IE892463L

IE892463L - Preparation of n-allylanilines and n-alkylanilines

Info

Publication number: IE892463L
Application number: IE892463A
Authority: IE
Inventors: Jean Desmurs; Jeanpierre Lecouve
Original assignee: Rhone Poulenc Chimie
Priority date: 1988-07-29
Filing date: 1989-07-28
Publication date: 1990-01-29
Also published as: ATE74901T1; IE63657B1; JPH0269445A; FR2634761A1; DE68901227D1; EP0353130A1; JPH0551575B2; FR2634761B1; EP0353130B1

Abstract

The present invention relates to a process for monoalkylation on the nitrogen of an aniline by bringing the latter and an alkylating agent into contact in an organic solvent in homogeneous liquid phase in the presence of an iodide and of a stoichiometric quantity of a non-quaternisable base.

Description

63657 2 The present invention relates to a process for the preparation of N-allylanilines and N-alkylanilines. It more particularly relates to the preparation of N-allylanilines and in further preferred manner to the preparation of N-monoallyl anilines.

The preparation of N-monoallylanilines is particularly important in the case of trifluoromethylaniline, because the monoallyl derivative obtained is an important intermediate in the synthesis of a herbicide, such as is described in French Patent No. 2 305 43^. According to the latter, for the preparation of the desired herbicide, N-1-(3- . 10 trifluoromethylphenyl)-3-chloro-4-chloromethyl-2-pyrrolidone, it is necessary to start with a trifluoromethylaniline one of whose hydrogen atoms is protected by an acetyl group prior to carrying out allylation, in order to prevent the formation of secondary diallylation products, which are of no use.

The industry has for a considerable time attempted to obtain monoallyltrifluoromethylaniline directly in a single stage, in place of the three stages described in French Patent No. 2 305 ^3^, with good yields calculated on the basis of the starting substance used, viz. 3-trifluoromethylaniline, which is a very onerous compound which the 2Q industry does not wish to lose.

A first solution to this problem was proposed in US Patent No. ^ 701 560, which describes a process for the allylation of 3-trifluoromethylaniline in a two-phase medium, namely water and an organic solvent in the presence of a mineral base, e.g. caustic soda 25 or a carbonate, and in the presence of catalytic quantities of a quaternizable tertiary amine. In order to obtain a small quantity of diallyl by-products, it is necessary to limit the 3-trifluoromethylaniline conversion rate and therefore to work in the presence of an allyl halide deficiency. The text states that the ratio 3Q of 3-trifluoromethylaniline to allyl halide is preferably approximately 2:1. The N-monoallylaniline yields calculated on the 3-trifluoromethylaniline introduced do not exceed 40%, which is inadequate for the process to be economically viable.

The allylation reaction on anilines other than 3-3 5 trifluoromethylaniline are described in inter alia US Patent No. 2 286 678, which in particular describes the allylation of 4- 3 hydroxyaniline in a medium constituted by an alcohol and in the presence of a carbonate as the neutralizing agent.

The indicated N-monoallylhydroxyaniline yields do not exceed those of the aforementioned patent and there is also appreciable 5 formation of diallyl derivatives, which it is sought to avoid. Therefore this method cannot be used in the present case.

US Patent No. 3 668 254 describes a process consisting of allylating U-aminodiphenylamine with 2,3-dichloropropene in the presence of triethylamine. As in the two previous cases, the indicated 10 yields do not exceed 10%. Moreover, the triethylamine is used in a higher than stoichiometric quantity compared with the allyl halide. From the economic standpoint this method is particularly uninteresting, because the yields are low and the cost of the starting materials used is high.

US Patent No. 3 819 708 describes the alkylation of paraphenylenediamines in various solvents in the presence of a tertiary amine such as triethylamine or a mineral base as the neutralizing agent of the hydracid formed. The alkylating agents described are much less reactive than allyl halides and the dialkylating problem is much less 20 important. The selectivity, i.e. the monoalkyl product yield compared with the dialkyl derivatives, is not described.

Despite the existence of a large amount of literature describing the alkylation or allylation of various anilines, no process has made it possible to provide a good transformation or conversion rate of the 25 starting aniline and obtain a good selectivity for the N-mono-substituted aniline compared with the disubstituted aniline.

The present invention provides a process for the N-monoalkylation or N-monoallylation of an aniline, comprising putting into contact an aniline and an alkylating or allylating agent in an organic solvent in 30 a homogeneous liquid phase in the presence of an iodide and a stoichiometric quantity of a non-quaternizable base.

The alkylating or allylating agent may be an alkyl sulphate or halide, whose alkyl chain can have unsaturations, can be straight or branched, and can have halogen, aryl, aralkyl, haloaryl and/or 35 nitroaryl substituents. Among the halides, preference is given to the use of chlorides and bromides, in particular chlorides, because they are less expensive. 4 Among the alkyl arid allyl halides, the present invention is concerned more particularly with allyl halides, because they (and particularly the chloride) are not very reactive with respect to alkylation.

Among suitable alkylating and allylating agents are allyl iodide, allyl chloride, allyl bromide, benzyl chloride, benzyl bromide, isopropyl bromide, crotyl chloride and l-chloro-2-butene.

The process according to the present invention is applicable to all anilines. However, it is of particular interest for slightly basic 10 anilines, i.e. for anilinium ions having a pKa below 4.5. In the case of reactive anilines, whose proton form has a pKa higher than 4.5, the use of onium makes it possible to considerably shorten the reaction time or reduce the reaction temperature, the two criteria being very frequently linked with one another.

The preferred anilines, i.e. having a pKa below 4.5, are represented by the following Formula (I): nh2 (i) The iodides which can be used within the scope of the present invention are preferable iodides of oniums, alkali metal iodides and allyl iodides.

The oniums used in the process of the invention are more 35 particularly those derived from nitrogen, phosphorus, arsenic, sulphur, selenium, oxygen, carbon or iodine. These oniums are coordinated to hydrocarbon radicals. The onium ions derived from nitrogen, phosphorus or arsenic are quadricoordinated and those derived from sulphur, selenium, oxygen, carbon or S=0 are tricoordinated.

The hydrocarbon radicals coordinated to these different elements are alkyl, alkenyl, aryl, cycloalkyl or arylalkyl radicals, which are optionally substituted, whereby two coordinated hydrocarbon radicals can together form a single bivalent radical.

The following are examples of oniums: alkylammoniums and arylammoniums such as: tetraethyl ammonium, tetrabutyl ammonium, * dodecyltrimethyl ammonium, tetrapropyl ammonium, tetrapentyl ammonium, tetrahexyl ammonium, tetraheptyl ammonium, tetraoctyl ammonium, tetradecyl ammonium, benzyltrimethyl ammonium, benzyltributyl ammonium, benzyltriethyl ammonium, phenyltrimethyl ammonium, methyltriphenyl ammonium, alkylphosphoniums such as: tetramethyl phosphonium, tetrabutyl phosphonium, trimethylphenyl phosphonium, methyltri (isopropyl) phosphonium, methyltriphenyl phosphonium, methyltribenzyl phosphonium, tetraethyl phosphonium, tetraphenyl phosphonium, tetraphenyl arsonium. sulphoniums such as: trimethyl sulphonium, triethyl sulphonium, triphenyl sulphonium, miscellaneous oniums such as: trimethyl sulphoxonium, triphenyl carbenium, triethyl oxonium.

Within the class of oniums, preference is given to the use of those having a molecular weight between 150 and MOO and preferably between 200 and 300. Among the particularly suitable oniums are ammoniums, whereof the four alkyl groups are similar and have four to five carbon atoms.

The onium can be soluble in the reaction medium, when there would be a reaction in a homogeneous medium, or insoluble in solid form and there would then be a reaction in the two-phase solid - liquid medium. The onium can also be supported on a polymeric or mineral resin.

Reference is made among the "supported" oniums to: tetrabutyl ammonium fluoride on silica gel, tributyl ammonium chloride on the polymer marketed e.g. by FLUKA, methyltributyl phosphonium chloride linked with polystyrene e.g. marketed by FLUKA.

The reaction will then take place in a two-phase solid - liquid medium.

Among the alkali metal iodides, reference can be made to potassium or sodium iodide. These iodides can be used as they are, or in the presence of a complexing agent.

The complexing agents can be chosen from among the macrocyclic 5 polyethers known in general as "crown ethers", which are described in US patent 3562295. They can also be chosen from among tertiary amines having three polyalkyleneoxy groups, such as those described in US patent 4343745. Among the amines, particular reference can be made to: tris(316-dioxaheptyl)-amine 10 tris(3,6,9-trioxadecyl)-amine tris(3,6-dioxaoctyl)-amine tr is(3,6,9-trioxaundecyl)-amine tris(3,6-dioxanonyl)-amine tris(3,6,9-trioxadodecy1)-amine. 1 5 The base used in the process according to the invention is used for neutralizing the hydracid released during alkylation. It can be chosen from among mineral bases such as sodium hydroxide or carbonates, or from among organic bases such as sodium acetate, or non-quaternizable tertiary amines. Non-quaternizable tertiary amines are all the tertiary amines 20 having at least one branched alkyl chain and preferably at least two branched alkyl chains. Among these amines, reference is made in exemplified manner to: diisopropylallyl amine diisopropylethyl amine 2 5 triisopropyl amine.

Among the bases referred to above, preference is given to the use of diisopropylethyl amine.

The solvent constituting the reaction medium must solubilize the allyl or alkyl halide and aniline, whereby the onium or the base can be 30 solid and are not solubilized by the reaction medium. However, it is preferable for both of them to be soluble in the reaction medium. The solvents are chosen from among: aliphatic hydrocarbons such as: hexane cyclohexane heptane octane 8 aromatic hydrocarbons such as toluene xylene. halogenated hydrocarbons such as: chloroform methylene chloride chlorobenzene carbontetrachloride dichloroethane. 1 q alcohols such as ethanol isopropanol butanol octanol 1 5 polar aprotic solvents such as N,N-dimethyl formamide acetonitrile N-methylpyrrolidone. non-quaternizable tertiary amines such as 20 diisopropylethyl amine.

Among the solvents mentioned, preference is given to the use of heptane or diisopropylethyl amine.

For a better performance of the invention, preference is given to the use of an approximately stoichiometric quantity of alkyl or allyl halide 25 relative to the aniline.

The onium is used in a catalytic quantity, i.e. in a molar quantity between 0.025 and 0.2 relative to the aniline.

The reaction temperature is advantageously between 0 and 150°C. It will vary as a function of the reagents used, particularly as a function 30 of the pKa of the aniline and the nature of the halide. The reaction pressure is preferably atmospheric pressure. The reaction lasts between one and a few hours.

The present invention will be described in greater detail with the aid of the following non-limitative examples. 9 In the following examples, the term conversion rate (TT) is understood to mean: TT number of moles of aniline converted ^ number of moles of aniline introduced RT number of moles of product formed ^ number of moles of aniline converted Selectivity Quantity of N-allyl or N-alkyl formed ^ Quantity of N-allyl or N-alkyl formed + dialiyl or dialkyl quantity formed EXAMPLES 1 AND 2 INFLUENCE OF AMMONIUM IODIDES Into a 30 ml reactor are introduced 0.64 g of m-trifluoromethylaniline (4mM) 0.3 g of allyl chloride (4mM), 2 ml of solvent, 0.51 g of diisopropylethyl-amine (4 mM) and optionally 0.4 mM of ammonium iodide. The reaction 15 mixture is heated for 210 minutes at 80°C. At the end of the reaction and after cooling 5 ml of N soda are added. The organic products are extracted by 3 x 10 ml of isopropyl ether. The organic phase collected is diluted to 50 ml in a graduated flask for dosing by gas chromatography.

• TEST .'AMMONIUM • *******1"*****"*"" TT m.

TFMA jj-Allyl RT • N,N Dialiyl RT BAL-ANCE SELECTIVITY Cl : . 7-5 5 • : too x ************** o: ICG X • I '^NBt^r ••••««•*•••••••••••• 72.5 5 : 93.1 X • 8.8 X too X 931 X . >Buur 73.7 : : £8.1 X li X 97-5* 91-2 X EXAMPLES 3 AND 4 INFLUENCE OF THE NATURE OF THE ONIUM The procedure of example 1 is repeated introducing 0.64 g of m-trifluoromethyl aniline (4 mM), 0.3 g of allyl chloride (4 mM), 2 ml of 5 heptane, 0.51 g of diisopropylallyl amine (4 mM) and 0.4 mM of onium iodide. The reaction is carried out at 80°C for 4 hours.

TEST • ONIUM *TT m. TFMA • N-Allyl RT Dialiyl RT o : 3 (flt)3 s I : 18.4 * 83.3 I tracts 4 1 : 64 .S 5 • • 31.4 I .3 * 1 o EXAMPLES 5 AND 10 AND COMPARATIVE EXAMPLES 2 AND 3 INFLUENCE OF ALKALINE IODIDES OR COMPLEX ALKALINE IODIDES The procedure of example 1 is repeated introducing 0.64 g of m? trifluoromethyl aniline (4 mM), 0.3 g of allyl chloride (4 mM), 2 ml of heptane, 0.51 g of diisopropylethyl amine (4 mM), 0.4 mM of 15 iodide and optionally 0.4 mM of a complexing agent (TDA1 means triodioxaheptylamine). 11 TEST SALT COMPLEXING AGENT TT m. TFMA N-Allyl RT Dialiyl RT C2 Ha cl 0 X C3 Ha Br lx Ha 1 75.7 X 88 X 8.4 X 6 Na I 15cro»n5 93.2 X 81.7 X 14,5 X 7 Ha 1 TSft - 1 Bo X 83 X 7.5 X 8 XI 56 X 95.3 X 4,8 X * Kl I8cr ovnb 6o X 91.8 X 6.8 X KI TDfl - 1 74 X 78.8 X 6.7 X EXAMPLES 11 TO 25 INFLUENCE OF THE REACTION TIME The procedure of example 1 is repeated with the introduction of 1.28 g of m-trifluoromethyl aniline (8 mM), 0.6 g of allyl chloride 15 (8 mM), 4 ml of heptane, 1.02 g of diisopropylethyl amine (8 mM) and 0.8 mM of sodium iodide. The reactions are performed at different temperatures. 12 Results at 70°C. 1 < • • '• „„ : TIME . TEST . • • IN : : min.

TT m.

TFMA 1 : 1 SELECT-N- : Dialiyl '-BAL- *• Ivm Allyl : RT • ANCE • till RT '• - •••• ♦ di * • • « : 11 : 240 72.2 * • • • • • • 83 * : 13.2 * :97.2 * : 86.2 * • • • • : 12 : 120 (9.4* • « « 79.8 * : 11.4 * : 34 *: 87.5 * • • i • : 13 : SO 55* • « i • t • .3 * ; 8 * : 102 S : 92 * • • : U : 30 14 * • • • * • • • « • 54.5 5 : traces : 33 * : 100 * • • : 15 : 20 3.9 * • « 4 • • • 66 X : 0 * : 94 *: 100 * Results at 80°C.

TEST : • • TIME IN MIN.

TT m.

TFMA N- Allyl RT Dialiyl RT • • t « :bal- : •ANCE : • • SELECTIVITY • ID 240 80-5 t 73 * 14.5 * • • : 84.5 * i * * • • 120 80.2 * 80.3 * 13-7 * • t : 35 it: 85.3 * 18 : 60 72* 75.4 5 .8 * • • : 90 * : 37.4 * 13 : 57* 79 5 9 5 • • • * :?3.5 * : 89.7 * • : 26* 70 5 * « « • • :93.5 * : « « 93-3* 13 Results at 90°C.

TEST TIME IN MIN.

TT m. TFMA N-Allyl RT Dialiyl RT BAL^-ANCE SELECT- ! TIVITY ! 21 240 87,5 X 73.2 X 17.6 X 92 X 80.6 X : «n 4* 120 76.2 X 79.7 X 13.6 X 95 X 85.4 X : 23 GO 77 X 83,7 5 13.4 X 37.3 X 86.2 X : 73 X 77 X 12,4 X 93 X 8S.3 X : 37 X 93,7 X 9,4 X 101 X 90.8 X : 1 EXAMPLES 26 TO 29 allylation by allyl iodide The procedure of example 1 is repeated with the introduction of 0.64 g of m-trifluoromethyl aniline (4 mH), 4 mM of allyl iodide, 2 ml of heptane, 0.51 g of diisopropylethyl amine (4 mH) and 15 optionally 0.4 mH of allyltriethyl ammonium bromide. 14 at 80°C for 4 hours TEST ALLYLATING ..M.m.

AMMONIUM TT m.

-IIMA— N-Allyl ...JiT.

Dialiyl RT.

SELECT- „iy_m 26 no 91.3 * 73.71 23.3 X 76 X 27 yes 89.5 * 79.4 X 17.6 X 8KB X at 25°C for 150 min.

TEST '.ALLYLATING I...AfiEKT.

» AMMONIUM TT m. TFMA....

N-Allyl RT Dialiyl JBX SELECT-.J-iLLXX 28 : l/V no 76.7 X 76,8 X 13 X 85,5 X * yes 84.5 X 76.5 X 16 X 82.51

Claims

1. A process for the N-monoalkylation or N-monoallylation of an aniline, comprising putting into contact an aniline and an alkylating 5 or allylating agent in an organic solvent in a homogeneous liquid phase in the presence of an iodide and a stoichiometric quantity of a non-quaternizable base.

2. A process according to Claim 1, in which the alkylating or 10 allylating agent is an allyl halide.

3. A process according to Claim 2, in which the allylating agent is allyl chloride. 15

4. A process according to .any one of Claims 1 to 3, in which the aniline has a pKa below 4.5.

5. A process according to Claim 4, in which the aniline is a haloaniline, a perhaloalkylaniline, a perhaloalkoxyaniline, a 20 perhaloalkylthioaniline or a nitroaniline of Formula (I) nh2 in which R represents a halogen atom, a nitro group, or a group of 30 formula -ACn X2n+1 in which X represents a halogen atom, A a covalent bond or a sulphur or oxygen atom, and n is 0, 1 or 2.

6. A process according to any preceding claim, in which the iodide is an onium iodide or an alkali metal iodide. 35

7. A process according to Claim 6, in which the onium is an ammonium with a molecular weight between 150 and 400. 16

8. A process according to Claim 7, in which the ammonium has a molecular weight between 200 and 300.

9. A process according to Claim 6, 7 or 8, in which the onium is a 5 supported onium.

10. A process according to any preceding claim, in which the non-quaternizable base is a mineral or organic base. 10

11. A process according to Claim 10, in which the non-quaternizable base is sodium acetate or a tertiary amine carrying at least one branched alkyl group.

12. A process according to Claim 11, in which the non-quaternizable 15 base is a tertiary amine carrying at least two branched alkyl groups.

13. A process according to Claim 11, in which the base is di isopropylethylamine. 20

14. A process according to Claim 11, in which the base is diisopropylallylamine or triisopropylamine.

15. A process according to any preceding claim, in which the molar ratio of the alkylating or allylating agent to the aniline is 25 approximately 1:1.

16. A process according to any preceding claim, in which the molar ratio of the onium to the aniline is between 0.025:1 and 0.20:1. 30

17. A process according to any preceding claiirvin which the solvent is an aromatic or aliphatic hydrocarbon solvent, an alcohol, an aprotic polar solvent or a non-quaternizable tertiary amine.

18. A process according to Claim 17,in which the solvent is heptane 35 or diisopropylethylamine. 17

19. A process according to Claim 1, substantially as hereinbefore described in any one of the Examples.

20. An N-alkylaniline or N-allylaniline when prepared by a process according to any one of Claims 1 to 19. F. R. KELLY & CO., AGENTS FOR THE APPLICANTS.