Article Cite This: Macromolecules XXXX, XXX, XXX−XXX
pubs.acs.org/Macromolecules
One-Pot Multicomponent Tandem Reactions and Polymerizations for Step-Economic Synthesis of Structure-Controlled Pyrimidine Derivatives and Poly(pyrimidine)s Wen Tian,† Rongrong Hu,*,† and Ben Zhong Tang*,†,‡ †
Downloaded via LUND UNIV on November 26, 2018 at 14:06:54 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
State Key Laboratory of Luminescent Materials and Devices, Center for Aggregation-Induced Emission, South China University of Technology, Guangzhou 510640, China ‡ Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, China S Supporting Information *
ABSTRACT: The development of new polymerization methodologies for the construction of π-conjugated polymers with unique electronic and photophysical properties is of great importance. Multicomponent tandem polymerizations (MCTPs), featured with high synthetic efficiency and convenience, have proved their potential in the synthesis of polymers with πconjugated structures. Herein, a new multicomponent tandem reaction of alkyne, guanidine hydrochloride, DMSO, and O2 was reported through the combination of four sequential Glaser coupling−nucleophilic addition−heterocyclization−oxidation reactions in a one-pot procedure. The corresponding MCTP of diyne, guanidine hydrochloride, DMSO, and O2 was also developed in the presence of CuCl, N,N,N′,N′-tetramethylethylenediamine, and Cs2CO3 to afford conjugated poly(pyrimidine) with well-defined structure, high yield of 87%, and high molecular weight of 25300 g/mol. A mechanistic study of the reaction and a kinetic study of the polymerization were conducted, enabling facile modulation of polymer mainchain structure from rigid conjugated backbone to flexible nonconjugated backbone by simply tuning the atmosphere of the MCTP from air to nitrogen. The poly(pyrimidine)s enjoy outstanding thermal stability and good solubility, whose hydrophobicity and photophysical property are influenced by their subtle structural difference. This MCTP directly converts monomers with simple structure to complex heterocycle-containing products in a step-economic manner and constructs new functional substituted pyrimidine rings embedded in the polymer main chain, providing a compact approach for the efficient and convenient synthesis of structurally controllable poly(heterocycle)s and the construction of polymer materials with potential high-tech applications.
■
INTRODUCTION The development of modern polymer materials is highly dependent on the exploration of new polymerization methodologies.1,2 π-Conjugated polymers, including linear conjugated and cross-conjugated structures such as benzophenone and divinyl ketones with unique electronic and photophysical properties,3,4 have attracted much attention and are in great demand in the applications such as fluorescence chemosensors,5,6 organic light-emitting diodes,7,8 polymer solar cells,9−11 thermoelectric materials,12−14 and organic field-effect transistors.15−18 Today, the widely used synthetic methods for π-conjugated polymers are mainly transition-metal-catalyzed coupling reactions such as Suzuki−Miyaura, Heck, Sonogashira, and Stille reactions.19−23 The syntheses of polymers with © XXXX American Chemical Society
complex structures such as heterocycle-containing conjugated polymers generally suffer from tedious procedures, timeconsuming monomer preparation, and painful isolation/ purification, which remain a great challenge. New synthetic methodologies with high efficiency and convenience are hence urgently needed for the construction of advanced functional polymers with unique structures. Of all the recently developed polymerization methodologies for the synthesis of conjugated polymers,24−28 multicomponent tandem polymerization (MCTP) is a powerful strategy because of its high synthetic efficiency, simple procedure, Received: November 1, 2018
A
DOI: 10.1021/acs.macromol.8b02335 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules diverse product structure, and high atom economy. Most importantly, the in-situ construction of new functional groups such as heterocycles in MCTPs is difficult to achieve by other synthetic approaches.29−31 Multiple steps are combined in a specific order in a one-pot MCTP with simple monomers and procedures. The intermediate formed from the first step directly undergoes the following reactions upon addition of new reagents without any isolation and purification, producing desired product with high efficiency and specificity. For example, conjugated polythiophenes and polypyrazoles with well-defined structures, high molecular weights (Mws), and high yields can be facilely obtained through the MCTPs consisted of the modified Sonogashira coupling reaction of alkyne/carbonyl chloride and the sequential addition− cyclization reactions.32,33 Moreover, MCTP is also efficient in controlling the sequence of functional moieties on polymer main chains. For example, structural-regulated and sequencecontrolled poly(tetrahydropyrimidine)s can be accessed via a metal-free MCTP of activated alkynes, aromatic diamines, and formaldehyde. The polymer backbone structure can be further modulated from poly(tetrahydropyrimidine)s to poly(dihydropyrrolone)s by simply changing the temperature and monomer loading ratio.34 Glaser coupling is a well-known reaction to produce 1,3diyne under the catalysis of CuCl and N,N,N′,N′-tetramethylethylenediamine (TMEDA) (reaction A), which is extensively used in polymer synthesis.35−37 Recently, a heterocyclization between 1,4-diphenyl-1,3-diyne (2) and guanidine hydrochloride (3) (reaction B) was reported in the presence of Cs2CO3 in DMSO to produce carbonyl-2-aminopyrimidine (4) in excellent yield.38 In this work, taking advantage of the common high efficiency, simple operation, and mild conditions of both reactions A and B, a multicomponent tandem reaction (MCTR) (reaction C) was designed by combining these two reactions in a one-pot procedure to afford the pyrimidine product concisely from simple reactants. In the proposed MCTR, the intermediate 1,3-diyne 2 is produced in situ from Glaser coupling reaction of phenylacetylene (1), which then undergoes further reaction with the freshly added 3 directly in the reaction solution. Through a nucleophilic addition, an anion of buta-1,2,3-triene intermediate A might be formed, followed by heterocyclization and aromatization to afford compound 5, which then undergoes oxidation to furnish product 4 (Scheme 1).38−40 Through similar one-pot coupling−addition−cyclization−oxidation multiple steps, the corresponding MCTP is also developed for the compact synthesis of poly(pyrimidine) with high yield and large Mw from simple monomers. The tetraphenylethene-containing diyne monomer is designed because its twisted bulky structure can prevent intermolecular interactions and hence benefit the solubility of product, which also endows the poly(pyrimidine) with aggregation-induced emission characteristics. Furthermore, the chemical structure and properties of the poly(pyrimidine) can be tuned by simply modulating the reaction atmosphere, demonstrating the controllability of this MCTP.
Scheme 1. Proposed Multicomponent Tandem Reaction and Its Mechanism
THF, DMF, o-DCB, and DMSO at room temperature for 4 h in the presence of CuCl and TMEDA (Table S1). Guanidine hydrochloride (3), Cs2CO3, and DMSO were then added into the reaction solution without any pretreatment to conduct the following reactions in situ at 120 °C for 12 h. As expected, the desired carbonyl-2-aminopyrimidine (4) was directly produced in all the tested solvents with good to excellent yields, suggesting good compatibility of these two reactions. Among all the tested solvents, o-DCB or DMSO provided the best results. The amount of CuCl was then optimized in DMSO to achieve 94% yield of 4, demonstrating the successful combination of the coupling−addition−cyclization−oxidation reaction pathways in this one-pot MCTR. Multicomponent Tandem Polymerization. To utilize this MCTR in the synthesis of aromatic heterocycliccontaining conjugated polymers and develop the corresponding polymerization, diyne monomer 6 was synthesized, and its polymerization was conducted under the aforementioned optimal conditions of the MCTR. As the first step, 6 was reacted in DMSO in air at 50 °C in the presence of CuCl and TMEDA. However, insoluble precipitates were formed in 15 min in DMSO due to the poor solubility of the polymer intermediate P1′ generated from the self-coupling of 6, which inhibited further tandem reactions of P1′ with the newly added monomer 3, Cs2CO3, and DMSO at 120 °C (Scheme 2A). To balance the reactivity of all the reactions and solubility of the polymer intermediate or product, various solvent systems were tested for the first step of the MCTP. o-DCB was found to possess both good solubility of P1′ and good compatibility with the following reactions. The o-DCB/DMSO mixed solvents with varied ratios were hence investigated for the MCTP, and o-DCB/DMSO (v/v, 1:1) was the optimal solvent, delivering soluble polymer with high yield of 87% and a large Mw of 25300 g/mol (Table S2). The monomer concentration of 6, temperature, and reaction time of the second step were then optimized in o-DCB/DMSO (v/v, 1:1) (Tables S3−S5). Increasing the concentration of 6
■
RESULTS AND DISCUSSION Multicomponent Tandem Reaction. To combine Glaser coupling reaction of alkyne and the reaction of 1,3-diyne and guanidine hydrochloride into a one-pot MCTR, it is crucial that the solvents and conditions of each reaction are compatible. The Glaser coupling reaction of phenylacetylene (1) was hence performed in different solvents such as CH2Cl2, B
DOI: 10.1021/acs.macromol.8b02335 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules Scheme 2. Multicomponent Tandem Polymerizations for the Synthesis of (A) P1 in Air or (B) P2 under Nitrogen
Figure 1. 1H NMR spectra of (A) 6, (B) 8, (C) P1, (D) 9, and (E) P2 and 13C NMR spectra of (F) 6, (G) 8, (H) P1, (I) 9, and (J) P2 in DMSOd6.
C
DOI: 10.1021/acs.macromol.8b02335 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules
Figure 2. (A) Stacked in-situ IR profiles collected at different instants of the polymerization solution of 3 and 6 in DMSO in air after the addition of 3. (B) In-situ IR spectra of DMSO and DMSO solutions of 3, 6, 8, and P1, and the polymerization solution of 3 and 6 after reaction in air for 12 h. (C) Time-dependent peak intensity at 1662, 1557, 1360, and 1186 cm−1. (D) 3D-FTIR profile of the polymerization solution of 3 and 6 in air.
from 0.05 to 0.1 M or elongating the first step-reaction time at low monomer concentration could both improve the polymerization result. Further increasing the concentration to 0.2 M led to insoluble gel. Raising the temperature of the second step above 120 °C benefits neither yield nor Mw. The time course of the MCTP suggested that satisfactory results could be obtain in 8 h after the addition of 3. To elucidate which oxidant, DMSO or O2 in air, provides the oxygen atom in the carbonyl group of the product, the second steps of the MCTR and MCTP were performed under nitrogen, affording compound 5 in 88% yield and polymer P2 with a Mw of 19300 g/mol in 83% yield, respectively (Scheme 2B). This evidence proved that O2 in air contributed the oxygen atoms to the newly formed carbonyl groups. Structural Characterization. Model compounds 8 and 9 were then synthesized to assist the structural characterization (Scheme S1). The HR-MS analyses of the compounds were 783.3282 (8, calcd 783.3250) and 769.3426 (9, calcd 769.3457), proving their expected structures (Figures S1 and
S2). The NMR spectra of 6, 8, 9, P1, and P2 were then compared to confirm the polymer structures. In the 1H NMR spectra, the resonance of terminal alkyne protons Ha of monomer 6 at δ 4.16 and 4.18 from trans-/cis-isomers, respectively, disappeared in all the spectra of 8, 9, P1, and P2, suggesting the total consumption of alkyne functional groups. Meanwhile, in the spectra of 8 and P1, new peaks emerged at δ ∼ 7.28, representing the characteristic aromatic protons Hb on the newly formed pyrimidine rings. The strong electronwithdrawing pyrimidine rings and carbonyl groups had influenced their neighboring aromatic protons and resulted in two new peaks at δ ∼ 7.88 (Hc) and 7.75 (Hd) downfield. On the other hand, in the spectra of 9 and P2, a new CH2 peak at δ ∼ 3.76 (He) and a new NH2 peak at δ ∼ 6.57 (Hf) both emerged, and only a single peak appeared at δ ∼ 7.70 downfield, representing the neighboring aromatic protons Hd of the pyrimidine rings and proving the absence of carbonyl group in 9 and P2 (Figure 1A−E). Similarly, in the 13C NMR spectra of 8, 9, P1, and P2, the resonances of the acetylene D
DOI: 10.1021/acs.macromol.8b02335 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules carbons of 6 at δ 83.28 and 81.14 disappeared, and the characteristic pyrimidine carbon resonance at δ 103.97−104.77 appeared. Most importantly, the carbonyl peaks at δ ∼ 193.02 emerged only in the spectra of 8 and P1, and the methylene peaks at δ ∼ 43.01 emerged only in the spectra of 9 and P2 (Figure 1F−J). It should be noticed that in both the structures of P1 and P2, there are three possible moieties randomly distributed on the polymer backbone which do not show difference in their NMR spectra (Scheme 2). The NMR analysis confirmed the expected product structures, suggesting that by simply tuning the reaction atmosphere from air to nitrogen, the carbonyl groups could be completely replaced with the methylene groups in the products, which proves the crucial role of O2 in the oxidation. To investigate the role of DMSO in this reaction besides solvent, DMSO-d6 was used as the solvent for the MCTR of 1 and 3 under nitrogen while the other reaction conditions maintain the same to afford product 5′. From the comparison of the 1H NMR spectra of 5 and 5′, it is obvious that the characteristic methylene peak located at δ ∼ 3.89 and the aromatic pyrimidine peak located at δ ∼ 7.07 have both dramatically decreased from the spectra of 5 to that of 5′, while the other peaks remain unchanged, indicating that the methylene group and pyrimidine proton in 5′ are deuterated (Figure S3). In other words, these protons are partially originated from DMSO-d6. Moreover, in the IR spectra of 8, 9, P1, and P2, the absorption peak of 6 associated with the stretching vibration of CC at 2104 cm−1 and the absorption peaks of P1′ associated with the stretching vibration of CC−CC at 2202−2140 cm−1 were absent, demonstrating the total conversion of CC or CC−CC bonds (Figure S4). Meanwhile, new absorption bands emerged at 3400 and 3481 cm−1 in all the spectra of 8, 9, P1, and P2, proving the formation of NH2 groups. The new absorption peak of the stretching vibration of CO at ∼1666 cm−1 emerged only in the spectra of 8 and P1, which was not observed in the spectra of 9 and P2, in accordance with their expected structures. Kinetic Study of the MCTP. In-situ IR spectrometry was then used to monitor the MCTP after the addition of 3, Cs2CO3, and DMSO under the optimized conditions in air. The stacked 2D-FTIR profile suggested that three new peaks emerged in the spectra of the polymerization system at ∼1557, 1360, and 1186 cm−1, corresponding to the stretching vibrations from the CN of the pyrimidine rings, C−NH2, and C−C near the carbonyl group (Figure 2A).41,42 The in-situ IR spectra of 3, 6, 8, P1, and DMSO were compared with the polymerization mixture to confirm each peak (Figure 2B), indicating that the carbonyl peak from the product at ∼1674 cm−1 is overlapped with the peak from 3 at 1662 cm−1. The time-dependent peak intensity and the kinetic variation of the 3D-FTIR profiles at 1186, 1360, 1557, and 1662 cm−1 were recorded to follow the track of the consumption of the reactants and the generation of the pyrimidine rings (Figure 2C,D). The intensity of the newly formed pyrimidine peaks increased rapidly in 3 h, which were then gradually saturated, suggesting rapid completion of the reaction. Meanwhile, the peak intensity at 1662 cm−1 dropped promptly in the first 9 min due to the fast consumption of guanidine hydrochloride, which was then rapidly increased and became saturated in about 3 h because of the newly formed carbonyl group in P1 located in the same area.
The polymerization was also monitored under nitrogen by the in-situ IR spectrum for comparison (Figure S4). Different than the polymerization in air, the peak intensity at 1662 cm−1 shows continuous decrease because no carbonyl group is formed in such conditions, which only represents the CN stretching vibration from monomer 3. Similarly, the peak intensities at 1560, 1361, and 1186 cm−1 also increased upon polymerization because of the formation of pyrimidine rings in P2. Under the guidance of the in-situ IR analysis, the polymerization times of the MCTP of 3 and 6 were further optimized in air with less time (Table S6). A high yield of 87% and Mw of 16800 g/mol can be obtained in 3 h, demonstrating high efficiency of this polymerization. Solubility, Hydrophobicity, and Thermal Stability. The subtle structural difference between P1 and P2 has a large influence on their physical properties such as solubility and hydrophobicity. Although they both share a large number of rigid aromatic components, P1 with carbonyl bridges possesses a more rigid polymer backbone than P2 with flexible methylene bridges. While they both can be well dissolved in polar solvents such as DMSO and DMF, P2 possess better solubility than P1 in other organic solvents such as THF. Moreover, both P1 and P2 enjoy good film-forming ability which can be spin-coated on glass slides to form tough thin films. The static water contact angles of the polymer films were then measured to be 118° (P1) and 76° (P2) by the sessile drop method, suggesting a more hydrophobic surface of P1 than that of P2 (Figure 3A,B).
Figure 3. Water contact angle of (A) P1 and (B) P2. (C) TGA thermograms under N2 with a heating rate of 10 °C min−1. E
DOI: 10.1021/acs.macromol.8b02335 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules
Figure 4. (A) Absorption spectra of 8, 9, P1, and P2 in DMF solutions. Concentration: 10 μM. (B) Emission spectra of 8, 9, P1, and P2 in solid states. (C) Emission spectra of P1 in DMF/H2O mixtures (10 μM) with different f w. λem = 361 nm. (D) Plots of the relative peak emission intensity (I/I0) of 8, 9, P1, and P2 versus the water fractions.
The large number of aromatic components and the conjugated structures endow these poly(pyrimidine)s excellent thermal stability, although significant difference is observed for P1 and P2. Thermogravimetric analysis of the polymers under nitrogen suggested that the degradation temperatures with 5 wt % weight loss for P1 and P2 are 428 and 529 °C, respectively, and a high yield of carbonized residue of 72 wt % was achieved for both polymers even when they were heated to 850 °C, proving their high thermal resistance (Figure 3C). Compared with the carbonyl bridges in P1 that may break to form radical species under pyrolysis, the CH2 bridges in P2 are more stable, which leads to a higher decomposition temperature of P2. Photophysical Properties. With their large conjugated structure, the photophysical properties of 8, 9, P1, and P2 are systematically investigated to reveal their structure−property relationship. The absorbance of these compounds was measured in DMF solutions, and the absorption maxima of 8 and P1 are 356 and 361 nm, respectively, which were redshifted compared with that of 9 (323 nm) and P2 (339 nm),
suggesting the extended cross-conjugation from the electronwithdrawing carbonyl bridge (Figure 4A). The photoluminescence behaviors of them were then investigated. The DMF solutions of 8 and P1 are faintly emissive, while those of 9 and P2 are totally nonemissive. However, in their solid states, their emission was greatly enhanced with fluorescence quantum efficiencies up to 56%, demonstrating typical aggregation-induced emission characteristics which benefited from their tetraphenylethene moieties. The emission maxima of 8 (512 nm) and P1 (549 nm) are red-shifted compared with that of 9 (450 nm) and P2 (537 nm), respectively (Figure 4B). For 8 and P1, the emission maxima of their solid powders also red-shifted compared with those of their DMF solutions, indicating the existence of intermolecular interactions and more planar configuration in the solid states than in solutions (Table S7). Moreover, the photoluminescence properties of these compounds were then studied in DMF/water mixtures with different water contents (Figure 4C,D and Figures S6−S8). Compound 8 was nonemissive in DMF solution or DMF/ F
DOI: 10.1021/acs.macromol.8b02335 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules
solvent was removed under reduced pressure, the crude product was obtained and purified by silica gel chromatography (petroleum ether/ ethyl acetate = 6/1, v/v) to obtain compound 8 as a yellow powder in 93% yield. 1H NMR (500 MHz, DMSO-d6) δ (TMS, ppm): 7.89− 7.87 (d, 2H), 7.76−7.74 (d, 2H), 7.28 (s, 1H), 7.17−7.12 (m, 20H), 7.13−7.08 (d, 2H), 7.01−6.98 (m, 14H). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 193.02, 165.37, 164.74, 163.50, 149.51, 146.46, 143.38, 143.23, 143.16, 143.08, 143.01, 142.71, 141.96, 140.39, 140.09, 140.01, 134.93, 133.21, 131.56, 131.34, 131.11, 131.04, 130.52, 128.05, 128.42, 128.35, 127.53, 127.30, 127.23, 126.85, 130.97. FT-IR (KBr disk), v (cm−1): 3490, 3408, 3050, 3019, 1666, 1596, 1569, 1535, 1441, 1359, 1257, 1217, 747, 698, 623. HRMS: calcd for C57H41N3O: 783.3250; found: 783.3282. Synthetic Procedure of the MCTR under Nitrogen. Into a 50 mL Schlenk tube equipped with a magnetic stirrer were placed CuCl (2 mg, 0.02 mmol) and TMEDA (7 mg, 0.06 mmol) in 2 mL of oDCB. The mixture was bubbled with a slow stream of oxygen and stirred at 50 °C for 15 min. Monoyne 7 (356 mg, 1.0 mmol) was dissolved in 3 mL of o-DCB, which was then added into the catalyst. The resulting solution was stirred for 4 h at room temperature. Afterward, guanidine hydrochloride (3) (115 mg, 1.2 mmol), Cs2CO3 (652 mg, 2.0 mmol), and 5 mL of DMSO were added. The reaction mixture was stirred at 120 °C under nitrogen for 12 h. After the reaction mixture was cooled to room temperature, 150 mL of NaCl solution (5 M) was added, and ethyl acetate (3 × 50 mL) was used to extract the product for three times. The organic phases were combined and dried with MgSO4. After the solvent was removed under reduced pressure, the crude product was obtained and purified by silica gel chromatography (petroleum ether/ethyl acetate = 6/1, v/ v) to obtain compound 9 as a white powder in 89% yield. 1H NMR (500 MHz, DMSO-d6) δ (TMS, ppm): 7.73−7.72 (d, 2H), 7.15− 6.94 (m, 34H), 6.90−6.88 (d, 2H), 6.88 (s, 1H), 6.57 (s, 2H), 3.76 (s, 2H). 13C NMR (125 MHz, DMSO-d6) δ (ppm): 170.83, 164.17, 163.87, 145.85, 143.68, 143.60, 143.46, 143.31, 141.81, 141.73, 140.84, 140.46, 137.25, 135.60, 131.41, 131.19, 131.04, 128.95, 128.27, 127.23, 127.00, 126.49, 126.00, 104.71, 43.01. FT-IR (KBr disk), v (cm−1): 3490, 3408, 3292, 3180, 3059, 3028, 1620, 1575, 1535, 1496, 1441, 1353, 1075, 1026, 756, 698, 626. HRMS: calcd for C57H43N3: 769.3457; found: 769.3426. Synthetic Procedure of the MCTP in Air. Into a 50 mL Schlenk tube equipped with a magnetic stirrer were placed CuCl (0.8 mg, 0.008 mmol) and TMEDA (2.8 mg, 0.024 mmol) in 2 mL of o-DCB. The mixture was bubbled with a slow stream of oxygen and stirred at 50 °C for 15 min. Diyne 6 (152 mg, 0.40 mmol) was dissolved in 2 mL of o-DCB, which was then added into the catalyst. The resulting solution was stirred for 2 h at room temperature. Afterward, guanidine hydrochloride (3) (46 mg, 0.48 mmol), Cs2CO3 (261 mg, 0.80 mmol), and 4 mL of DMSO were added. The reaction mixture was stirred at 120 °C in air for 12 h. The polymerization mixture was diluted with 5 mL of DMSO, which was then added dropwise into 200 mL of methanol through a cotton filter to form precipitates. The precipitates were allowed to stand for 4 h, which were then filtered, washed with methanol (3 × 20 mL), and dried under vacuum at 45 °C to a constant weight to afford P1 as a yellow powder in 87% yield. Mw = 25300 g/mol and Mw/Mn = 1.90. 1H NMR (500 MHz, DMSOd6) δ (TMS, ppm): 7.88, 7.75, 7.27, 7.12, 6.98. 13C NMR (125 MHz, DMSO-d6) δ (ppm): 192.96, 165.37, 164.62, 163.50, 149.29, 146.22, 142.78, 142.03, 141.21, 140.84, 135.15, 133.28, 131.11, 128.50, 127.38, 126.85, 103.97. FT-IR (KBr disk), v (cm−1): 3490, 3408, 3194, 3059, 3019, 1669, 1599, 1565, 1535, 1441, 1402, 1356, 1250, 1220, 1181, 1014, 975, 754, 698. Synthetic Procedure of the MCTP under Nitrogen. Into a 50 mL Schlenk tube equipped with a magnetic stirrer were placed CuCl (0.8 mg, 0.008 mmol) and TMEDA (2.8 mg, 0.024 mmol) in 2 mL of o-DCB. The mixture was bubbled with a slow stream of oxygen and stirred at 50 °C for 15 min. Diyne 6 (152 mg, 0.40 mmol) was dissolved in 2 mL of o-DCB, which was then added into the catalyst. The resulting solution was stirred for 2 h at room temperature. Afterward, guanidine hydrochloride (3) (46 mg, 0.48 mmol), Cs2CO3 (261 mg, 0.80 mmol), and 4 mL of DMSO were added. The reaction
water mixtures with low water content (
