MXPA00003690A - Process for preparing a 1,1,1-trifluoro-2-aminoalkane - Google Patents
Process for preparing a 1,1,1-trifluoro-2-aminoalkaneInfo
- Publication number
- MXPA00003690A MXPA00003690A MXPA/A/2000/003690A MXPA00003690A MXPA00003690A MX PA00003690 A MXPA00003690 A MX PA00003690A MX PA00003690 A MXPA00003690 A MX PA00003690A MX PA00003690 A MXPA00003690 A MX PA00003690A
- Authority
- MX
- Mexico
- Prior art keywords
- formula
- optionally substituted
- compound
- primary amine
- process according
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 24
- 239000000203 mixture Substances 0.000 claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 238000010438 heat treatment Methods 0.000 claims abstract description 10
- 238000004821 distillation Methods 0.000 claims abstract description 8
- 239000003701 inert diluent Substances 0.000 claims abstract description 7
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 4
- 150000003141 primary amines Chemical class 0.000 claims description 17
- WGQKYBSKWIADBV-UHFFFAOYSA-N Benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 4
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
- 150000003939 benzylamines Chemical class 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 150000003512 tertiary amines Chemical class 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 238000010533 azeotropic distillation Methods 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N o-xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 abstract 1
- SNMLKBMPULDPTA-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-amine Chemical compound CC(N)C(F)(F)F SNMLKBMPULDPTA-UHFFFAOYSA-N 0.000 description 9
- 125000004432 carbon atoms Chemical group C* 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N P-Toluenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- 238000010992 reflux Methods 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- -1 benzylidene compound Chemical class 0.000 description 4
- 230000003197 catalytic Effects 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical compound CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N Benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- FXZWPZMCZNJILD-UHFFFAOYSA-N N-[(6-bromopyridin-3-yl)methyl]ethanamine;hydrochloride Chemical compound Cl.CCNCC1=CC=C(Br)N=C1 FXZWPZMCZNJILD-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 150000003974 aralkylamines Chemical class 0.000 description 1
- 229940095076 benzaldehyde Drugs 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000000875 corresponding Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000855 fungicidal Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- 230000000749 insecticidal Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Abstract
The invention relates to a process for the preparation of a 1,1,1-trifluoro-2-aminoalkane of formula I wherein R1 represents an optionally substituted alkyl group;which comprises heating a mixture consisting essentially of a compound of formula II wherein R1 has the meaning given, and R2 represents an optionally substituted aryl group, a primary amine, and optionally a base and/or an inert diluent, whereby the compound of formula I is removed by distillation during the heating procedure.
Description
PROCESS FOR PREPARING A 1, 1, l-TRIFLUORO-2- AMINOALCANO
Background of the Invention
The invention relates to a new process for the preparation of 1,1,1-trifluoro-2-aminoalkanes, which comprises reacting the corresponding N-alkylidene benzylamines with a primary amine, from which the product is removed by distillation. The 1,1,1-trifluoro-2-aminoalkanes are useful as intermediates for the preparation of a variety of compounds that are useful as agrochemicals, pharmaceuticals or dyes. In particular, they are key intermediates in the preparation of benzamide insecticides, as described for example in DE 36 11 193 and 7 (1,1,1-trifluoroalk-2-ylamino) -6- (halophenyl) -triazolopyrimidines fungicides, which are described, for example, in WO 98/46608. T. Ono, et al., J. Org. Chem. 61, 1996, 6563-6569 describes a method for the preparation of 1,1,1-trifluoro-2-aminopropane by rearrangement of N- (1,1,1-trifluoroisopropylidene) benzylamine to N-benzylidene-1, , 1-trifluoroisopropylamine. The resulting benzylidene compound is hydrolysed to REF hydrochloride: 33135 amine with hydrochloric acid, using ether as diluent. The amine hydrochloride is separated from the benzaldehyde and the free amine is prepared by the action of triethylamine in the amine hydrochloride. Thus, the known art process requires several steps to produce the desired 1, 1, 1-trifluoro-2-aminoalkanes. The new process has been found to be advantageous to produce 1,1,1-trifluoro-2-aminoalkanes in up to only two steps.
Brief Description of the Invention
The 1,1,1-trifluoro-2-aminoalkanes of formula I
wherein R 1 represents an optionally substituted alkyl group; can be obtained in high yields by heating a mixture consisting essentially of a compound of formula II
wherein R1 has the given meaning, and R2 represents an optionally substituted aryl group; a primary amine, and optionally a base and / or an inert diluent, wherein the compound of formula I is removed by distillation during the heating process. It is an object of the present invention to provide a new efficient process for the preparation of 1,1,1-trifluoro-2-aminoalkanes of formula I. Other objects and advantages of the present invention will be apparent to those skilled in the art from the following description and the appended claims.
Detailed Description of the Preferred Modalities The invention relates to a new process for the preparation of the compounds of formula I by heating a mixture consisting essentially of a compound of formula II, a primary amine and optionally a base and / or an inert diluent. The advantage of the new process is that the compound of formula I is obtained directly in high yields and high purity by distillation during the heating process. Generally speaking, unless otherwise stated herein, the term "alkyl" as used herein with respect to a radical or moiety refers to a straight or branched chain moiety or moiety. As a rule, such radicals have up to 10, in particular up to 6 carbon atoms. Suitably an alkyl radical has from 1 to 6 carbon atoms, preferably from 1 to 3 carbon atoms. A particularly preferred alkyl radical is the methyl group. Generally speaking, unless otherwise stated herein, the term "aryl" as used herein with respect to a radical or moiety refers to an aryl group having 6, 10 or 14 carbon atoms, preferably 6 or 10 carbon atoms. carbon. A particularly preferred aryl radical is the phenyl group which is optionally substituted by one or more halogen atoms, nitro, cyano, alkyl, preferably C__6 alkyl, alkoxy, preferably C__6 alkoxy. Suitable primary amines are primary amines having from 2 to 20 carbon atoms, preferably from 6 to 14 carbon atoms. Primary amines having a boiling point higher than the boiling point of the compound of formula I are preferred, in particular aralkylamines which are optionally substituted by one or more halogen atoms, alkyl, preferably C__6 alkyl, alkoxy, preferably C__6 alkoxy, more preferably benzylamine. The reaction is preferably carried out with a molar ratio of compound of formula II to primary amine from 1: 1 to 1: 1.5, in particular from 1: 1.1 to 1: 1.3, is more preferred at a ratio of 1.2. Suitable inert diluents are cyclic ethers, aliphatic ethers, aliphatic hydrocarbons or aromatic hydrocarbons. HE. they prefer aromatic hydrocarbons having from 6 to 14 carbon atoms, in particular benzene, toluene, xylene or mesitylene. Suitable bases are tertiary amines, in particular bicyclic tertiary amines, such as 1,8-diazabicyclo [5.4.0] undecen-7 (DBU) or 1,5-diazabicyclo [3.4.0] nonen-5 (DBN). The reaction is preferably carried out in the presence of catalytic amounts of a base, in particular in a molar ratio of compound of formula II based on 1: 0.001 to 1: 0.1, more than 1: 0.005 to 1: 0.05 is preferred. A preferred embodiment of the present invention is a process wherein: "the reaction is carried out at temperatures between 80 and 140 ° C; preferably between 90 ° C and 130 ° C, in particular between 95 ° C and 120 ° C; it is more preferred at about 115 ° C; • the reaction is carried out at atmospheric pressure; • the reaction mixture consists of a compound of formula II, a primary amine and a catalytic amount of a base, preferably DBU. • R1 represents a C__4 alkyl group which is optionally substituted by one or more halogen atoms or an alkoxycarbonyl or hydroxycarbonyl group, in particular wherein R1 represents a methyl group;
The compound of formula II is more preferably N- (1,1-l-trifluoroisopropylidene) benzylamine. The compound of formula II can be prepared by means of a condensation reaction between 1, 1-trifluoro-2-oxoalkane and benzylamine or a commercially available salt thereof, as described for example in T. Ono, et al. ., loe. cit .. In a preferred embodiment of the invention the preparation of the compound of formula I is carried out in a post-synthesis comprising the steps of a) condensation of a 1,1,1-trifluoro-2-oxo-alkane of formula III,
(lll) CF,
and an optionally substituted benzylamine of formula
IV,
H2N- CH2- R2 (IV)
preferably by azeotropic removal of the water formed during the reaction with the aid of an inert aromatic diluent in the presence of an acid, preferably p-toluenesulfonic acid, and b) treating the resulting N- (1,1,1-trifluoroalkylidene-2-yl) benzylamine with a primary amine in the presence of a base and / or an inert aromatic diluent at elevated temperatures, from which the desired compound of formula I is distilled.
After the condensation step (a), preferably using mixture of mesitylene and toluene as an inert diluent in the presence of p-toluenesulfonic acid the reaction water together with optionally the low-boiling diluent, preferably toluene, are separated by a water separator An excess of the primary amine and catalytic amounts of the base, preferably benzylamine and DBU are added at a temperature of 70 ° C to 120 ° C, in particular to about 90 ° C and the compound released from formula I is ground in a column and it is collected in a trap cooled with ice.
The obtained crude product can be purified according to standard methods for example by distillation, recrystallization or chromatographic methods. However, the crude product obtained according to the process of this invention is, as a rule, sufficiently pure to be used as an intermediate without further purification. In a particularly preferred embodiment of the process according to this invention, a mixture of the compound of formula II, in particular N- (1,1,1-trifluoroisopropylidene) benzylamine, a primary amine, preferably benzylamine and a catalytic amount of a base, preferably DBU is heated to a temperature of about 115 ° C. The amine of formula I, in particular 2-amino-1,1,1-trifluoropropane, is obtained by distillation during the reaction. The reaction temperature of about 115 ° C is maintained until no more amine is distilled. To facilitate a further understanding of the invention, the following illustrative examples are presented. The invention is not limited to the specific embodiments described or illustrated, but embraces the full scope of the appended claims.
Example 1 Preparation of N- (1,1,1-trifluoroisopropylidene) benzylamine
3360 g of 1,1,1-trifluoroacetone were added to a solution of 1.5 g of p-toluenesulfonic acid in 10 1 of toluene after cooling down to 0 ° C. Subsequently, 3225 g of benzylamine were dosed in 3 hours at a temperature in the range of 0 to 10 ° C. The reaction mixture was heated with reflux for 15 hours. The reaction water was distilled and subsequently the mixture was cooled to room temperature. The solvent was removed in vacuo to yield 5420 g of a crude mixture containing 71.7% N- (1,1,1-trifluoroisopropylidene) benzylamine. The mixture was used for the preparation of 2-amino-1,1,1-trifluoropropane without further purification.
Example 2 Preparation of 2-amino-1,1,1-trifluoropropane
4634 g of N- (1,1,1-trifluoroisopropylidene) benzylamine obtained in Example 1 was placed in a three-necked flask with stirrer, dropping funnel and descending condenser with an ice-cooled flask. 2755 g of benzylamine were added and the mixture was heated to 90 ° C. 20 ml of DBU were added and the 2-amino-1,1,1-trifluoropropane began to distill. The reaction mixture was heated to 115 ° C and 25 ml of DBU were subsequently added. The reaction temperature was maintained at 115 ° C until no more 2-amino-1,1,1-trifluoropropane distilled. 1857 g of the pure product having a boiling point of 46-47 ° C were collected.
Example 3 Preparation of 2-amino-1,1,1-trifluoropropane
In a three-necked flask with a reflux condenser and a dropping funnel, a mixture of 300 ml of toluene, 200 ml of mesitylene, 112 g of 1,1,1-trifluoroacetone and 0.5 g of p-toluene sulphonic acid was added. cooled to 0 ° C with magnetic stirring. To this mixture was added 112.5 g of benzylamine drop by drop keeping the temperature below 10 ° C. The reaction mixture was heated to reflux overnight. After cooling to room temperature the reflux condenser was replaced by a trap
Dean-Stark and the mixture was heated to reflux to remove the water of reaction. After separation of the reaction water, the mixture was cooled to room temperature and the Dean-Stark trap was replaced by a
rectification. A mixture of 153 g of benzylamine and 2 ml of DBU was added slowly and the mixture was heated to 95 ° C. 2-Amino-1,1,1-trifluoropropane was distilled and collected in an ice-cooled trap. Another 28 ml of DBU was added little by little until no
distilled 2-amino-1,1,1-trifluoropropane. Yield: 77 g. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is the one that results
of the present description of the invention.
^ WMftHt ^ aá
Claims (12)
1. A process for the preparation of a 1,1,1-trifluoro-2-aminoalkane of formula I wherein R 1 represents an optionally substituted alkyl group; characterized in that it comprises heating a mixture consisting essentially of a compound of formula II where . - ^ -..- .. * U * »M. R1 has the given meaning, and R2 represents an optionally substituted aryl group; a primary amine, and optionally a base and / or an inert diluent, wherein the compound of formula I is removed by distillation during the heating process.
2. A process according to claim 1, characterized in that the reaction is carried out at a temperature of 80 to 140 ° C.
3. A process in accordance with the claim 1, characterized in that the reaction is carried out at atmospheric pressure.
4. A process according to claim 1, characterized in that the diluent is an optionally substituted aromatic hydrocarbon, preferably toluene, xylene or mesitylene.
5. A process according to claim 4, characterized in that the molar ratio of compound of formula II to primary amine is from 1: 1 to 1: 1.5.
6. A process according to claim 1, characterized in that the primary amine has a boiling point higher than the boiling point of the compound of formula I.
7. A process according to claim 1, characterized in that the primary amine is an optionally substituted benzylamine.
8. A process according to claim 1, characterized in that a tertiary amine is used as a base.
9. A process in accordance with the claim 8, characterized in that the tertiary amine is 1,8-diazabicyclo [5.4.0] undecen-7 (DBU).
10. A process according to claim 1, characterized in that it comprises the steps of: a) condensation of a 1,1,1-trifluoro-2-oxo-alkane of formula III, R1- ^ ° (lll) CF, _.- »..... . - * -. * wherein R1 has the given meaning, and an optionally substituted benzylamine of formula IV, H2N-CH2-R2 (IV) wherein R2 has the given meaning, by azeotropic removal of the water formed during the reaction with the aid of an inert aromatic diluent; and b) treating the resulting N- (1,1,1-trifluoroalkylidene-2-yl) benzylamine with a primary amine in the presence of a base and / or an inert aromatic diluent at elevated temperatures, from which the desired compound of formula is distilled I.
11. A process in accordance with the claim I, characterized in that R1 represents a C__4 alkyl group which is optionally substituted by one or more halogen atoms or an alkoxycarbonyl group.
12. A process in accordance with the claim II, characterized in that R1 represents a methyl group. AMINOALCANO SUMMARY OF THE INVENTION The invention relates to a process for the preparation of a 1,1,1-trifluoro-2-aminoalkane of formula I wherein R 1 represents an optionally substituted alkyl group; which comprises heating a mixture consisting essentially of a compound of formula II wherein R: has the given meaning, and R2 represents an optionally substituted aryl group; a primary amine, and optionally a base and / or a ~ ~ * '- "-" * "* - • inert diluent, from which the compound of formula I is removed by distillation during the heating process.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/292,687 | 1999-04-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA00003690A true MXPA00003690A (en) | 2002-07-25 |
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