SE433350B - ortho-halogenoalkyl-2-halogeno acetananilide derivatives which are intermediates in the production of ortho- (alkoxymethyl)-2-halogeno acetanilide herbicides. - Google Patents

Abstract

The present invention concerns new ortho-halogenoalkyl-2- halogeno acetanilide compounds and a process for their production. The compounds are used as intermediates in the production of N-substituted-2',6'-disubstituted-2-halogeno acetanilide derivatives, which selectively control unwanted vegetation in agricultural crops.

Description

8002281-7, 2 The compounds of the invention have the formula R _ 9 C - CH X R is hydrogen, methyl, chloromethyl or bromomethyl; R 1 is hydrogen, halogen, tgig-butyl, trifluoromethyl or X 2 -C 1 -R 2 X 1 R 2 is hydrogen, chlorine, bromine or straight chain alkyl containing 1 to 4 carbon atoms; Y 1 is hydrogen, halogen, tEQ-butyl, trifluoromethyl or X 2 - C - R 2 X 1 X 1 and X 2 are independently hydrogen, chlorine or bromine, provided that when R 2 is straight chain alkyl containing 1 to 11 carbon atoms, only one of X 1 and X 2 may be hydrogen, chlorine or bromine and further provided that Rz, X1 and X2 cannot simultaneously be chlorine or bromine. The term "straight chain alkyl containing 1 to 4 carbon atoms" refers to methyl, ethyl-n-propyl and n-butyl. The term "halogen" refers to chlorine, bromine, fluorine and iodine atoms. Chlorine and bromine are preferred.

The compounds of the invention are prepared according to the following new procedure: I C12, Brz or NBS. N 1: 1 Wherein R "is hydrogen, halogen, tert-butyl, tritluoromethyl or H - C_Rn HR" 'is hydrogen, or straight chain alkyl containing 1 to 4 carbon atoms, when n is zero, R is methyl and the other substituents have the meanings given above.

In accordance with the above reaction scheme, the appropriate starting material is dissolved, i.e. a compound of the type described in formula II, in a suitable volume of solvent, which is inert to halogenation. Examples of suitable solvents are carbon tetrachloride, chloroform, petroleum ether, methylene chloride and the like, preferably carbon tetrachloride. At this point, a catalyst, e.g. benzoyl chloride, is added to the mixture to facilitate the reaction. To this mixture is added a stoichiometrically equivalent amount of a halogenating agent selected from molecular chlorine, molecular bromine, Nsuccinimide (NBS) or other N-bromine equivalents, such as e.g. N-bromo-N-methylacetamide or N-bromophthalimide. It is also possible to use more than stoichiometrically equivalent amounts of halogenating agents. The resulting mixture is exposed to external and / or internal ultraviolet and / or white light and the reaction is allowed to proceed.

The reactants are usually added at room temperature, i.e. about '25 ° C, and then kept close to desolation, but even lower temperatures can be used, as illustrated in the following examples.

The resulting reaction product is easily separated from the reaction mixture by conventional means. For example. unreacted halogenating agent and succinimide can be removed by filtration, while the solvent can be removed by stripping or distillation, preferably low temperature distillation in vacuo.

The product is usually purified by crystallization from suitable solvents. aoozza fi-7 10 15 20 25 30 35 4 The starting materials, ie. the compounds of formula II, are known, e.g. from US-A-B 442 945, 3,6737,847, 3,966,811 and GB-A-1,455,474.

In the process described above, chlorination or bromination of glo-alkyl-Z-haloacetanilides, in contrast to grtq-alkoxy-Z-haloacetanilides, does not lead to halogenation of the phenyl ring, i.e. nuclear halogenation. When the halogenation is carried out with molecular chlorine using 2'-6'-dimethyl-N-methyl-Z-chloroacetanilide as starting material, both the N-methyl and ring (benzyl D-methyl groups are comparable at comparable rates. When the o_r * ¿q- described here The alkyl-Z-chloro-acetanilides are subjected to bromination, the process is slower and more selective than in chlorination, so for optimal results molecular bromine (dissolved in CCl 4) is added dropwise to a refluxing and illuminated (UV and / or white light) solution. of amide containing about 0.196 benzoyl peroxide When Z-halogen-N-methyl-Zβ-dialkyl acetanilides are brominated using Brz, generally only the side chain carbon of the phenyl ring is brominated.

Bromination with molecular bromine (Brz) of Z-chloroacetanilides of the type described in formula II gives rise to halogen exchange to varying degrees, with partial formation of Z-bromoacetanilides. Secondary and tertiary anilides are sensitive to this yield when produced in large quantities at higher bromine and amide concentrations. The bromine in the Z position is derived from the exchange of chlorine with HBr to give HCl. Halogen exchange can be minimized by nitrogen treatment to facilitate the removal of bromine (HBr). To avoid halogen exchange and still retain the benefits of bromination, recrystallized N-bromosuccinimide (NBS) or a similar N-bromine equivalent, e.g. N-bromo-N-methylacetamide or N-bromophthalimide, optionally with added benzoyl peroxide, the preferred reagent. Only equimolar amounts of this manageable material are needed to give exclusively benzylic side chain bromination, with the formation of the by-product succinimide.

Molecular bromine or NBS bromines exclusively a gitg-methyl group in the presence of a grtg-t-butyl group. Chlorine, on the other hand, is not as selective, with some chlorination of the t-butyl moiety.

The manner in which the compounds of the invention may be prepared is further illustrated in the following examples. Example 1 ~ Preparation of 2'-6'-bis (1-bromomethyl) -2-bromo-N-methylacetanilide. 2-Chloro-N-methyl-2'-6'-diethyl acetanilide (23.9 g, 0.1 mol) was placed in 300 ml of carbon tetrachloride with 0.2 g of benzoyl peroxide. After heating to reflux, 16.0 g of bromine (0.2 mol) in 50 ml of CCl 4 * were added dropwise to the mixture, which was then exposed to both internal UV and external white light. Solvent was removed in vacuo and the crude product was dissolved in ethyl acetate. The solid product was repeatedly recrystallized from ethyl acetate to give 2'-6'-bis (1-bromomethyl) -2-bromo-N-methyl-acetanilide, m.p. 1e2-164 ° C.

Analysis. Calculated for CUHMBrBNO: C, 35.32; Br, 54.24; N, 3.17 C, 35.18; Br, 54.29; N, 3.16.

Example 2 Found: Preparation of 2 '- (bromomethylLoss-butyl-Z-bromo-N-methylacetanilide.

To 38.0 g (0.15 moi) of 2-chloro-N, 2'-dimethyl-Q-t-butylacetanilide (33 g, 0.15 moi) dissolved in CCl 4 was added 0.2 g of benzoyl peroxide and the mixture was heated to reflux. Bromine (24.0 g, 0.15 mol) in 50 ml of CClu was added dropwise to the above mixture. After the addition (1-1 / 2 h) and further reflux (0.5 h), the material was stripped to remove solvent. After scraping, the residue solidified. The product was recrystallized from heptane and identified as 2'- (bromomethyl) -6'-t-butyl-2-bromo-N-methylacetanilide, m.p. 86-87 ° C, yield 65%.

Analysis. Calculated for C 14 41-1 19 Br 2 NO: C, 44.59; Br, 42.38; N, 3.71 C, 44.62; Br, 42.27; N, 3.72.

Example Gel 3 Preparation of 2-chloro-N, 2'-6'-tris (bromomethylacetanilide.

Found: 2-Chloro-N- (chloromethyl) -2'-6'-dimethylacetanilide (0.04 mol, 10 g) was placed in 100 ml of CCl 2 containing 0.14 g of benzoyl peroxide and the mixture was heated to reflux with internal 0.2A UV lighting and external 150V / white light. To this mixture was added 13 g of bromine in 50 ml of CCl 4. After the theoretical amount of bromine was added, an additional 3.0 g of bromine was added. The mixture was cooled, the solvent was removed and the resulting viscous oil was triturated with ether to give a solid which by NMR indicated 2-chloro-N-2'-6'-tris (bromomethyldacetanilide. The crude product was not further purified but treated with 200 ml boiling methanol to give 2 ', 6'-bis (bromomethyl) -Z-chloro-N- (nethoxymethylacetanilide, m.p. 127.5-129 ° C.

Example 4 Preparation of 2 '- (bromomethyl-Z-chloro-β-butylacetanilide. 2-Chloro-β-methyl-Gt-butylacetanilide (5.6 g, 0.025 mol) was placed in about 120 ml of CCl Bromine (4.0 g, 0.025 mol) in 50 ml of CClu was added dropwise. After the addition, NMR monitoring showed that the reaction was complete. After removal of the solvent in vacuo, 7.0 g of white solid was recovered. recrystallization from isopropanol melted the product, 2 '- (bromomethyl) ~ 2-chloro-Gt-butylacetanilide, at 14z-147 ° C, yield 23%. 10 15 20 25 30 35 8002281 -7 6 Analysis: Calculated for C BH "BrCl NO: C, 49.00; Br, 35.08; Cl, 11.13.

Found: C, 47.93; Br, 24.50; Cl, 10.83.

Example 5 Preparation of 2-chloro-N, 2 ', 6'-tris (chloromethylacetanilide. 2-chloro-N, 2', octrimethyl-acetanilide (2.1l, 0.1 mol) »was placed in 200 ml of CCl and an internal 0.2 Å UV source was illuminated in a 500 ml flask. Chlorine (0.1 mol, 7.0 g) was introduced below the surface with stirring. The reaction was mildly exothermic, with temperatures rising from 200 to 40 g. After all the chlorine was added, a substantially colorless solution was obtained, the mixture was cooled to about 5 ° C, and an additional 0.1 mole of chlorine was added, and finally a third molar equivalent of chlorine was added to the mixture, and the material was allowed to stand for about 48 hours. Aliquots of this oil were recrystallized from pentanethers to give crystals identified as 2-chloro-N, 2 ', 6' tris (chloromethydacetanilide, m.p. 70-75 ° C. The shrimp product was not further purified, but treated directly with boiling methanol to give Z-ldor-N- (methoxymethyl) -2 ', 6'bis (chloromethyl) acetanilide The compound of Example 5 can also be prepared using 2-Chloro-N- (chloromethyl) -2 ', 6'-dimethylacetanilide as starting material. Example 6 Preparation of 2 '- (Bromomethyl) -6' - t-butyl-2-chloro-N- (chloromethylacetanalidide.

To 17.3 g (0.06 mol) of 2-chloro-N-chloromethyl-2 '- (methyl) -6'-t-butyl acetanilide dissolved in 250 ml of C614 was added 11.2 g (0.063 mol). recrystallized N-bromosuccinimide (NBS) and 0.25 g of benzoyl peroxide. The resulting mixture was heated to desolation and 500 ml of the 3-neck flask was illuminated by low current dipping UV and external white light. The reaction was monitored by NMR and was substantially complete in about 0.5 hours. After standing at room temperature for about 48 hours, 2.2 g of the product was isolated, 2 '- (bromomethyl) -G-β-butyl Z-chloro-N (chloromethyl fi-acetanilide, m.p. 12Al-125 ° C. Additional amount (7.9 g) was recovered after partial evaporation of the solvent. The product was not further purified, but reacted with methanol to give 2 '- (bromomethyl) -2- Example 7 Preparation of 2 '- (bromomethyl) GLÉ-butyl-Z-chloro-N-methylacetanilide.

Z-chloro-β-butyl-N, 2'-dimethylacetanilide (17.5 g, 0.069 mol) was dissolved in 250 ml of CCl 3 with 0.2 g of benzoyl peroxide and 13 g (0.072 mol) of recrystallized NBS using illumination and flask size as in Example 6. The reaction was completed in about 0.5 h, with succinimide fl superimposed on top of the ClCl 2 solution. The material was filtered and the filtrate was washed with water and vacuum dried to remove the solvent to give 24.9 g of residue. The residue was recrystallized from hexane to give 14.8 g of product. A second recrystallization from hexane gave 2'- (bromomethyl) -6'-β-butyl-2-chloro-N-methylacetanilide, mp 112-114 ° C; yield 63%.

Analysis: Calculated for C 141-1 Br Cl NO: »C, 50.54; Br, 24.02; Cl, 10.66. c, 50.33; ßr, '21 +, e3; cl, 10.61. Egemgel 8 Preparation of 2 '- (chloromethyl) -6'-methyl-Z-chloroacetanilide. Found: 2 ', 6'-Dimethyl-Z-chloroacetanylide was chlorinated according to the procedure of Example 5 to give a white solid, identified as 2' - (chloromethyl) -6'-methyl-2-chloroacetanilide, mp 133- 134 ° C.

Analysis: Calculated for C H Cl 2 NO: m U C, 51.74; H, 4.77; N, 6.03.

C, 51.69; H, 4.66; N, 6.03. Example 9 Preparation of 2 ', 6'-bis (bromomethyl) -2-chloro-N- (chloromethylacetanilide.

Found: 2-chloro-N- (100 ml CCl 3 with 0.14 g benzoyl peroxide. The material was heated to reflux and the flask was illuminated with low current immersible UV and external white light. To the mixture was added dropwise 13.0 g molecular bromine in 50.0 g). 3.0 g of additional bromine were added when NMR showed that the reaction was complete, the mixture was cooled and the solvent was removed in vacuo The resulting viscous oil was triturated with ether to give a solid, identified as 2 ', 6'-bis ( bromomethyl-Z-chloro-N- (chloromethylacetanilide. The product was not further purified, but treated with methanol to give 2 ', 6'-bis (bromomethylD-Z-chloro-N- (methoxymethylacetanilide).

Example 10 Preparation of 2 '- (dibromomethyl) -6'-t-butyl-2-chloroacetanilide.

The compound of Example 4 (9.54 g, 0.03 mol) was added to 300 ml of ClCl 3 containing 0.3 g of benzoyl peroxide. Two white lamps were used to irradiate the reaction vessel. Then 4.8 g of bromine was added in 50 ml of CCl, dropwise to the irradiated mixture while maintaining a gentle nitrogen spray in the reaction medium.

The irradiation was removed after about 1.5 hours and the mixture was allowed to stand and cool overnight. The solid precipitate was filtered to give 10.4 g of a first crop and 1.4 g of a second crop. The solid was recrystallized from isopropanol to give 2 '- (dibromomethyl- (fl-t-butyl-2-chloroacetanilide, m.p. 145-147 ° C, 99% yield. ~ Analysis: Calculated for Cl 31-1 16Br 2 Cl NO: Funnct Found: C, 39.28; H, 4.06; N, 3.52.

C, 38.99; H, 4.10; N, 3.58. EXAMPLE 11 Preparation of 2 '- (bromomethyl) -2, G-dichloroacetanilide.

To 300 ml of C614 in a 500 ml flask was added 15.0 g of 2,6'-dichloro-2'-methylacetanilide (0.068 mol) and 0.5 g of benzoyl peroxide. The reaction vessel was irradiated with two outer white lamps. The reaction mixture was heated to reflux and then 10.9 g of bromine (Brz) in 50 ml of CCl An additional 2.5 g of Brz was added when NMR indicated that the reaction was incomplete. Solvent was removed in vacuo. and the crude solid was recrystallized from isopropanol and vacuum sublimed (0.05 mm) to give 2 '- (bromomethyl) -2,6'-dichiotacetannide, mp 155-159 ° C, yield 52%. a Analyst Calculated for c9Hsßfc12 Note c, 36.40; H, 2.72; N, 4.72.

Found: C, 26.18; H, 2.72; N, 4.80. in Example Gel 12 Preparation of 2 '- (bromomethyl) -2,3'-dichloro-G-t-butylacetanilide.

In a 1 liter flask, 2,3'-dichloro-2'-methyl-G-t-butylacetanilide (15.0 g, 0.055 mmol) was dissolved in 600 mL of CCl Irradiation was given by two external white lamps.

The reaction mixture was heated to reflux and then 8.8 g of molecular bromine in 50 ml of CCl 4 was added. Excess solvent was removed in vacuo and the solid product was recrystallized twice to give 2 '- (bromomethyl) ~ 2,3' - t-clath-eu-butyl acetane, melting point 1s2_lsa ° c, yield 65%.

Analysis: Calculated for C 13 H 16 BrCl 2 NO: C, 44.22; H, 4.57; N, 3.97. Found: C, 44.09; H, 4.62; N, 3.96.

Example 13 Preparation of 2 ', 3'-bis (bromomethyl) -2-chloro-GHI-butylacetanilide. In a 1 liter ash, 15 g (0.059 mol) of 2-chloro-2', 3 '-dimethyl-9-3 were dissolved. - butyl acetanilide in 600 ml CCI 4. Irradiation was given by two white headlights.

The reaction mixture was heated to reflux and treated with nitrogen.

Then 9.44 g (0.059 mol) of elemental bromine in 50 ml of CCl was added dropwise. After a second molar equivalent of molecular bromine was added, and after about 48 hours, the mixture was filtered and the solid was recrystallized from isopropanol to give 2 ', 3'-bis (bromomethyl) -Z-chloro-Qt-butylacetanilide, m.p. -182 ° C (vacuum sublimation m.p. 195-197 ° C). Analysis: Calculated for CL 4 H 18 Br 2 Cl NO: C, 40.85; H, 4.41; N, 3.40.

Found: C, 40.60; H, 4.37; N, 3.40.

Example gel 14 Preparation of 2 '- (bromomethyl) -2-chloroacetanilide.

Z-chloro-Zm-methylacietanilide (4.0 g, 0.02 mol) and N-bromosuccinimide (3.9 g, 0.02 mol) were dissolved in 300 ml of CCl 4 with 0.3 g 2,2'-azobis (Z-methyl-propionitrile).

The mixture was illuminated with a spotlight and heated to reflux for 2.5 hours. At this time, the mixture was allowed to cool to room temperature, after which it was filtered, washed once with water, dried over MgSO 4, filtered again and purified to give a white solid. The solid was recrystallized from toluene to give 2.2 g of product, 2 '- (bromomethyl-D-chloroacetanilide, melting point: 125 DEG-127 DEG C., 32% yield. "Analysis: Calculated for C9 H9 BrCl NO: Found: C, 41.17; H, 3.46; N, 5.311.

C: 01.35; H, 3.40; N, 5.30.

Example 15 Preparation of 2 '- (bromomethyl) -6' - (trifluoromethyl-D-chloroacetanilide.

To 12.5 g (0.05 mol) of 2'-methyl-6 '- (trifluoromethyl) -2-chloroacetanilide was added 300 ml of carbon tetrachloride and 10.0 g (0.056 mol) of recrystallized NBS in a 1 liter flask. The mixture was kept at room temperature for about 1-1.5 hours and then kept at 70-75 ° C for about 4-5 hours. The crude product was isolated as a solid (corrosive) 17.7 g; recrystallization from isopropanol gave 9.8 g of product, 2 '- (bromomethyl) -6' - (trifluoromethyl-Z-chloroacetanilide, m.p. 98-101 ° C, 59.449 yield.

Analysis: Calculated for C 10 OH 8 Cl1 BrF 0; C, 36.34; H, 2, # 1 +; N, 4.20.

C, 35.94; H, 2.27; N, 4.19.

Example 16 Preparation of 2-chloro-N-chloromethylacetanilide. Found: In a suitable flask equipped with a stirrer, gas inlet tube, thermometer and internal low pressure UV lamp was charged 200.0 ml of CClu solution containing 0.1 mol of 2-chloro-N-methylacetanilide. One molar equivalent of gaseous chlorine was slowly introduced at room temperature into the flask. The solution was then elucidated, and after a short initial period, the temperature of the solution rose to 38 ° C due to the exothermic chlorination. NMR of the CCM solution showed complete reaction after a 10% excess of chlorine had been introduced. After vacuum treatment to remove gases and solvents, 98% yield of Z-chloro-N- (chloromethyl) acetanilide was obtained as a heat sensitive oil, which had the following NMR: 10 (cbci3), 653.9 (s, zn, clcijzö, d , 55 (s, 2H, cicnzn), J 7.6 (broad s, 51-1, Arn).

The compounds of the invention have been found to exhibit excellent herbicidal activity and to be useful in the preparation of certain gtg- (alkoxymethyl-Z-haloacetanilides which are active herbicides. The process by which these latter compounds are prepared comprises reacting the former 8 Described compounds of formula I with an alcohol, preferably in the presence of metal cations, eg potassium, sodium, silver, lead, mercury, etc., or other Lewis acids, Lex. AlCl3, SnCl4, ZnCl2, etc. When using the new compounds It was found that the halogen on the glq-haloalkyl groups, especially halomethyl, which were attached to the ring (benzylic) in the Z-haloacetanilide molecule of formula I, could be selectively replaced by a suitable alcohol without disturbing the otherwise labile Z Although the invention has been described in connection with specific embodiments, the details therein should not be construed as limitations, but various valents, changes and modifications may be made without departing from the spirit and spirit of the invention.

Claims (2)

8002281-7 11 Patent claim 1. Compound, characterized by the formula: O II R C - CH X \ / 2 N X R '2 1. "" .C 32 X1 Y1 where X is chlorine, bromine or iodine; R is hydrogen, methyl, chloromethyl, or bromomethyl; R 1 is hydrogen, halogen, tert-butyl, trifluoromethyl or R 2 is hydrogen, chlorine, bromine or straight chain alkyl containing 1 to 4 carbon atoms; Y I is hydrogen, halogen, E1t-butyl, trifluoromethyl or X. 2 -ç-Rg 3 X1 X1 and X2 are independently equal to hydrogen, chlorine or bromine moieties, provided that when Rz is straight chain alkyl containing 1 to 4 carbon atoms, only one of X1 and X2 can be equal to hydrogen, chlorine or bromine and further provided that Rz, X and X are not at the same time equal to chlorine or bromine. The present invention relates to grtl-haloalkyl-Z-haloacetanilide compounds and process for their preparation. The compounds are useful as intermediates in the preparation of N-substituted-ZLQ-disubstituted 2. -haloacetanilide derivatives, which selectively regulate unwanted vegetation in agricultural crops.