ITMI20131225A1 - NEW FLUORURED ORGANIC COMPOUNDS, PROCEDURE FOR THEIR PREPARATION AND THEIR USE AS INTERMEDIATE SUMMARY - Google Patents

Description

DESCRIPTION of the invention entitled:

"New organic fluorinated compounds, process for their preparation and their use as synthesis intermediates"

Summary of the invention

The present invention relates to new fluorinated organic compounds, in particular fluoroalkyl ethers, useful in various industrial applications and as synthesis intermediates in the preparation of complex compounds, and a process for their preparation.

Context of the invention

The chemistry of fluorinated organic compounds has been extensively studied to provide products with various industrial uses thanks to their repellent properties towards water and oil and their high chemical stability.

For example, perfluorinated ethers or hydrofluoroethers constitute a class of products used in many applications and in particular as lubricants, inert fluids, hydro- and / or lipo-repellents and also as solvents.

By way of example, WO2011 / 053628 describes hydrofluoroethers which can be used as heat exchangers.

These compounds are also useful as versatile synthesis intermediates, so-called "building blocks", very suitable for the preparation of more complex molecules.

Aims of the invention

It is a first aim of the invention to provide new perfluorinated organic compounds that can be used in many industrial applications.

It is another object of the invention to provide new perfluorinated organic compounds useful as synthesis intermediates.

Description of the invention

According to one of its aspects, the invention relates to the compounds of formula (I)

- n is 1, 2, 3, 4, or 5

- m is 1, or 2

- R1 represents a group selected from -CF3e - [CF2] 2- [CH2] q-O-R3 where q 1 or 2; - R2 represents a group selected from -CHR4-CR5 = CR6R7; -CR4 = CR5-CHR6R7; - R3 represents a group selected from -CHR4-CR5 = CR6R7 and -CR4 = CR5-CHR6R7; And

- R4, R5, R6 and R7 represent, each independently, a hydrogen or a C1-C4alkyl;

or, when R1 is -CF3, R2 also represents a group selected from

in which

t is 1, 2, 3, 4 or 5; p is 1 or 2; and the symbol

indicates the bond that connects the substituent group with the oxygen atom of the formula (I).

Preferred compounds of formula (I) are the compounds in which R1 is CF3 and R4, R5, R6 and R7 are H.

Other preferred compounds of formula (I) are the compounds in which R2 and R3 are identical to each other.

Other preferred compounds of formula (I) are the compounds in which m is 1.

Other preferred compounds of formula (I) are the compounds in which p is 1.

Other preferred compounds of formula (I) are the compounds in which t is 2 or 4.

The compounds of formula (I) in which R2e / or R3 represent -CHR4-CR5 = CR6R7 can be prepared starting from the corresponding alcohols or diols of formula (II)

wherein n is as defined above and R8 represents a CF3 group or a - [CF2] 2- [CH2] q-OH group; where q is 1 or 2

by reaction with a compound of formula (III)

(III)

where L is a halogen and R4, R5, R6 and R7 are as defined above, in the presence of a strong base.

Preferred compounds of formula (III) are the compounds in which L is selected from chlorine and bromine.

A particularly preferred compound of formula (III) is a 2-propenyl-halide, advantageously 2-propenyl-bromide.

A preferred strong base is an alkali metal hydroxide, such as sodium hydroxide.

The reaction is generally carried out with heating; by way of example, the reaction mixture can be heated to about 60-80 ° C, for example to about 70 ° C.

It is not necessary to add a solvent to the reaction but if desired, it is possible to add a solvent (or a mixture of solvents) as long as it is inert with respect to the reaction process. Among these, ethers are preferred, for example ethyl ether, THF or dioxane.

At the end of the reaction, the compound is isolated according to methods well known to those skilled in the art, for example by extraction in a suitable organic solvent and if desired the compound is purified, for example by distillation.

The compounds of formula (I) in which R 2 is (a) or (b), can be prepared by reacting a 1,4-halo-2-butene with a suitable alcohol of formula

(IV)

in which n and m are as defined above, for example according to the following schemes

These reactions can be carried out in bulk or without solvent or, especially when the starting reagents are solid, in the presence of one or more solvents. The aprotic organic agents are suitable solvents and among these ethers are preferred, among which THF. Alternatively, aromatic or aliphatic fluorinated solvents can be used. The same is true for compounds where m and p are equal to 2.

The compounds of formula (I) in which R2 is (c) and the compounds of formula (I) in which R2e / or R3 represent -CR4 = CR5-CHR6R7 can be prepared starting from the same compounds of formula (I), in which the double bond it is found in the adjacent position, by means of a reaction with ruthenium catalysts which allows to transpose the double bond.

In other words, the compounds of formula (I) in which R2 is (c) can be prepared by subjecting the corresponding compounds of formula (I) in which R2 is (a), or (b) and in which p and t have the desired meaning in the compounds of formula (I) in which R2 is (c), to a transposition reaction of the double bond in the presence of ruthenium catalysts.

For example, the compounds of formula (I) in which R2 is (c) and t is equal to 4 and m and p are equal to 1, can be prepared according to the following scheme

The isomerization reaction can be carried out with or without irradiation by means of a UV lamp; said reaction can be carried out in the presence or absence of solvent. Often preferred are THF; benzotrifluoride and substituted benzotrifluorides; perfluoro ethers and perfluorohydroethers.

Similarly, compounds can be prepared in which R2 is (c) and m is equal to 2 and when R2 is (c) and t is 1, 2, 3 and 5, using the suitable starting compounds.

For the reaction of Scheme C, carbene catalysts of the Grubbs type, well known to those skilled in the art, or homogeneous ruthenium hydride catalysts described for example in Urbala, M. Appl, can be used as ruthenium-based catalysts. Catal., A2010, 377, 27–34.

Of the preferred catalysts, according to the invention, are the Ru (H, Cl, CO) (triphenylphosphine) 3, Ru (H, H, CO) (triphenylphosphine) 3 and Ru (Cl2, CO) (triphenylphosphine) 3 catalysts. The Ru (H, Cl, CO) (triphenylphosphine) 3 catalyst is preferred according to the present invention.

Said catalysts are added in a percentage by moles ranging from 5 to 0.0001% with respect to the moles of starting compound (if it has only one double bond), preferably in the ratio of 0.1 to 0.005%. If two double bonds per compound are to be transposed, the said quantities must be doubled. For the double bond transposition reaction, the starting compound of formula (I) whose double bond is to be transposed, which is preferably previously dried, is reacted with the catalyst without a solvent or in a suitable solvent, such as for example tetrahydrofuran (THF). The reaction mixture is heated and the reaction proceeded to completion. The skilled in the art can of course follow the progress of the reaction with the conventional techniques. The desired compound of formula (I) can finally be isolated as described above.

A substance with basic inorganic or organic properties is added together with the ruthenium catalyst. Among these substances, for example, alkali metal carbonates, alkali metal hydroxides, ammonia, pyridine, aniline and primary secondary and tertiary aliphatic and cycloaliphatic amines can be used. Among these preferred are the tertiary aliphatic amines such as trimethyl amine, triethyl amine, tripropyl amine and tributyl amine, methyl piperidine and methyl morpholine.

The basic substance, for example the amine, is added in a molar ratio of 1 to 10 times higher than that of the ruthenium catalyst. Therefore, for a ruthenium catalyst used at 0.1% by moles with respect to the allyl functional group to be isomerized, the content of the base (or tributylamine in the most preferred case) is 0.5% by moles.

Alternatively, and according to a preferred embodiment of the invention, the transposition of the double bond can be obtained by irradiation in the ultraviolet (always in the presence of the homogeneous Ruthenium catalyst), for example by irradiation with a high pressure mercury lamp.

It has in fact been observed that the reaction times can be reduced, up to 10 times less (for example, instead of 10 hours, only 1 hour of reaction) by conducting the reaction under irradiation with a UV lamp with a wavelength in the ultraviolet between 290 and 400 nm. The value of the preferred irradiation wavelength is between 340 and 370 nm, 365 nm being the even more preferred value.

The use of the UV lamp can possibly be combined with the addition of a basic substance, such as an amine, always in the presence of the ruthenium catalyst. Detailed examples of reactions are provided in the experimental section of the present disclosure.

As mentioned, the compounds of formula (I) find application in various industrial sectors but can also be used as “building blocks” substances and, following chemical transformations, allow access to new and more complex molecules. The presence of the double bond in fact provides the compounds of the invention with the ability to react easily, for example with alkyl chains carrying a halide or to polymerize, if reacted appropriately, as reported below.

Thus, according to another of its aspects, the invention relates to the use of compounds of formula (I) as synthetic intermediates.

By way of example, the compounds of formula (I) can constitute starting materials for the subsequent introduction of other alkyl chains, fluorinated or non-fluorinated, to form "multiblock" chains, i.e. linear structures in which fluorinated chains , generally no longer than 6 carbon atoms, are alternated with chains of hydrogenated carbon atoms containing oxygen atoms. Molecules with this molecular structure can have various industrial uses.

The following diagrams illustrate some of the possible transformations of the compounds of the invention. The details of the reactions and the operating conditions are reported in the experimental section of this description.

where x indicates the number of repetitions of the monomer.

Said cationic polymerization reaction (schemes IV, V, VIII, IX) is preferably carried out in the presence of acid catalysts of the strong protic acid type, such as sulfuric acid, phosphoric acid, triflic acid (CF3SO3H) and higher homologues and hydrofluoric acid; Lewis acids such as BF3, AlCl3, SnCl4, TiCl4. The reaction can also be carried out in the presence of small quantities of water or alcohols such as methanol, ethanol, propanol, butanol; of latent acids (photoacids) such as triflates of diariliodonium and triflates of triphenylsulfonium. Said catalysts are advantageously used in a percentage by moles comprised between 0.01 and 1%, preferably 0.1 - 0.5%, with respect to the moles of the starting compound.

The compounds from (IIa) to (IIi) of the following formula

new and represent a further aspect of the invention, as well as the process for their preparation.

Experimental Section

Example 1

The C6H2F11OH fluorinated alcohol (86.64 ml, 0.468 moles) is loaded into a 300 ml autoclave, equipped with mechanical stirring together with powdered NaOH (37.44 g, 0.936 moles) and allylbromide (40.44 ml, 0.468 moles). The mixture is reacted under stirring for 7 h at 80 ° C. At the end of the reaction the crude product is extracted with diethyl ether. The product is purified by distillation and 108.21 g of a colorless liquid are obtained (e.g. 142-145 ° C, d = 1.49 g / cm <3>) with a yield of 67%.

<1> H NMR (300 MHz, CDCl3): δ 5.79 (ddt, <3> Jtrans = 17.2 Hz, <3> Jcis = 10.3 Hz, <3> JH, H = 5.7 Hz, 1H, CH), 5.24 ( ddt, <3> Jtrans = 17.2 Hz, <2> Jgem = 1.5 Hz, <4> JH, H = 1.4 Hz, 1H, = CH), 5.18

By following the synthesis procedures as reported in example 1 and using heptafluoro-1H, 1H-butanol as starting material, the compound in question is obtained, with a yield of 70%. E.g. 98-100 ° C.

Preparative reaction scheme and use of homogeneous Ru catalysts

The fluorinated ether of Example 1 is dried on molecular sieves and loaded into an autoclave (30.00 g, 88.2 mmol) together with 20 ml of THF, the catalyst catMETiumRF3 (trade name, purchased from Evonik) (0.072 g, 8.82x10 <- 2> mmol, 0.10%) is added in an autoclave air atmosphere. The mixture is then reacted under stirring at 120 ° C for 10 hours and at 60 ° C for a further 4 hours.

The reaction crude is purified by distillation and 20.71 g of pure product were recovered with a yield of 67% and an E / Z ratio of 25/75.

1H, 1H-8H, 8H-perfluorootandiol C8H6F12O2 (1,000 g, 2.76 mmol) is loaded into the autoclave together with allyl-bromide (0.48 ml, 5.52 mmol) and powdered NaOH (0.442 g, 11.04 mmol). The reaction is carried out for 7 hours at 80 ° C. The crude product was then extracted from the salts with diethyl ether. The product is purified by distillation and a colorless liquid is obtained with e.g. 72-75 ° C at 1.0 mmHg and a yield of 62%.

Following the procedure of Example 3, using a double molar quantity of catalyst of the type carbonyl chlorine hydride (triphenylphosphine) ruthenium (II) (CAS RN 16971-33-8) and using as starting material the product of Example 4 is obtained the product in question as a mixture of 3 distereoisomers: cis-cis, trans-trans, cis-trans. Examples of transformation of the compounds of the invention

Example 6

Reactions of Scheme I

Addition reaction:

67 g (0.15 moles) of perfluorohexyl-iodide, 50 g (0.144 moles) of the fluoroallether of example 1 and 50 ml of a 10% sodium bisulfite solution are loaded into a flask. The mixture is heated to 80 ° C under stirring and 1 g of AIBN is dosed in 4 equal portions. It is left to react for about 3 hours, always at 80 ° C under stirring. The reaction crude is recovered by separating the heavy organic phase from the aqueous one. 119 g are obtained with a yield of 96%.

Reduction reaction:

20 g of the reaction raw product of the previous addition reaction are loaded into the autoclave. A solution containing 70 ml of ethyl acetate, 50 ml of methanol and 7 g of sodium acetate is added. 1g of Pd / C suspended in 20 ml of methanol is added. The mixture is reacted under the pressure of 3 atmospheres of hydrogen for 3 hours. The raw reaction is filtered in order to remove the catalyst and the solvents are eliminated in the rotary evaporator. 100 ml of water and 100 ml of ethyl ether are added to the residual solid. The phases are separated and after elimination of the organic solvent the reaction raw product is purified by distillation.

Example 7

Summary of:

Following the experimental indications of example 6 and using the material of example 2 as the starting allyl system and perfluoro propyl iodide, after reduction, the derivative in question is obtained.

Example 8

Reactions of Scheme II

The synthesis procedure is that described in example 6. The starting building block is the product of example 3.

Reactions of Scheme III

The synthesis procedure is that described in example 6. The moles of the various reactants were considered double compared to those of the starting diallyl ether.

Reactions of Scheme IV

10 g of the vinyl fluorine monomer of Example 3 is dissolved in chlorobenzene and heated to 80 ° C under stirring in a flask. 0.2 g of BF3eterate are added and the system is allowed to react for about 2 h. The solvent was removed on the rotary evaporator and dissolved in deuterated methanol to be analyzed via <1> H NMR.

Example 9

Scheme B - Compound of formula (I) in which R2 is a group (a) m and p = 1 t = 4

In a 250 ml autoclave equipped with mechanical stirring, 30 g (0.1 moles) of the fluorinated alcohol C5F11CH2OH, 4 g (0.1 moles) of ground sodium hydroxide, 6.25 g (0.5 moles) are loaded ) of cis 1,4-dichloro-2-butene. The mixture was reacted for 8 hours at 80 ° C. The clean product was obtained as a colorless liquid by vacuum distillation (bp 107-108 ° C at 0.4 mmHg). 21 g were obtained with a yield of 64%. 1H NMR (300.1 MHz, CDCl3): δ 5.78 (m, 2H, CH =), 4.22 (m, 4H, CH2CH =), 3.93 (tt, 3JH, F = 13.8 Hz, 4JH, F = 1.5 Hz, 4H, CF2CH2); 13C NMR (75.5 MHz, CDCl3): δ 129.1 (CH =), 122.0-103.0 (C5F11), 68.0 (= CHCH2O), 66.9 (t, 2JC, F = 25.5, CF2CH2). 19F NMR (282.3 MHz, CDCl3): δ -81.64 (t, 3JF, F = 10.6 Hz, CF3), -120.06 (m, CF2), -123.45 (m, CF2), -124.08 (m, CF2), - 126.89 (m, CF2).

Example 10

Scheme A - Compound of formula (I) in which R2 is a group (b) m and p = 1 t = 4

In a 250 ml autoclave equipped with mechanical stirring, 30 g (0.1 mol) of the fluorinated alcohol C5F11CH2OH, 4 g (0.1 mol) of ground sodium hydroxide, 10 g (0.047 mol) of trans- 1,4-dibromo-2-butene and 20 ml of THF. It is left to react for 7 hours at 80 ° C and 21.9 g of the trans product (72% yield) are obtained as a colorless liquid with bp 116-118 ° C at 0.4 mmHg.

1H NMR (300.1 MHz, CDCl3): δ 5.83 (m, 2H, CH =), 4.16 (m, 4H, CH2CH =), 3.93 (tt, 3JH, F = 13.7 Hz, 4JH, F = 1.5 Hz, 4H, CF2CH2); 13C NMR (75.5 MHz, CDCl3): � 128.8 (CH =), 122.5-103.5 (C5F11), 72.0 (= CHCH2O), 66.7 (t, 2JC, F = 25.6, CF2CH2).

19F NMR (282.3 MHz, CDCl3): δ -81.50 (t, 3JF, F = 10.6 Hz, CF3), -120.06 (m, CF2), -123.45 (m, CF2), -124.04 (m, CF2), - 126.79 (m, CF2).

Example 11

Scheme C - Compound of formula (I) in which R2 is a group (c) m and p = 1 t = 4

You can start from the cis or trans isomer (example 9 or example 10)

In a 30 ml glass reactor equipped with screw cap and magnetic stirring, the following are loaded: 2g (3 mmol) of the cis isomer of Example 9, 0.146 g (0.153 mmol) of the Ru [(PPh3) 3HCOCl] catalyst, 0.182ml (0.76mmol) of n-tributylamine. The mixture is allowed to react at 140 ° C for 6 hours. The product is obtained by fractional distillation under vacuum as a mixture of cis and trans and a yield of 52%. 1H NMR (300.1 MHz, CDCl3): δ 6.30 (d, 3Jtrans = 12.6 Hz, 1H, CH = CHCH3), 6.01 (d , 3Jcis = 5.9 Hz, 1H, CH = CHCH3), 4.91 (dq, 3Jtrans = 12.7 Hz, 3JH, H = 7.5 Hz, 1H, CH = CHCH2), 4.58 (qd, 3Jcis = 6.2 Hz, 3JH, H = 7.3 Hz, 1H, CH = CHCH2), 4.19 (tt, 3JH, F = 13.3 Hz, 4JH, F = 1.5 Hz, 2H, CF2CH2), 4.11 (tt, 3JH, F = 13.3 Hz, 4JH, F = 1.4 Hz, 2H, CF2CH2), 3.92 (m, 2H, OCH2), 3.59 (m, 2H, OCH2), 2.40 (m,, 2H, = CHCH2), 2.23 (m, 2H, = CHCH2) .13C NMR (75.5 MHz, CDCl3): δ 146.6 (CH = CHCH2, trans), 145.7 (CH = CHCH2, cis), 129.5-107.5 (C5F11), 105.0 (CH = CHCH2, cis), 102.4 (CH = CHCH2, trans), 73.1 (CH2 ), 72.1 (CH2), 68.4 (t, 2JC, F = 28.1, CF2CH2, cis), 67.5 (t, 2JC, F = 26.9, CF2CH2, trans), 27.6 (CH2, cis), 24.1 (CH2, trans) . 19F NMR (282.3 MHz, CDCl3): δ -81.15 (m CF3), -119.93 (m, CF2), -123.20 (m, CF2), -123.81 (m, CF2), -126.50 (m, CF2).

If the reaction is carried out in the presence of a high pressure mercury lamp with a wavelength of 365 nm and an intensity of 21Kw, the reaction times are halved and the yield becomes 78%.

Example 12

Reactions of Schemes VI or VII

12a. Addition reaction

67 g (0.15 moles) of perfluorohexyl iodide, 103.5 g (0.15 moles) of the product of Example 9 or Example 10 and 50 ml of a 5% solution of sodium meta are loaded into a flask. bisulfite. The mixture is heated to 80 ° C under stirring and 1 g AIBN (Azoisobutyronitrile) is dosed in 4 equal portions. The mixture is left to react for 3 hours at 80 ° C under stirring. The solid reaction crude is recovered by filtration and washed with water. 162 g of raw material are obtained with a yield of 95%

12b. Hydrogenation reaction

100 g (0.088 moles) of the raw product of the addition reaction are loaded into the autoclave. A solution containing 300 ml of ethyl acetate, 150 ml of methanol and 20 g of sodium acetate is added to the autoclave. 3 g of Pd on carbon suspended in 50 ml of methanol are added. The mixture is reacted under the pressure of 20 atmospheres of hydrogen for 3 hours. The raw is filtered in order to remove the catalyst and the solvents are eliminated in the rotary evaporator. To the residual solid are added 300 ml of water and 300 ml of ethyl ether. The phases are separated and the organic phase evaporated in the rotary evaporator. The product is purified by vacuum distillation. 68.9 g are obtained with a yield of 69%.

Example 13

Reaction of schemes VIII and IX (Cationic polymerization process)

In a 500 ml reactor, provided with mechanical stirring, 150 g (0.23 moles) of the product of process II, 200 ml of ethyl ether and 45 g (0.46 moles) of concentrated sulfuric acid are added. The reaction mixture is allowed to react for 6 hours. At the end of the reaction, 100 ml of water are added and vigorously washed, this operation is performed 3 times. The organic phase is evaporated in the rotary evaporator and the polymer recovered. About 43 grams were obtained.

Claims (18)

CLAIMS 1. Compounds of formula (I) - n is 12, 3, 4, or 5; - m is 1 or 2; - R1 represents a group chosen from -CF3e - [CF2] 2- [CH2] q-O-R3 where q is 1 or 2; - R2 represents a group selected from -CHR4-CR5 = CR6R7; -CR4 = CR5-CHR6R7; - R3 represents a group selected from -CHR4-CR5 = CR6R7 and -CR4 = CR5-CHR6R7; And - R4, R5, R6 and R7 represent, each independently, a hydrogen or a C1-C4alkyl; or, when R1 is -CF3, R2 also represents a group selected from in which p is 1 or 2; t is 1, 2, 3, 4, or 5; e the symbol indicates the bond that connects the substituent group with the oxygen atom of the formula (I). 2. Compounds of formula (I) according to claim 1, wherein R1 is CF3. 3. Compounds of formula (I) according to claim 1 or 2, wherein R2 and R3 are identical to each other. 4. Compounds of formula (I) according to any one of claims 1 to 3, wherein R4, R5, R6 and R7 are hydrogen. 5. Compounds of formula (I) according to any one of claims 1 to 4 wherein m and p are equal to 1 and t is 2 or 4. 6. Use of a compound of formula (I) according to any one of claims 1 to 5, as a reaction intermediate. 7. Process for the preparation of compounds of formula (I) wherein R2 and / or R3 represent -CHR4-CR5 = CR6R7 according to any one of claims 1 to 4, which comprises reacting a compound of formula (II) (II) where n is 1, 2, 3, 4, or 5; m is 1 or 2 and R8 represents a CF3 group or a - [CF2] 2- [CH2] q-OH group, where q is 1 or 2 with a compound of formula (III) (III) wherein L is halogen and R4, R5, R6 and R7 are as defined in claims 1 or 4, in the presence of a strong base. 8. Process according to claim 7, wherein L is selected from chlorine and bromine. 9. Process according to claim 7, wherein the compound of formula (III) is a 2-propenyl-halide. 10. Process according to claim 9 wherein the compound of formula (III) is 2-propenyl-bromide. 11. Process according to any one of claims 7 to 10, wherein said strong base is an alkali metal hydroxide. 12. Process according to any one of claims 7 to 11 wherein the reaction takes place at 60-80 ° C. 13. Process for the preparation of the compounds of formula (I) in which R2 is (a) or (b), can be prepared by reacting 1,4-halo-2-butene with a suitable alcohol of formula (IV) wherein n and m and t are as defined in claim 1 or 5. 14. Process for the preparation of the compounds of formula (I) wherein R2e / or R3 represent -CR4 = CR5-CHR6R7, which comprises subjecting the compounds of formula (I) wherein R2e / or R3 represent -CHR4-CR5 = CR6R7ad a double bond transposition reaction in the presence of ruthenium catalysts. 15. Process for the preparation of the compounds of formula (I) wherein R2 is comprising subjecting the corresponding compounds of formula (I) wherein R2 to a double bond transposition reaction in the presence of ruthenium catalysts. 16. Process according to claim 14 or 15, wherein said catalyst is selected from Ru (H, Cl, CO) (triphenylphosphine) 3, Ru (H, H, CO) (triphenylphosphine) 3 and Ru (Cl2, CO) ( triphenylphosphine) 3. 17. Process according to any of claims 14 to 16, characterized in that it is conducted in the presence of a base and / or under ultraviolet radiation. 18. Compounds of formula (IIa) - (IIi)