A method for photocatalytic synthesis of 2-(bromomethyl)naphthalene

Abstract

The present invention discloses a method for photocatalytically synthesizing 2-(bromomethyl)naphthalene. The preparation method of 2-(bromomethyl)naphthalene disclosed in the present invention comprises the following steps: in the presence of light, in the presence of an organic base and a phosphite, in a halogenated hydrocarbon solvent, 2-(dibromomethyl)naphthalene is subjected to a reduction reaction to obtain 2-(bromomethyl)naphthalene. The preparation method of the present invention has one or more of the following advantages: high efficiency, high speed, high yield, low cost, good selectivity and conducive to industrial production.

Description

Technical Field

[0001] The invention relates to a method for photocatalytically synthesizing 2-(bromomethyl)naphthalene. Background Art

[0002] 2-(Bromomethyl)naphthalene is an intermediate for synthesizing Centanafadine hydrochloride, and its synthesis method has been widely reported at home and abroad. In Japanese patent JP200139904, 2-(halogenated methyl)naphthalene is synthesized by 2-methylnaphthalene and dibromohydantoin in the presence of azobisisobutyronitrile as the catalyst. During the reaction, the catalyst is easily deactivated, resulting in reaction failure. At the same time, the reaction conversion rate is only 87%, and the yield is low. In Chinese patent CN116348440A, 2-(halogenated methyl)naphthalene is prepared by using 2-methylnaphthalene in a solvent selected from halogenated hydrocarbons, aliphatic esters and aliphatic hydrocarbons, and reacting with a halogenating agent under light irradiation. However, in the synthesis method of 2-(bromomethyl)naphthalene reported in the prior art, 2-(dibromomethyl)naphthalene is often produced due to side reactions, which not only reduces the yield of synthesizing 2-(bromomethyl)naphthalene, but also increases the difficulty of purifying 2-(bromomethyl)naphthalene. Therefore, it is an urgent problem to develop a synthesis method that is efficient, high-yield, has simple synthesis steps, mild reaction conditions, low cost, environmentally friendly, and suitable for large-scale production and can reduce 2-(dibromomethyl)naphthalene to 2-(bromomethyl)naphthalene. Summary of the invention

[0003] The technical problem to be solved by the present invention is to overcome the defects of the prior art method for reducing 2-(dibromomethyl)naphthalene to 2-(bromomethyl)naphthalene, such as low efficiency, low yield, complicated synthesis steps, severe reaction conditions, high cost, environmental unfriendliness, and unsuitability for scale-up production. To this end, the present invention provides a method for preparing 2-(bromomethyl)naphthalene, which has one or more of the following advantages: high efficiency, high yield, simple synthesis steps, mild reaction conditions, low cost, environmental friendliness, and suitability for scale-up production.

[0004] The present invention solves the above-mentioned technical problems through the following technical solutions.

[0005] The present invention provides a method for preparing 2-(bromomethyl)naphthalene, which comprises the following steps: in the presence of light, in the presence of an organic base and a phosphite, in a halogenated hydrocarbon solvent, 2-(dibromomethyl)naphthalene is subjected to a reduction reaction to obtain 2-(bromomethyl)naphthalene;

[0006]

[0007] The wavelength of the illumination is 350-500nm;

[0008] The organic base is N(R 1)3, each R 1 are independently C1-6 alkyl;

[0009] The phosphite is , R 2 and R 3 are independently C1-6 alkyl.

[0010] In certain preferred embodiments of the present invention, certain reagents, conditions or operations in the method for preparing 2-(bromomethyl)naphthalene are defined as follows, and the reagents, conditions or operations not mentioned are the same as those described in any scheme of the present invention (referred to as "in a certain scheme of the present invention"). For other invention items of the present invention, the same abbreviation as that of the present invention is adopted and no further description is given.

[0011] In one embodiment of the present invention, in the reduction reaction, before the reaction starts, 2-(bromomethyl)naphthalene is present in the reaction system;

[0012] The molar ratio of the 2-(bromomethyl)naphthalene to the 2-(dibromomethyl)naphthalene is preferably 15-20, for example 17.4.

[0013] In one embodiment of the present invention, in the reduction reaction, before the reaction starts, only an organic base, a phosphite, 2-(dibromomethyl)naphthalene and a halogenated hydrocarbon solvent exist in the reaction system.

[0014] In one embodiment of the present invention, in the reduction reaction, the wavelength of the light is 395 nm or 450 nm.

[0015] In one embodiment of the present invention, in the reduction reaction, the wavelength of the light is 380-410 nm, preferably 390-400 nm, for example 395 nm.

[0016] In a certain embodiment of the present invention, in the reduction reaction, the power of the light is above 80W, preferably 80-120W, for example 100W.

[0017] In a certain embodiment of the present invention, in the reduction reaction, the light source brand of the illumination is Jiadeng; the light source of the illumination is preferably Jiadeng LS / E14 E27 e40 B22.

[0018] In one embodiment of the present invention, in the reduction reaction, each R 1 are independently C1-3 alkyl, such as isopropyl or ethyl.

[0019] In a certain embodiment of the present invention, in the reduction reaction, the organic base is N,N-diisopropylethylamine.

[0020] In a certain embodiment of the present invention, in the reduction reaction, the molar ratio of the organic base to the 2-(dibromomethyl)naphthalene is 1.5-15, such as 2.5 or 9.26.

[0021] In one embodiment of the present invention, in the reduction reaction, each R 2 and R 3 are independently C1-3 alkyl, such as ethyl.

[0022] In one embodiment of the present invention, in the reduction reaction, the phosphite is diethyl phosphite.

[0023] In one embodiment of the present invention, in the reduction reaction, the phosphite is .

[0024] In a certain embodiment of the present invention, in the reduction reaction, the molar ratio of the phosphite to the 2-(dibromomethyl)naphthalene is 0.25-2.5, such as 0.5 or 1.85.

[0025] In one embodiment of the present invention, in the reduction reaction, the halogenated hydrocarbon solvent is a C 1-6 Alkanes, such as C substituted with 1, 2 or 3 halogens selected from F, Cl and Br 1-3 Alkanes, further for example dichloromethane.

[0026] In one embodiment of the present invention, in the reduction reaction, the concentration of 2-(dibromomethyl)naphthalene in the halogenated hydrocarbon solvent is 0.005-0.4 mol / L, for example, 0.01 mol / L or 0.24 mol / L.

[0027] In a certain embodiment of the present invention, in the reduction reaction, the wavelength of the light is 395 nm; the organic base is N,N-diisopropylethylamine; the phosphite is diethyl phosphite; the halogenated hydrocarbon solvent is dichloromethane;

[0028] Preferably, the reduction reaction also satisfies one or more of the following conditions:

[0029] (1) The temperature of the reduction reaction is 39°C;

[0030] (2) The power of the illumination is 100W;

[0031] (3) the molar ratio of the phosphite to the 2-(dibromomethyl)naphthalene is 0.5;

[0032] (4) In the halogenated hydrocarbon solvent, the concentration of 2-(dibromomethyl)naphthalene is 0.24 mol / L.

[0033] In a certain embodiment of the present invention, the reduction reaction is carried out by any of the following methods:

[0034] Scheme 1: Dissolve an organic base, a phosphite, 2-(dibromomethyl)naphthalene and 2-(bromomethyl)naphthalene in dichloromethane, and react at 35-45°C in the presence of light until 2-(dibromomethyl)naphthalene disappears or no longer reacts;

[0035] The molar ratio of the 2-(bromomethyl)naphthalene to the 2-(dibromomethyl)naphthalene is preferably 15-20, such as 17.4;

[0036] Scheme 2: Dissolve the organic base, phosphite and 2-(dibromomethyl)naphthalene in dichloromethane and react at 35-45°C in the presence of light until 2-(dibromomethyl)naphthalene disappears or no longer reacts;

[0037] Preferably, the reduction reaction described in Scheme 2 also satisfies one or more of the following conditions:

[0038] (1) The temperature of the reduction reaction is 39°C;

[0039] (2) The power of the illumination is 100W;

[0040] (3) the molar ratio of the phosphite to the 2-(dibromomethyl)naphthalene is 0.5;

[0041] (4) In the halogenated hydrocarbon solvent, the concentration of 2-(dibromomethyl)naphthalene is 0.24 mol / L.

[0042] In one embodiment of the present invention, the progress of the reduction reaction is monitored by conventional detection methods in the art (e.g., HPLC), and the disappearance or no-reaction of one of the raw materials in the reaction solution is generally used as the reaction endpoint. The reaction time of the reduction reaction is preferably 6-20 h, such as 8 h or 12 h.

[0043] In one embodiment of the present invention, the temperature of the reduction reaction is 20-50°C, such as 25°C or 39°C.

[0044] In one embodiment of the present invention, the temperature of the reduction reaction is 30-50°C, preferably 35-45°C, for example 39°C.

[0045] In one embodiment of the present invention, the reduction reaction is carried out under air atmosphere.

[0046] In one embodiment of the present invention, the reduction reaction is carried out under normal pressure.

[0047] In a certain embodiment of the present invention, in the reduction reaction, the materials used only involve the materials mentioned in the specification, and do not involve other materials.

[0048] The present invention also provides a method for preparing 2-(bromomethyl)naphthalene, which comprises the following steps: in the presence of light, in a halogenated hydrocarbon solvent, dimethylnaphthalene and dibromohydantoin undergo bromination reaction to obtain 2-(bromomethyl)naphthalene;

[0049] ;

[0050] The power of the light is above 80W, and the wavelength of the light is 390-400nm.

[0051] In one embodiment of the present invention, in the bromination reaction, the wavelength of the light is 395 nm.

[0052] In one embodiment of the present invention, in the bromination reaction, the power of the light is 80-120W, for example, 100W.

[0053] In one embodiment of the present invention, the temperature of the bromination reaction is 20-40°C, for example 30°C.

[0054] In one embodiment of the present invention, in the bromination reaction, the light source brand of the illumination is Jiadeng; the light source of the illumination is preferably Jiadeng LS / E14 E27 e40 B22.

[0055] In one embodiment of the present invention, in the bromination reaction, the halogenated hydrocarbon solvent is a C 1-6 Alkanes, such as C substituted with 1, 2 or 3 halogens selected from F, Cl and Br 1-3 Alkanes, further for example dichloromethane.

[0056] In one embodiment of the present invention, in the bromination reaction, the molar volume ratio of the amount of dimethylnaphthalene added to the halogenated hydrocarbon solvent is 0.17-0.21 mol / L, for example 0.19 mol / L.

[0057] In one embodiment of the present invention, in the bromination reaction, the molar volume ratio of the amount of dibromohydantoin fed to the halogenated hydrocarbon solvent is 0.09-0.11 mol / L, preferably 0.10 mol / L.

[0058] In a certain embodiment of the present invention, in the bromination reaction, the molar ratio of the dibromohydantoin to the dimethylnaphthalene is 0.5-0.6, for example, 0.54.

[0059] In one embodiment of the present invention, the dibromohydantoin is added into the reaction system in multiple batches;

[0060] Preferably, the molar ratio of the amount of dimethylnaphthalene charged to the amount of the first batch of dibromohydantoin charged is 1:(0.25-0.45), for example 1:0.38.

[0061] In one embodiment of the present invention, the dibromohydantoin is added into the reaction system in two batches;

[0062] Preferably, when the dibromohydantoin is added to the reaction system in two batches, the molar ratio of the first batch of dibromohydantoin to the second batch of dibromohydantoin is (2-3):1, for example, 2.3:1 or 2.4:1;

[0063] Preferably, when the dibromohydantoin is added to the reaction system in two batches, the molar ratio of the amount of dimethylnaphthalene to the amount of the second batch of dibromohydantoin is 1:(0.1-0.2), for example, 1:0.16;

[0064] Preferably, when the dibromohydantoin is added to the reaction system in two batches, the second batch of dibromohydantoin is added in the form of a solution of dibromohydantoin dissolved in a halogenated hydrocarbon solvent; in the solution, the molar volume ratio of the feeding amount of the dibromohydantoin to the halogenated hydrocarbon solvent is 0.09-0.11 mol / L, for example 0.10 mol / L.

[0065] In one embodiment of the present invention, the halogenated hydrocarbon solvent is added to the reaction system in multiple batches;

[0066] Preferably, the molar volume ratio of the feeding amount of the dimethylnaphthalene to the first batch of halogenated hydrocarbon solvent is 0.05-0.29 mol / L, preferably 0.1-0.29 mol / L, more preferably 0.2-0.29 mol / L, further preferably 0.25-0.29 mol / L, for example 0.27 mol / L.

[0067] In one embodiment of the present invention, the halogenated hydrocarbon solvent is added to the reaction system in two batches;

[0068] Preferably, when the halogenated hydrocarbon solvent is added to the reaction system in two batches, the volume ratio of the first batch of halogenated hydrocarbon solvent to the second batch of halogenated hydrocarbon solvent is (2-3):1, for example 2.3:1.

[0069] In one embodiment of the present invention, the dibromohydantoin is added to the reaction in multiple batches, and the halogenated hydrocarbon solvent is added to the reaction in multiple batches;

[0070] The dimethylnaphthalene is first mixed with the first batch of dibromohydantoin and the first batch of halogenated hydrocarbon solvent for reaction; then the remaining dibromohydantoin and the remaining halogenated hydrocarbon solvent are added into the reaction system at once or in multiple times (preferably at once);

[0071] The molar volume ratio of the feeding amount of the dimethylnaphthalene to the first batch of halogenated hydrocarbon solvent is 0.05-0.29 mol / L, preferably 0.1-0.29 mol / L, more preferably 0.2-0.29 mol / L, further preferably 0.25-0.29 mol / L, for example 0.27 mol / L;

[0072] The molar ratio of the amount of dimethylnaphthalene to the amount of the first batch of dibromohydantoin is 1:(0.25-0.45), for example, 1:0.38;

[0073] Preferably, when the dibromohydantoin is added to the reaction system in two batches, the second batch of dibromohydantoin is added in the form of a solution of dibromohydantoin dissolved in a halogenated hydrocarbon solvent; in the solution, the molar volume ratio of the feeding amount of the dibromohydantoin to the halogenated hydrocarbon solvent is 0.09-0.11 mol / L, for example 0.10 mol / L.

[0074] In one embodiment of the present invention, the bromination reaction is carried out in a flow synthesis reactor; the flow synthesis reactor is preferably a tubular reactor, more preferably a tubular reactor equipped with a light irradiation mechanism;

[0075] The tubular reactor preferably meets one or more of the following conditions:

[0076] (1) The light source is the core, and the pipeline surrounds the light source;

[0077] (2) With spiral nozzle;

[0078] (3) Transparency.

[0079] In a certain embodiment of the present invention, the bromination reaction is carried out in a tubular reactor;

[0080] Preferably, the reaction liquid of the bromination reaction needs to pass through 1-5 sections (e.g., 2 sections) of tubular reactors to complete the bromination reaction;

[0081] The diameter of each tubular reactor is preferably 1.00-50 mm, such as 1.25 mm or 25 mm;

[0082] The length of each tubular reactor is preferably 8-16 m, for example 12 m;

[0083] In each tubular reactor, the flow rate of the reaction liquid is preferably 0.4-0.8 m / s, for example 0.6 m / s;

[0084] In each tubular reactor, the residence time of the reaction solution is preferably 10-40 s, such as 20 s.

[0085] In a certain embodiment of the present invention, the reaction time of the bromination reaction is 20-100 s, preferably 20-60 s, for example 40 s.

[0086] In one embodiment of the present invention, the bromination reaction is carried out under air atmosphere.

[0087] In one embodiment of the present invention, the bromination reaction is carried out under normal pressure or pressure.

[0088] In a certain embodiment of the present invention, in the bromination reaction, the materials used only involve the materials mentioned in the specification and do not involve other materials.

[0089] In a certain embodiment of the present invention, the bromination reaction is carried out by the following steps:

[0090] Step (1): in the presence of light, solution A is passed through a tubular reactor A to obtain solution B;

[0091] The solution A is a halogenated hydrocarbon solvent solution of dimethylnaphthalene and dibromohydantoin;

[0092] In the solution A, the concentration of dimethylnaphthalene is preferably 0.05-0.29 mol / L, more preferably 0.2-0.29 mol / L, further preferably 0.25-0.29 mol / L, for example 0.27 mol / L;

[0093] In the solution A, the concentration of dibromohydantoin is preferably 0.09-0.11 mol / L, for example 0.1 mol / L;

[0094] In the solution A, the molar ratio of dibromohydantoin to dimethylnaphthalene is preferably 0.36-0.40, such as 0.38;

[0095] In the tubular reactor A, the flow rate of solution A is preferably 0.4-0.8 m / s, for example 0.6 m / s;

[0096] The residence time of solution A in the tubular reactor A is preferably 10-40 s, for example 20 s;

[0097] In the tubular reactor A, the temperature of solution A is preferably 20-40°C, for example 30°C;

[0098] Step (2): mixing solution B and solution C to obtain solution D, and passing the solution D through tubular reactor B in the presence of light;

[0099] The solution C is a halogenated hydrocarbon solvent solution of dibromohydantoin;

[0100] In the solution C, the concentration of dibromohydantoin is preferably 0.09-0.11 mol / L, for example 0.1 mol / L;

[0101] The ratio of the amount of the substance containing dibromocaine in the solution C to the amount of the substance containing dimethylnaphthalene in the solution A is preferably 0.15-0.17, for example 0.16;

[0102] In the tubular reactor B, the flow rate of the solution D is preferably 0.4-0.8 m / s, for example 0.6 m / s;

[0103] The residence time of the solution D in the tubular reactor B is preferably 10-40 s, for example 20 s;

[0104] In the tubular reactor B, the temperature of the solution D is preferably 20-40°C, such as 30°C.

[0105] In one embodiment of the present invention, in step (1) and step (2), the wavelength of the light is independently 390-400 nm, for example, 395 nm.

[0106] In a certain embodiment of the present invention, in step (1) and step (2), the power of the illumination is independently 80 W or more, preferably 80-120 W, for example 100 W.

[0107] In a certain embodiment of the present invention, in step (1) and step (2), the brand of the light source for illumination is Jiadeng; the light source for illumination is preferably Jiadeng LS / E14 E27 e40 B22.

[0108] In one embodiment of the present invention, in step (1) and step (2), the halogenated hydrocarbon solvent is independently C substituted with one or more halogens. 1-6 Alkanes, such as C substituted with 1, 2 or 3 halogens selected from F, Cl and Br 1-3 Alkanes, further for example dichloromethane.

[0109] In one embodiment of the present invention, in step (1) and step (2), the tubular reactor A and the tubular reactor B are tubular reactors equipped with a light irradiation mechanism, which meet one or more of the following conditions:

[0110] (1) The light source is the core, and the pipeline surrounds the light source;

[0111] (2) Equipped with spiral nozzle;

[0112] (3) Transparency.

[0113] In a certain embodiment of the present invention, in the step (1) and the step (2), the diameters of the tubular reactor A and the tubular reactor B are independently preferably 1.00-50 mm, for example 1.25 mm or 25 mm;

[0114] The lengths of the tubular reactor A and the tubular reactor B are independently preferably 8-16 m, for example 12 m.

[0115] In one embodiment of the present invention, the volume ratio of the solution A to the solution C is 2.1-2.5, for example, 2.3 or 2.4.

[0116] In one embodiment of the present invention, in step (1), before solution A enters tubular reactor A, the following treatment is performed: solution A is thoroughly mixed;

[0117] The preferred operation of the thorough mixing is as follows: Solution A is passed through a spiral nozzle.

[0118] In one embodiment of the present invention, in step (2), before mixing solution B with solution C, solution B is treated as follows: filtering;

[0119] The filtration is preferably performed using a bag filter;

[0120] The filtration is preferably performed at 10-20°C (eg 15°C).

[0121] In one embodiment of the present invention, in step (2), before the solution D enters the tubular reactor B, the following treatment is performed: the solution D is fully mixed;

[0122] The preferred operation of the thorough mixing is as follows: solution D is passed through a spiral nozzle.

[0123] In a certain embodiment of the present invention, the bromination reaction is carried out by the following steps:

[0124] Dimethylnaphthalene and dibromohydantoin are dissolved in dichloromethane to obtain solution A, and solution A enters into tubular reactor A through a spiral nozzle to react under the presence of light;

[0125] After the reaction is completed, solution B is obtained, and solution B is filtered using a bag filter. Solution B is then mixed with solution C to obtain solution D. Solution D passes through a spiral nozzle and enters the tubular reactor B to react under the presence of light.

[0126] In one embodiment of the present invention, the method for preparing 2-(bromomethyl)naphthalene further comprises the following steps: in the presence of light, in the presence of an organic base and a phosphite, in a halogenated hydrocarbon solvent, 2-(dibromomethyl)naphthalene is subjected to a reduction reaction to obtain 2-(bromomethyl)naphthalene;

[0127]

[0128] The wavelength of the illumination is 350-500nm;

[0129] The organic base is N(R 1)3, each R 1 are independently C1-6 alkyl;

[0130] The phosphite is , R 2 and R 3 are independently C1-6 alkyl.

[0131] In one embodiment of the present invention, after the bromination reaction is completed, the reaction solution obtained from the bromination reaction is directly used for the reduction reaction without any treatment;

[0132] The reaction solution contains 2-(dibromomethyl)naphthalene and 2-(bromomethyl)naphthalene;

[0133] In the reaction solution, the molar ratio of the 2-(bromomethyl)naphthalene to the 2-(dibromomethyl)naphthalene is preferably 15-20, for example 17.4.

[0134] In one embodiment of the present invention, in the reduction reaction, before the reaction starts, 2-(bromomethyl)naphthalene is also present in the reaction system;

[0135] The molar ratio of the 2-(bromomethyl)naphthalene to the 2-(dibromomethyl)naphthalene is preferably 15-20, for example 17.4.

[0136] In one embodiment of the present invention, in the reduction reaction, before the reaction starts, only an organic base, a phosphite, 2-(dibromomethyl)naphthalene and a halogenated hydrocarbon solvent exist in the reaction system.

[0137] In one embodiment of the present invention, in the reduction reaction, the wavelength of the light is 395 nm or 450 nm.

[0138] In one embodiment of the present invention, in the reduction reaction, the wavelength of the light is 380-410 nm, preferably 390-400 nm, for example 395 nm.

[0139] In a certain embodiment of the present invention, in the reduction reaction, the power of the light is above 80W, for example 80-120W, and further for example 100W.

[0140] In a certain embodiment of the present invention, in the reduction reaction, the light source brand of the illumination is Jiadeng; the light source of the illumination is preferably Jiadeng LS / E14 E27 e40 B22.

[0141] In one embodiment of the present invention, in the reduction reaction, each R 1 are independently C1-3 alkyl, such as isopropyl or ethyl.

[0142] In a certain embodiment of the present invention, in the reduction reaction, the organic base is N,N-diisopropylethylamine.

[0143] In a certain embodiment of the present invention, in the reduction reaction, the molar ratio of the organic base to the 2-(dibromomethyl)naphthalene is 1.5-15, such as 2.5 or 9.26.

[0144] In one embodiment of the present invention, in the reduction reaction, each R 2 and R 3 are independently C1-3 alkyl, such as ethyl.

[0145] In one embodiment of the present invention, in the reduction reaction, the phosphite is .

[0146] In a certain embodiment of the present invention, in the reduction reaction, the molar ratio of the phosphite to the 2-(dibromomethyl)naphthalene is 0.25-2.5, such as 0.5 or 1.85.

[0147] In one embodiment of the present invention, in the reduction reaction, the halogenated hydrocarbon solvent is a C 1-6 Alkanes, such as C substituted with 1, 2 or 3 halogens selected from F, Cl and Br 1-3 Alkanes, further for example dichloromethane.

[0148] In one embodiment of the present invention, in the reduction reaction, the concentration of 2-(dibromomethyl)naphthalene in the halogenated hydrocarbon solvent is 0.005-0.4 mol / L, for example, 0.01 mol / L or 0.24 mol / L.

[0149] In a certain embodiment of the present invention, in the reduction reaction, the wavelength of the light is 395 nm; the organic base is N,N-diisopropylethylamine; the phosphite is diethyl phosphite; the halogenated hydrocarbon solvent is dichloromethane;

[0150] Preferably, the reduction reaction also satisfies one or more of the following conditions:

[0151] (1) The temperature of the reduction reaction is 39°C;

[0152] (2) The power of the illumination is 100W;

[0153] (3) the molar ratio of the phosphite to the 2-(dibromomethyl)naphthalene is 0.5;

[0154] (4) In the halogenated hydrocarbon solvent, the concentration of 2-(dibromomethyl)naphthalene is 0.24 mol / L.

[0155] In a certain embodiment of the present invention, the reduction reaction is carried out by any of the following methods:

[0156] Scheme 1: dissolving an organic base, a phosphite, 2-(dibromomethyl)naphthalene and 2-(bromomethyl)naphthalene in dichloromethane, and reacting at 35-45° C. in the presence of light until 2-(dibromomethyl)naphthalene disappears or no longer reacts; the molar ratio of the 2-(bromomethyl)naphthalene to the 2-(dibromomethyl)naphthalene is preferably 15-20, for example 17.4;

[0157] Scheme 2: Dissolve an organic base, a phosphite, and 2-(dibromomethyl)naphthalene in dichloromethane, and react at 35-45°C in the presence of light until 2-(dibromomethyl)naphthalene disappears or stops reacting.

[0158] In one embodiment of the present invention, the progress of the reduction reaction is monitored by conventional detection methods in the art (e.g., HPLC), and the disappearance or no-reaction of one of the raw materials in the reaction solution is generally used as the reaction endpoint. The reaction time of the reduction reaction is preferably 6-20 h, such as 8 h or 12 h.

[0159] In one embodiment of the present invention, the temperature of the reduction reaction is 20-50°C, such as 25°C or 39°C.

[0160] In one embodiment of the present invention, the temperature of the reduction reaction is 30-50°C, preferably 35-45°C, for example 39°C.

[0161] In one embodiment of the present invention, the reduction reaction is carried out under air atmosphere.

[0162] In one embodiment of the present invention, the reduction reaction is carried out under normal pressure.

[0163] In a certain embodiment of the present invention, in the reduction reaction, the materials used only involve the materials mentioned in the specification, and do not involve other materials.

[0164] Unless otherwise specified, the terms used in this invention may be defined as follows:

[0165] "Amount ratio of substances" refers to the numerical value of the ratio of the amount of a substance to the amount of another substance. For example, "the amount ratio of the dibromohydantoin to the dimethylnaphthalene is 0.52-0.56" means "the amount ratio of the dibromohydantoin to the dimethylnaphthalene is (0.52:1)-(0.56:1)"; the expressions such as "volume ratio" have similar rules and meanings to "amount ratio of substances" and will not be repeated here.

[0166] In the present invention, the "wavelength of light" refers to the wavelength of light emitted by the light source.

[0167] In the present invention, the "reaction time" of the bromination reaction refers to the time that the raw material mixture (i.e., the reaction solution obtained by mixing 2-methylnaphthalene, dibromohydantoin and a halogenated hydrocarbon solvent) stays in the photochemical reactor used in the present invention. In the case of using a flow synthesis reactor or the like as a photochemical reactor for a continuous reaction, the reaction time refers to the residence time of the raw material mixture under light irradiation.

[0168] A "flow synthesis reactor" is a device in which materials involved in a chemical reaction are continuously introduced into the reactor, while reaction products and other materials also continuously flow out of the reactor. A flow synthesis reactor usually uses a tubular reactor, and the size of the tube can be appropriately selected according to the production scale; the shape of the tube can be straight, curved or spiral, etc. A temperature regulating mechanism can be provided in the flow synthesis reactor. A "tubular reactor" is a type of "flow synthesis reactor".

[0169] In the "flow synthesis reactor" and "tubular reactor" used in the present invention, the material of the pipeline used for the reaction is not particularly limited, as long as it has excellent chemical resistance and can transmit light from the light source, such as glass or chemical-resistant transparent synthetic resin.

[0170] On the basis of being in accordance with the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0171] The reagents and raw materials used in the present invention are commercially available.

[0172] The positive progressive effect of the present invention is that the preparation method of 2-(bromomethyl)naphthalene provided by the present invention has one or more of the following advantages: high efficiency, high yield, simple synthesis steps, mild reaction conditions, low cost, environmental friendliness and suitability for large-scale production. DETAILED DESCRIPTION

[0173] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0174]

[0175] Tubular reaction conditions: tubular reactor pipe diameter: 1.25 mm; flow rate: 0.6 m / s; length: 12 m; residence time per reactor: 20 s; total reaction time: 40 s

[0176] Testing equipment:

[0177] 1. Instruments and Equipment

[0178] Gas Chromatograph: Agilent 7890 or equivalent GC system

[0179] Detector: flame ionization detector (FID);

[0180] Column: Agilent DB-1, 10m×0.18mm×0.18μm (Part No.: 121-1012)

[0181] 2 Main reagents and materials

[0182] Ethyl acetate (AR grade)

[0183] 3 Chromatographic conditions

[0184] Column temperature: 50℃(1min), 20℃ / min, 300℃(2min)

[0185] Vaporization temperature: 300℃

[0186] Detection temperature: 320℃

[0187] Injection volume: 1µL

[0188] Split ratio: 50:1

[0189] Column flow rate (N2): 1.0ml / min (constant flow)

[0190] Run time: 26 minutes

[0191] Tail blowing flow (N2): 30.0ml / min

[0192] Hydrogen flow rate (H2): 40.0 ml / min

[0193] Air flow rate (Air): 400.0 ml / min

[0194] Abbreviations used in this invention:

[0195]

[0196] Example 1

[0197] 8.55g (60mmol) of 2-methylnaphthalene (2MN) and 6.48g (22.68mmol) of dibromohydantoin (1,3-dibromo-5,5-dimethylhydantoin) were dissolved in 225ml of dichloromethane, passed through a transparent tubular reactor with a spiral nozzle, and induced the reaction at 30°C under 395nm wavelength light (20s). After the reaction, the remaining dibromohydantoin 2.78g (9.72mmol) and 97ml of dichloromethane solution were passed into the reaction solution after passing through a 15°C filter, and passed through a transparent tubular reactor with a spiral nozzle at 30°C, and further reacted for 20s under 395nm wavelength light. After the reaction, GC detection was performed, and the results were as follows:

[0198]

[0199] Example 2

[0200] 8.55 g (60 mmol) of 2-methylnaphthalene (2MN) and 6.48 g (22.68 mmol) of dibromohydantoin (1,3-dibromo-5,5-dimethylhydantoin) were dissolved in 225 ml of dichloromethane and passed through a transparent tubular reactor with a spiral nozzle. The reaction was initiated at 30°C under light of 395 nm (20 s). After the reaction was completed, the remaining dibromohydantoin (2.78 g (9.72 mmol)) and 97 ml of dichloromethane were passed through a 15°C filter. The solution was passed through a transparent tubular reactor with a spiral nozzle at 30°C, and further reacted for 20 seconds under light of 395nm wavelength. Then, 0.83g (6mmol) of diethyl phosphite and 3.87g (30mmol) of N,N-diisopropylethylamine (DIPEA) were added to the reaction solution, and stirred and refluxed at 39°C for 8h under light of 395nm to convert the dibromo impurity (2-(dibromomethyl)naphthalene, abbreviated as 2DBMN) into 2BMN (i.e. 2-(bromomethyl)naphthalene). After the reaction, GC detection was performed, and the results were as follows:

[0201]

[0202] The reaction formula of Example 2 is as follows:

[0203]

[0204] Example 3

[0205] 36 g (120 mml) of 2-(dibromomethyl)naphthalene (2DMN) was added into a reaction bottle, followed by 500 ml of dichloromethane, 8.3 g (60 mmol) of diethyl phosphite and 38.7 g (300 mmol) of DIPEA. The mixture was refluxed at 39°C for 12 h under 395 nm illumination to obtain 2-(bromomethyl)naphthalene (DMN). After the reaction, GC detection was performed and the yield was 83.2%.

[0206]

[0207] Example 4 Screening of bromination reaction conditions:

[0208] Based on Example 1, only the light source model was changed, and other reaction conditions and operations were the same as in Example 1. The results are as follows:

[0209]

[0210] As mentioned above, other reaction conditions and operations are the same as in Example 1, only the concentration of reactants is changed:

[0211]

[0212] The preparation methods reported in Examples 1 and 6 of the prior art CN116348440A use a large amount of solvent (more than twice that of the present application) and have low reaction efficiency (due to the low concentration of reactants, the amount of 2BMN produced per unit volume of reaction liquid is less; and the reaction time in CN116348440A is 25 minutes, while Example 1 of the present application only takes 40 seconds, which is only 2.7% of the reaction time of the prior art).

[0213] Example 5

[0214] Based on Example 3, only the reducing agent and LED lamp used were changed, and other reaction conditions and operations were the same as in Example 3. The results are as follows:

[0215]

[0217] Comparative Example 1

[0218] Process in JP200139904: 35 ml of cyclohexane and 8.55 g (60 mmol) of 2-methylnaphthalene are added to a four-necked flask, the temperature is raised to 65-75°C, 0.03 g (0.2 mmol) of azobisisobutyronitrile and 10.05 g (35 mmol) of dibromohydantoin are added, the temperature is kept at 85°C for 2 h, and the product is hydrolyzed with 48% sodium hydroxide to obtain NP167-A.

[0219] The process in CN116348440A is as follows: a mixed solution (2MN: 0.1 mol / L, NBS: 0.105 mol / L) obtained by dissolving 2MN and a halogenating agent NBS in DCM is supplied to a flow synthesis reactor with a jacket temperature maintained at 20°C under light irradiation of light source 1 (300-400 nm) in an air atmosphere for a reaction time of 25 min, and the mixture is circulated to react. At this time, a diaphragm pump is used to maintain the supply rate of the mixed solution at 24 ul / min, and the obtained reaction solution contains 2BMN (chemical purity 94.2%, selectivity 100%).

[0220]

Claims

1. A method for preparing 2-(bromomethyl)naphthalene, comprising the following steps: In the presence of light, in the presence of an organic base and a phosphite, in a halogenated hydrocarbon solvent, 2-(dibromomethyl)naphthalene undergoes a reduction reaction to obtain 2-(bromomethyl)naphthalene; ； The wavelength of the illumination is 350-500nm; The organic base is N(R 1 )3, each R 1 are independently C1-6 alkyl; The phosphite is , R 2 and R 3 are independently C1-6 alkyl.

2. The preparation method according to claim 1, characterized in that It meets one or more of the following conditions: (1) In the reduction reaction, 2-(bromomethyl)naphthalene is present in the reaction system before the reaction starts; (2) In the reduction reaction, before the reaction starts, only an organic base, a phosphite, 2-(dibromomethyl)naphthalene and a halogenated hydrocarbon solvent exist in the reaction system; (3) In the reduction reaction, the wavelength of the light is 395 nm or 450 nm; (4) During the reduction reaction, the power of the light is 80 W or more; (5) In the reduction reaction, each R 1 are independently C1-3 alkyl; (6) In the reduction reaction, the molar ratio of the organic base to the 2-(dibromomethyl)naphthalene is 1.5-15; (7) In the reduction reaction, each R 2 and R 3 are independently C1-3 alkyl; (8) In the reduction reaction, the molar ratio of the phosphite to the 2-(dibromomethyl)naphthalene is 0.25-2.5; (9) In the reduction reaction, the halogenated hydrocarbon solvent is a C 1-6 Alkanes; (10) In the reduction reaction, the concentration of 2-(dibromomethyl)naphthalene in the halogenated hydrocarbon solvent is 0.005-0.4 mol / L; (11) The temperature of the reduction reaction is 20-50°C.

3. The preparation method according to claim 2, characterized in that: It meets one or more of the following conditions: (1) In the reduction reaction, before the reaction starts, 2-(bromomethyl)naphthalene is still present in the reaction system; the molar ratio of the 2-(bromomethyl)naphthalene to the 2-(dibromomethyl)naphthalene is 15-20; (2) During the reduction reaction, the power of the illumination is 80-120 W; (3) In the reduction reaction, each R 1 is independently isopropyl or ethyl; (4) In the reduction reaction, the molar ratio of the organic base to the 2-(dibromomethyl)naphthalene is 2.5 or 9.26; (5) In the reduction reaction, each R 2 and R 3 are independently ethyl; (6) In the reduction reaction, the molar ratio of the phosphite to the 2-(dibromomethyl)naphthalene is 0.5 or 1.85; (7) In the reduction reaction, the halogenated hydrocarbon solvent is a C substituted with one, two or three halogens selected from F, Cl and Br. 1-3 Alkanes; (8) In the reduction reaction, the concentration of 2-(dibromomethyl)naphthalene in the halogenated hydrocarbon solvent is 0.01 mol / L or 0.24 mol / L; (9) The temperature of the reduction reaction is 25°C or 39°C.

4. The preparation method according to claim 3, characterized in that: It meets one or more of the following conditions: (1) In the reduction reaction, the organic base is N,N-diisopropylethylamine; (2) In the reduction reaction, the phosphite is diethyl phosphite; (3) In the reduction reaction, the halogenated hydrocarbon solvent is dichloromethane; (4) During the reduction reaction, the power of the light is 100W.

5. The preparation method according to claim 1, characterized in that: In the reduction reaction, the wavelength of the light is 395 nm; the organic base is N,N-diisopropylethylamine; the phosphite is diethyl phosphite; and the halogenated hydrocarbon solvent is dichloromethane.

6. The preparation method according to claim 5, characterized in that: It meets one or more of the following conditions: (1) The temperature of the reduction reaction is 39°C; (2) The power of the illumination is 100W; (3) the molar ratio of the phosphite to the 2-(dibromomethyl)naphthalene is 0.5; (4) In the halogenated hydrocarbon solvent, the concentration of 2-(dibromomethyl)naphthalene is 0.24 mol / L.

7. The preparation method according to claim 1, characterized in that: The reduction reaction is carried out by the following steps: dissolving an organic base, a phosphite, 2-(dibromomethyl)naphthalene and 2-(bromomethyl)naphthalene in dichloromethane, and reacting them at 35-45° C. in the presence of light until 2-(dibromomethyl)naphthalene disappears or no longer reacts.

8. The preparation method according to claim 7, characterized in that: The molar ratio of the 2-(bromomethyl)naphthalene to the 2-(dibromomethyl)naphthalene is 15-20.

9. The preparation method according to claim 1, characterized in that: The reduction reaction is carried out by the following steps: dissolving an organic base, a phosphite and 2-(dibromomethyl)naphthalene in dichloromethane, and reacting at 35-45° C. in the presence of light until 2-(dibromomethyl)naphthalene disappears or no longer reacts.

10. The preparation method according to claim 7, characterized in that: It meets one or more of the following conditions: (1) The temperature of the reduction reaction is 39°C; (2) The power of the illumination is 100W; (3) the molar ratio of the phosphite to the 2-(dibromomethyl)naphthalene is 0.5; (4) In the halogenated hydrocarbon solvent, the concentration of 2-(dibromomethyl)naphthalene is 0.24 mol / L.

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