WO2009152219A1

WO2009152219A1 - (n-heterocyclic carbene) copper salt complex as latent click catalyst

Info

Publication number: WO2009152219A1
Application number: PCT/US2009/046861
Authority: WO
Inventors: Steven Patrick Nolan; Osama M. Musa
Original assignee: Henkel Corporation
Priority date: 2008-06-11
Filing date: 2009-06-10
Publication date: 2009-12-17
Also published as: TW200950884A

Abstract

A latent catalyst for the reaction of azides and alkynes has the structure in which G and G' independently are a lower alkyl (C₁ to C₂₀); R and R' independently are an aliphatic or an aromatic group, preferably a straight or branched chain C₅ to C₃₆ group, optionally with cyclic moieties incorporated into the chain and capped with a monovalent moiety, such as CH₃, OH, OSiR"₃, or NR"₂ (in which R" is an alkyl or aryl group).

Description

(N-HETEROCYCLIC CARBENE) COPPER SALT COMPLEX AS LATENT CLICK CATALYST

BACKGROUND OF THE INVENTION

[0001] This invention relates to a latent catalyst for the [3+2] cycloaddition reaction of azides and alkynes.

[0002] The reaction of azides and alkynes catalyzed by copper(l) to yield 1 ,2,3-triazoles, known as Click chemistry, is a popular Huisgen 1 ,3-dipolar cycloaddition. The reaction proceeds through mild and neutral conditions in high efficiency, making it effective for applications in both biology and material science. [(NHC)CuX] complexes (in which NHC = N-heterocyclic carbene; X = Cl or Br) are highly efficient catalysts for the Huisgen [3+2] cycloaddition of azides and alkynes. However, their efficiency can be a disadvantage with respect to the storage and handling stabilities of materials such as adhesives, encapsulants, paintings, coatings, inks, and photoresists using this chemistry. In such cases, latent catalysts are valuable tools for controlling the initiation step in polymerization or curing processes, thus improving storage stability. A catalyst can be defined as latent when it is inert under normal conditions, such as ambient temperature and light, but active under certain external stimulus, such as heating or photoirradiation. To date, there have been no reported latent catalysts for use with the Click chemistry.

SUMMARY OF THE INVENTION

[0003] In one embodiment, this invention is a curable composition comprising an azide, an alkyne, and latent catalyst to catalyze the [3+2] cycloaddition reaction of the azide and alkyne, in which the latent catalyst has either of the following generic structures:

in which G and G' are independently a lower alkyl (C₁ to C₂₀); R and R' independently are an aliphatic or an aromatic group, preferably a straight or branched chain C₅ to C₃₆ group, optionally with cyclic moieties incorporated into the chain, the chain capped with a monovalent moiety, such as CH₃, OH, OSiFT₃, or NR"₂ in which R" is an alkyl or aryl group. Hereinafter, either one of these structures will be deemed to represent and include the other as well.

[0004] In a particular embodiment, this invention is a curable composition comprising an azide and an alkyne, and a latent catalyst, in which the latent catalyst is the copper salt of N,N-bis(2,6-diisopropyl-phenyl)imidazolin-2-ylidene) (hereinafter abbreviated as [(NHCPOCuCI]), which has the structure:

DETAILED DESCRIPTION OF THE INVENTION

[0005] The latent catalysts used in the curable compositions of this invention are prepared by the reaction of a copper(l) salt with an N-heterocyclic carbene to give a compound having one of the generic structures disclosed above.

[0006] Depending on the length and structure of the R and R' groups, the practitioner can design into the catalyst specific properties, such as, solubility, miscibility, reactivity, polarity, that will aid in the compatibility of the catalyst with the Click chemistry resin system.

[0007] Suitable solvents for the preparation of the catalysts are any in which the catalyst has either no or low reactivity. Such solvents include, but are not limited to, dimethyl- sulfoxide (DMSO), acetone, toluene, tetrahydrofuran (THF), cyclopentylmethylether.

[0008] When the catalysts of this invention are used in curable compositions for the [3+2] cycloaddition reaction of azides and alkynes, in a solvent that imparts no or low reactivity to the catalyst, the composition can remain unreactive for periods of time as long as a week. Suitable solvents for the curable composition are the same as those used to prepare the catalyst, and include, but are not limited to, DMSO, acetone, toluene, THF, and cyclopentylmethylether. [0009] The curable compositions may be prepared substantially without any solvent, although the presence of solvent in a minor amount may be needed.

[0010] Activation of the catalysts is obtained by the application of heat, typically up to temperatures 60⁰C or lower, or by the addition of water to the reaction medium. Higher temperatures are not favored because it is likely thermal degradation of the reactants will occur. The amount of water needed to trigger the action of the catalyst will be an effective amount. An effective amount will be in a ratio of water to organic solvent of from 0.1 : 1.0 to 1.0 : 1.0. The ratio will vary depending on the organic solvent, and the optimal ratio can be determined by one skilled in the art without undue experimentation. As an added advantage, the use of water leads to the precipitation of the formed triazoles, facilitating the isolation step.

[0011] A typical [3+2] cycloaddition reaction of an azide and alkyne can be depicted by the following reaction scheme:

in which 1week means that the reactants were held for one week in a latency period without any initiation by the catalyst. Initiation occurred in step (2) with the addition of water and the application of heat to 60°C.

[0012] In general, the amount of the latent Cu(I) catalyst will range from 0.01 % to 5% by weight of the alkyne and azide containing compounds. In one embodiment, the amount of catalyst will range from 0.1 % to 2.0% by weight of alkyne and azide. In another embodiment, the amount of catalyst will range from 0.05% to 1.0% by weight of alkyne and azide. Lower amounts of catalyst will require longer reaction times.

[0013] The reactants containing azide functionality used in the inventive process can be monomeric, oligomeric, or polymeric, and can be aliphatic or aromatic, with or without heteroatoms (such as, oxygen, nitrogen and sulfur). In addition, the azides can have additional functionality. Examples of the various azides that can be used include tosyl azide and sulfonyl azides (which can yield sulfonyl triazoles, N-acylsulfonamides, or azetidimines). [0014] The reactants containing alkyne functionality can be aliphatic or aromatic and can have various electronic and steric properties. Preferably the alkyne is not reactive at room temperature, such as is, for example, ethyl propiolate.

[0015] Depending on the end application, one or more fillers may be included in the azide/alkyne compositions and usually are added for improved rheological properties and stress reduction. Examples of suitable nonconductive fillers include alumina, aluminum hydroxide, silica, fused silica, fumed silica, vermiculite, mica, wollastonite, calcium carbonate, titania, sand, glass, barium sulfate, zirconium, carbon black, organic fillers, and halogenated ethylene polymers, such as, tetrafluoroethylene, trifluoroethylene, vinylidene fluoride, vinyl fluoride, vinylidene chloride, and vinyl chloride. Examples of suitable conductive fillers include carbon black, graphite, gold, silver, copper, platinum, palladium, nickel, aluminum, silicon carbide, boron nitride, diamond, and alumina. These conductive fillers also act as synergistic catalysts with the above described copper catalysts.

[0016] The filler particles may be of any appropriate size ranging from nano size to several mm. The choice of such size for any particular end use is within the expertise of one skilled in the art. Filler may be present in an amount from 10% to 90% by weight of the total composition. More than one filler type may be used in a composition and the fillers may or may not be surface treated. Appropriate filler sizes can be determined by the practitioner, but, in general, will be within the range of 20 nanometers to 100 microns.

[0017] EXAMPLE 1 : SOLVENT SCREENING

[0018] In order to test for appropriate solvents for the Click reaction using the inventive latent catalyst, the reaction of benzyl azide and phenylacetylene was conducted in various solvents and the conversion times, as detected by 1 H NMR, were recorded. Reaction of benzyl azide and phenylacetylene under standard cycloaddition conditions in water and isobutanol (t-BuOH), led to 6% conversion. High conversions were reached in tetrahydrofuran (THF) and isopropanol (i-PrOH). Water and dimethylformamide (DMF) were less efficient solvents, but conversion did occur. No conversion was detected after one week of stirring in acetone or dimethylsulfoxide (DMSO), which makes acetone and DMSO particularly suitable for use for latency. The results are reported in TABLE 1.

[0019] TABLE 1. SOLVENT SCREENING REACTION OF BENZYL AZIDE AND PHENYLACETYLENE IN VARIOUS SOLVENTS

entry # solvent conversion time conversion time

3 days one week

1 water/t-BuOH 6% 6%

(1:1)

2 THF 46% 96%

3 i-PrOH 42% 63%

4 water 21 % 26%

5 DMF 6% 16%

6 Acetone 0% 0%

7 DMSO 0% 0%

[0020] EXAMPLE 2. ACTIVATION FOR THE LATENT CATALYST

[0021] To show the activation of the latent catalyst using heat, benzyl azide and phenylacetylene were heated in DMSO at 60°C for eight hours in the presence of the catalyst Cu salt of N,N-bis(2,6-diisopropyl-phenyl)imidazolin-2-ylidene) and showed a conversion of 83%.

[0022] The same reaction was performed in acetone and showed a conversion of only 9%, which became 22% when water was added.

[0023] In order to show the activation of the latent catalyst in the presence of both water and heat, a series of azide/alkyne reactions were conducted according to the following protocol: in a vial fitted with a screw cap, azide 1 (1.0 mmol), alkyne 2 (1.1 mmol), latent catalyst [(NHCPr'jCuCI] (10 mg, 2 mol %) and technical DMSO (1 mL) were loaded. The solution was stirred at room temperature for at least one week and controlled by GC-MS to ensure the absence of reaction. Then, water (1 mL) was added and the reaction mixture was heated at 60⁰C. After total consumption of the starting azide or no further conversion, the corresponding triazole was collected by filtration and washed with water and pentane. (Alternatively, the triazole could be recovered after extraction with EtOAc.) In all examples, the crude products were estimated to be greater than 95% pure by 1 H NMR. In no case, were precautions to exclude oxygen taken. Copper disproportionation with precipitation of metal copper was never observed. The results are reported in Table 2. [0024] A reaction in the absence of the copper catalyst was also carried out. Under optimized conditions, in tetrahydrofuran with 2 mol% catalyst at room temperature, 46% of the starting benzyl azide remained unreacted after 24 hours of heating and the reaction did not reach completion even after seven days. Furthermore, as expected, a mixture of regioisomers was formed in a ratio 1 ,4/1 ,5 = 60/40, with the 1 ,4 isomer being the desired catalyzed product. This indicates that the catalyst indeed is initiating the azide/alkyne reaction after a period of latency.

[0025] TABLE 2. LATENT-[(NHCPR')CUCL]-CATALYZED FORMATION OF TRIAZOLES 3A TO 3L

Triazole Triazole Product Structure time yield * number (hour) (%)

3a 1 98

Ph

HepU 1 83

N'%

3g

Bu 0.5 97^**

Ts- , N _N N ^{^} N

3m 18 20

Ph

* Isolated yields are average of two runs.

** Reaction run in a mixture DMSO/water at 60°C without latent period.

*** 1 o% of the starting azide also recovered.

**** Reaction run in MeCN, 1H NMR conversion.

[0026] All the precedent reactions were carried out on a 1-mmol scale and required 1 ml_ of each solvent. A ratio DMSO : water = 1 : 0.6 was found optimal in the reaction of benzyl azide and pheπylacetylene and it was successfully applied to a 15 mmol-scale synthesis.

[0027] EXAMPLE 3. LATENT-[(NHCPR')CUCL]-CATALYZED FORMATION OF TRIAZOLES WITHOUT HOLD IN LATENCY PERIOD

[0028] For the sake of comparison, some of the entries in Table 2 were also performed without passing through the latent one week period. Similar or slightly shorter reaction times were required in those cases and reached comparable yields, illustrating the stability of the catalyst in solution. [0029] EXAMPLE 4. SYNTHESIS OF [(NHCPR'JCUCL]

[0030] In a vial, copper(l) chloride (0.171 g, 1.5 mmol), NHCPr^1- HCI) (Strem) (0.586 g, 1.25 mmol) and sodium methoxide (0.132 g, 1.88 mmol) were loaded inside a glovebox and stirred in dry toluene (4 ml_) overnight at room temperature outside the glovebox. After filtration of the reaction mixture over a plug of celite (DCWI), the filtrate was mixed with pentane to form a precipitate. A second filtration afforded the title complex as a white solid (0.526 g, 86%). Spectroscopic data were in accordance with reported values. [0031] Crystal structure data for [(NHCPr')CuCI], C27H38CICuN2-2CH2CI2, M = 659.44, monoclinic, a = 9.5227(11)A, b = 16.4203(19)A, C = 11.0548(13) A, ( = 103.810(2)°, V = 1678.6(3) A3; T = 150(2) K, space group P21/m, Z = 2, absorption coefficient = 1.069 mm-1. Of 13663 reflections collected in the range 1.2°-22.5°, 2289 were unique reflections (Rint = 0.109) and were used in all calculations. The final wR2 was 0.0801 (all data). CCDC 649761.

UTILITY

[0032] Azide and alkyne compositions containing the latent catalysts described in this specification are suitable for use as adhesives, encapsulants, paintings, coatings, inks, and photoresists. The presence of the latent catalyst extends the shelf life of the compositions and allows for the use of a reactive chemistry in these end applications.

Claims

WHAT IS CLAIMED

1. A curable composition comprising an azide, an alkyne, and a latent catalyst having either one of the structures

in which

G and G' independently are a C₁ to C₂o alkyl;

R and R' independently are an aliphatic or an aromatic group.

2. The curable composition according to claim 1 in which R and R' on the latent catalyst independently are a straight or branched chain C₅ to C₃₆ alkyl, optionally with cyclic moieties incorporated into the chain, the chain capped with a monovalent organic moiety selected from the group consisting of CH₃, OH, OSiR"₃, or NR"₂, in which R" is alkyl or aryl.

3. The curable composition according to claim 1 in which the latent catalyst is N₁N- bis(2,6-diisopropyl-phenyl)imidazolin-2-ylidene) CuCI.

4. The curable composition according to claim 1 in which the latent catalyst can be activated by the application of heat.

5. The curable composition according to claim 4 in which the latent catalyst can be activated by the application of heat under 60⁰C.

6. The curable composition according to claim 4 in which the latent catalyst can be further activated by the presence of water.

7. The curable composition according to claim 6 in which the water is present in a ratio of 0.1 : 1.0 to 1 : 1 water to organic solvent.