阅读说明：本技术 用于在芳环上多种取代的烷基芳烃的α-H位卤化的工艺 (Process for alpha-H halogenation of alkyl aromatic hydrocarbons with various substitutions on the aromatic ring ) 是由 莉迪亚·维拉·乔凡纳·德卢卡 西尔维亚·加斯帕 安东尼奥·瓦伦托尼 加布里埃莱·穆拉斯 安德 于 2018-10-17 设计创作，主要内容包括：描述了一种工艺,该工艺允许在芳环或杂芳环上任选地进一步取代的烷基芳烃的α-H位的卤化。(A process is described which allows the halogenation of the alpha-H position of alkylaromatic hydrocarbons optionally further substituted on the aromatic or heteroaromatic ring.)

1. A process for the preparation of alkylaromatic hydrocarbons selectively halogenated at the carbon atom of an alkyl substituent bonded directly to an aromatic or heteroaromatic ring by reacting the corresponding non-halogenated alkylaromatic hydrocarbon compound exclusively with trichloroisocyanuric acid in the complete absence of solvents and any metal catalysts or chemical additives, in the presence of irradiation with visible light.

2. The process according to claim 1, wherein the alkylaromatic hydrocarbon is a compound consisting of an aromatic or heteroaromatic ring having at least one alkyl chain as a substituent.

3. The process according to claims 1 and 2, wherein the aromatic or heteroaromatic ring is selected from: benzene, pyridine, quinoline, isoquinoline, and alkyl is a straight or branched chain alkyl having from 1 to 5 carbon atoms.

4. A process according to any one of claims 1 to 3, wherein the aromatic or heteroaromatic ring is further substituted by one or more substituents selected from: CH (CH)₃、C(CH₃)₃、Cl、CN、NO₂F, phenyl.

5. The process of any one of claims 1-4, wherein the starting materials: the alkylaromatic hydrocarbon/trichloroisocyanuric acid is in a stoichiometric ratio of between 4:2 and 2:0.5, preferably 3: 1.

6. The process according to any one of claims 1-5, wherein the starting materials are reacted at a temperature between 20 ℃ and 35 ℃ and under an inert atmosphere under solar irradiation for a time between 5 minutes and 12 hours.

7. The process of claim 6, wherein the irradiation is performed with a solar simulator or a tungsten lamp or a blue light emitting diode, or by simply exposing the reaction reactor to sunlight.

8. The process of any one of claims 1-7, wherein the final product is isolated via filtration through a silica pad.

9. The process according to any one of claims 1-8, wherein the alkylaromatic hydrocarbon is toluene and the product obtained is benzyl chloride.

10. The process according to any one of claims 1-9, wherein the following final product is obtained:

Technical Field

The present invention relates to the field of processes for the synthesis of chemical products, in particular to processes for the halogenation of the alpha-H position of alkylaromatic hydrocarbons (alkylacenes) optionally variously substituted on the aromatic ring.

Prior Art

As is known, alkylaromatics halogenated in the alkyl chain, such as, for example, benzyl chloride, are important intermediates in Industrial preparation, for example for the preparation of amphetamine-based pharmaceuticals, synthetic resins, dyes, fuel additives and photographic developing solutions (Ullmann's Encyclopedia of Industrial Chemistry, Weinheim: Wiley-VCH,2005, https:// doi.org/10.1002% 2F14356007.a 06-233. pub 2).

In particular, the industrial production of benzyl chloride is based on two main processes.

The first method (see scheme 1(a)) is the thermal or photochemical chlorination of toluene with chlorine gas in both batch and continuous reactors, wherein the hydrogen atoms are replaced by chlorine atoms. The chlorination of toluene is carried out by a series of reactions in which benzyl chloride is produced along with benzyl dichloride and benzyl trichloride byproducts (classified as hazardous materials according to TSCA) as well as ortho-, meta-and para-chlorotoluenes derived from chlorination by aromatic rings of alkyl chloride products.

A second method used industrially (see scheme 1(b)) is the Chloromethylation of Benzene (Gustave louis blanc bulb. soc. chim. france 1923,33,313, Whitmore, FC, Ginsburg, Abram, Rueggeberg, Walter, Tharp, i., Nottorf, h., cannonon, m., Carnahan, f., Cryder, D, FLeming, g., Goldberg, g., Haggard, h., her, c., Hoover, t., Lovell, h., Mraz, r, Noll, c., oaklo, ott, Patterson, h., Van, r., Walter, r., Zook, h., tzerk, h., tiger, waisberk, waisberlo, willogeny, berlogenk, berloklo, klo, berloklo, berlo, berloklo, berlo, berloklo, p.

Scheme 1

These methods are due to the use of corrosive gaseous reagents (HCl, Cl) which are difficult to handle₂) The reactor complexity due to the use of gaseous components, the harsh reaction conditions are greatly limited and have very low yields and conversions of the desired product (about 40%).

Furthermore, several examples of chlorination of methyl groups have been reported in the literature, these examples envisaging the use of compounds such as Cl₂、SO₂Cl₂、NaOCl、tBuOCl、Et₄NCl chlorinating agent, but in these cases the reaction conditions, yield and conversion are also unsatisfactory.

In particular, in s.h. combe, a.hosseini, a.parra, p.r.schereiner, j.org.chem.2017,82, 2407-.

Scheme 2

However, this method does not have an optimal stoichiometric ratio of reagents and involves the use of a metal catalyst (Cu (OAc)₂) Radical initiator (CBr)₄) Additive (NHPI, N-hydroxyphthalimide) and dichloromethane as solvent. The reaction provided the product in 58% yield and provided incomplete conversion.

In view of the above, it is clearly of scientific and industrial interest to develop a green process that occurs in high yield and high conversion for the chlorination of the methyl groups of toluene and, in general, of alkyl aromatic hydrocarbons optionally substituted on the aromatic ring.

Summary of The Invention

A process is described which allows the halogenation of the alpha-H position of alkylaromatic hydrocarbons, optionally further substituted on the aromatic or heteroaromatic ring, by reaction of the corresponding non-halogenated alkylaromatic hydrocarbons exclusively with trichloroisocyanuric acid under irradiation with visible light.

Detailed Description

The present process enables to overcome the above mentioned problems by allowing to obtain alkylaromatics selectively halogenated on the carbon atom of the alkyl substituent directly bonded to the aromatic or heteroaromatic ring by exclusively using the corresponding non-halogenated alkylaromatics and trichloroisocyanuric acid in case of irradiation with visible light.

In other words, the object of the present invention is a process for producing alkylaromatics selectively halogenated on the carbon atom of an alkyl substituent directly bonded to an aromatic or heteroaromatic ring, said process comprising contacting the corresponding non-halogenated alkylaromatic exclusively with the acid trichloroisocyanuric acid, in the complete absence of a solvent and any metal catalyst or chemical additive, under irradiation with visible light.

According to the invention, alkylaromatic hydrocarbons mean compounds consisting of an aromatic or heteroaromatic ring having at least one alkyl chain as substituent.

The aromatic ring may be, for example: benzene, pyridine, quinoline, isoquinoline, pyrrole.

Alkyl means a straight or branched chain alkyl group having from 1 to 5 carbon atoms. As mentioned, in addition to the alkyl chains described above, the aromatic rings may be further substituted, for example, by: CH (CH)₃、C(CH₃)₃、Cl、CN、NO₂F, phenyl.

Hereinafter, the halogenation of toluene according to scheme 3 reported below is described in detail.

Scheme 3

According to the invention, the starting materials toluene and trichloroisocyanuric acid are in a stoichiometric ratio of between 4:2 and 2:0.5, preferably 3: 1.

The process is carried out simply by mixing the reagents in a reactor and exposing the mixture to irradiation at room temperature with stirring; the benzyl chloride was then collected by filtration.

The reaction time is generally between 5 minutes and 12 hours, and the reaction is preferably carried out at room temperature, generally between 20 ℃ and 35 ℃, and under an inert atmosphere (e.g., under argon).

Irradiation may be performed with a solar simulator (solar simulator), or may be performed simply by exposing the reaction reactor to sunlight, which obviously must be made of a material that is transparent to sunlight (e.g. transparent colourless glass). Irradiation may also be achieved by using an artificial light source such as a tungsten lamp or a blue light emitting diode.

The reaction takes place in the complete absence of solvent and any metal catalyst or chemical additive.

The reaction product was easily isolated by simple filtration over a pad of silica, which allowed easy removal of the isocyanuric acid formed as a result of the reaction and benzyl dichloride formed in very small amounts (18%) (the only by-product of the reaction, since no by-product derived from chlorination of the benzene ring was formed).

Furthermore, the conversion of toluene is almost quantitative (94%, in this case the highest conversion up to now is also achieved). When the reaction is performed using an artificial light source such as a tungsten lamp or a blue light emitting diode, benzyl chloride is obtained in yields of 70% and 71%, respectively.

Examples

3.6mmol (0.3318g) of toluene were placed in a 25mL two-necked flask equipped with a magnetic stirrer under an argon atmosphere; then, 1.2mmol (0.279g) of trichloroisocyanuric acid was added.

The flask was placed on a shaker and placed under a solar simulator at room temperature (25 ℃) for 8 h.

The reaction was monitored by Thin Layer Chromatography (TLC) and NMR analysis, and finally, when the toluene concentration was below 6%, the product was purified by passing through a silica pad.

Characterization of benzyl chloride obtained by Nuclear Magnetic Resonance (NMR) spectroscopy is reported below:

a colorless oil; (0.346g, 76% yield).

¹H NMR(400MHz,CDCl₃):7.48-7.29(m,5H),4.61(s,2H)。

¹³C NMR(100MHz,CDCl₃):137.5,128.7,128.5,128.4,46.2。

The obtained spectral data are consistent with those reported in The literature (S.H. Comme, A.Hosseini, A.Parra, P.R. Schreiner, The Journal of Organic Chemistry 2017,82, 2407-.

Proceeding in a similar manner starting from the corresponding alkylaromatic compound optionally further substituted on the aromatic (or heteroaromatic) ring, the following reported products are obtained in similar yields and purities:

thus, the present process is configured as a green, solvent-free process with very high yields and conversions and with a very simple product isolation procedure (filtration through a silica pad). Thus, the present process allows to avoid the use of any solvent, to avoid the use of harsh reaction conditions, the atom economy of the process is very high, and the yields and conversions are optimal.