Process for preparation of alkenyl halides

Abstract

Alkenyl halides, such as alkenyl bromides or alkenyl chlorides, are produced by a process comprising the steps of forming a reaction mixture containing alkyl dibromides or chlorobromoalkanes and allylmagnesium bromide and / or allylmagnesium chloride, and then producing the alkenyl halides in the reaction mixture.

Description

[0001] Citation of Related Applications This application is filed on January 23, 2024 as a PCT International Patent Application and claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 481,612 filed on January 26, 2023, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0002] The present disclosure generally relates to methods for preparing alkenyl halides, and more particularly, to the synthesis of alkenyl bromides from allyl magnesium halides and alkyl dibromides, and the synthesis of alkenyl chlorides from allyl magnesium halides and chlorobromoalkanes. The resulting alkenyl bromides and chlorides can be used to produce metallocene compounds having alkenyl substituents. Background Art

[0003] Very few alkenyl halides are commercially available, and in particular those with four or more carbon atoms. Conventional synthesis schemes require harsh reaction conditions and the use of expensive transition metal catalysts. Therefore, it would be beneficial to have a synthesis scheme that produces the desired alkenyl halide in high yield under mild reaction conditions and without the use of a transition metal catalyst. Therefore, the present invention is generally directed to these purposes. Summary of the Invention

[0004] This summary is provided to introduce a selection of concepts that are further described herein in a simplified form. This summary is not intended to identify required or essential features of the claimed subject matter. This summary is also not intended to limit the scope of the claimed subject matter.

[0005] Disclosed herein are methods for producing alkenyl halides. For example, a method for producing an alkenyl bromide according to one aspect of the present invention may include: (a) forming a reaction mixture comprising an alkyl dibromide and allylmagnesium bromide, allylmagnesium chloride, or a combination thereof, and (b) producing the alkenyl bromide in the reaction mixture. In this aspect, the reaction mixture may be substantially free of Li2CuCl4.

[0006] In another aspect of the present disclosure, a method for producing an alkenyl chloride may include: (A) forming a reaction mixture comprising a chlorobromoalkane and allylmagnesium bromide, allylmagnesium chloride, or a combination thereof at a contact temperature in a range of 15° C. to 90° C., and (B) producing the alkenyl chloride in the reaction mixture.

[0007] The foregoing summary of the invention and the following detailed description are provided as examples and are illustrative only. Therefore, the foregoing summary of the invention and the following detailed description should not be considered restrictive. Furthermore, features or variations other than those described herein may also be provided. For example, certain aspects may involve various feature combinations and sub-combinations described in the detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 Bar graphs comparing allylmagnesium bromide in ethereal (Et2O) and allylmagnesium chloride in tetrahydrofuran (THF) in the synthesis of alkenyl bromides are presented.

[0009] Figure 2 Presented is a bar graph comparing alkyl dibromides and chlorobromoalkanes in the synthesis of alkenyl halides using allylmagnesium chloride in THF.

[0010] Figure 3 Presented is a bar graph comparing alkyl dibromides of varying chain lengths with chlorobromoalkanes of varying chain lengths in the synthesis of alkenyl halides using allylmagnesium chloride in THF.

[0011] Figure 4 Presented is a bar graph summarizing the effect of solvent on the synthesis of alkenyl bromides using allylmagnesium chloride in THF.

[0012] Figure 5 Presented is a bar graph summarizing the effect of solvent on the synthesis of alkenyl chlorides using allylmagnesium chloride in THF.

[0013] Figure 6 Presented is a bar graph summarizing the effect of reaction temperature on the synthesis of alkenyl bromides using allylmagnesium bromide in Et2O.

[0014] Figure 7 Presented is a bar graph summarizing the effect of reaction temperature on the synthesis of alkenyl chlorides using allylmagnesium bromide in Et2O.

[0015] Figure 8 Presented is a bar graph summarizing the effect of reaction temperature on the synthesis of alkenyl halides using allylmagnesium chloride in THF.

[0016] Figure 9 Presented is a bar graph summarizing the effect of excess alkyl dibromide on the synthesis of alkenyl bromides using allylmagnesium chloride in THF.

[0017] Figure 10 Presented is a bar graph summarizing the effect of reaction time on the synthesis of alkenyl bromides using allylmagnesium chloride in THF.

[0018] Figure 11Presented is a bar graph summarizing the effect of reaction temperature on the synthesis of alkenyl chlorides using allylmagnesium chloride in THF.

[0019] definition In order to more clearly define the terms used herein, the following definitions are provided. Unless otherwise indicated, the following definitions apply to the present disclosure. If the term is used in the present disclosure, but is not specifically defined in this article, the definition in IUPAC Compendium of Chemical Terminology, the 2nd edition (1997) can be applied, as long as the definition does not conflict with any other disclosure or definition used in this article, or any claim applying the definition will not be uncertain or not established. If any definition or usage provided by any file incorporated herein by reference conflicts with the definition or usage provided herein, the definition or usage provided herein shall be used as the criterion.

[0020] Herein, features of the subject matter may be described such that within a particular aspect, combinations of different features are contemplated. For each aspect and / or feature disclosed herein, all combinations that do not adversely affect the designs, compositions, processes, and / or methods described herein are contemplated, with or without explicit description of a particular combination. Additionally, unless explicitly stated otherwise, any aspect and / or feature disclosed herein may be combined to describe inventive features consistent with the present disclosure.

[0021] In the present disclosure, although compositions, processes / methods and systems are described in terms of “comprising” various materials, steps and components, unless otherwise indicated, the compositions, processes / methods and systems may also “consist essentially of” or “consist of” the various materials, steps or components. Unless otherwise indicated, the terms “a”, “an” and “the” are intended to include plural alternatives, such as at least one.

[0022] Generally speaking, element families use Chemical and Engineering News , 63(5), 27, 1985. In some cases, element groups may be referred to using the common name assigned to the group; for example, alkali metals refer to Group 1 elements, alkaline earth metals refer to Group 2 elements, transition metals refer to Groups 3 through 12 elements, and halogens or halides refer to Group 17 elements.

[0023] For any particular compound or group disclosed herein, unless otherwise indicated, any name or structure presented is intended to encompass all conformational isomers, positional isomers, stereoisomers, and mixtures thereof that may result from a particular set of substituents. Unless otherwise indicated, a name or structure also encompasses all enantiomers, diastereomers, and other optical isomers, if any, in both enantiomeric and racemic forms, as well as mixtures of stereoisomers, as known to those skilled in the art. For example, a general reference to a hexene (or hexenes) includes all straight or branched, acyclic or cyclic hydrocarbon compounds having six carbon atoms and one carbon-carbon double bond; a general reference to pentane includes n-pentane, 2-methylbutane, and 2,2-dimethylpropane; and a general reference to butyl includes n-butyl, sec-butyl, isobutyl, and tert-butyl.

[0024] The present invention discloses several types of scopes. When disclosing or claiming any type of scope, it is intended to disclose or claim separately each possible numeral that such scope can reasonably encompass, including the endpoints of the scope and any sub-range and the combination of sub-ranges encompassed therein. For example, in aspects of the present invention, the scope of the mol ratio of alkyl dibromide (or chlorobromoalkane) to allyl magnesium bromide and / or allyl magnesium chloride can be 0.8:1 to 10:1. By disclosing that mol ratio can be in the range of 0.8:1 to 10:1, it is intended to state that mol ratio can be any mol ratio in the scope, and for example, any scope or combination of scopes from 0.8:1 to 10:1 can be included, such as 0.8:1 to 2:1, 1:1 to 10:1, 1:1 to 5:1, 1.5:1 to 10:1, 1.5:1 to 5:1, 1.5:1 to 4:1, 2:1 to 6:1 or 2:1 to 4:1 etc. Equally, all other scopes disclosed herein should be interpreted in a manner similar to this example.

[0025] In general, an amount, size, formulation, parameter, range, or other quantity or characteristic is "about" or "approximately," whether or not expressly stated as such. Whether or not modified by the term "about" or "approximately," the claims include equivalents to the quantity or characteristic.

[0026] Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, typical methods and materials are described herein.

[0027] All publications and patents mentioned herein are incorporated herein by reference in their entirety for the purpose of describing and disclosing, for example, the constructs and methodologies that are described in the publications and patents, which might be used in connection with the presently described invention. DETAILED DESCRIPTION

[0028] Herein, alkenyl halides are synthesized in high yields from allylmagnesium halides and alkyldibromides or allylmagnesium halides and chlorobromoalkanes under mild reaction conditions and without the use of transition metal catalysts.

[0029] Synthesis of vinyl halides Herein, the first method is a method for producing an alkenyl bromide, and this first method may comprise (or consist essentially of, or consist of): (a) forming a reaction mixture comprising (or consisting essentially of, or consisting of): an alkyl dibromide and allylmagnesium bromide, allylmagnesium chloride, or a combination thereof, and (b) producing the alkenyl bromide in the reaction mixture. The reaction mixture may be substantially free of Li2CuCl4. The reaction mixture may also be substantially free of other transition metal catalysts, such as tris(acetylacetonato)iron (Fe(acac)3).

[0030] The alkyl dibromide reactant utilized in the first method is not particularly limited (e.g., the alkyl dibromide may be linear or branched), and may often include C1-C 12 Alkyl dibromide, such as C1-C8 alkyl dibromide, C1-C4 alkyl dibromide, C2-C 12 Alkyl bromide, C2-C6 alkyl dibromide or C2-C4 alkyl dibromide, etc. Similarly, the alkenyl bromide produced in the first method is not particularly limited (for example, the alkenyl bromide can be linear or branched), and often can include a compound having the formula CH2=CH-CH2-(CH2) n Compounds of Br, wherein n is an integer from 1 to 12, 1 to 8, or 1 to 4 in one aspect, and from 2 to 12, 2 to 6, or 2 to 4 in another aspect.

[0031] The second method provided herein is a method for producing an alkenyl chloride, and this second method can comprise (or consist essentially of, or consist of): (A) forming a reaction mixture at a contact temperature in the range of 15°C to 90°C, the reaction mixture comprising (or consisting essentially of, or consisting of): a chlorobromoalkane and allylmagnesium bromide, allylmagnesium chloride, or a combination thereof, and (B) producing the alkenyl chloride in the reaction mixture.

[0032] The chlorobromoalkane reactant utilized in the second method is not particularly limited (e.g., the chlorobromoalkane may be linear or branched), and may often include C1-C 12 Chlorobromoalkanes, such as C1-C8 chlorobromoalkanes, C1-C4 chlorobromoalkanes, C2-C 12Chlorobromoalkanes, C2-C6 chlorobromoalkanes or C2-C4 chlorobromoalkanes, etc. Similarly, the alkenyl chloride produced in the second method is not particularly limited (for example, the alkenyl chloride can be linear or branched), and can often include alkenyl chlorides having the formula CH2=CH-CH2-(CH2) n A compound of Cl wherein n is an integer from 1 to 12, from 1 to 8, or from 1 to 4 in one aspect, and from 2 to 12, from 2 to 6, or from 2 to 4 in another aspect.

[0033] In general, the features of the first and second methods (e.g., alkenyl halides, alkyl dibromides or chlorobromoalkanes, allyl magnesium bromide or allyl magnesium chloride, the relative amounts of reactants, and the conditions under which the formation step and the generation step are performed) are described independently herein, and these features can be combined in any combination to further describe the disclosed methods for producing alkenyl halides. In addition, unless otherwise stated, additional method steps can be performed before, during, and / or after any step in any method disclosed herein, and can be utilized without limitation and in any combination to further describe these methods. In addition, any alkenyl halide products produced according to the disclosed methods are within the scope of the present disclosure and are encompassed herein.

[0034] In step (a) of the first method and step (A) of the second method, the Grignard reactant can be allylmagnesium bromide, allylmagnesium chloride or a combination thereof. Thus, on the one hand, the reaction mixture can comprise (or consist essentially of, or consist of) an alkyl dibromide (or chlorobromoalkane) and allylmagnesium bromide (e.g., and a solvent such as diethyl ether), while on the other hand, the reaction mixture can comprise (or consist essentially of, or consist of) an alkyl dibromide (or chlorobromoalkane) and allylmagnesium chloride (e.g., and a solvent such as THF). However, on the other hand, the reaction mixture can comprise (or consist essentially of, or consist of) an alkyl dibromide (or chlorobromoalkane) and a mixture of allylmagnesium bromide and allylmagnesium chloride (e.g., and an ether solvent).

[0035] Allyl magnesium halide can be purchased before step (a) or (A) or produced in the same or nearby reactor.If purchased or produced at a remote location or at a different time, the material can be stored under appropriate conditions well known to those of ordinary skill in the art, such as protected by an inert gas to avoid the influence of moisture or oxygen.If purchased, allyl magnesium halide can reach any available concentration in ethereal solvents (such as ether or THF), with concentrations up to 30 weight %. The solutions often purchased are 1 or 2 molar solutions containing ethereal solvents.

[0036] Independently, the step (a) and (b) of the first method for producing alkenyl halide and the step (A) and (B) of the second method can be carried out with multiple temperature and time period.The time period in step (a) or step (A) is referred to as contact time, and the time period in step (b) or step (B) is referred to as reaction time.Contact time and reaction time are normally different.Similarly, the alkyl dibromide (or chlorobromoalkane) in step (a) or step (A) initially contacts with allyl magnesium bromide and / or allyl magnesium chloride to form the temperature at which reaction mixture resides and is referred to as contact temperature, and the reaction mixture temperature in step (b) or step (B) is referred to as reaction temperature.For example, contact temperature and reaction temperature can be identical or different.As illustrative example, in step (a), alkyl dibromide and allyl magnesium bromide and / or allyl magnesium chloride can be initially combined to form reaction mixture at contact temperature T1, and after this initial combination, the temperature of reaction mixture can be increased to reaction temperature T2 to allow (b) to produce alkenyl bromide in reaction mixture.

[0037] The contact temperature and the reaction temperature can independently be a minimum temperature of 15°C, 20°C, 30°C or 40°C; additionally or alternatively, a maximum temperature of 90°C, 70°C or 60°C. In general, the contact temperature and the reaction temperature can independently be a temperature ranging from any minimum temperature disclosed herein to any maximum temperature disclosed herein. Thus, suitable non-limiting contact or reaction temperature ranges may include the following: 15°C to 90°C, 15°C to 70°C, 20°C to 90°C, 20°C to 70°C, 30°C to 90°C, 30°C to 70°C or 40°C to 60°C. These temperature ranges are also intended to encompass situations where the contact temperature and / or reaction temperature is presented in a range of different temperatures, rather than a single fixed temperature, wherein at least one temperature falls within the corresponding range.

[0038] Advantageously, in order to achieve surprisingly high product yields and selectivities discussed further below, the first and second methods do not require a transition metal catalyst. In one aspect, for example, the reaction mixture can be substantially free of Li2CuCl4, i.e., the reaction mixture contains less than or equal to 1 wt% copper, where the weight percentage is based on the elemental weight of copper present in any form in the reaction mixture. More often, the reaction mixture contains less than or equal to 1000 ppm (by weight) copper, less than or equal to 250 ppm copper, less than or equal to 100 ppm copper, less than or equal to 50 ppm copper, or less than or equal to 10 ppm copper.

[0039] In another aspect, the reaction mixture contains less than or equal to 1 wt %, less than or equal to 1000 ppm (by weight), less than or equal to 250 ppm, less than or equal to 100 ppm, less than or equal to 50 ppm, or less than or equal to 10 ppm of any individual transition metal, based on the elemental weight of the transition metal present in any form in the reaction mixture. Individual transition metals that are substantially absent from the reaction mixture include Group 3 to Group 12 transition metals; alternatively, Group 6 to Group 11 transition metals; or alternatively, chromium, manganese, iron (e.g., from Fe(acac)3), cobalt, nickel, copper, palladium, or any combination thereof.

[0040] In the first and second methods, the molar ratio of the alkyl dibromide (or chlorobromoalkane) to allylmagnesium bromide, allylmagnesium chloride, or a combination thereof is not particularly limited and can often range from 0.8:1 to 10:1, 0.8:1 to 2:1, 1:1 to 10:1, or 1:1 to 5:1. However, it can be advantageous, as demonstrated in the examples below, to have a molar excess of the alkyl dibromide in the first method and a molar excess of the chlorobromoalkane in the second method. Thus, suitable molar ratios of the alkyl dibromide (or chlorobromoalkane) to allylmagnesium bromide, allylmagnesium chloride, or a combination thereof may include 1.5:1 to 10:1, 1.5:1 to 5:1, 1.5:1 to 4:1, 2:1 to 6:1, or 2:1 to 4:1, etc.

[0041] The contact time in the step (a) of the first method and the second method and step (A) is not limited to any specific range. That is to say, alkyl dibromide (or chlorobromoalkane) and allyl magnesium bromide and / or allyl magnesium chloride can be quickly contacted initially, or contact a longer time period, and then start to react and / or produce corresponding alkenyl halide in step (b) or step (B). Therefore, step (a) and step (A) can be carried out independently, for example, in the scope of being as short as 1-30 second to carrying out in the time period as long as 1-6 hour. In some aspects, the contact time can be in the range of 1 minute to 2 hours or 5 minutes to 1 hour.

[0042] Although the reaction time required to produce the desired alkenyl bromide or alkenyl chloride can vary significantly based on the reaction temperature, the molar ratio of the reactants, etc., typically, the alkenyl bromide in the first method (or the alkenyl chloride in the second method) can be produced within a time period ranging from 15 minutes to 10 hours. More often, the alkenyl bromide (or alkenyl chloride) can be produced within a time period ranging from 15 minutes to 5 hours, such as 30 minutes to 5 hours, 30 minutes to 4 hours, or 1 hour to 3 hours.

[0043] The corresponding alkenyl bromide and alkenyl chloride produced in the first method and the second method can be formed in the presence of a solvent. Any suitable solvent can be used, but hydrocarbon solvents and ether solvents can be conveniently used. Therefore, in one aspect of the present invention, the reaction mixture in the first method and the second method can also include a hydrocarbon solvent, and the exemplary and non-limiting examples of suitable hydrocarbon solvents include pentane, hexane, heptane, octane, decane, benzene, toluene, xylene, ethylbenzene, etc. If necessary, a mixture or combination of two or more hydrocarbon solvents can be used. On the other hand, the reaction mixture in the first method and the second method can also include an ether solvent, and the exemplary and non-limiting examples of suitable ether solvents include dimethyl ether, ethyl ether (Et2O), methyl ethyl ether, cyclopentyl methyl ether (CPME), methyl tert-butyl ether (MTBE), furan, dihydrofuran, tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), 4-methyltetrahydropyran (4-MeTHP), 1,4-dioxane, etc. If necessary, a mixture or combination of two or more ether solvents can be used. The solvent may be present in any relative amount in the reaction mixture, and the presence of solvent can affect product yield and by-product formation, as shown in the examples below.

[0044] In alternative aspects, the reaction mixture in the first method and the second method can be substantially free of added solvent, i.e., the reaction mixture contains less than or equal to 5% by weight of additional solvent. In this regard, the solvent from the allyl magnesium halide solution will become part of the reaction mixture. Most commonly, this solvent is an ether solvent. More often, in this regard, based on the gross weight of the reaction mixture, the reaction mixture can contain less than or equal to 1% by weight of additional solvent, or less than or equal to 0.5% by weight of additional solvent.

[0045] Surprisingly, the first method and the second method have effectively converted the corresponding reactants and produced alkenyl bromides or alkenyl chlorides with high yields. The molar yield of the alkenyl bromide in the reaction mixture in the first method (or the molar yield of the alkenyl chloride in the reaction mixture in the second method) can be at least 40 mol%, and more often at least 50 mol%, at least 60 mol%, at least 70 mol%, at least 80 mol%, at least 85 mol% or at least 90 mol%. These molar yields are based on allyl magnesium bromide or allyl magnesium chloride reactants, or the mole number of its combination (if utilizing more than a reactant).

[0046] Advantageously, these high molar yields of the desired alkenyl halide are often accompanied by relatively small amounts of diolefin by-products. The molar amount of diolefin by-products in the reaction mixture is generally less than or equal to 20 mol%, and more often less than or equal to 15 mol%, less than or equal to 10 mol%, less than or equal to 5 mol%, less than or equal to 2 mol%, or less than or equal to 1 mol%. As described above, these molar yields are based on the moles of allylmagnesium bromide and / or allylmagnesium chloride reactants.

[0047] The first and second methods achieve unexpectedly high molar selectivity of alkenyl halides relative to diolefin byproducts. For example, the molar selectivity ratio of alkenyl bromides (or alkenyl chlorides) to diolefin byproducts in the reaction mixture can be at least 5: 1, at least 6: 1, at least 8: 1, at least 10: 1, at least 15: 1, at least 20: 1, at least 50: 1, or at least 100: 1; additionally or alternatively, the molar selectivity ratio can be less than or equal to 300: 1, less than or equal to 250: 1, less than or equal to 200: 1, less than or equal to 150: 1, less than or equal to 100: 1, or less than or equal to 50: 1. In general, the molar selectivity ratio of alkenyl bromides (or alkenyl chlorides) to diolefin byproducts can be within the range of any minimum selectivity ratio disclosed herein to any maximum selectivity ratio disclosed herein. Thus, suitable non-limiting ranges for molar selectivity ratios may include the following: 5:1 to 300:1, 5:1 to 100:1, 6:1 to 200:1, 6:1 to 50:1, 8:1 to 150:1, 10:1 to 250:1, 10:1 to 100:1, 15:1 to 150:1, 20:1 to 200:1, 50:1 to 300:1, 100:1 to 300:1, or 100:1 to 200:1.

[0048] Optionally, the first method and the second method may further include a quenching step, and additionally or alternatively, a step of separating at least a portion (and in some cases all) of the alkenyl bromide (or alkenyl chloride) from the reaction mixture (after step (b) or after step (B)) to form a product mixture. Any suitable separation technique may be used, such as extraction, filtration, evaporation, distillation, etc. If desired, a combination of two or more of these techniques may be utilized. In one aspect, the reaction may be quenched with water, alcohol, or a mixture thereof, alone or in combination with a hydrocarbon solvent.

[0049] Also optionally, the first and second methods may further comprise the step of separating at least a portion (and in some cases, all) of the alkyl dibromide (or chlorobromoalkane) from the reaction mixture using any suitable technique (such as extraction, filtration, evaporation, distillation, or the like, or a combination thereof) (after step (b) or after step (B)). After separation, the alkyl dibromide or chlorobromoalkane may optionally be recycled to the reaction mixture (in step (a) or in step (A)).

[0050] Example The present invention is further illustrated by the following examples, which should not be construed as limiting the scope of the present invention in any way. Various other aspects, modifications, and their equivalents may occur to one of ordinary skill in the art after reading the description herein without departing from the spirit of the present invention or the scope of the appended claims.

[0051] General experimental procedures: Synthesis: All experiments were carried out on a 10 mmol scale based on AllylMgX (X = Br or Cl) under a nitrogen atmosphere. AllylMgBr (1 mol / L Et2O solution) and allylMgCl (2 mol / L THF solution) were purchased from Aldrich. In the presence or absence of a solvent, the alkyl dihalide was placed in a flask. The flask was kept in a water bath to maintain a contact temperature close to room temperature (about 23°C), and AllylMgX was added dropwise to the flask. After completing the addition of AllylMgX, the flask was kept in a water bath for another 5 to 10 minutes. The water bath was then removed and the flask was maintained at the desired reaction temperature for the desired time period. For experiments where the reaction temperature was higher than room temperature, the flask was heated in an oil bath to the desired reaction temperature. The reaction was quenched with water in the flask, followed by addition of a known amount of toluene (using toluene as an internal standard to quantify the product). The reaction mixture was extracted with Et2O or pentane and then analyzed with GC / MS and GC / FID.

[0052] Product analysis: The products were confirmed by GC / MS and the corresponding standards of the analyzed compounds. The products were quantified by GC / FID using toluene as the internal standard.

[0053] Confirmation experiment operation (Confirmation run) about product separation: 1-bromo-3-chloropropane (2.9 mL, 29.5 mmol) is packed in flask.Flask is remained in water-bath to maintain the contact temperature near room temperature (about 23 DEG C), and AllylMgCl THF solution (31 mmol, 15.5 mL of the THF solution containing 2 mole / L) is added dropwise in flask.After completing adding AllylMgCl solution, flask is kept in water-bath in addition for 10 minutes.Then, remove water-bath and flask is kept in addition for 1 hour under the reaction temperature near room temperature.React with water quencher in flask, and extract with pentane (20 mLx 2).Remove solvent and obtain product (6-chloro-1-hexene) (3.2 g, 91.4% productive rate), be colorless liquid, purity is 95%.

[0054] Figure 1 It was demonstrated that, under identical reaction conditions, the reaction of 1,3-dibromopropane with allylmagnesium chloride in THF produced twice as much 6-bromohex-1-ene (72 mol% based on AllylMgCl) as the reaction of 1,3-dibromopropane with allylmagnesium bromide in Et2O (36 mol% based on AllylMgBr). Using allylmagnesium chloride in THF also produced significantly more diene byproducts than using allylmagnesium bromide in Et2O. The reaction conditions were a 1:1 reactant molar ratio and a 2:1 volume ratio of diethyl ether to THF at room temperature (approximately 23°C) for 2 hours.

[0055] Under the same reaction conditions, Figure 2 The reaction of 1-bromo-3-chloropropane with allylmagnesium chloride showed a greater yield of 6-chlorohex-1-ene (81 mol % based on AllylMgCl) than the yield of 6-bromohex-1-ene (72 mol % based on AllylMgCl) in the reaction of 1,3-dibromopropane with allylmagnesium chloride. The use of 1-bromo-3-chloropropane also produced significantly less diene byproduct, with a molar ratio of 6-chlorohex-1-ene to diene byproduct of 162:1.

[0056] Under the same reaction conditions and using allylmagnesium chloride, Figure 3 The effects of the chain lengths of alkyl dibromides (used to generate alkenyl bromides) and chlorobromoalkanes (used to generate alkenyl chlorides) in the synthesis of alkenyl halides are summarized. Longer dihalide chain lengths lead to higher molar yields.

[0057] Under the same reaction conditions, Figure 4Shown are the effects of no additional solvent (pure alkyl dihalide), 15 mL of ether:THF (2:1 volume ratio, THF (5 mL) from the Grignard reagent, alkyl dihalide dissolved in 10 mL of Et2O), and 15 mL of THF (THF (5 mL) from the Grignard reagent, alkyl dihalide dissolved in 10 mL of THF) on the yield of 6-bromohex-1-ene produced from the reaction of 1,3-dibromopropane with allylmagnesium chloride and the yield of 5-bromopent-1-ene produced from the reaction of 1,2-dibromoethane with allylmagnesium chloride. While there was no significant effect on product yields, the presence of additional solvent with the alkyl dihalide appeared to reduce the formation of diene byproducts.

[0058] Figure 5 Similar to Figure 4 , except that the alkyl dibromide reactant was replaced by an analogous chlorobromoalkane (and yielded an analogous alkenyl chloride). The presence of diethyl ether surprisingly reduced the product yield.

[0059] Figure 6 This study summarizes the effects of reaction temperature on the synthesis of two alkenyl bromides of varying chain lengths. Allyl magnesium bromide in Et2O was reacted with either 1,3-dibromopropane or 1,2-dibromoethane at a 1:1 reactant molar ratio in 20 mL of solvent (1:1 diethyl ether:THF by volume) at room temperature, 40°C, or 60°C for 2 hours. Unexpectedly, increasing the reaction temperature significantly increased the yield of the corresponding alkenyl bromide. The amount of diolefin byproduct also increased with increasing reaction temperature.

[0060] Figure 7 Similar to Figure 6 , except that the alkyl dibromide reactant was replaced by an analogous chlorobromoalkane (and thus produced an analogous alkenyl chloride). Surprisingly, the yield of the corresponding alkenyl chloride increased significantly with increasing reaction temperature, while the amount of diolefin byproduct did not seem to be affected by reaction temperature.

[0061] Figure 8 Similar to Figures 6 and 7 , except that AllylMgCl THF solution was used instead of AllylMgBr Et2O solution, the reactant molar ratio of 1,2-dibromoethane to AllylMgCl was 2:1, and the reactant molar ratio of 1-bromo-2-chloroethane to AllylMgCl was 1:1. Interestingly, under the experimental conditions, the reaction temperature had no significant effect on the molar yield of the corresponding alkenyl halide or the amount of diolefin byproduct.

[0062] Figure 9The effects of excess alkyl dibromide on the synthesis of alkenyl bromides over a 2-hour reaction at room temperature and contact temperature without the addition of additional solvent are summarized. Increasing the dibromide:AllyMgCl molar ratio from 1:1 to 3:1 unexpectedly increases the molar yield of the corresponding alkenyl bromide while decreasing the production of diolefin byproducts. The molar selectivity of diolefin byproducts increases from 4:1-5:1 at a 1:1 reactant molar ratio to 17:1-23:1 at a 3:1 reactant molar ratio.

[0063] Figure 10 This study summarizes the effects of reaction time on the synthesis of alkenyl bromides in 15 mL of THF at room temperature and contact temperature. The reactant molar ratio of 1,2-dibromoethane:AllylMgCl was 3:1, and the reactant molar ratio of 1,3-dibromoethane:AllylMgCl was 2:1. Increasing the reaction time increased the molar yield of the corresponding alkenyl bromide, and under the experimental conditions, the production of diene byproducts was slightly increased.

[0064] Figure 11 Similar to Figure 10 , except that the alkyl dibromide reactant was replaced by an analogous chlorobromoalkane (and thus produced an analogous alkenyl chloride), and the molar ratio of chlorobromoalkane:AllylMgCl was 1:1. The yield of the corresponding alkenyl chloride increased significantly with increasing reaction time, while surprisingly, the amount of diolefin byproduct did not appear to be affected by reaction time.

[0065] The following general conclusions can be drawn from the experiments and data discussed above. AllylMgCl in THF is more active than AllylMgBr in EtO, and excess alkyl dibromide increases product yields and reduces diene formation. Yields also generally increase with increasing reaction temperature and time, and transition metal catalysts are not required to achieve high yields of the desired alkenyl halide.

[0066] The present invention has been described herein with reference to numerous aspects and specific embodiments. Numerous variations will occur to those skilled in the art in light of the detailed description. All such obvious variations are within the full intended scope of the appended claims. Other aspects of the present invention may include, but are not limited to, the following (aspects are described as "comprising," but may alternatively be "consisting essentially of" or "consisting of"): Aspect 1. A method for producing an alkenyl bromide, the method comprising: (a) forming a reaction mixture comprising (or consisting essentially of, or consisting of): an alkyl dibromide and allylmagnesium bromide, allylmagnesium chloride, or a combination thereof, and (b) producing the alkenyl bromide in the reaction mixture, wherein the reaction mixture is substantially free of Li2CuCl4.

[0067] Aspect 2. The method as defined in aspect 1, wherein the alkyl dibromide comprises C1-C 12 Alkyl dibromide, C1-C8 alkyl dibromide, C1-C4 alkyl dibromide, C2-C 12 Alkyl dibromide, C2-C6 alkyl dibromide or C2-C4 alkyl dibromide.

[0068] Aspect 3. The method as defined in aspect 1 or 2, wherein the alkenyl bromide comprises a compound having the formula CH2=CH-CH2-(CH2) n A compound of Br, wherein n is an integer from 1 to 12, from 1 to 8, from 1 to 4, from 2 to 12, from 2 to 6, or from 2 to 4.

[0069] Aspect 4. A method for producing an alkenyl chloride, the method comprising: (A) forming a reaction mixture at a contact temperature in the range of 15°C to 90°C, the reaction mixture comprising (or consisting essentially of, or consisting of): a chlorobromoalkane and allylmagnesium bromide, allylmagnesium chloride, or a combination thereof, and (B) producing the alkenyl chloride in the reaction mixture, for example, at a reaction temperature in the range of 15°C to 90°C.

[0070] Aspect 5. The method as defined in aspect 4, wherein the chlorobromoalkane comprises C1-C 12 Chlorobromoalkanes, C1-C8 chlorobromoalkanes, C1-C4 chlorobromoalkanes, C2-C 12 Chlorobromoalkanes, C2-C6 chlorobromoalkanes or C2-C4 chlorobromoalkanes.

[0071] Aspect 6. The method as defined in aspect 4 or 5, wherein the alkenyl chloride comprises a compound having the formula CH2=CH-CH2-(CH2) n Cl, wherein n is an integer from 1 to 12, from 1 to 8, from 1 to 4, from 2 to 12, from 2 to 6, or from 2 to 4.

[0072] Aspect 7. A method as defined in any one of aspects 1 to 6, wherein the reaction mixture comprises (or consists essentially of, or consists of) the alkyl dibromide (or the chlorobromoalkane), the allylmagnesium bromide, and a solvent (e.g., Et2O).

[0073] Aspect 8. The method as defined in any one of aspects 1 to 6, wherein the reaction mixture comprises (or consists essentially of, or consists of) the alkyl dibromide (or the chlorobromoalkane), the allylmagnesium chloride, and a solvent (e.g., THF).

[0074] Aspect 9. The method as defined in any one of aspects 1 to 8, wherein the reaction mixture in step (a) or step (A) is formed at a contact temperature in the range of 15°C to 90°C or any range disclosed herein, such as 15°C to 70°C, 20°C to 90°C, 20°C to 70°C, 30°C to 90°C, 30°C to 70°C or 40°C to 60°C.

[0075] Aspect 10. The method as defined in any one of aspects 1 to 9, wherein the alkenyl bromide in step (b) or the alkenyl chloride in step (B) is produced at a reaction temperature in the range of 15°C to 90°C, or any range disclosed herein, such as 15°C to 70°C, 20°C to 90°C, 20°C to 70°C, 30°C to 90°C, 30°C to 70°C, or 40°C to 60°C.

[0076] Aspect 11. The method as defined in any one of aspects 1 to 10, wherein the reaction mixture is substantially free of Li2CuCl4, ie, the reaction mixture contains less than or equal to 1 wt% copper (elemental basis).

[0077] Aspect 12. The method as defined in any one of aspects 1 to 10, wherein the reaction mixture contains less than or equal to 1000 ppm (by weight), less than or equal to 250 ppm, less than or equal to 100 ppm, less than or equal to 50 ppm, or less than or equal to 10 ppm of copper (elemental basis).

[0078] Aspect 13. The method as defined in any one of aspects 1 to 12, wherein the reaction mixture contains less than or equal to 1 wt %, less than or equal to 1000 ppm (by weight), less than or equal to 250 ppm, less than or equal to 100 ppm, less than or equal to 50 ppm, or less than or equal to 10 ppm of a transition metal (elemental basis), e.g., nickel, iron, palladium, etc.

[0079] Aspect 14. The method as defined in any one of aspects 1 to 13, wherein the molar ratio of the alkyl dibromide (or the chlorobromoalkane) to the allylmagnesium bromide, the allylmagnesium chloride, or the combination thereof is within any range disclosed herein, for example, 0.8:1 to 10:1, 0.8:1 to 2:1, 1:1 to 10:1, 1:1 to 5:1, 1.5:1 to 10:1, 1.5:1 to 5:1, 1.5:1 to 4:1, 2:1 to 6:1, or 2:1 to 4:1.

[0080] Aspect 15. The method as defined in any one of aspects 1 to 14, wherein the alkenyl bromide (or the alkenyl chloride) is produced within a time period ranging from 15 minutes to 10 hours, 15 minutes to 5 hours, 30 minutes to 5 hours, 30 minutes to 4 hours, or 1 hour to 3 hours.

[0081] Aspect 16. The method as defined in any one of aspects 1 to 15, wherein the molar yield of the alkenyl bromide (or the alkenyl chloride) in the reaction mixture is at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85% or at least 90% based on the allylmagnesium bromide, the allylmagnesium chloride or the combination thereof.

[0082] Aspect 17. The method as defined in any one of aspects 1 to 16, wherein the molar amount of diolefin by-product in the reaction mixture is less than or equal to 20%, less than or equal to 15%, less than or equal to 10%, less than or equal to 5%, less than or equal to 2%, or less than or equal to 1%, based on the allylmagnesium bromide, the allylmagnesium chloride, or the combination thereof.

[0083] Aspect 18. A process as defined in any one of Aspects 1 to 17, wherein the molar selectivity ratio of the alkenyl bromide (or the alkenyl chloride) to diolefin byproduct in the reaction mixture is at least 5:1, at least 6:1, at least 8:1, at least 10:1, at least 15:1, at least 20:1, at least 50:1, or at least 100:1; and is less than or equal to 300:1, less than or equal to 250:1, less than or equal to 200:1, less than or equal to 150:1, less than or equal to 100:1, or less than or equal to 50:1; or any suitable range from any minimum value to any maximum value.

[0084] Aspect 19. A method as defined in any one of aspects 1 to 18, wherein the reaction mixture is substantially free of additional solvent other than the Grignard reagent (i.e., the reaction mixture contains less than or equal to 5 wt. % of additional solvent other than the Grignard reagent), or the reaction mixture contains less than or equal to 1 wt. % of additional solvent other than the Grignard reagent, or less than or equal to 0.5 wt. % of additional solvent other than the Grignard reagent, based on the total weight of the reaction mixture.

[0085] Aspect 20. The method as defined in any one of Aspects 1 to 18, wherein the reaction mixture further comprises any suitable solvent, for example, an ether solvent selected from dimethyl ether, ethyl ether, methyl ethyl ether, furan, dihydrofuran, tetrahydrofuran (THF) or any combination thereof; and / or a hydrocarbon solvent selected from pentane, hexane, heptane, octane, decane, benzene, toluene, xylene, ethylbenzene or any combination thereof.

[0086] Aspect 21. The method as defined in any one of Aspects 1 to 20, further comprising the step of separating at least a portion (and in some cases all) of the alkenyl bromide (or the alkenyl chloride) from the reaction mixture (after step (b) or after step (B)) using any suitable technique or any technique disclosed herein, such as extraction, filtration, evaporation, distillation, etc. or any combination thereof to form a product mixture.

[0087] Aspect 22. The method as defined in any one of Aspects 1 to 21, further comprising the steps of separating at least a portion (and in some cases all) of the alkyl dibromide (or the chlorobromoalkane) from the reaction mixture (after step (b) or after step (B)) using any suitable technique or any technique disclosed herein, such as extraction, filtration, evaporation, distillation, etc. or any combination thereof, and optionally recycling at least a portion of the alkyl dibromide to the reaction mixture (in step (a) or in step (A)).

Claims

1. A method for producing an alkenyl bromide, the method comprising: (a) forming a reaction mixture comprising an alkyl dibromide and allylmagnesium bromide, allylmagnesium chloride, or a combination thereof; and (b) producing the alkenyl bromide in the reaction mixture; wherein the reaction mixture is substantially free of Li2CuCl4.

2. The method of claim 1, wherein the alkyl dibromide comprises C1-C 12 Alkyl dibromide, C1-C8 alkyl dibromide, C1-C4 alkyl dibromide, C2-C 12 Alkyl dibromide, C2-C6 alkyl dibromide or C2-C4 alkyl dibromide.

3. The method of claim 1 or 2, wherein the alkenyl bromide comprises an alkyl bromide having the formula CH2=CH-CH2-(CH2) n A compound of Br, wherein n is an integer from 1 to 12, from 1 to 8, from 1 to 4, from 2 to 12, from 2 to 6, or from 2 to 4.

4. A method for producing an alkenyl chloride, the method comprising: (A) forming a reaction mixture comprising a chlorobromoalkane and allylmagnesium bromide, allylmagnesium chloride, or a combination thereof at a contact temperature in the range of 15° C. to 90° C.; and (B) generating the alkenyl chloride in the reaction mixture.

5. The method of claim 4, wherein the chlorobromoalkanes comprise C1-C 12 Chlorobromoalkanes, C1-C8 chlorobromoalkanes, C1-C4 chlorobromoalkanes, C2-C 12 Chlorobromoalkanes, C2-C6 chlorobromoalkanes or C2-C4 chlorobromoalkanes.

6. The method of claim 4 or 5, wherein the alkenyl chloride comprises an alkylene chloride having the formula CH2=CH-CH2-(CH2) n Cl, and wherein n is an integer from 1 to 12, 1 to 8, 1 to 4, 2 to 12, 2 to 6, or 2 to 4.

7. The process of any one of claims 1 to 6, wherein the reaction mixture comprises the alkyl dibromide (or the chlorobromoalkane), the allylmagnesium bromide, and a solvent.

8. The process of any one of claims 1 to 6, wherein the reaction mixture comprises the alkyl dibromide (or the chlorobromoalkane), the allylmagnesium chloride, and a solvent.

9. The process of any one of claims 1 to 8, wherein the reaction mixture in step (a) or step (A) is formed at a contact temperature in the range of 15°C to 90°C, 15°C to 70°C, 20°C to 90°C, 20°C to 70°C, 30°C to 90°C, 30°C to 70°C, or 40°C to 60°C.

10. The process of any one of claims 1 to 9, wherein the alkenyl bromide in step (b) or the alkenyl chloride in step (B) is produced at a reaction temperature in the range of 15°C to 90°C, 15°C to 70°C, 20°C to 90°C, 20°C to 70°C, 30°C to 90°C, 30°C to 70°C, or 40°C to 60°C.

11. The process of any one of claims 1 to 10, wherein the reaction mixture is substantially free of Li2CuCl4, and / or the reaction mixture contains less than or equal to 1 wt% copper (elemental basis).

12. The process of any one of claims 1 to 10, wherein the reaction mixture contains less than or equal to 1000 ppm (by weight), less than or equal to 250 ppm, less than or equal to 100 ppm, less than or equal to 50 ppm, or less than or equal to 10 ppm copper (elemental basis).

13. The process of any one of claims 1 to 12, wherein the reaction mixture contains less than or equal to 1 wt %, less than or equal to 1000 ppm (by weight), less than or equal to 250 ppm, less than or equal to 100 ppm, less than or equal to 50 ppm, or less than or equal to 10 ppm of a transition metal (elemental basis), such as nickel, iron, or palladium.

14. The process of any one of claims 1 to 13, wherein the molar ratio of the alkyl dibromide (or the chlorobromoalkane) to the allylmagnesium bromide, the allylmagnesium chloride, or the combination thereof is in the range of 0.8: 1 to 10: 1, 0.8: 1 to 2: 1, 1: 1 to 10: 1, 1: 1 to 5: 1, 1.5: 1 to 10: 1, 1.5: 1 to 5: 1, 1.5: 1 to 4: 1, 2: 1 to 6: 1, or 2: 1 to 4:

1.

15. The method of any one of claims 1 to 14, wherein the alkenyl bromide (or the alkenyl chloride) is produced over a time period ranging from 15 minutes to 10 hours, 15 minutes to 5 hours, 30 minutes to 5 hours, 30 minutes to 4 hours, or 1 hour to 3 hours.

16. The process of any one of claims 1 to 15, wherein the molar yield of the alkenyl bromide (or the alkenyl chloride) in the reaction mixture based on the allylmagnesium bromide, the allylmagnesium chloride, or the combination thereof is at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, or at least 90%.

17. The process of any one of claims 1 to 16, wherein the molar amount of diolefin byproduct in the reaction mixture is less than or equal to 20%, less than or equal to 15%, less than or equal to 10%, less than or equal to 5%, less than or equal to 2%, or less than or equal to 1%, based on the allylmagnesium bromide, the allylmagnesium chloride, or the combination thereof.

18. The process of any one of claims 1 to 17, wherein the molar selectivity ratio of the alkenyl bromide (or the alkenyl chloride) to diolefin byproduct in the reaction mixture is at least 5: 1, at least 6: 1, at least 8: 1, at least 10: 1, at least 15: 1, at least 20: 1, at least 50: 1, or at least 100: 1; and less than or equal to 300: 1, less than or equal to 250: 1, less than or equal to 200: 1, less than or equal to 150: 1, less than or equal to 100: 1, or less than or equal to 50: 1; or ranges from any minimum value to any maximum value, such as 5: 1 to 250:

1.

19. The process of any one of claims 1 to 18, wherein the reaction mixture is substantially free of additional solvent other than the solution of allylmagnesium bromide, allylmagnesium chloride, or the combination thereof (the reaction mixture contains less than or equal to 5 wt. % additional solvent other than the solution of allylmagnesium bromide, allylmagnesium chloride, or the combination thereof), or the reaction mixture contains less than or equal to 1 wt. % additional solvent other than the solution of allylmagnesium bromide, allylmagnesium chloride, or the combination thereof, or less than or equal to 0.5 wt. % additional solvent other than the solution of allylmagnesium bromide, allylmagnesium chloride, or the combination thereof, based on the total weight of the reaction mixture.

20. The process of any one of claims 1 to 18, wherein the reaction mixture further comprises an ether solvent (such as dimethyl ether, ethyl ether, methyl ethyl ether, furan, dihydrofuran, tetrahydrofuran (THF) or any combination thereof) and / or a hydrocarbon solvent (such as from the group consisting of pentane, hexane, heptane, octane, decane, benzene, toluene, xylene, ethylbenzene or any combination thereof).

21. The method according to any one of claims 1 to 20, further comprising the steps of: At least a portion of the alkenyl bromide (or the alkenyl chloride) is separated from the reaction mixture (after step (b) or after step (B)) to form a product mixture.

22. The method according to any one of claims 1 to 21, further comprising the steps of: At least a portion of the alkyl dibromide (or the chlorobromoalkane) is separated from the reaction mixture after step (b) or after step (B) and optionally recycled to the reaction mixture in step (a) or in step (A).

Images