iii) adding gradually, preferably dropwise, to the reaction mixture of step ii) a mixture of dimethyl sulfate in an amount of between 2.2 to 2.6 mole dimethyl sulfate per mole of 9,9-bis(hydroxymethyl)fluorene and toluene and between 400 and 500 milliliter toluene per mole of 9,9-bis(hydroxymethyl)fluorene used over a period of between 2 and 3 hours at a temperature of between 15 and 20° C.; [0070] iv) stirring the reaction mixture obtained in step iii) for a period of between 6 and 8 hours at a temperature of between 15 and 20° C.; [0071] v) adding water to the reaction mixture obtained in step iv) in an amount of between 600 and 800 milliliter per mole of 9,9-bis(hydroxymethyl)fluorene used and stirring for a period of time between 5 and 25 minutes at a temperature of between 15 and 20° C.; [0072] vi) allowing the reaction mixture obtained in step v) to separate in an organic layer and a water layer; [0073] vii) separate the organic layer formed in step iv) from the water layer; [0074] viii) washing the organic layer obtained in step vii) with water in an amount of between 400 and 500 milliliter water per mole of 9,9-bis(hydroxymethyl)fluorene used; [0075] ix) extracting the water layer obtained in step vii) with toluene in an amount of between 100 and 250 milliliter per mole of 9,9-bis(hydroxymethyl)fluorene used to obtain an organic extract layer; [0076] x) evaporating the dioxane and the toluene from the organic layer formed in step vii) and the organic extract layer obtained in step ix) to obtain crude 9,9-bis(methoxymethyl)fluorene; [0077] xii) recrystallize the crude 9,9-bis(methoxymethyl)fluorene from between 1000 and 1200 milliliter of methanol per mole of 9,9-bis(hydroxymethyl)fluorene used and dry under vacuum to obtain 9,9-bis(methoxymethyl)fluorene.

[0078] Examples of 1,3-diethers that can be prepared using the present invention according to Formula II include 1,3-dimethoxypropane, 1,3-diethoxypropane, 1-methoxy-3-ethoxypropane, 1-methoxy-3-butoxypropane, 1-methoxy-3-cyclohexoxypropane, 2,2-dimethyl-1,3-dimethoxypropane, 2,2-diethyl-1,3-dimethoxypropane, 2,2-di-n-butyl-1,3-dimethoxypropane, 2,2-diiso-butyl-1,3-dimethoxypropane, 2-ethyl-2-n-butyl-1,3-dimethoxypropane, 2-n-propyl-2-cyclopentyl-1,3-dimethoxypropane, 2,2-dimethyl-1,3-diethoxypropane, 2-n-propyl-2-cyclohexyl-1,3-diethoxypropane, 2-(2-ethylhexyl)-1,3-dimethoxypropane, 2-isopropyl-1,3-dimethoxypropane, 2-n-butyl-1,3-dimethoxypropane, 2-sec-butyl-1,3-dimethoxypropane, 2-cyclohexyl-1,3-dimethoxypropane, 2-phenyl-1,3-diethoxypropane, 2-cumyl-1,3-diethoxypropane, 2-(2-phenyllethyl)-1,3-dimethoxypropane, 2-(2-cyclohexylethyl)-1,3-dimethoxypropane, 2-(p-chlorophenyl)-1,3-dimethoxypropane, 2-(diphenylmethyl)-1,3-dimethoxypropane, 2-(1-naphthyl)-1,3-dimethoxypropane, 2-(fluorophenyl)-1,3-dimethoxypropane, 2-(1-decahydronaphthyl)-1,3-dimethoxypropane, 2-(p-t-butylphenyl)-1,3-dimethoxypropane, 2,2-dicyclohexyl-1,3-dimethoxypropane, 2,2-di-n-propyl-1,3-dimethoxypropane, 2-methyl-2-n-propyl-1,3-dimethoxypropane, 2-methyl-2-benzyl-1,3-dimethoxypropane, 2-methyl-2-ethyl-1,3-dimethoxypropane, 2-methyl-2-phenyl-1,3-dimethoxypropane, 2-methyl-2-cyclohexyl-1,3-dimethoxypropane, 2,2-bis(pchlorophenyl)-1,3-dimethoxypropane, 2,2-bis(2-cyclohexylethyl)-1,3 dimethoxypropane, 2-methyl-2-iso butyl-1,3-dimethoxypropane, 2-methyl-2-(2-ethylhexyl)-1,3-dimethoxy propane, 2-methyl-2-isopropyl-1,3-dimethoxypropane, 2,2-diphenyl-1,3-dimethoxypropane, 2,2-dibenzyl-1,3-dimethoxypropane, 2,2-bis(cyclohexylmethyl)-1,3-dimethoxypropane, 2,2-diiso butyl-1,3-diethoxypropane, 2-iso butyl-2-isopropyl-1,3-dimethoxypropane, 2,2-di-sec-butyl-1,3-dimethoxypropane, 2,2-di-t-butyl-1,3-dimethoxypropane, 2,2-dineopentyl-1,3-dimethoxypropane, 2-isopropyl-2-isopentyl-1,3-dimethoxypropane, 2-phenyl-2-benzyl-1,3-dimethoxypropane, 2-cyclohexyl-2-cyclohexylmethyl-1,3-dimethoxypropane, 2-isopropyl-2-(3, 7-dimethyloctyl) 1,3-dimethoxypropane, 2,2-diisopropyl-1,3-dimethoxypropane, 2-isopropyl-2-cyclohexylmethyl-1,3-dimethoxypropane, 2,2-diisopentyl-1,3-dimethoxypropane, 2-isopropyl-2-cyclohexyl-1,3-dimethoxypropane, 2-isopropyl-2-cyclopentyl-1,3-dimethoxypropane, 2,2-dicylopentyl-1,3-dimethoxypropane, 2-n-heptyl-2-n-pentyl-1,3-dimethoxypropane, 9,9-bis(methoxymethyl)fluorene, 1,3-dicyclohexyl-2,2-bis(methoxymethyl)propane, 3,3-bis(methoxymethyl)-2,5-dimethylhexane, or any combination of the foregoing. In an embodiment, the internal electron donor is 1,3-dicyclohexyl-2,2-bis(methoxymethyl)propane, 3,3-bis(methoxymethyl)-2,5-dimethylhexane, 2,2-dicyclopentyl-1,3-dimethoxypropane and combinations thereof.

[0079] A specific example of a compound according to Formula II is 9,9-bis (methoxymethyl) fluorene:

##STR00004##

[0080] In an embodiment, the 1,3-diol compound according to Formula I is 9,9-bis(methoxymethyl)fluorene.

[0081] Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. A single processor or other unit may fulfil the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measured cannot be used to advantage.

[0082] The scope of the present invention is defined by the appended claims. One or more of the objects of the invention are achieved by the appended claims.

EXAMPLES

[0083] The present invention is further elucidated based on the Examples below which are illustrative only and not considered limiting to the present invention.

Example 1—Procedure for Preparation of 9,9-bis(methoxymethyl)fluorine (BMMF)

[0084] To a two litre round bottom flask is added 200 mL dioxane, 200 mL toluene and 100 g (0.44 moles) 9,9-bis(hydroxymethyl)fluorine (BHMF) under stirring. The mixture is cooled to room temperature. To this mixture, 173.7 g (3.1 moles) potassium hydroxide is added. The mixture is stirred for 30 minutes. Gradually 133.8 g (1.06 moles) dimethylsulphate (DMS) and 200 mL of toluene is added over the course of 2-3 hours at a temperature of 15-20° C. The reaction mixture is subsequently stirred at the same temperature until the reaction is complete. The reaction progress is checked using Thin Layer Chromatography (TLC) with a diluted sample of approximately 2-5%. For the TLC a mixture of 20% ethylacetate and 80% heptane is used. The reaction is considered complete when 9,9-bis(hydroxymethyl)fluorine is absent from the TLC plate, and the 9,9-bis(methoxymethyl)fluorine is present in majority quantity, possible with a faint spot of mono-O-alkylated 9,9-bis(hydroxymethyl)fluorine. The reaction progress can also be monitored with gas chromatography (GC). The reaction is then considered complete when more than 95% is 9,9-bis(methoxymethyl)fluorine. If the reaction is not complete, stirring is continued for 1-2 hours at room temperature before the reaction progress is checked again.

[0085] After completion of the reaction, 300 mL of water is added. The mixture is stirred for 15 minutes and the organic layer is separated. If the organic layer is not clear, it can be filtered through a Hyflow bed. After separation, the organic layer is washed with 200 mL water, and the aqueous layer is extracted with 50-100 mL toluene. The combined toluene and dioxane layer is distilled and the last traces are removed by applying vacuum. A solid residue (85-90 g) is obtained. To this solid residue, 500 mL methanol is added, and the mixture is refluxed for 15-30 minutes. The mixture is subsequently cooled to 10° C. and maintained at that temperature for 2 hours. The mixture is filtered, and the solid product is washed twice with 25 mL of chilled methanol. The product is dried at 50-60° C. under vacuum.

[0086] Purity of the product is determined by Gas Chromatography. If the purity is less then desired, 100-150 methanol can be added to make a slurry of the product, and the product can be filtered. Distilling the methanol allows to recover the 9,9-bis(methoxymethyl)fluorine.

[0087] The wet weight of the product was 85 gram. The dry weight of 9,9-bis(methoxymethyl)fluorine obtained was 70-80 gram. The crude product obtained had a purity of >95% as assessed with Gas Chromatography. Finally purified using methanol gave more than 90% yield and purity of more than 99% as assessed by Gas Chromatography. The appearance of the product is white to off-white.

Example 2

[0088] Charge 10 mL dioxane, 10 mL toluene and 5 g (0.022 moles) 9,9-bis(hydroxymethyl)fluorine (BHMF) under stirring. To this mixture, 6.2 g (0.155 moles) sodium hydroxide added.

[0089] The mixture is stirred for 30 minutes. Gradually 7.85 g (0.055 moles) iodomethane is added over the course of 30 min at a temperature of 15-20° C.

[0090] The reaction mixture is subsequently stirred at the same temperature and progress is checked using Thin Layer Chromatography (TLC) with a diluted sample of approximately 2-5%.

[0091] For the TLC a mixture of 20% ethyl acetate and 80% heptane is used.

[0092] The reaction was not complete after 24 hours stirring and shows about 20% unreacted 9,9-bis(hydroxymethyl)fluorine, 9,9-bis(methoxymethyl)fluorine about 50% as major and mono-O-alkylated 9,9-bis(hydroxymethyl)fluorine.

[0093] The reaction was checked again but there was no further progress.

[0094] Substituting iodomethane for dimethyl sulfate, dialkylation does not go to completion.

Example 3

[0095] Charge 10 mL dioxane, 10 mL toluene and 5 g (0.022 moles) 9,9-bis(hydroxymethyl)fluorine (BHMF) under stirring. To this mixture, 6.2 g (0.155 moles) sodium hydroxide and water (20 ml) is added.

[0096] The mixture is stirred for 30 minutes. Gradually 7.85 g (0.055 moles) iodomethane is added over the course of 30 min at a temperature of 15-20° C.

[0097] The reaction mixture is subsequently stirred at the same temperature and progress is checked using Thin Layer Chromatography (TLC) with a diluted sample of approximately 2-5%.

[0098] For the TLC a mixture of 20% ethyl acetate and 80% heptane is used.

[0099] The reaction was slow and was not complete after 24 hours stirring and shows about 65% unreacted 9,9-bis(hydroxymethyl)fluorine, 9,9-bis(methoxymethyl)fluorine about 30% and mono-O-alkylated 9,9-bis(hydroxymethyl)fluorine.

[0100] The reaction was checked again but there was no further progress.

[0101] Using 30% caustic solution it is found reaction is very slow and does not go to completion after overnight stirring.