Hydrobromination method

Abstract

A process for synthesizing a product of formula Br(CH.sub.2).sub.nR by hydrobromination, by reacting: a reagent of formula (I) R1-CHCHR2 in which R1 and R2, identical or different, are chosen from H or an alkyl radical comprising 1 to 30 carbon atoms, which is saturated or unsaturated, linear or branched, functionalized or non-functionalized, with a molar excess of HBr relative to the reagent of formula (I), in the presence of a radical initiator, and optionally in the presence of at least one solvent, said process including a step A of mixing at least reagent I and the HBr, each of the latter arriving in the form of a flow of liquid into a mixing device dA.

Claims

1. A process for synthesizing a product of formula R1-CHBrCH.sub.2R2 by hydrobromination by reacting: a) a reagent of formula (I) R1-CHCHR2 in which R1 and R2, which may be identical or different, are chosen from H or an alkyl radical comprising from 1 to 30 carbon atoms, which is saturated or unsaturated, linear or branched, and functionalized or non-functionalized, b) with a molar excess of HBr relative to the reagent of formula (I), in the presence of a radical initiator, and optionally in the presence of at least one solvent, said process comprising a step A of mixing at least the reagent I and the HBr, each of the latter arriving respectively in the form of a liquid stream in a mixing device dA, wherein a turbulent flow system prevails, so as to reach, at the end of this step A, a degree of conversion included in the range of from 10% to 100%, and wherein the process further comprises a step B of spontaneous continuation of the reaction in a device dB in which a transient or laminar flow system prevails, so as to reach, at the end of this step, a degree of conversion of greater than 90%, wherein the residence times in the devices dA and dB are such that the degree of conversion at the end of step A is included in the range of from 10% to 90%, while the degree of conversion at the end of step B is included in the range of from 90% to 100%.

2. The process of claim 1, wherein the turbulent flow system of step A is characterized by a Reynolds number >1800.

3. The process of claim 1, wherein the residence time of step A is less than 10 minutes.

4. The process of claim 1, wherein the residence time of step A is less than the reaction time.

5. The process of claim 1, wherein the radical initiator is chosen from air, O.sub.2, peroxide, a diazo compound, or a radical generator.

6. The process of claim 1, wherein the reagent (I) used is in liquid form, either melted at a temperature above its melting point, or dissolved in a solvent.

7. The process of claim 1, wherein the hydrobromination is carried out in a homogeneous liquid medium.

8. The process of claim 1, wherein the HBr used is in liquid form, liquefied under its saturated vapor pressure or in solution in a solvent.

9. The process of claim 1, wherein the solvent comprises at least one of the following solvents: benzene, fluorobenzene, chlorobenzene, trifluorotoluene (BTF), ethylbenzene, toluene, xylene, cyclohexane, methylcyclohexane, heptane, isooctane, 1,1,1-trichloroethane and dibromomethane, and mixtures thereof.

10. The process of claim 1, wherein the process uses at least one solvent chosen from aliphatic solvents, optionally as a mixture with at least one other solvent chosen from aromatic solvents, or halogenated solvents.

11. The process of claim 1, wherein the optional solvents arrive in the mixing device at a temperature included in the range of from 50 C. to 20 C.

12. The process of claim 1, wherein the compound of formula (I) and the optional solvent arrive in the mixing device dA in a stream Fa, while the HBr, the optional solvent and the initiator arrive in the mixing device dA in a second stream Fb during step A, the ratio of the streams Fa and Fb being kept substantially constant, and the stream Fr resulting from the mixing of the streams Fa and Fb is directed from the outlet of the mixing device dA into the reaction finishing device dB.

13. The process of claim 1, wherein the device dA comprises a device of about one decimeter, one centimeter, one millimeter or one micrometer.

14. The process as claimed in claim 1, wherein the device dA comprises at least one reactor and/or at least one mixer, each having: a small total internal volume, generally included in the range of from 1 microliter to 200 liters, a value of the ratio between its internal surface area and its internal volume of greater than 50 m.sup.2 m.sup.3, a characteristic dimension, namely the shortest distance between two walls facing one another, included in the range of from 1 m to 1 m.

15. The process of claim 1, wherein the step A of mixing at least the reagent I and the HBr is carried out under flow rate and pressure conditions such that, within the mixing device dA, the circulating reactive fluids have short characteristic times, namely a residence time of less than 10 minutes, preferably included in the range of from 0.01 second to 5 minutes.

16. The process of claim 1, wherein during step A, the temperature of entry of the compound I into the mixing device dA is included in the range of from 0 to 100 C., it being understood that, if the compound I enters alone, it is at a temperature above the melting point Mp of the compound I, whereas if it enters diluted in a solvent, said mixture of compound I and solvent enters dA at a temperature included in the range of from 0 to 50 C.

17. The process of claim 1, wherein during step A, the HBr entry, temperature, when it enters diluted in a solvent, is included in the range of from 50 C. to 50 C.

18. The process of claim 1, wherein the HBr reagent is in an excess of at least 0.1 mol % relative to the reagent of formula (I).

19. The process of claim 1, wherein the HBr/optional total solvent weight ratio is included in the range of from 1% to 30%.

20. The process of claim 1, wherein the reagent 1/optional total solvent weight ratio is included in the range of from 1% to 80%.

21. The process of claim 1, wherein the radical initiator/HBr ratio is included in the range of from 0.01% to 80%.

22. The process of claim 1, wherein the hydrobromination is carried out at a temperature included in the range of from 50 to 50 C.

23. The process of claim 1, wherein the hydrobromination reaction is carried out at least partially in adiabatic mode.

24. The process of claim 1, wherein at the end of step A, the temperature at which the product leaves the device dA is above the crystallization temperature of the product, preferably included in the range of from 50 C. to 50 C.

Description

EXAMPLES

(1) The process of the invention is illustrated by the examples hereinafter.

Examples of Tests 1 to 4 (According to the Invention)

(2) In the following examples, various solvents indicated in table 1 are tested. In these examples, the procedure is the same as that described for test 4 of table 1, using a micromixer.

(3) Description of the micromixer: two streams are introduced according to four side jets Ja (2 jets opposite one another) and Jb (2 jets opposite one another), Ja being the solution of C11 (optionally molten) and Jb the solvent containing the HBr. The jets are each inclined by an angle of 90 relative to the vertical formed by these four jets. The mixing chamber has a volume of 0.32 ml.

(4) Test 4 (according to the invention): A solution is prepared with 5.03 g of gaseous hydrobromic acid in 38.5 g of methylcyclohexane, by sending a stream of HBr into the solvent cooled to 20 C. In parallel, a solution is prepared with 352 g of undecylenic acid in 462 g of methylcyclohexane, through which a stream of oxygen is passed. The latter solution is maintained at 20 C. The two solutions are then sent (HBr/MeCHx flow rate=50 ml/min, C11/MeCHx flow rate=25 ml/min) to a micromixer which enables intimate mixing of the two streams of liquid. The solution exiting this process is composed of 11-bromoundecanoic acid, methylcyclohexane and residual HBr. This solution is plunged into a container containing water in order to eliminate the residual HBr. The organic phase is washed three times with 500 ml of water and then evaporated under reduced pressure so as to remove the methylcyclohexane.

(5) The results obtained are:

(6) Conversion=99.9%

(7) Yield=95.0%

(8) Expression of the results:

(9) The yield (or percentage of product P, in this case % Br11) is determined by the following formula:

(10) $\%P=\frac{\mathrm{Surface}\mathrm{of}\mathrm{the}\mathrm{product}P}{\mathrm{Total}\mathrm{surface}}100$

(11) Surface=area or intensity of the peak of the chromatogram measured by gas chromatography (GC).

(12) In the case of the undecylenic acid hydrobromination reaction, the following will particularly be determined: the percentage of residual undecylenic acid (% C11) the percentage of 10-bromoundecanoic acid (% Br10) the percentage of 9-bromoundecanoic acid (% Br9) the percentage of 11-hydroxyundecanoic acid (% C11-OH) the percentage of 11-bromoundecanoic acid (% Br11).

(13) The total surface in the above formula represents the sum of the peaks: residual C11, C11-OH, Br9, Br10, Br11 of the final reaction mixture. The degree of conversion C of the undecylenic acid is determined by the following formula: C=100% starting C11.

Comparatives of Tests 1 to 4 (Using a Column)

(14) In the comparatives, various solvents indicated in table 1 are tested, but using the process and the device of the prior art (column), according to the following operating conditions described in the case of test 2 (comparative):

(15) Test 2 (Comparative):

(16) the solvent is a 70/30 v/v cyclohexane/benzene mixture,

(17) 15% by weight of undecylenic acid (C11) dissolved in the solvents,

(18) column regulated at 0 C. in the top part and 10 C. in the bottom part,

(19) C11/solvent entry temperature=12.5 C.,

(20) C11/solvent flow rate=80 g/min,

(21) HBr flow rate=6.32 g/min, i.e. a molar excess of 20% relative to the C11,

(22) air flow rate=0.196 l/min,

(23) H.sub.2 flow rate=0.184 l/min.

(24) Yield=95.0%.

(25) Table 1 below compares tests 1 to 4 (various solvents) carried out with a column (comparative) or with a micromixer (according to the invention):

(26) TABLE-US-00001 TABLE 1 Solvent Good solvent MCB Poor solvent 11-Bromo Yield (mono- Methyl- Compar- Invention chloro- Cyclo- cyclo- atives (Micro- Tests Benzene benzene) hexane hexane (column) mixer) 1 100% 95.7% 95.9% 2 30% 70% 95.0% 95.3% 3 80% 20% 94.0% 95.0% 6 100% 93.6% 95.0%

(27) As shown in the tests of table 1, when benzene is replaced with a poor solvent in the existing processes, 1% of 11-Bromo yield is lost (95% with benzene, 94% in a column with the best of the poor solvents). Surprisingly, in the process of the invention, the same poor solvent allows, on the contrary, a level of 11-Bromo yield which has been recovered (95%) or which is better (for the same hydrobromination reaction). Unexpectedly, the best gap (increase) in yield is observed in the case of the poor solvents with the process of the invention.

Example 7

(28) In these tests, the micromixer was replaced by a Venturi mixer.

(29) Description of the Venturi mixer: a glass Venturi 11 cm long is fed by two pipes with an internal diameter of 4 mm and an external diameter of 6 mm.

(30) An 80/20 by volume cyclohexane/methylcyclohexane (CHx/MeCHx) mixture is sent to an absorption column via a peristaltic pump at a flow rate of 150 ml/min. HBr gas is sent to the absorption column medium at a flow rate of 9.7 g/min, i.e. a molar excess of 11% relative to the C11. The pure C11 acid is sent, at 50 C., to the mixing device (Venturi mixer) at a flow rate of 19.9 g/min, representing a concentration by weight of 14.5% relative to the total solvent. The HBr-saturated organic solution is sent to the mixing device via a gear pump at a flow rate of 150 ml/min. The oxygen is injected into the circuit just after the gear pump with an injection system: capillary tube immersed in the liquid at a flow rate of 0.04 nl/min. The mixing device is followed by a PFA (perfluoroalkoxy) pipe with an internal diameter of 4 mm and a length of 4 m.

(31) TABLE-US-00002 Solvent Oxygen Pure C11 HBr % flow flow flow flow T C. T C. Con- % rate rate rate rate column column ver- 11- ml/min nl/min g/min g/min bottom bottom sion Bromo 150 0.040 19.9 9.7 20 17 99.94 95.00

(32) The degree of conversion and the yield of 11-bromo, obtained with the Venturi mixer, are identical to those obtained with the micromixer.

Example 8

(33) In this test, the micromixer was replaced with a simple glass T, T-shaped mixer.

(34) Description of the T-shaped mixer used: The glass T of 5 cm long is fed by two pipes with an internal diameter of 4 mm and an external diameter of 6 mm. These pipes form an angle of 90 between them.

(35) The 80/20 by volume CHx/MeCHx mixture is sent to an absorption column via a peristaltic pump at a flow rate of 150 ml/min. HBr gas is sent to the absorption column medium at a flow rate of 9.7 g/min, i.e. a molar excess of 11% relative to the C11. The pure C11 acid is sent, at 50 C., to the T-mixer at a flow rate of 19.9 g/min, representing a concentration by weight of 14.5% relative to the total solvent. The HBr-saturated organic solution is sent to the T-mixing device via a gear pump at a flow rate of 150 ml/min. The oxygen is injected into the circuit just after the gear pump with the injection system: capillary tube immersed in the liquid at a flow rate of 0.04 nl/min. The mixing device is followed by a PFA pipe with an internal diameter of 4 mm and a length of 4 m.

(36) TABLE-US-00003 Solvent Oxygen Pure C11 HBr T C. T C. flow rate flow rate flow rate flow rate column Mixer T C. % % ml/min nl/min g/min g/min bottom entry Coil exit conversion 11-Bromo 150 0.040 19.9 9.7 20 7 26-27 C. 99.95 94.80

(37) The degree of conversion and the yield of 11-bromo, obtained with this T-mixer, are identical to those obtained with the micromixer.