JP7158717B2 - Electrophilic azidating or diazotizing agents - Google Patents

Description

The present invention relates to electrophilic azidating or diazotizing agents, and in particular to azidoimidazolium derivatives.

Azide chemistry began about 150 years ago, has been the subject of much research, and in recent years has been revived in medicine, biology, and materials science. For example, organic azides (R—N ₃ ) have been used as primary amine equivalents for a long time. It was discovered and has become an indispensable compound in the fields of chemical biology and materials. This Click cyclization can reliably bind two different units at the molecular level, and is used, for example, for binding substrates and labels when searching for the active site of proteins, and for reliable extension reactions in polymer synthesis. .

In addition, many organic azides and azidating agents are explosive, and there is a demand for the development of a safe and simple method for synthesizing azide compounds that can be used even by researchers unfamiliar with synthetic chemistry. Currently, azide compounds have a commercial production volume of only 1000 t/a over the past 30 to 40 years, except for the production of explosives. In particular, organic azides are expected to be used for photolabeling, and there is a great demand for synthetic methods and reagent development for arylazides having an azide group in the aromatic ring that serves as the core of functional materials such as organic semiconductors and solar cells. expensive.

By the way, organic azides are generally synthesized by a nucleophilic method in which an organic halide (R-X, X: halogen; R ⁺ equivalent) is reacted with an azide ion (N ₃ ⁻ ). could not be synthesized. On the other hand, if there is an inverse combination, that is, an electrophilic technique of reacting an azide cation (N ₃ ⁺ ) with a carbon nucleophile (R ⁻ ), it is expected that arylazides can be easily synthesized. With few practical synthetic methods available, the development of safe reagents for the electrophilic azidation of aromatic compounds is highly desirable.

The present inventors discovered a non-explosive and safe reactant 2-azido-1,3-dimethylimidazolinium hexafluorophosphate for introducing a diazo group (=N ₂ ) into a nucleophilic compound (nucleophilic agent). (ADMP) (see Non-Patent Document 1). Conventionally, diazo transfer agents were exclusively sulfonyl azide (RSO ₂ N ₃ ), whereas ADMP is a reactant with a novel structure, and most conventional diazotization agents such as naphthols and amines with low nucleophilicity have been used. It is possible to diazotize compounds that could not be obtained. ADMP is also characterized by being an easy-to-handle solid and is non-explosive. Until now, highly reactive diazotization agents were highly explosive and were not commercially available. , has been marketed by more than 20 companies worldwide.

M. Kitamura et al., Eur. J. Org. Chem. 2011, 458.

An object of the present invention is to provide a novel non-explosive and safe electrophilic azidating agent capable of electrophilically aziding a nucleophilic compound. Another object of the present invention is to provide a novel non-explosive and safe electrophilic diazotizing agent capable of electrophilically diazotizing a nucleophilic compound.

As a result of research to solve the above problems, the present inventors have found that, in consideration of the selection of a counter anion and the stability of by-products eliminated during the azidation reaction or diazotization reaction, an azidating agent or The inventors have found that by designing a diazotization agent, it is possible to control the azide reaction or diazotization reaction of a nucleophilic compound, and have completed the present invention.

That is, the present invention is as follows.
<1> An azidoimidazolium derivative characterized by being represented by the following formula [1].

（式中、Ｒ及びＲ’は、それぞれ有機基を示し、Ｘ^－は、対アニオンを示す。）

(In the formula, R and R' each represent an organic group, and X ^- represents a counter anion.)

（式中、Ｒ^１～Ｒ^４は、それぞれアルキル基、アリール基、アラルキル基を示し、Ｒ^５及びＲ^６は、それぞれ水素原子、アルキル基、アルコキシ基、ハロゲン原子又はニトロ基を示す。） <2> The azidoimidazolium derivative according to <1>, wherein each of R and R' is an aryl group.
<3> The azidoimidazolium derivative according to <1> or <2>, characterized by being represented by the following formula [1A].

(In the formula, R ¹ to R ⁴ each represent an alkyl group, an aryl group, or an aralkyl group, and R ⁵ and R ⁶ each represent a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, or a nitro group.)

（式中、ｉＰｒは、イソプロピル基を示し、Ｒ^５及びＲ^６は、それぞれ水素原子、炭素数１～４のアルキル基、炭素数１～４のアルコキシ基、ハロゲン原子又はニトロ基を示す。） <4> The azidoimidazolium according to any one of <1> to <3>, wherein X ^- is one selected from PF ₆ ^- , BF ₄ ^- , CF ₃ SO ₃ ^- and Cl ^- derivative.
<5> The azidoimidazolium derivative according to any one of <1> to <4>, characterized by being represented by the following formula [1B].

(In the formula, iPr represents an isopropyl group, and R ⁵ and R ⁶ each represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a halogen atom or a nitro group.)

<6> The azidoimidazolium derivative according to any one of <3> to <5>, wherein R ⁵ and R ⁶ are hydrogen atoms.
<7> The azidoimidazolium derivative according to any one of <1> to <6>, which is an azidating agent used for aziding a nucleophilic compound.
<8> The azidoimidazolium derivative according to any one of <1> to <6>, which is a diazotizing agent used for diazotizing a nucleophilic compound.
<9> The azidoimidazolium derivative according to <7> or <8>, wherein the nucleophilic compound is an aromatic compound.

（式中、Ｒ及びＲ’は、それぞれ有機基を示し、Ｘ^－は、PF₆ ^－、BF₄ ^－、又はCF₃SO₃ ^－を示す。）
〈１１〉Ｒ及びＲ’が、それぞれアリール基であることを特徴とする〈１０〉記載のイミダゾリウム誘導体。 <10> An imidazolium derivative represented by the following formula [2].

(In the formula, R and R' each represent an organic group, ^and X- represents PF ₆ ^- , BF ₄ ^- , or CF ₃ SO ₃ ^- .)
<11> The imidazolium derivative according to <10>, wherein each of R and R' is an aryl group.

（式中、Ｒ^１～Ｒ^４は、それぞれアルキル基、アリール基、アラルキル基を示し、Ｒ^５及びＲ^６は、それぞれ水素原子、アルキル基、アルコキシ基、ハロゲン原子又はニトロ基を示す。） <12> The imidazolium derivative according to <10> or <11>, characterized by being represented by the following formula [2A].

(In the formula, R ¹ to R ⁴ each represent an alkyl group, an aryl group, or an aralkyl group, and R ⁵ and R ⁶ each represent a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, or a nitro group.)

（式中、ｉＰｒは、イソプロピル基を示し、Ｒ^５及びＲ^６は、それぞれ水素原子、炭素数１～４のアルキル基、炭素数１～４のアルコキシ基、ハロゲン原子又はニトロ基を示す。） <13> The imidazolium derivative according to any one of <10> to <12>, which is represented by the following formula [2B].

(In the formula, iPr represents an isopropyl group, and R ⁵ and R ⁶ each represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a halogen atom or a nitro group.)

<14> The imidazolium derivative according to any one of < ¹² > or < ¹³ >, wherein R5 and R6 are hydrogen atoms.

The azidoimidazolium derivatives of the present invention are novel non-explosive and safe electrophilic azidating agents capable of electrophilically aziding nucleophilic compounds. Since the azidating agent of the present invention has an electrophilic reaction mechanism that has never been seen before, it is possible to synthesize an arylazide having an aromatic azide group.
In addition, the azidoimidazolium derivative of the present invention is a novel non-explosive and safe electrophilic diazotizing agent, and can electrophilically diazotize a nucleophilic compound.

The azidoimidazolium derivative of the present invention is characterized by being represented by the following formula [1].

Here, in formula [1], R and R' each represent an organic group and may be the same or different. Also, X ^- represents a counter anion.

Examples of organic groups represented by R and R' include aliphatic groups and aromatic groups.
The aliphatic group may be linear, branched or cyclic, and may be saturated or unsaturated. Aliphatic groups can also be interrupted by heteroatoms (a heteroatom can be present between carbon linkages). The number of carbon atoms is preferably about 1 to 10, more preferably about 1 to 4.

The aromatic group may be a group containing an aromatic ring or a group containing a heterocyclic ring. The number of carbon atoms is preferably about 3-14, more preferably about 4-10.

The aliphatic group and aromatic group may have a substituent, and examples of the substituent include an alkyl group, an alkoxy group, an aryl group, an aralkyl group, a halogen atom, and a nitro group.

Among these, R and R' are preferably substituted or unsubstituted aryl groups, and particularly preferably substituted aryl groups.
Specifically, an azidoimidazolium derivative represented by the following formula [1A] can be mentioned.

Here, in formula [1A], R ¹ to R ⁴ each represent an alkyl group, an aryl group, or an aralkyl group, and may be the same or different. Examples of alkyl groups include alkyl groups having 1 to 10 carbon atoms. Examples of aryl groups include aryl groups having 6 to 10 carbon atoms. Examples of aralkyl groups include groups in which these groups are combined. R ¹ to R ⁴ are particularly preferably isopropyl groups (iPr).

In formula [1A], R ⁵ and R ⁶ each represent a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom or a nitro group, and R ⁵ and R ⁶ may be the same or different. may The alkyl group preferably has about 1 to 4 carbon atoms, and examples thereof include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl groups. can be exemplified. As the alkoxy group, those having about 1 to 4 carbon atoms are preferable, and examples thereof include the alkoxy groups having the aforementioned alkyl groups. A fluorine atom, a chlorine atom, a bromine atom, and an iodine atom can be illustrated as a halogen atom. Among these, R ⁵ and R ⁶ are preferably a hydrogen atom, an isopropyl group, an iodine atom and a nitro group, and particularly preferably a hydrogen atom. We have actually prepared azidoimidazolium derivatives of these preferred substituents.

Counter anions for X ⁻ in formula [1] include PF ₆ ⁻ , BF ₄ ⁻ , CF ₃ COO ⁻ , CF ₃ SO ₃ ⁻ , CH ₃ SO ₃ ⁻ , CH ₃ BF ₃ ⁻ , Cl ⁻ , Br ⁻ , I ⁻ , NO ₃ ⁻ and the like can be mentioned. Among these, PF ₆ ^- , BF ₄ ^- , CF ₃ SO ₃ ^- and Cl ^- are preferred, and PF ₆ ^- and BF ₄ ^- are particularly preferred in terms of safety and reactivity.

As the azidoimidazolium derivative of the present invention, an azidoimidazolium derivative represented by the following structural formula is particularly preferable.

The azidoimidazolium derivative of the present invention is non-explosive and safe, and can be used as an azidation agent for azidation of nucleophilic compounds. Azidation by this azidating agent has an electrophilic reaction mechanism that has never been seen before, so it is possible to synthesize an arylazide having an azide group in an aromatic group. Further, the azidoimidazolium derivative of the present invention is expected to be utilized in chemical biology and material fields in addition to the field of synthesis. For example, the azidoimidazolium derivative of the present invention can be used to synthesize a functional material having an aromatic base nucleus. It can be used for marking.

Similarly, the azidoimidazolium derivative of the present invention is non-explosive and safe, and can be used as a diazotizing agent for diazotizing nucleophilic compounds.

A second imidazolium derivative of the present invention is characterized by being represented by the following formula [2]. Using the imidazolium derivative represented by the formula [2], the azidoimidazolium derivative of the present invention represented by the above formula [1] can be produced.

In formula [2], R and R' each represent an organic group and may be the same or different. X- represents PF ₆ ^- , BF ₄ ^{- or} CF ₃ SO ₃ ^- .
R and R' in formula [2] have the same meanings as in formula [1].

The method for producing the azidoimidazolium derivative represented by the formula [1] will be described below by taking the azidoimidazolium derivative represented by the following formula [1B] as an example.

First, an imidazolium derivative represented by the following formula [3B] is reacted with a hexafluorophosphate to produce an imidazolium derivative represented by the formula [2B].

The compound represented by formula [3B] can be obtained by the method described in "P. tang, W. Wang, T. Ritter, J. Am. Chem. Soc., 2011, 133(30), 11482-11484". can be synthesized by

Specifically, the imidazolium derivative represented by the formula [2B] can be obtained, for example, by mixing a solution containing the imidazolium derivative represented by the formula [3B] and a solution containing a hexafluorophosphate, and It can be obtained by reacting at a temperature below the boiling point, preferably between room temperature and the boiling point of the solvent, followed by separation and purification. Here, examples of the hexafluorophosphate include lithium hexafluorophosphate, sodium hexafluorophosphate, potassium hexafluorophosphate, magnesium hexafluorophosphate, etc., which are easily available and can be compared. Potassium hexafluorophosphate is preferred because it is inexpensive. Ammonium hexafluorophosphate (PF ₆ ⁻ [NR ₄ ] ⁺ , R: alkyl group or aryl group) can also be used _. ⁻ [N(C ₄ H ₉ ) ₄ ] ⁺ ) is preferred.
Moreover, organic solvents, such as alcohol, acetonitrile, acetone, tetrahydrofuran, and dimethylformamide, can be used as a solvent.

Subsequently, the imidazolium derivative represented by the formula [2B] is reacted with an azide salt to produce the azidoimidazolium derivative represented by the formula [1B].

Specifically, the azidoimidazolium derivative represented by the formula [1B] can be obtained, for example, by adding an azide salt to a solution containing the imidazolium derivative represented by the formula [2], preferably at a temperature below the boiling point of the solvent. can be obtained by reacting at a temperature between room temperature and the boiling point of the solvent, followed by separation and purification. Examples of the azide salt include lithium azide, sodium azide, and potassium azide, and sodium azide is preferred from the viewpoint of easy availability and low cost. As the solvent, alcohols such as methanol, ethanol, 2-propanol, tert-butanol, ethylene glycol and 2-methoxyethanol, and organic solvents such as acetonitrile, acetone, tetrahydrofuran and dimethylformamide can be used, with acetonitrile being preferred. .

Next, azidation of a nucleophilic compound using the azidoimidazolium derivative of the present invention represented by formula [1] as an azidating agent will be described.

Here, examples of the nucleophilic compound that can be used in the present invention include monosubstituted phenols, disubstituted phenols, naphthols, ketones, and the like. The azidating agent of the present invention is particularly characterized in that it is possible to synthesize an arylazide (phenolazide) having an azide group on an aromatic ring, which has been difficult to synthesize conventionally.

As a nucleophilic compound, specifically, a compound represented by the following formula [4] can be used.

In formula [4], ^R7 and R8, which may be the ^same or different, represent a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an aldehyde group, or a carboxylic acid ester group. The number of carbon atoms in the ester portion of an alkyl group, an alkoxy group, or a carboxylic acid ester group is preferably about 1 to 4.

Specifically, for example, to a solution containing a base, a nucleophilic compound, and the azidation agent of the present invention, an azide salt as a reaction accelerator is added as necessary, and the temperature is below the boiling point of the solvent, preferably It can be obtained by reacting at a temperature between room temperature and the boiling point of the solvent, followed by separation and purification. Here, as the azide salt, those used for synthesizing the azidoimidazolium derivative represented by the formula [1] can be used, and sodium azide is preferable from the viewpoint of availability and low cost. As the solvent, similarly, those used in the synthesis of the azidoimidazolium derivative represented by the formula [1] can be used. , 2-methoxyethanol is preferred, and 2-methoxyethanol is particularly preferred. In this reaction, the azide salt as a reaction accelerator is preferably added in an amount of 0.1 to 2.0 equivalents relative to the nucleophilic compound, and addition of about 0.5 to 1.5 equivalents Even if there is, the reaction can be sufficiently accelerated. The base is not particularly limited as long as it is a substance commonly used as a base, and examples thereof include diisopropylamine, diethylamine, lithium diisopropylamide, and the like.

The present inventors consider the following reaction mechanism for azidation using the azidating agent of the present invention.

A nucleophilic compound (nucleophilic agent: Nu ⁻ ) attacks the azide terminal of the azidoimidazolinium derivative of the present invention (the azidation agent of the present invention) having a structure having a double bond in the five-membered ring to form an intermediate formation and elimination of the N-heterocyclic carbene (NHC) results in electrophilic azidation. Heterocyclic carbenes are generally a stable class of compounds, but NHCs having double bonds in their five-membered rings in particular have aromatic properties and are very stable. That is, it is considered that the reaction can be controlled by controlling the stability of the desorbed by-product.

Next, diazotization of a nucleophilic compound using the azidoimidazolium derivative of the present invention represented by formula [1] as a diazotizing agent will be described.
The diazotization reaction is basically the same as the above-mentioned azide reaction, but the diazotization reaction is realized by not adding an azide salt such as sodium azide from the outside.

The present invention will be described below using specific examples, but the scope of the present invention is not limited to these examples.

As shown below, an azidoimidazolium derivative represented by formula [1] was produced using an imidazolium derivative represented by formula [3] as a starting material.

<Synthesis of imidazolium derivative represented by formula [3]>
The imidazolium derivative represented by formula [3] is prepared according to the method described in "P. tang, W. Wang, T. Ritter, J. Am. Chem. Soc., 2011, 133(30), 11482-11484". Synthesized.

<Synthesis of imidazolium derivative represented by formula [2]>
The imidazolium derivative represented by formula [2] was synthesized as follows.
KPF ₆ (3.91 g, 21.3 g, 21.3 mmol) in acetonitrile (5 mL) was added and the solution was stirred at room temperature for 1 hour. After adding water (20 mL) to the reaction solution, the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. After removing the anhydrous sodium sulfate by filtration, the solvent was distilled off under reduced pressure to obtain a solid. The solid was dried in vacuo to give N,N'-1,3-bis(2,6-diisopropylphenyl)-2-chloroimidazolium hexafluorophosphate [2] as a white solid (11.4 g, 95%).

(Physical data of imidazolium derivative represented by formula [2])
¹ H NMR (CDCl ₃ , 400MHz) δ 7.93 (s, 2H), 7.66 (t, J = 7.9 Hz, 2H), 7.42 (d, J = 7.8 Hz, 4H), 2.32 (sep, J = 6.8 Hz, 4H), 1.29 (d, J = 6.8 Hz, 12H), 1.22 (d, J = 6.8 Hz, 12H).
^13C NMR ( _CDCl3 , 126 MHz) δ 145.07, 133.63, 133.04, 128.27, 126.99, 125.37, 29.36, 24.02, 23.43.
IR (ATR) 3649, 3165, 2961, 1629, 1549, 1496, 1458, 1324, 1217, 1060, 831, 755 cm ^-1
Anal. Found: C, _56.87 ; H, 6.26; N, 4.94%. _Calcd for _{C27H36ClF6N2P} : _C , 56.99; H, 6.38;

<Synthesis of azidoimidazolium derivative represented by formula [1]>
The azidoimidazolium derivative represented by formula [1] was synthesized as follows.
NaN ₃ ( 1.24 g, 19.1 mmol) was added and stirred at room temperature for 40 hours. After removing the solid by filtration through celite, the filtrate was distilled off under reduced pressure to precipitate a solid. After dissolving the solid in acetonitrile, diethyl ether was added to the solution to precipitate crystals. The resulting solid was collected by filtration and dried under reduced pressure to obtain N,N'-1,3-bis(2,6-diisopropylphenyl)-2-azidoimidazolium hexafluorophosphate [1] as a white solid. (9.49 g, 86%).

(Physical data of azidoimidazolium derivative represented by formula [1])
¹ H NMR (CDCl ₃ , 400MHz) δ 7.67 (t, J = 7.8 Hz, 2H), 7.66 (s, 2H), 7.40 (d, J = 7.8 Hz, 4H), 2.48 (sep, J = 6.8 Hz, 4H), 1.32 (d, J = 6.8 Hz, 12H), 1.25 (d, J = 6.8 Hz, 12H).
^13C NMR ( _CDCl3 , 126 MHz) δ 145.88, 137.28, 133.34, 126.85, 125.15, 123.59, 29.26, 23.83, 23.52
IR (ATR) 2964, 2928, 2158, 1588, 1560, 1528, 1501, 1458, 1389, 1328, 1240, 1132, 1057, 912, 836, 727, 698 cm ^-1
Anal. Found: C, _56.42 ; H, 6.12; N, 12.46%. Calculated for _C27H36F6N5P : C, _56.34 ; H, _6.30 ;

For the purpose of changing the counter anion, in the same manner as in Example 1, an imidazolium derivative represented by formula [3] was used as a starting material to produce an azidoimidazolium derivative represented by formula [1].

Table 1 below shows the conditions in each reaction of the above reaction formula and the yield of the obtained compound.

Using the azidoimidazolium derivative of the present invention represented by the formula [1] produced in Example 1 (the azidating agent of the present invention), in the compound of the formula [4] shown below, R ⁷ and R 2,4-dimethylphenol, where ⁸ is _CH3 , was azidated to synthesize 2-azido-4,6-dimethylphenol.

Specifically, the azidating agent of the present invention (516 mg, 0.90 mmol) was added and stirred at room temperature for 30 minutes. After NaN ₃ (48.8 mg, 0.75 mmol) was added to the reaction solution, it was further stirred for 4 hours. After water was added to the reaction solution, organic matter was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, ethyl acetate was distilled off under reduced pressure to obtain a crude product. The resulting crude product was purified by silica gel chromatography (hexane:ethyl acetate) to give 2-azido-4,6-dimethylphenol (107 mg, 0.66 mmol) in 88% yield.

(Physical data of 2-azido-4,6-dimethylphenol)
¹ H NMR (CDCl ₃ , 400 MHz) δ 6.73 (s, 2H), 5.16(s, 1H), 2.26(s, 3H), 2.20 (s, 3H).
^13C NMR ( _CDCl3 , 126 MHz) δ 143.10, 129.85, 128.09, 125.00, 124.9, 115.83, 20.56, 15.51.
IR(ATR) 3415, 3025, 2921, 2119, 1614, 1498, 1324 cm ^-1 .
Found: C, 58.89; H, 5.64; N, 25.37%. Calculated for _C8H9N3O : C, _58.88 ; H, 5.56; N _, 25.75%.

Azidation was carried out in the same manner as in Example 3 using a compound of the formula [4] in which R ⁷ and R ⁸ are the following combinations (1) to (3) as the nucleophilic compound.
( ¹ ) ^R7 = _CH3 , R8=Cl
(2) R ⁷ =t-Bu, R ⁸ =OMe
( ³ ) ^R7 =CHO, R8= _CH3

As a result, an azide compound shown below was obtained.

The yield of the azide compound obtained from the nucleophilic compound (1) was 19%, the yield of the azide compound obtained from the nucleophilic compound (2) was 51%, and the yield of the azide compound obtained from the nucleophilic compound (3) was 19%. The yield of the azide compound obtained was 61%.

Further, as the nucleophilic compound, a compound of formula [4] in which R ⁷ and R ⁸ are the following combinations (4) to (8) was used, and azidation was carried out in the same manner as in Example 4.
(4) R ⁷ = H (hydrogen atom), R ⁸ = Me
(5) R ⁷ =H, R ⁸ = t-Bu
( ⁶ ) ^R7 =H, R8=OMe
( ⁷ ) ^R7 =H, R8=Cl
( ⁸ ) ^R7 =H, R8= _CO2Me

The yield of the obtained azide compound is shown in Table 2 below.

Using the azidoimidazolium derivative of the present invention represented by formula [1] produced in Example 1, the compound represented by formula [4] was diazotized.

Specifically, the azidoimidazo of the present invention was added to a 2-methoxyethanol solution (4 mL) of a phenol (91.4 mg, 0.75 mmol) represented by the formula [4] and diisopropylamine (151 mg, 1.5 mmol). A lium derivative (diazotizing agent) (516 mg, 0.90 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. After water was added to the reaction solution, organic matter was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, ethyl acetate was distilled off under reduced pressure to obtain a crude product. The resulting crude product was purified by silica gel chromatography (hexane:ethyl acetate) to give diazobenzoquinone.
The yield of diazobenzoquinone obtained is shown below.

In Example 6, diazotization was carried out in the same manner except that the phenol represented by formula [4] was changed to naphthol. The reaction time was 15 minutes. The yield is shown below.

A ketone compound (acetophenone) was diazotized using the azidoimidazolium derivative of the present invention represented by the formula [1] produced in Example 1.

Specifically, a tetrahydrofuran solution (6.5 mL) of acetophenone (43 mg, 0.36 mmol) and lithium diisopropylamide (0.46 mmol) was stirred at -78°C for 2 hours. After that, the azidoimidazolium derivative (diazotization agent) (200 mg, 0.35 mmol) of the present invention was added, and the mixture was stirred at -78°C for 4 hours. After water was added to the reaction solution, organic matter was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, ethyl acetate was distilled off under reduced pressure to obtain a crude product. The obtained crude product was purified by silica gel chromatography (hexane:ethyl acetate) to obtain a diazotized product.
The yield of the obtained diazotized product is shown below.

Azidation of 2,4-dimethylphenol was carried out using various azidoimidazolium derivatives. Specifically, azidoimidazolium derivatives were produced from the following four imidazolium derivatives (precursors), and 2,4-dimethylphenol was azidated. The yield is shown below.

The azidoimidazolium derivative of the present invention is a novel non-explosive and safe electrophilic azidating agent or diazotizing agent, and is expected to be used not only in the field of synthesis but also in chemical biology and materials. Industrially useful.

Claims (12)

An azidoimidazolium derivative characterized by being represented by the following formula [1].

(In the formula, R and R' each represent an aryl group , and X ^- represents a counter anion.) The azidoimidazolium derivative according to claim 1 , characterized by being represented by the following formula [1A].

(In the formula, R ¹ to R ⁴ each represent an alkyl group, an aryl group, or an aralkyl group, and R ⁵ and R ⁶ each represent a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, or a nitro group.) 3. The azidoimidazolium derivative according to claim 1 or 2 , wherein X ^- is one selected from PF ₆ ^- , BF ₄ ^- , CF ₃ SO ₃ ^- and Cl ^- . The azidoimidazolium derivative according to any one of claims 1 to 3 , characterized by being represented by the following formula [1B].

(In the formula, iPr represents an isopropyl group, and R ⁵ and R ⁶ each represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a halogen atom or a nitro group.) ^5. The azidoimidazolium derivative according to claim 2 or 4 ^, wherein R5 and R6 are hydrogen atoms. The azidoimidazolium derivative according to any one of claims 1 to 5 , which is an azidation agent used for azidating a nucleophilic compound. The azidoimidazolium derivative according to any one of claims 1 to 5 , which is a diazotizing agent used for diazotizing a nucleophilic compound. 8. The azidoimidazolium derivative according to claim 6 , wherein the nucleophilic compound is an aromatic compound. An imidazolium derivative represented by the following formula [2].

(In the formula, R and R' each represent an aryl group , ^and X- represents PF ₆ ^- , BF ₄ ^- , or CF ₃ SO ₃ ^- .) The imidazolium derivative according to claim 9 , characterized by being represented by the following formula [2A].

(In the formula, R ¹ to R ⁴ each represent an alkyl group, an aryl group, or an aralkyl group, and R ⁵ and R ⁶ each represent a hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, or a nitro group.) The imidazolium derivative according to claim 9 or 10 , characterized by being represented by the following formula [2B].

(In the formula, iPr represents an isopropyl group, and R ⁵ and R ⁶ each represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a halogen atom or a nitro group.) 12. The imidazolium derivative according to claim ¹⁰ or 11 ^, wherein R5 and R6 are hydrogen atoms.