Next Article in Journal
High-Throughput Method for the Simultaneous Determination of Doxorubicin Metabolites in Rat Urine after Treatment with Different Drug Nanoformulations
Previous Article in Journal
Kinetic and Molecular Docking Studies to Determine the Effect of Inhibitors on the Activity and Structure of Fused G6PD::6PGL Protein from Trichomonas vaginalis
Previous Article in Special Issue
Triptycene Derivatives: From Their Synthesis to Their Unique Properties
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 27
Issue 4
10.3390/molecules27041176
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Tethered Blatter Radical for Molecular Grafting: Synthesis of 6-Hydroxyhexyloxy, Hydroxymethyl, and Bis(hydroxymethyl) Derivatives and Their Functionalization †

by
Szymon Kapuściński
1,2,
Bindushree Anand
2,
Paulina Bartos
1,
Jose M. Garcia Fernandez
3,* and
Piotr Kaszyński
1,2,4,*
1
Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland
2
Centre for Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland
3
Institute for Chemical Research, CSIC, University of Sevilla, Americo Vespucio 49, 41092 Sevilla, Spain
4
Department of Chemistry, Middle Tennessee State University, Murfreesboro, TN 37132, USA
*
Authors to whom correspondence should be addressed.
†
Dedicated to Professor Mieczysław Mąkosza.
Molecules 2022, 27(4), 1176; https://doi.org/10.3390/molecules27041176
Submission received: 13 January 2022 / Revised: 30 January 2022 / Accepted: 1 February 2022 / Published: 9 February 2022
(This article belongs to the Special Issue Advances in Organic Synthesis: A Theme Issue in Honor of Professor Mieczysław Mąkosza)
Browse Figures
Versions Notes

Abstract

:
Synthetic access to 7-CF3-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl radicals containing 4-(6-hydroxyhexyloxy)phenyl, 4-hydroxymethylphenyl or 3,5-bis(hydroxymethyl)phenyl groups at the C(3) position and their conversion to tosylates and phosphates are described. The tosylates were used to obtain disulfides and an azide with good yields. The Blatter radical containing the azido group underwent a copper(I)-catalyzed azide–alkyne cycloaddition with phenylacetylene under mild conditions, giving the [1,2,3]triazole product in 84% yield. This indicates the suitability of the azido derivative for grafting Blatter radical onto other molecular objects via the CuAAC “click” reaction. The presented derivatives are promising for accessing surfaces and macromolecules spin-labeled with the Blatter radical.

1. Introduction

Functionalization of flat surfaces [1,2,3,4,5,6,7,8,9], polymers [10,11,12,13,14], well-defined macromolecules (dendrimers [15,16,17,18], cyclodextrins [19,20,21,22], fullerene [23], and nanotubes [24]), and nanoparticles [25,26,27,28,29,30] with stable radicals is becoming an important avenue for obtaining materials [31,32] for advanced technologies [33], which include organic electronics [11,34], spintronics [1,3,6], contrast agents in bioimaging [15,35,36], and energy storage [12,37,38,39]. This effort has concentrated mainly on the traditional stable radicals, such as nitroxides [6,14,15,16,17,18,19,32], tris(2,4,6,-trichlorophenyl)methyl (TTM) [7,9], and verdazyl [40], while the exploration of 1,4-dihydrobenzo[e][1,2,4]triazin-4-yls (so-called Blatter radicals) as active components of these materials began only recently and is rapidly intensifying.
Radicals have been chemisorbed onto an Au surface using the SR [1,2,6,26,41] and C≡CH [7,42] groups, and the latter was used to graft radicals onto reduced Si surfaces [42]. Chemisorption of radicals and typical organic molecules onto other surfaces has been accomplished using PO(OR)2 groups (metal oxide substrates, e.g., Fe3O4 [25] and LSMO [6]), COOH group (GaAs) [43] and siloxanes (for SiOx and indium tin oxide–ITO–substrates) [44]. Grafting of radicals onto macromolecules has been achieved using a variety of acylation and condensation reactions [15,16,17,18,35,45,46]. One of the most efficient grafting methods involves the Cu(I)-catalyzed [3+2] cycloaddition (“click”) reaction between an azide and a terminal alkyne, leading to the formation of the [1,2,3]triazole ring with the 1,4-substitution pattern [47,48,49]. This approach has been applied to grafting ethynyl-containing radicals into systems with pending azido groups [24,25,29,50]. It should be added that radical polymers have also been obtained by polymerization of monomers containing stable radicals using, e.g., Rh catalysts, ring opening metathesis polymerization (ROMP), and electropolymerization methods [13,14,40].
The 1,4-dihydrobenzo[e][1,2,4]triazin-4-yls [33,51], formal derivatives of the prototypical 1,3-diphenyl derivative known as the Blatter radical [52] A (Figure 1), are exceptionally stable, π-delocalized radicals characterized by favorable redox behavior with a narrow electrochemical window (~1.2 V) [37,38] and a broad absorption in the visible range [53]. The stability of Blatter radical A is further enhanced by placing the CF3 group in the C(7) position leading to derivative B, the so-called “super stable” radical [54]. For these reasons, 1,4-dihydrobenzo[e][1,2,4]triazin-4-yls are promising paramagnetic structural elements of functional materials [33], and have been explored as photoconductive liquid crystals [55,56,57], sensors [58], photodetectors [59], and also in spintronics [41,60,61].
There are still relatively few studies on Blatter radicals chemisorbed on surfaces or grafted on macromolecules, mainly due to insufficiently developed access to derivatives with appropriate functional groups. For instance, Blatter radical containing two Au-anchoring SMe groups (C, Figure 1) was chemisorbed on the Au(111) surface and the interactions of the resulting molecular films with the surface were investigated in detail [41]. Acetylene derivative D was prepared and reacted with an azidonorbornene derivative under the “click” reaction conditions to give a norbornene-containing monomer, which was polymerized using the ROMP method. The acetylene derivative D could also be used for chemisorption onto the Au surface. Finally, bis(triethoxysilyl) derivative E was used for grafting the Blatter radical onto mesoporous silica [62] and could also be used for the functionalization of Si and metal surfaces with native oxides.
Despite progress in functional derivatives of the Blatter radical, there is a need to broaden the range of intermediates containing active functionalities for grafting onto diverse types of surfaces and macromolecules.
Herein we describe three derivatives of the “super stable” Blatter radical containing the 6-hydroxyhexyloxy (Ia, Figure 2) or hydroxymethyl (IIa and IIIa) substituents on the C(3)–Ph ring as key intermediates to functional derivatives suitable for grafting onto low dimensional systems. We report a conversion of the alcohols Ia–IIIa to the corresponding tosylates Ib–IIIb and phosphates Ic and IIc, and transformations of the tosylates to disulfides Id and IId, and azide Ie. As a proof of concept, we demonstrate the “click” reaction of azide Ie with an alkyne.

2. Results and Discussion

2.1. Synthesis of Hydroxyl Derivatives Ia–IIIa

Radicals Ia–IIIa containing versatile hydroxyl groups were prepared using the recently discovered regioselective azaphilic addition of aryllithium to benzo[e][1,2,4]triazines [63]. Thus, phenyllithium was reacted with benzo[e][1,2,4]triazines 1–3, and the resulting anions were oxidized with air to the corresponding radicals Ia–IIIa, which were conveniently isolated by column chromatography (SiO2 support) in yields up to 92% (Scheme 1). It should be noted that both hydroxy (1 and 3) and acetoxy (2) derivatives were suitable starting materials for this reaction affording the corresponding radicals in comparable yields. The route to Ia involving addition of phenyllithium to compound 4, the O-benzyl protected alcohol 1 (Scheme 2), followed by Pd-catalyzed reductive debenzylation of the resulting radical If (Scheme 1) turned out to be inefficient. While the PhLi addition and formation of If worked well (yield up to 64%, Scheme 2), debenzylation of If gave only decomposition products. This presumably resulted from the more vigorous conditions needed for the removal of the O-benzyl group in the alkyl benzyl ethers than in the aryl analogues.
The requisite alcohols 1 and 3 and acetate 2 were obtained in two steps following an established general procedure [57,63,64], as shown in Scheme 2. Thus, the readily available benzhydrazides 5–7 were N-arylated with 1-fluoro-2-nitro-5-trifluoromethylbenzene. The resulting hydrazides 8–10 were subsequently cyclized under reductive conditions (Sn powder/AcOH) followed by oxidation of the dihydro products with Ag2O or NaIO4 giving benzo[e][1,2,4]triazines 2–4 in good overall yields (40–75%). Interestingly, during reductive cyclization of 9 at temperatures above 100 °C, the hydroxymethyl group underwent esterification with AcOH, used as the solvent and reagent in this reaction, and acetate 2 was isolated in 45% yield. The analogous acetate was not observed in the case of cyclization of hydrazide 10 conducted at ambient temperatures.
The hydroxyhexyloxy derivative 1 was obtained in 31% overall yield by Pd-catalyzed debenzylation of 4, followed by aerial oxidation of the dihydro form. As noted above, debenzylation of 4 required longer-than-typical reaction times. The obtained hydroxy derivative 1 turned out to be sensitive to elevated temperatures: concentration of solutions of purified 1 on a rotavap at 40 °C resulted in its decomposition and formation of a foul-smelling orange oil. Handling of 1 at lower temperatures avoided this problem, and pure product was obtained.
Benzhydrazides 5–7 were obtained by hydrazinolysis of the corresponding methyl benzoates with hydrazine hydrate.

2.2. Synthesis of Tosylates and Phosphates

Reactions of alcohols Ia–IIIa with tosyl chloride gave the desired tosylates Ib–IIIb in 82–96% yield (Scheme 3). The relatively high stability of Ib allowed for isolation of the pure compound using standard silica gel chromatography. In contrast, tosylates IIb and IIIb were sensitive to chromatography conditions and were used for the next step as crude materials.
Phosphorylation of alcohols Ia and IIa with diethyl chlorophosphate in the presence of DMAP and Et3N gave the phosphates Ic and IIc, respectively, isolated in about 85% yield (Scheme 3).

2.3. Transformation of Tosylates: Preparation of Disulfides and Azide

Disulfides Id and IId were obtained in 18% yield from tosylates Ib and IIb using a general procedure [65] involving reactions with the thiosulfate (S2O32−) nucleophile in DMSO, followed by oxidation of the resulting mercaptan with I2 (Scheme 4).
In contrast, the preparation of azide Ie was straightforward and more efficient. Thus, reaction of toslyate Ib with NaN3 in DMF gave azide Ie isolated in yields up to 73% yield (Scheme 4).

2.4. Copper(I)-Catalyzed Azide-Alkyne Cycloaddition of Azide Ie

Compound Ie represents the first azido derivative of the Blatter radical, and its suitability for the Cu(I)-catalyzed cycloaddition reaction (“click”) with alkynes, the CuAAC reaction, required experimental verification. Thus, the azide Ie was reacted with phenylacetylene in the presence of Cu(I), generated in situ from CuSO4 and sodium ascorbate, according to a general literature method [66]. The “click” product, [1,2,3]triazole Ig, was isolated in a high yield of 84% (Scheme 5). This result compares to 53% yield of [1,2,3]triazole formation in an analogous CuAAC reaction of acetylene-substituted Blatter radical D (Figure 1) with an azido derivative of norbornene [13].
Pure Ig showed no decomposition during storage for 4 years under ambient conditions, according to thin-layer chromatography analysis.

2.5. Spectroscopic Characterization of Radicals

All radicals I–III exhibit low-intensity broad absorption in the entire visible range, as shown for Ia in Figure 3. Consequently, the compounds appear dark brown in solutions and nearly black in the solid state. EPR analysis of the radicals conducted in benzene solutions revealed seven principal lines resulting from hyperfine splitting with three 14N nuclei modulated with additional smaller splitting by 19F and 1H nuclei, as shown for derivative Ia in Figure 3. For some radicals, the principal lines are less resolved, presumably due to aggregation in benzene solutions (see the Supplementary Materials). Analysis demonstrated that the aN hfcc values for radicals I–III are consistent with those for other Blatter radical derivatives, and are about 7.6 G for aN(1) and about 4.5–4.9 G for aN(2) and aN(4). Simulation of the experimental spectra indicates that the aF hfcc value is in a range of 3.2–3.6 G.

3. Conclusions

The “super stable” Blatter radical B was substituted at the C(3) phenyl ring with a long tether (O(CH2)6-X, I), a short tether (CH2-X, II) or two anchoring groups (2 × CH2-X, III). The key intermediates contain the hydroxyl group (X = OH, a), which could be used for grafting in condensation (acylation) and addition (e.g., carbamination) reactions. The hydroxyl derivatives Ia–IIIa are efficiently converted to tosylates Ib–IIIb, which served as electrophilic intermediates to disulfides Id and IId (for chemisorption onto Au surfaces) and azide Ie (for the CuAAC reaction). Tosylates IIb and IIIb can additionally be exploited to attach the Blatter radical to hydroxyl-functionalized partners through the formation of benzyl-type ether linkages. Following prior work on the synthesis and supramolecular properties of cyclodextrin–xylylene hybrids [67,68,69,70], we have conducted preliminary experiments supporting the viability of such an approach, and the results will be published in due course.
The demonstration of efficient “click” reaction of azide Ie with PhC≡CH paves the way to grafting radical B onto surfaces and macromolecules functionalized with terminal ethynyl groups. This method represents a more versatile approach to paramagnetic materials, since many macromolecules substituted with the propargyl group are available.
The presented results constitute a promising approach to novel paramagnetic polymers with high radical density, e.g., for polymer electrodes with high charge storage capacity and for high-density paramagnetic surfaces for spintronic applications. This work is continued in our laboratory.

4. Materials and Methods

General. Reagents and solvents were purchased and used as received. THF was dried over Na metal in the presence of benzophenone and distilled before use. Column chromatography was performed on silica gel. For separation of radicals silica gel was passivated by mixing with CH2Cl2 containing 2% of Et3N and removal of the solvent to dryness (rotovap). Reported yields refer to analytically pure samples. NMR spectra were recorded with a Bruker AVIII 500 or 600 instrument. Chemical shifts are reported relative to solvent (CDCl3) residual peaks (1H NMR: δ = 7.26 ppm and 13C NMR: δ = 77.16 ppm) [71]. All 13C NMR spectra are proton-decoupled. IR spectra were measured in KBr pellets with a FTIR NEXUS spectrometer. High-resolution mass spectrometry (HRMS) measurements were performed using SYNAPT G2-Si High-Definition Mass Spectrometry equipped with an ESI or APCI source and Quantitative Time-of-Flight (QuanTof) mass analyzer. Melting points were determined in capillaries with a MEL-TEMP II apparatus and are uncorrected. If not stated otherwise, reactions were carried out under argon atmosphere in flame-dried flasks with addition of the reactants via syringe. Subsequent manipulations were conducted in air.
EPR spectra of radicals I–III were recorded on an X-band EMX-Nano EPR spectrometer at ambient temperature using dilute and degassed solutions in distilled benzene in a concentration range of 2–5 × 10−4 M. Additional details are shown in the SI.
Preparation of radicals Ia–IIIa via PhLi addition to benzo[e][1,2,4]triazines 1-3. A general method. To a solution of the appropriate benzo[e][1,2,4]triazine derivative 1, 2, or 3 (0.792 mmol) in dry THF (10 mL), PhLi (1.9 M in dibutyl ether, 1.24 mL, 2.360 mmol) was added dropwise at −5 °C under argon and the reaction mixture was stirred at this temperature for 1 h, then for 1 h at rt under air. Water was added and the product was extracted with CH2Cl2 (3×). The combined organic extracts were dried (Na2SO4), and volatiles were removed on a rotavap. Pure product was isolated by column chromatography followed by recrystallization (MeCN).
1-Phenyl-3-[4-(6-hydroxyhexyloxy)phenyl]-7-trifluoromethyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (Ia). Starting from triazine 1. Yield: 322 mg (87–94% range yield) of pure Ia as a brown solid: mp 145–146 °C; IR (KBr) v 3400, 2932, 2854, 1607, 1514, 1393, 1356, 1314, 1246, 1118, 1063, 841 cm−1; UV (CH2Cl2) λmax (log ε) 291 (4.58), 413 (3.65), 504 (3.20) nm; EPR (benzene) aN 7.57, 4.54, 4.87, aF 3.51 G, g = 2.0048; HRMS (ESI-TOF) [M+H]+ m/z calcd for C26H26F3N3O2: 469.1977; found: 469.1984. Anal. Calcd for C26H25F3N3O2: C, 66.66; H, 5.38; N, 8.97. Found: C, 66.46; H, 5.45; N, 8.77.
1-Phenyl-3-(4-hydroxymethylphenyl)-7-trifluoromethyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (IIa). Staring from triazine 2. The crude product was passed through a passivated silica gel plug (pet. ether/AcOEt 1:1) and recrystallized (MeCN) to give 279 mg (92% yield) of pure IIa as an olive solid: mp 204–205 °C; IR (KBr) v 3366, 3275, 3054, 1592, 1489, 1397, 1355, 1315, 1265, 1166, 1117, 1062, 1013, 905 cm−1; EPR (benzene) aN 7.40, 4.59, 4.90, aF 3.24 G, g = 2.0034; HRMS (ESI-TOF) [M+H]+ m/z calcd for C21H16F3N3O: 383.1245; found: 383.1233. Anal. Calcd for C21H15F3N3O: C, 65.97; H, 3.95; N, 10.99. Found: C, 66.10; H, 4.06; N, 11.25.
1-Phenyl-3-[3,5-bis(hydroxymethyl)phenyl]-7-trifluoromethyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (IIIa). Starting from triazine 3. The crude product was passed through a passivated silica gel plug (pet. ether/AcOEt 1:1) and recrystallized (MeCN) to give IIIa as an olive solid (251 mg, 77% yield): mp 180–181 °C; IR (KBr) v 3394, 3219, 3066, 2858, 1709, 1592, 1490, 1427, 1396, 1322, 1278, 1130, 1070, 875, 841, 765, 692 cm−1; EPR (benzene) aN 7.64, 4.60, 4.79, aF 3.49 G, g = 2.0038; HRMS (ESI-TOF) [M+H]+ m/z calcd for C22H18F3N3O2: 413,1351; found: 413.1355.
Preparation of 1-phenyl-3-[4-(6-tosyloxyhexyloxy)phenyl]-7-trifluoromethyl- 1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (Ib). To a solution of alcohol Ia (500 mg, 1.07 mmol) in dry CH2Cl2 (6 mL), pyridine (0.25 mL, 3.10 mmol) and tosyl chloride (305 mg, 1.60 mmol) were added and the reaction mixture was stirred at rt overnight under argon. The reaction mixture was washed with H2O, brine and dried (Na2SO4). Organic solvents were removed on a rotavap and the residue was passed through a silica gel plug (CH2Cl2/EtOAc 19:1) to give 637 mg (96% yield) of pure tosylate Ib as a brown solid: mp 120–121 °C; IR (KBr) v 2940, 2864, 1605, 1390, 1355, 1316, 1244, 1172, 1119, 960, 842 cm−1; HRMS (ESI-TOF) [M+H]+ m/z calcd for C33H32F3N3O4S: 623.2066; found: 623.2062. Anal. Calcd for C33H31F3N3O4S: C, 63.65; H, 5.02; N, 6.75; S, 5.15. Found: C, 63.65; H, 5.16; N, 6.63; S, 5.03.
Preparation of tosylates IIb and IIIb. A general method. To a solution of alcohol IIa or IIIa (0.79 mmol) and tosyl chloride (300 mg, 1.57 mmol) in dry THF (10 mL), 60% NaH in mineral oil (475 mg, 11.85 mmol) was added in portions over 30 min. The suspension was stirred at rt for another 30 min, and water was added dropwise to neutralize the unreacted NaH. The reaction mixture was extracted with CH2Cl2 (3×). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The crude product was passed through a silica gel plug passivated with Et3N (pet ether/AcOEt 4:1) to give IIb or IIIb as green-brown solid. The product was immediately used for the next step without further purification
1-Phenyl-3-[4-(tosyloxymethyl)phenyl]-7-trifluoromethyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (IIb). Starting from IIa. Yield: 413 mg (98% yield) of IIb as a brown solid; HRMS (ESI-TOF) [M+H]+ m/z calcd for C28H22F3N3O3S: 537.1334; found: 537.1330.
1-Phenyl-3-[3,5-bis(tosyloxymethyl)phenyl]-7-trifluoromethyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (IIIb). Starting from IIIa. Yield: 558 mg (98% yield) of IIIb as a brown solid; HRMS (ESI-TOF) [M+H]+ HRMS, m/z calcd for C36H30F3N3O6S2: 721,1528; found: 721.1536.
Preparation of phosphates Ic and IIc. A general method. To a solution of alcohol Ia or IIa (0.2 mmol, 1.0 equiv.), DMAP (0.02 mmol, 0.1 equiv.) and Et3N (1.0 mmol, 5 equiv.) dissolved in THF (2 mL) diethyl chlorophosphate (1.0 mmol, 5 equiv.) was added slowly via syringe. During the addition, a white precipitate formed. The reaction mixture was stirred at rt for 1 h until substrate was no longer present in the reaction mixture (TLC control). The reaction was quenched with sat. NH4Cl solution, extracted with CH2Cl2, and the product was purified by column chromatography (pet. ether/AcOEt 3:2).
1-Phenyl-3-[4-(6-diethoxyphosphoryloxyhexyloxy)phenyl]-7-trifluoromethyl- 1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (Ic). Starting from Ia. Yield: 103.9 mg (86% yield) of phosphate Ic as a soft waxy material; IR (KBr) v 2925, 2854, 1607, 1490, 1399, 1318, 1248, 1165, 1108, 1027, 829, 698 cm−1; EPR (benzene) aN 7.56, 4.78, 4.53, aF 3.56 G, g = 2.0037; HRMS (ESI-TOF) [M+H]+ m/z calcd for C30H35N3O5F3P: 605.2266; found: 605.2273.
1-Phenyl-3-[4-(diethoxyphosphoryloxymethyl)phenyl]-7-trifluoromethyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (IIc). Starting from IIa. Yield: 86.1 mg (83% yield) of phosphate IIc as a soft waxy material; IR (KBr) v 2925, 2854, 1593, 1492, 1422, 1323, 1265, 1166, 1120, 1036, 824, 698 cm−1; EPR (benzene) aN 7.59, 4.63, 4.72, aF 3.56 G g = 2.0046; HRMS (ESI-TOF) [M+H]+ m/z calcd for C25H25N3O4F3P: 519.1535; found: 519.1529.
Preparation of disulfides Id and IId. A general method. A mixture of tosylate Ib or IIb (0.64 mmol) and solid Na2S2O3 (102 mg, 0.64 mmol) in DMSO (15 mL) was stirred at 60 °C overnight. The reaction mixture was cooled to rt and extracted with AcOEt (3×). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The residue was dissolved in CH2Cl2 (10 mL) and solid I2 (49 mg, 0.19 mmol) was added and stirred at rt for 10 min, filtered, the solid was washed with CH2Cl2 and the filtrate was evaporated. The crude product was passed through a passivated silica gel plug (pet. ether/AcOEt 5:1) and recrystallized (MeCN) to give pure product Id or IId as brown solids.
Disulfide Id. Starting from Ib. Yield: 55.0 mg (18% yield); mp 73 °C; IR (KBr) v 2936, 2855, 1605, 1512, 1487, 1426, 1398, 1319, 1251, 1170, 1115, 1060, 840, 695 cm−1; UV (CH2Cl2) λmax (log ε) 292 (4.82), 384 (4.01), 503 (3.34) nm; EPR (benzene) aN 7.32, 4.66, 4.55, aF 3.32 G, g = 2.0038; HRMS (ESI-TOF) [M]+ m/z calcd for C52H48F6N6O2S2: 966.3184; found: 966.3218. Anal. Calcd for C52H48F6N6O2S2: C, 64.58; H, 5.00; N, 8.69; S, 6.63. Found: C, 64.30; H, 5.10; N, 8.63; S, 6.84.
Disulfide IId. Starting from IIb. Yield: 45.8 mg (18% yield); mp 170 °C; IR (KBr) v 3073, 1592, 1488, 1397, 1316, 1264, 1116, 1062, 905, 844, 763, 693 cm−1; UV (CH2Cl2) λmax (log ε) 284 (4.89), 374 (4.04), 430 (3.78), 498 (3.42) nm; HRMS (ESI-TOF) [M]+ m/z calcd for C42H28F6N6S2: 794.1721; found: 794.1726. Anal. Calcd for C42H28F6N6S2: C, 63.47; H, 3.55; N, 10.57; S, 8.07. Found: C, 63.45; H, 3.61; N, 10.46; S, 8.05.
Preparation of 1-phenyl-3-[4-(6-azidohexyloxy)phenyl]-7-trifluoromethyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (Ie). To a solution of tosylate Ib (750 mg, 1.204 mmol) in dry DMF (18 mL) sodium azide (391 mg, 6.02 mmol) was added in one portion and the reaction mixture was stirred for 5 h at 50 °C under argon. After the reaction is completed (no starting material detected by TLC), H2O and brine were added, and the product was extracted with CH2Cl2 (3×). The organic layer was washed with H2O (3×), then with brine, and dried (Na2SO4). Solvents were removed and the residue was purified by column chromatography (SiO2, CH2Cl2 100%) to give 432 mg (73% yield) of pure azide Ie as brown solid: mp 88-90 °C; IR (KBr) v 2939, 2857, 2098 (N3), 1606, 1397, 1354, 1317, 1247, 1113 cm−1; EPR (benzene) aN 7.57, 4.82, 4.98, aF 3.33 G, g = 2.0049; HRMS (ESI-TOF) [M+H]+ m/z calcd for C26H25F3N6O: 494.2042; found: 494.2031.
Preparation of 1-phenyl-3-[4-(6-benzyloxyhexyloxy)phenyl]-7-trifluoromethyl -1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (If). Radical If was obtained in 44–64% yield by addition of PhLi to triazine 4 according to the general procedure for preparation of alcohol Ia–IIIa. The crude product was passed through a silica gel plug (pet. ether/Et2O 3:2) and recrystallized (EtOH) to give pure If as a brown solid: mp 98–100 °C; HRMS (ESI-TOF) [M]+ m/z calcd for C33H31F3N3O2: 558.2368; found: 558.2363. Anal. Calcd for C33H31F3N3O2: C, 70.95; H, 5.59; N, 7.52. Found: C, 70.95; H, 5.56; N, 7.62.
Preparation of 1-phenyl-3-[4-(6-[1,2,3]triazolylhexyloxy)phenyl]-7-trifluoromethyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (Ig). To a solution of CuSO4 × 5H2O (~3 mg), sodium ascorbate (~3 mg) and benzoic acid (~3 mg) in t-BuOH/H2O 1:2 (4 mL) a mixture of phenylacetylene (20.0 mg, 0.196 mmol) and azide Ie (95.0 mg, 0.192 mmol) was added at rt. The resulting mixture was stirred for 5 h (TLC monitoring, CH2Cl2, Rf = 0.08 and 0.45 for product Ig and azide Ie, respectively). CH2Cl2 was added and the organic phase was washed with H2O and brine and dried (Na2SO4). Solvents were removed in vacuum and the product was purified by column chromatography (SiO2, CH2Cl2 100% gradient to CH2Cl2/EtOAc 4:1) to give 97 mg (84% yield) of pure triazole Ig as a brown solid: mp 160 °C dec.; IR (KBr) v 2943, 1607, 1400, 1357, 1319, 1246, 1121, 837, cm−1; UV (CH2Cl2) λmax (log ε) 290 (4.58), 411 (3.62), 504 (3.20) nm; EPR (benzene) aN 7.59, 4.73, 4.87, aF 3.50 G, g = 2.0054; HRMS (ESI-TOF) [M+H]+ m/z calcd for C34H31F3N6O: 596.2511; found: 596.2506. Anal. Calcd for C34H30F3N6O: C, 68.56; H, 5.08; N, 14.11. Found: C, 68.59; H, 5.00; N, 13.97.
Preparation of 3-[4-(6-hydroxyhexyloxy)phenyl]-7-trifluoromethylbenzo[e][1,2,4] triazine (1). A solution of benzyloxy derivative 4 (3.00 g 6.23 mmol) in THF (35 mL) was added to a suspension of 5% Pd/C (2.60 g) in EtOH (35 mL), and the resulting mixture was hydrogenated (50 psi) overnight. The reaction mixture was passed through a Celite pad and oxidized by exposure to air (TLC monitoring) and the solvents were removed under reduced pressure (cold bath!). Crude product was purified by column chromatography (SiO2, CH2Cl2/EtOAc 4:1) to give 0.76 g (31% yield) of pure product 1 as a yellow solid: mp 144–145 °C; 1H NMR (600 MHz, CDCl3) δ 8.82 (s, 1H), 8.74 (d, J = 8.9 Hz, 2H), 8.16 (d, J = 8.8 Hz, 1H), 8.08 (dd, J1 = 8.9 Hz, J2 = 1.9 Hz, 1H), 7.10 (d, J = 8.9 Hz, 2H), 4.11 (t, J = 6.5 Hz, 2H), 3.69 (t, J = 6.5 Hz, 2H), 1.87 (quint, J = 7.0 Hz, 2H), 1.64 (quint, J = 7.1 Hz, 2H), 1.56 (quint, J = 7.5 Hz, 2H), 1.48 (quint, J = 7.4 Hz, 2H), 1.25 (s, 1H); 13C{1H} NMR (126 MHz, CDCl3) δ 162.8, 160.9, 144.9, 142.3, 131.2 (q, J = 34 Hz), 131.1, 130.9 (q, J = 3 Hz), 130.7, 127.9 (q, J = 4 Hz) 127.3, 123.3 (q, J = 273 Hz), 115.1, 68.2, 63.0, 32.8, 29.3, 26.0, 25.7; IR (KBr) v 3297, 2938, 2863, 1605, 1510, 1487, 1427, 1337, 1252, 1173, 1134, 1059, 1003, 908, 842, 699, 638 cm−1; HRMS (ESI-TOF) [M+H]+ m/z calcd for C20H21F3N3O2: 392.1586; found: 392.1590. Anal. Calcd for C20H20F3N3O2: C, 61.38; H, 5.15; N, 10.74. Found: C, 61.57; H, 5.12; N, 10.74.
Preparation of triazines 2–4. A general method. To a solution of hydrazide 8, 9 or 10 (6.96 mmol) in glacial AcOH (100 mL), Sn powder (4.54 g, 38.3 mmol) was added and stirred at rt for 2 h, and then at 115 °C for 30 min. After cooling, EtOAc and H2O were added, and the mixture was filtered through a Celite pad. The solution was extracted with two portions of EtOAc, and the combined organic extracts were washed with saturated aq. NaHCO3 (3×) and dried (Na2SO4). Solvents were removed on a rotavap, and the residue was dissolved in a CH2Cl2/MeOH mixture (1:1) and solid NaIO4 (2.23 g, 10.44 mmol) or Ag2O (354 mg, 1.52 mmol) was added. The mixture was stirred at rt until complete consumption of the dihydro form. The solution was filtered, and the solvents were removed under reduced pressure. The crude product was purified on silica gel and recrystallized to give pure triazines 2–4.
3-(4-Acetoxymethylphenyl)-7-trifluoromethylbenzo[e][1,2,4]triazine (2). Starting from hydrazide 9 using modified method. The suspension was stirred at 70 °C overnight and at 120 °C for 1 h. Solid Ag2O was used for oxidation. The crude product was purified by column chromatography (SiO2, pet. ether/AcOEt 4:1) and further by recrystallization (CH2Cl2/EtOH) to give 967 mg (40% yield) of triazine 2 as yellow crystals: mp 136–137 °C; 1H NMR (500 MHz, CDCl3) 8.84 (s, 1H), 8.76 (d, J = 8.3 Hz, 2H), 8.21 (d, J = 8.9 Hz, 1H), 8.11 (dd, J1 = 8.9 Hz, J2 = 1.9 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 5.23 (s, 2H), 2.16 (s, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 170.9, 160.6, 145.3, 142.1, 140.4, 134.8, 132.0 (q, J = 34 Hz), 131.1 (q, J = 3 Hz), 131.0, 129.5, 128.7, 128.0 (q, J = 4 Hz), 123.2 (q, J = 273 Hz), 65.8, 21.1; IR (KBr) v 3070, 1744, 1630, 1508, 1425, 1328, 1257, 1173, 1131, 1056, 1012, 901, 842, 641 cm−1; HRMS (AP-TOF) [M+H]+ m/z calcd for C17H13F3N3O2: 348.0960; found: 348.0961. Anal. Calcd for C17H12F3N3O2: C, 58,79; H, 3.48; N, 12.10. Found: C, 58.83; H, 3.45; N, 12.25.
3-[3,5-Bis(hydroxymethyl)phenyl]-7-trifluoromethylbenzo[e][1,2,4]triazine (3). Starting from hydrazide 10 using modified method. The suspension was stirred at rt overnight without further heating. Solid Ag2O was used for oxidation. The resulting crude product was purified by chromatography (SiO2, pet. ether/AcOEt 1:1) and further by recrystallization (AcOEt) to give 1.28 g (40–55% yield) of triazine 3 as yellow crystals: mp 174–175 °C; 1H NMR (500 MHz, DMSO-d6) δ 9.02 (s, 1H), 8.52 (s, 2H), 8.37 (s, 2H), 7.54 (s, 1H), 5.43 (t, J = 5.7 Hz, 2H), 4.66 (d, J = 5.6 Hz, 4H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 160.1, 145.0, 143.6, 141.7, 134.3, 131.4, 131.2, 130.3 (q, J = 33 Hz), 128.3, 127.8, 125.1, 123.3 (q, J = 273 Hz), 63.2; IR (KBr) v 3270, 3180, 2945, 2884, 1627, 1509, 1421, 1330, 1236, 1214, 1167, 1121, 1055, 1021, 846, 664 cm−1; HRMS (ESI-TOF) [M+H]+ m/z calcd for C16H13F3N3O2: 336,0960; found: 336.0964. Anal. Calcd for C16H12F3N3O2: C, 57.32; H, 3.61; N, 12.53. Found: C, 57.39; H, 3.58; N, 12.62.
Preparation of 3-[4-(6-benzyloxyhexyloxy)phenyl]-7-trifluoromethylbenzo[e][1,2,4] triazine (4). Starting from 8 using general method. The crude product was purified on column chromatography (SiO2, CH2Cl2 100%) to give 2.50 g (75% yield) of pure triazine 4 as an orange solid: mp 109–110 °C; 1H NMR (500 MHz, CDCl3) δ 8.80 (s, 1H), 8.71 (d, J = 8.9 Hz, 2H), 8.14 (d, J = 8.9 Hz, 1H), 8.06 (dd, J1 = 8.9 Hz, J2 = 1.7 Hz, 1H), 7.35 (d, J = 4.4 Hz, 4H), 7.30–7.27 (m, 1H), 7.07 (d, J = 8.9 Hz, 2H), 4.52 (s, 2H), 4.08 (t, J = 6.5 Hz, 2H), 3.51 (t, J = 6.5 Hz, 2H), 1.86 (quint, J = 6.9 Hz, 2H), 1.68 (quint, J = 7.0 Hz, 2H), 1.53–1.49 (m, 4H); 13C{1H} NMR (126 MHz, CDCl3) δ 162.8, 160.9, 144.8, 142.3, 138.7, 131.2 (q, J = 34 Hz), 131.1, 130.8 (q, J = 2 Hz), 130.7, 128.5, 127.9 (q, J = 3 Hz), 127.8, 127.6, 127.2, 123.3 (q, J = 273), 115.1, 73.0, 70.4, 68.3, 29.8, 29.3, 26.1, 26.0; IR (KBr) v 2939, 2849, 1603, 1509, 1426, 1322, 1258, 1178, 1128, 1089, 1055, 977, 842 cm−1; HRMS (ESI-TOF) [M+H]+ m/z calcd for C27H27F3N3O2: 482.2055; found: 482.2050. Anal. Calcd for C27H26F3N3O2: C, 67.35; H, 5.44; N, 8.73. Found: C, 67.32; H, 5.56; N, 8.50.
Preparation of hydrazides 5–7. A general method. The solution of methyl benzoate derivative (4.00 g, 24.0 mmol) and hydrazine monohydrate (8.0 mL) in EtOH (100 mL) was refluxed for 48 h. The reaction mixture was cooled and concentrated in vacuo. Crude hydrazides 6 and 7 were recrystallized from hot EtOH to give pure products as white crystals. The crude hydrazide 5 was dissolved in EtOAc, washed with H2O and dried (Na2SO4). Solvents were removed on rotavap, and the product was purified by column chromatography (SiO2, CH2Cl2/EtOAc 4:1 gradient to 1:3).
4-(6-Benzyloxyhexyloxy)benzhydrazide (5). Yield: 5.43 g (70% yield) of pure product 5 as a colorless solid: mp 88–89 °C; 1H NMR (500 MHz, DMSO-d6) δ 9.61 (s, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.35–7.30 (m, 4H), 7.27 (t, J = 6.9 Hz, 1H), 6.95 (d, J = 8.8 Hz, 2H), 4.44 (s, 4H), 3.99 (t, J = 6.5 Hz, 2H), 3.42 (t, J = 6.5 Hz, 2H), 1.70 (quint, J = 6.8 Hz, 2H), 1.55 (quint, J = 6.8 Hz, 2H), 1.44–1.34 (m, 4H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 165.6, 160.9, 138.7, 128.7, 128.2, 127.4, 127.3, 125.3, 114.0, 71.8, 69.5, 67.6, 29.2, 28.6, 25.5, 25.3; IR (KBr) v 3321, 2940, 2852, 2796, 1618, 1605, 1536, 1500, 1455, 1341, 1258, 1175, 1127, 1105, 1026, 942, 846, 740 cm−1; HRMS (ESI-TOF) [M+H]+ m/z calcd for C20H27N2O3: 343.2022; found: 343.2027. Anal. Calcd for C20H26N2O3: C, 70.15; H, 7.65; N, 8.18. Found: C, 70.10; H, 7.60; N, 8.36.
4-Hydroxymethylbenzhydrazide (6). Yield: 3.80 g (95% yield) of 6 as colorless crystals: 1H NMR (500 MHz, DMSO-d6) δ 9.73 (s, 1H), 7.78 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 5.30 (t, J = 5.7 Hz, 1H), 4.54 (d, J = 5.2 Hz, 2H), 4.48 (s, 2H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 166.0, 145.8, 131.7, 126.9, 126.1, 62.5; HRMS (ESI-TOF) [M+H]+ m/z calcd for C8H11N2O2: 167.0821; found: 167.0821. Anal. Cald for C8H10N2O2: C, 57.82; H, 6.07; N, 16.86. Found: C, 57.84; H, 6.04; N, 16.89.
3,5-Bis(hydroxymethyl)benzhydrazide (7). Yield: 4.24 g (90% yield) of 7 as colorless crystals: mp 173–174 °C; 1H NMR (500 MHz, DMSO-d6) δ 9.72 (s, 1H), 7.63 (s, 2H), 7.42 (s, 1H), 5.28 (t, J = 5.7 Hz, 2H), 4.52 (d, J = 5.4 Hz, 4H), 4.48 (s, 2H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 166.2, 142.5, 133.1, 127.2, 123.6, 62.8; IR (KBr) v 3263, 3149, 3051, 2929, 2872, 2783, 2664, 1638, 1536, 1460, 1355, 1260, 1156, 1045, 874, 704 cm−1; HRMS (ESI-TOF) [M+H]+ m/z calcd for C9H13N2O3: 197.0926; found: 197.0930. Anal. Calcd for C9H12N2O3: C, 55.09; H, 6.16; N, 14.28. Found: C, 55.08; H, 6.11; N, 14.03.
Preparation of hydrazides 8–10. A general method. To a solution of substituted benzhydrazide 5–7 (8.76 mmol) in dry DMSO (20 mL), 1-fluoro-2-nitro-5-trifluoromethylbenzene (1.83 g, 8.76 mmol) was added, and the reaction mixture was stirred at 70 °C overnight. The solution was cooled to rt and poured into a large amount of H2O and extracted with EtOAc. The organic layer was separated, washed with H2O (3x), then with brine, and dried (Na2SO4). Solvents were removed under vacuum and the crude product was recrystallized twice from EtOH to give corresponding pure hydrazide 5–7 as an orange solid.
N-(2-nitro-5-trifluoromethylbenzene)-4-(6-benzyloxyhexyloxy) benzhydrazide (8). From hydrazide 5. Yield: 3.85 g (83% yield) of 8 as an orange solid: mp 115–116 °C; 1H NMR (500 MHz, DMSO-d6) δ 10.74 (s, 1H), 9.69 (s, 1H), 8.32 (d, J = 8.8 Hz, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.34–7.30 (m, 5H), 7.27 (t, J = 6.8 Hz, 1H), 7.17 (dd, J1 = 8.8 Hz, J2 = 1.6 Hz, 1H), 7.06 (d, J = 8.8 Hz, 2H), 4.44 (s, 2H), 4.04 (t, J = 6.4 Hz, 2H), 3.43 (t, J = 6.4 Hz, 2H), 1.74 (quint, J = 6.8 Hz, 2H), 1.57 (quint, J = 6.8 Hz, 2H), 1.46–1.36 (m, 4H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 165.7, 161.9, 145.3, 138.8, 135.2 (q, J = 32 Hz), 133.5, 129.5, 128.2, 127.9, 127.4, 127.3, 123.9, 123.1 (q, J = 274 Hz), 114.4, 113.4, 111.8, 71.8, 69.6, 67.8, 29.2, 28.5, 25.5, 25.3; IR (KBr) v 3319, 3253, 2933, 2854, 1642, 1607, 1540, 1493, 1436, 1339, 1297, 1256, 1227, 1174, 1128, 937, 892, 844, 765, 731, 697 cm−1; HRMS (ESI-TOF) [M+H]+ m/z calcd for C27H29F3N3O5: 532.2059; found: 532.2062. Anal. Calcd for C27H28F3N3O5: C, 61.01; H, 5.31; N, 7.91. Found: C, 61.01; H, 5.36; N, 8.14.
N’-(4-(hydroxymethyl)phenyl)-2-nitro-5-(trifluoromethyl) benzhydrazide (9). From hydrazide 6. Yield: 3.05 g (98% yield) of 9 as yellow crystals: mp 189–190 °C; 1H NMR (500 MHz, DMSO-d6) δ 10.86 (s, 1H), 9.72 (s, 1H), 8.32 (d, J = 8.8 Hz, 1H), 7.92 (d, J = 8.3 Hz, 2H), 7.49 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 1.2 Hz, 1H), 7.18 (dd, J1 = 8.8 Hz, J2 = 1.8 Hz, 1H), 5.37 (t, J = 5.7 Hz, 1H), 4.59 (d, J = 5.7 Hz, 2H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 166.2, 147.2, 145.2, 135.2 (q, J = 32 Hz), 133.6, 130.3, 127.9, 127.4, 126.4, 123.1 (q, J = 273 Hz), 113.4, 111.8, 62.4; IR (KBr) v 3325, 3256, 1648, 1594, 1536, 1492, 1339, 1263, 1228, 1190, 1127, 1056, 935, 831, 763 cm−1; HRMS (ESI-TOF) [M+H]+ m/z calcd for C15H13F3N3O4: 356.0858; found: 356.0849. Anal. Calcd for C15H12F3N3O4: C, 50.71; H, 3.40; N, 11.83. Found: C, 50.78; H, 3.39; N, 12.00.
N’-(3,5-bis(hydroxymethyl)phenyl)-2-nitro-5-(trifluoromethyl)benzohydrazide (10). From hydrazide 7. Yield: 3.04 g (90% yield) of 10 as yellow crystals: mp 195–196 °C; 1H NMR (500 MHz, DMSO-d6) δ 10.89 (s, 1H), 9.73 (s, 1H), 8.33 (d, J = 8.6 Hz, 1H), 7.79 (s, 2H), 7.53 (s, 1H), 7.33 (d, J = 1.1 Hz, 1H), 7.17 (dd, J1 = 8.9 Hz, J2 = 1.7 Hz, 1H), 5.37 (t, J = 5.7 Hz, 2H), 4.59 (d, J = 5.6 Hz, 4H); 13C{1H} NMR (126 MHz, DMSO-d6) δ 166.5, 145.2, 143.0, 135.2 (q, J = 32 Hz), 133.6, 131.8, 128.2, 128.0, 123.9, 123.2 (q, J = 273 Hz), 113.4, 111.7, 62.6; IR (KBr) v 3260, 2952, 1648, 1590, 1489, 1339, 1263, 1182, 1130, 1057, 987, 882; HRMS (ESI-TOF) [M+H]+ m/z calcd for C16H15F3N3O5: 386,0964; found: 386.0962. Anal. Calcd for C16H14F3N3O5: C, 49.88; H, 3.66; N, 10.91. Found: C, 49.90; H, 3.47; N, 11.04.

Supplementary Materials

The following are available online: NMR (1H and 13C{1H}; Figures S1–S18), UV (Figures S19–S22) and EPR spectra (Figures S23–S30). The supporting information can be downloaded.

Author Contributions

Conceptualization, P.K. and J.M.G.F.; methodology and analysis, S.K., B.A. and P.B.; writing—original draft preparation, S.K.; writing—review and editing, P.K., P.B. and J.M.G.F.; supervision, P.K. and J.M.G.F.; funding acquisition, P.K. and J.M.G.F. All authors have read and agreed to the published version of the manuscript.

Funding

This work was financially supported by the Foundation for Polish Science (TEAM/2016-3/24), MCIN/AEI/10.13039/501100011033, “ERDF A way of making Europe” (RTI2018-097609-B-C21), and the Junta de Andalucía (P20_00166) and COST Action (CA18132-46179).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data obtained in this project are contained within this article and available upon request from the Authors.

Conflicts of Interest

The authors declare no conflict of interest.

Sample Availability

Samples of the compounds are not available from the authors.

References

  1. Giaconi, N.; Sorrentino, A.L.L.; Poggini, L.; Lupi, M.; Polewczyk, V.; Vinai, G.; Torelli, P.; Magnani, A.; Sessoli, R.; Menichetti, S.; et al. Stabilization of an Enantiopure Sub-Monolayer of Helicene Radical Cations on a Au(111) Surface through Noncovalent Interactions. Angew. Chem. Int. Ed. 2021, 60, 15276–15280. [Google Scholar] [CrossRef] [PubMed]
  2. Poggini, L.; Lunghi, A.; Collauto, A.; Barbon, A.; Armelao, L.; Magnani, A.; Caneschi, A.; Totti, F.; Sorace, L.; Mannini, M. Chemisorption of nitronyl–nitroxide radicals on gold surface: An assessment of morphology, exchange interaction and decoherence time. Nanoscale 2021, 13, 7613–7621. [Google Scholar] [CrossRef] [PubMed]
  3. Mas-Torrent, M.; Crivillers, N.; Mugnaini, V.; Ratera, I.; Rovira, C.; Veciana, J. Organic radicals on surfaces: Towards molecular spintronics. J. Mater. Chem. 2009, 19, 1691–1695. [Google Scholar] [CrossRef]
  4. Mas-Torrent, M.; Crivillers, N.; Rovira, C.; Veciana, J. Attaching Persistent Organic Free Radicals to Surfaces: How and Why. Chem. Rev. 2011, 112, 2506–2527. [Google Scholar] [CrossRef]
  5. Casu, M.B. Nanoscale Studies of Organic Radicals: Surface, Interface, and Spinterface. Accounts Chem. Res. 2018, 51, 753–760. [Google Scholar] [CrossRef]
  6. Poggini, L.; Cucinotta, G.; Sorace, L.; Caneschi, A.; Gatteschi, D.; Sessoli, R.; Mannini, M. Nitronyl nitroxide radicals at the interface: A hybrid architecture for spintronics. Rendiconti Lince 2018, 29, 623–630. [Google Scholar] [CrossRef]
  7. Junghoefer, T.; Nowik-Boltyk, E.M.; de Sousa, J.A.; Giangrisostomi, E.; Ovsyannikov, R.; Chassé, T.; Veciana, J.; Mas-Torrent, M.; Rovira, C.; Crivillers, N.; et al. Stability of radical-functionalized gold surfaces by self-assembly and on-surface chemistry. Chem. Sci. 2020, 11, 9162–9172. [Google Scholar] [CrossRef]
  8. Ajayakumar, M.R.; Alcón, I.; Bromley, S.T.; Veciana, J.; Rovira, C.; Mas-Torrent, M. Direct covalent grafting of an organic radical core on gold and silver. RSC Adv. 2017, 7, 20076–20083. [Google Scholar] [CrossRef] [Green Version]
  9. Ajayakumar, M.R.; Moreno, C.; Alcón, I.; Illas, F.; Rovira, C.; Veciana, J.; Bromley, S.T.; Mugarza, A.; Mas-Torrent, M. Neutral Organic Radical Formation by Chemisorption on Metal Surfaces. J. Phys. Chem. Lett. 2020, 11, 3897–3904. [Google Scholar] [CrossRef]
  10. Mukherjee, S.; Boudouris, B.W. Organic Radical Polymers: New Avenues in Organic Electronics; Springer: Berlin/Heidelberg, Germany, 2017. [Google Scholar]
  11. Tomlinson, E.P.; Hay, M.E.; Boudouris, B.W. Radical Polymers and Their Application to Organic Electronic Devices. Macromolecules 2014, 47, 6145–6158. [Google Scholar] [CrossRef]
  12. Friebe, C.; Schubert, U.S. High-Power-Density Organic Radical Batteries. Top. Curr. Chem. Collect. 2019, 375, 65–99. [Google Scholar] [CrossRef]
  13. Saal, A.; Friebe, C.; Schubert, U.S. Polymeric Blatter’s radical via CuAAC and ROMP. Macromol. Chem. Phys. 2021, 222, 2100194. [Google Scholar] [CrossRef]
  14. Zhang, K.; Monteiro, M.J.; Jia, Z. Stable organic radical polymers: Synthesis and applications. Polym. Chem. 2016, 7, 5589–5614. [Google Scholar] [CrossRef]
  15. Pinto, L.F.; Lloveras, V.; Zhang, S.; Liko, F.; Veciana, J.; Muñoz-Gómez, J.L.; Vidal-Gancedo, J. Fully Water-Soluble Polyphosphorhydrazone-Based Radical Dendrimers Functionalized with Tyr-PROXYL Radicals as Metal-Free MRI T1 Contrast Agents. ACS Appl. Bio. Mater. 2020, 3, 369–376. [Google Scholar] [CrossRef] [Green Version]
  16. Ali, B.M.; Velavan, B.; Sudhandiran, G.; Sridevi, J.; Nasar, A.S. Radical dendrimers: Synthesis, anti-tumor activity and enhanced cytoprotective performance of TEMPO free radical functionalized polyurethane dendrimers. Eur. Polym. J. 2020, 122, 109354. [Google Scholar] [CrossRef]
  17. Badetti, E.; Lloveras, V.; Muñoz-Gómez, J.L.; Sebastián, R.M.; Caminade, A.M.; Majoral, J.P.; Veciana, J.; Vidal-Gancedo, J. Radical dendrimers: A family of five generations of phosphorus dendrimers functionalized with TEMPO radicals. Macromolecules 2014, 47, 7717–7724. [Google Scholar] [CrossRef] [Green Version]
  18. Yordanov, A.T.; Yamada, K.-I.; Krishna, M.C.; Mitchell, J.B.; Woller, E.; Cloninger, M.; Brechbiel, M.W. Spin-Labeled Dendrimers in EPR Imaging with Low Molecular Weight Nitroxides. Angew. Chem. Int. Ed. 2001, 40, 2690–2692. [Google Scholar] [CrossRef]
  19. Mezzina, E.; Manoni, R.; Romano, F.; Lucarini, M. Spin-Labelling of Host-Guest Assemblies with Nitroxide Radicals. Asian J. Org. Chem. 2015, 4, 296–310. [Google Scholar] [CrossRef]
  20. Casati, C.; Franchi, P.; Pievo, R.; Mezzina, E.; Lucarini, M. Unraveling Unidirectional Threading of α-Cyclodextrin in a [2]Rotaxane through Spin Labeling Approach. J. Am. Chem. Soc. 2012, 134, 19108–19117. [Google Scholar] [CrossRef] [Green Version]
  21. Franchi, P.; Fanì, M.; Mezzina, E.; Lucarini, M. Increasing the Persistency of Stable Free-Radicals: Synthesis and Characterization of a Nitroxide Based [1]Rotaxane. Org. Lett. 2008, 10, 1901–1904. [Google Scholar] [CrossRef]
  22. Chechik, V.; Ionita, G. Bis spin-labelled cyclodextrins. New J. Chem. 2007, 31, 1726–1729. [Google Scholar] [CrossRef]
  23. Beejapur, H.A.; Campisciano, V.; Franchi, P.; Lucarini, M.; Giacalone, F.; Gruttadauria, M. Fullerene as a Platform for Recyclable TEMPO Organocatalysts for the Oxidation of Alcohols. ChemCatChem 2014, 6, 2419–2424. [Google Scholar] [CrossRef]
  24. Yang, C.; Guenzi, M.; Cicogna, F.; Gambarotti, C.; Filippone, G.; Pinzino, C.; Passaglia, E.; Dintcheva, N.T.; Carroccio, S.; Coiai, S. Grafting of polymer chains on the surface of carbon nanotubes via nitroxide radical coupling reaction. Polym. Int. 2016, 65, 48–56. [Google Scholar] [CrossRef]
  25. Tucker-Schwartz, A.K.; Garrell, R.L. Simple Preparation and Application of TEMPO-Coated Fe3O4 Superparamagnetic Nanoparticles for Selective Oxidation of Alcohols. Chem. A Eur. J. 2010, 16, 12718–12726. [Google Scholar] [CrossRef]
  26. Zawada, K.; Tomaszewski, W.; Megiel, E. A smart synthesis of gold/polystyrene core–shell nanohybrids using TEMPO coated nanoparticles. RSC Adv. 2014, 4, 23876–23885. [Google Scholar] [CrossRef]
  27. Hata, K.; Fujihara, H. Preparation and electrochemical polymerization of new multifunctional pyrrolethiolate-stabilized gold and palladium nanoparticles. Chem. Commun. 2002, 2714–2715. [Google Scholar] [CrossRef]
  28. Caragheorgheopol, A.; Chechik, V. Mechanistic aspects of ligand exchange in Au nanoparticles. Phys. Chem. Chem. Phys. 2008, 10, 5029–5041. [Google Scholar] [CrossRef]
  29. Schätz, A.; Grass, R.N.; Stark, W.J.; Reiser, O. TEMPO Supported on Magnetic C/Co-Nanoparticles: A Highly Active and Recyclable Organocatalyst. Chem. A Eur. J. 2008, 14, 8262–8266. [Google Scholar] [CrossRef]
  30. Gozdziewska, M.; Cichowicz, G.; Markowska, K.; Zawada, K.; Megiel, E. Nitroxide-coated silver nanoparticles: Synthesis, surface physicochemistry and antibacterial activity. RSC Adv. 2015, 5, 58403–58415. [Google Scholar] [CrossRef]
  31. Megiel, E. Surface modification using TEMPO and its derivatives. Adv. Colloid Interface Sci. 2017, 250, 158–184. [Google Scholar] [CrossRef]
  32. Hansen, K.-A.; Blinco, J.P. Nitroxide radical polymers—A versatile material class for high-tech applications. Polym. Chem. 2018, 9, 1479–1516. [Google Scholar] [CrossRef]
  33. Ji, Y.; Long, L.; Zheng, Y. Recent advances of stable Blatter radicals: Synthesis, properties and applications. Mater. Chem. Front. 2020, 4, 3433–3443. [Google Scholar] [CrossRef]
  34. Oyaizu, K.; Nishide, H. Radical Polymers for Organic Electronic Devices: A Radical Departure from Conjugated Polymers? Adv. Mater. 2009, 21, 2339–2344. [Google Scholar] [CrossRef]
  35. Rajca, A.; Wang, Y.; Boska, M.; Paletta, J.T.; Olankitwanit, A.; Swanson, M.A.; Mitchell, D.G.; Eaton, S.S.; Eaton, G.R.; Rajca, S. Organic Radical Contrast Agents for Magnetic Resonance Imaging. J. Am. Chem. Soc. 2012, 134, 15724–15727. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Francese, G.; Dunand, F.A.; Loosli, C.; Decurtins, S. Functionalization of PAMAM dendrimers with nitronyl nitroxide radicals as models for the outer-sphere relaxation in dentritic potential MRI contrast agents. Org. Magn. Reson. 2003, 41, 81–83. [Google Scholar] [CrossRef]
  37. Wilcox, D.A.; Agarkar, V.V.; Mukherjee, S.; Boudouris, B.W. Stable Radical Materials for Energy Applications. Annu. Rev. Chem. Biomol. Eng. 2018, 9, 83–103. [Google Scholar] [CrossRef]
  38. Suga, T.; Nishide, H. Stable Radicals: Fundamentals and Applied Aspects of Odd-Electron Compounds; Hicks, R.G., Ed.; Wiley & Sons Ltd.: Chichester, UK, 2010; pp. 507–519. [Google Scholar]
  39. Nevers, D.R.; Brushett, F.R.; Wheeler, D.R. Engineering radical polymer electrodes for electrochemical energy storage. J. Power Sources 2017, 352, 226–244. [Google Scholar] [CrossRef] [Green Version]
  40. Almubayedh, S.; Chahma, M. Electrosynthesis and characterization of stable radical-functionalized oligo/polythiophenes. N. J. Chem. 2015, 39, 7738–7741. [Google Scholar] [CrossRef]
  41. Low, J.Z.; Kladnik, G.; Patera, L.L.; Sokolov, S.; Lovat, G.; Kumarasamy, E.; Repp, J.; Campos, L.M.; Cvetko, D.; Morgante, A.; et al. The Environment-Dependent Behavior of the Blatter Radical at the Metal–Molecule Interface. Nano Lett. 2019, 19, 2543–2548. [Google Scholar] [CrossRef]
  42. De Sousa, J.A.; Bejarano, F.; Gutiérrez, D.; Leroux, Y.R.; Nowik-Boltyk, E.M.; Junghoefer, T.; Giangrisostomi, E.; Ovsyannikov, R.; Casu, M.B.; Veciana, J.; et al. Exploiting the versatile alkyne-based chemistry for expanding the applications of a stable triphenylmethyl organic radical on surfaces. Chem. Sci. 2020, 11, 516–524. [Google Scholar] [CrossRef] [Green Version]
  43. Ruthstein, S.; Artzi, R.; Goldfarb, D.; Naaman, R. EPR studies on the organization of self-assembled spin-labeled organic monolayers adsorbed on GaAs. Phys. Chem. Chem. Phys. 2005, 7, 524–529. [Google Scholar] [CrossRef]
  44. Glosz, K.; Stolarczyk, A.; Jarosz, T. Siloxanes—Versatile Materials for Surface Functionalisation and Graft Copolymers. Int. J. Mol. Sci. 2020, 21, 6387. [Google Scholar] [CrossRef]
  45. Fu, H.; Policarpio, D.M.; Batteas, J.D.; Bergbreiter, D.E. Redox-controlled ‘smart’ polyacrylamide solubility. Polym. Chem. 2010, 1, 631–633. [Google Scholar] [CrossRef]
  46. Schattling, P.; Jochum, F.D.; Theato, P. Multi-responsive copolymers: Using thermo-, light- and redox stimuli as three independent inputs towards polymeric information processing. Chem. Commun. 2011, 47, 8859–8861. [Google Scholar] [CrossRef]
  47. Binder, W.H.; Sachsenhofer, R. ‘Click’ chemistry in polymer and material science: An update. Macromol. Rapid Commun. 2008, 29, 952–981. [Google Scholar] [CrossRef]
  48. Johnson, J.A.; Finn, M.G.; Koberstein, J.T.; Turro, N.J. Construction of Linear Polymers, Dendrimers, Networks, and Other Polymeric Architectures by Copper-Catalyzed Azide-Alkyne Cycloaddition “Click” Chemistry. Macromol. Rapid Commun. 2008, 29, 1421. [Google Scholar] [CrossRef]
  49. Le Droumaguet, B.; Velonia, K. Click Chemistry: A Powerful Tool to Create Polymer-Based Macromolecular Chimeras. Macromol. Rapid Commun. 2008, 29, 1073–1089. [Google Scholar] [CrossRef]
  50. Kunz, T.K.; Wolf, M.O. Electrodeposition and properties of TEMPO functionalized polythiophene thin films. Polym. Chem. 2011, 2, 640–644. [Google Scholar] [CrossRef]
  51. Rogers, F.J.M.; Norcott, P.L.; Coote, M.L. Recent advances in the chemistry of benzo[e][1,2,4]triazinyl radicals. Org. Biomol. Chem. 2020, 18, 8255–8277. [Google Scholar] [CrossRef]
  52. Blatter, H.M.; Lukaszewski, H. A new stable free radical. Tetrahedron Lett. 1968, 9, 2701–2705. [Google Scholar] [CrossRef]
  53. Karecla, G.; Papagiorgis, P.; Panagi, N.; Zissimou, G.A.; Constantinides, C.P.; Koutentis, P.A.; Itskos, G.; Hayes, S.C. Emission from the stable Blatter radical. N. J. Chem. 2017, 41, 8604–8613. [Google Scholar] [CrossRef]
  54. Constantinides, C.P.; Koutentis, P.A.; Krassos, H.; Rawson, J.M.; Tasiopoulos, A.J. Characterization and Magnetic Properties of a “Super Stable” Radical 1,3-Diphenyl-7-trifluoromethyl-1,4-dihydro-1,2,4-benzotriazin-4-yl. J. Org. Chem. 2011, 76, 2798–2806. [Google Scholar] [CrossRef]
  55. Jasiński, M.; Szczytko, J.; Pociecha, D.; Monobe, H.; Kaszyński, P. Substituent-Dependent Magnetic Behavior of Discotic Benzo[e][1,2,4]triazinyls. J. Am. Chem. Soc. 2016, 138, 9421–9424. [Google Scholar] [CrossRef]
  56. Jasiński, M.; Szymańska, K.; Gardias, A.; Pociecha, D.; Monobe, H.; Szczytko, J.; Kaszyński, P. Tuning the Magnetic Properties of Columnar Benzo[e][1,2,4]triazin-4-yls with the Molecular Shape. ChemPhysChem 2019, 20, 636–644. [Google Scholar] [CrossRef]
  57. Shivakumar, K.I.; Pociecha, D.; Szczytko, J.; Kapuściński, S.; Monobe, H.; Kaszyński, P. Photoconductive bent-core liquid crystalline radicals with a paramagnetic polar switchable phase. J. Mater. Chem. C 2020, 8, 1083–1088. [Google Scholar] [CrossRef]
  58. Zheng, Y.; Miao, M.-S.; Kemei, M.C.; Seshadri, R.; Wudl, F. The Pyreno-Triazinyl Radical—Magnetic and Sensor Properties. Isr. J. Chem. 2014, 54, 774–778. [Google Scholar] [CrossRef]
  59. Zheng, Y.; Miao, M.-S.; Dantelle, G.; Eisenmenger, N.D.; Wu, G.; Yavuz, I.; Chabinyc, M.L.; Houk, K.N.; Wudl, F. A Solid-State Effect Responsible for an Organic Quintet State at Room Temperature and Ambient Pressure. Adv. Mater. 2015, 27, 1718–1723. [Google Scholar] [CrossRef]
  60. Ciccullo, F.; Calzolari, A.; Bader, K.; Neugebauer, P.; Gallagher, N.M.; Rajca, A.; van Slageren, J.; Casu, M.B. Interfacing a Potential Purely Organic Molecular Quantum Bit with a Real-Life Surface. ACS Appl. Mater. Interfaces 2018, 11, 1571–1578. [Google Scholar] [CrossRef]
  61. Ciccullo, F.; Gallagher, N.M.; Geladari, O.; Chasse, T.; Rajca, A.; Casu, M.B. A Derivative of the Blatter Radical as a Potential Metal-Free Magnet for Stable Thin Films and Interfaces. ACS Appl. Mater. Interfaces 2016, 8, 1805–1812. [Google Scholar] [CrossRef]
  62. Poryvaev, A.S.; Gjuzi, E.; Polyukhov, D.M.; Hoffmann, F.; Fröba, M.; Fedin, M.V. Blatter radical-grafted mesoporous silica as prospective nanoplatform for spin manipulation at ambient conditions. Angew. Chem. Int. Ed. 2021, 60, 8683–8688. [Google Scholar] [CrossRef]
  63. Constantinides, C.P.; Obijalska, E.; Kaszyński, P. Access to 1,4-dihydrobenzo[e][1,2,4]triazin-4-yl derivtives. Org. Lett. 2016, 18, 916–919. [Google Scholar] [CrossRef] [PubMed]
  64. Kaszyński, P.; Constantinides, C.P.; Young, V.G., Jr. The Planar Blatter Radical: Structural Chemistry of 1,4-Dihydrobenzo[e][1,2,4]triazin-4-yls. Angew. Chem. Int. Ed. 2016, 55, 11149–11152. [Google Scholar] [CrossRef] [PubMed]
  65. Abbasi, M.; Mohammadizadeh, M.R.; Saeedi, N. The synthesis of symmetrical disulfides by reacting organic halides with Na2S2O3·5H2O in DMSO. N. J. Chem. 2016, 40, 89–92. [Google Scholar] [CrossRef]
  66. Shao, C.; Wang, X.; Xu, J.; Zhao, J.; Zhang, Q.; Hu, Y. Carboxylic Acid-Promoted Copper(I)-Catalyzed Azide–Alkyne Cycloaddition. J. Org. Chem. 2010, 75, 7002–7005. [Google Scholar] [CrossRef]
  67. Neva, T.; Carmona, T.; Benito, J.M.; Przybylski, C.; Mellet, C.O.; Mendicuti, F.; Fernández, J.M.G. Dynamic Control of the Self-Assembling Properties of Cyclodextrins by the Interplay of Aromatic and Host-Guest Interactions. Front. Chem. 2019, 7, 72. [Google Scholar] [CrossRef]
  68. Neva, T.; Ortiz Mellet, C.; García Fernández, J.M.; Benito, J.M. Multiply–linked cyclodextrin–aromatic hybrids: Caps, hinges and clips. J. Carbohydr. Chem. 2019, 38, 470–493. [Google Scholar] [CrossRef]
  69. Neva, T.; Carbajo-Gordillo, A.I.; Benito, J.M.; Lana, H.; Marcelo, G.; Mellet, C.O.; De Ilarduya, C.T.; Mendicuti, F.; Fernández, J.M.G. Tuning the Topological Landscape of DNA–Cyclodextrin Nanocomplexes by Molecular Design. Chem. A Eur. J. 2020, 26, 15259–15269. [Google Scholar] [CrossRef]
  70. Balbuena, P.; Lesur, D.; Álvarez, M.J.G.; Mendicuti, F.; Mellet, C.O.; Fernández, J.M.G. One-pot regioselective synthesis of 2I,3I-O-(o-xylylene)-capped cyclomaltooligosaccharides: Tailoring the topology and supramolecular properties of cyclodextrins. Chem. Commun. 2007, 3270–3272. [Google Scholar] [CrossRef] [Green Version]
  71. Fulmer, G.R.; Miller, A.J.M.; Sherden, N.H.; Gottlieb, H.E.; Nudelman, A.; Stoltz, B.M.; Bercaw, J.E.; Goldberg, K.I. NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist. Organometallics 2010, 29, 2176–2179. [Google Scholar] [CrossRef] [Green Version]
Molecules 27 01176 g001 550
Figure 1. The structure of the prototypical Blatter radical (A), the “super stable” derivative (B), and functional derivatives (C–E).
Figure 1. The structure of the prototypical Blatter radical (A), the “super stable” derivative (B), and functional derivatives (C–E).
Molecules 27 01176 g001
Molecules 27 01176 g002 550
Figure 2. The structure of three types of radicals (I–III) for molecular grafting. Reported compounds: Ia–Ie, IIa–IId, IIIa and IIIb.
Figure 2. The structure of three types of radicals (I–III) for molecular grafting. Reported compounds: Ia–Ie, IIa–IId, IIIa and IIIb.
Molecules 27 01176 g002
Molecules 27 01176 sch001 550
Scheme 1. Synthesis of radicals (Ia–IIIa). Reagents and conditions: (i) 1. PhLi, THF, Ar, −5 °C, 1 h; 2. Air, 0.5 h, 77–92% yield; (ii) 1. Pd/C, H2, 50 psi, THF/EtOH, 2 days, 2. Air, 0% yield.
Scheme 1. Synthesis of radicals (Ia–IIIa). Reagents and conditions: (i) 1. PhLi, THF, Ar, −5 °C, 1 h; 2. Air, 0.5 h, 77–92% yield; (ii) 1. Pd/C, H2, 50 psi, THF/EtOH, 2 days, 2. Air, 0% yield.
Molecules 27 01176 sch001
Molecules 27 01176 sch002 550
Scheme 2. Preparation of benzo[e][1,2,4]triazines 1–3. Reagents and conditions: (i) 1-fluoro-2-nitro-5-trifluoromethylbenzene, DMSO, 70 °C, 7 h; (ii) 1. Sn, glacial AcOH, rt for 2 h, then 115 °C for 0.5 h; 2. NaIO4; (iii) 1. Pd/C, H2, THF/EtOH, 2 days; 2. Air.
Scheme 2. Preparation of benzo[e][1,2,4]triazines 1–3. Reagents and conditions: (i) 1-fluoro-2-nitro-5-trifluoromethylbenzene, DMSO, 70 °C, 7 h; (ii) 1. Sn, glacial AcOH, rt for 2 h, then 115 °C for 0.5 h; 2. NaIO4; (iii) 1. Pd/C, H2, THF/EtOH, 2 days; 2. Air.
Molecules 27 01176 sch002
Molecules 27 01176 sch003 550
Scheme 3. Synthesis of tosylates Ib–IIIb and phosphates Ic and IIc. Reagents and conditions: (i) TsCl, pyridine, CH2Cl2, rt, Ar, overnight, 82–96% yield; (ii) (EtO)2POCl, DMAP, Et3N, THF, rt, 1 h, Ar, 83–86% yield.
Scheme 3. Synthesis of tosylates Ib–IIIb and phosphates Ic and IIc. Reagents and conditions: (i) TsCl, pyridine, CH2Cl2, rt, Ar, overnight, 82–96% yield; (ii) (EtO)2POCl, DMAP, Et3N, THF, rt, 1 h, Ar, 83–86% yield.
Molecules 27 01176 sch003
Molecules 27 01176 sch004 550
Scheme 4. Synthesis of disulfides Id and IId, and azide Ie. Reagents and conditions: (i) 1. Na2S2O3, DMSO, 60 °C, overnight, 2. I2, CH2Cl2, rt, 10 min, 18% yield; (ii) NaN3, DMF, 50 °C, Ar, 5 h, 42–73% yield.
Scheme 4. Synthesis of disulfides Id and IId, and azide Ie. Reagents and conditions: (i) 1. Na2S2O3, DMSO, 60 °C, overnight, 2. I2, CH2Cl2, rt, 10 min, 18% yield; (ii) NaN3, DMF, 50 °C, Ar, 5 h, 42–73% yield.
Molecules 27 01176 sch004
Molecules 27 01176 sch005 550
Scheme 5. Synthesis of Ig via azide-alkyne “click” reaction. Reagents and conditions: (i) Phenylacetylene, CuSO4·5H2O, sodium L-ascorbate, benzoic acid, t-BuOH/H2O 1:2, rt, 5 h, 84% yield.
Scheme 5. Synthesis of Ig via azide-alkyne “click” reaction. Reagents and conditions: (i) Phenylacetylene, CuSO4·5H2O, sodium L-ascorbate, benzoic acid, t-BuOH/H2O 1:2, rt, 5 h, 84% yield.
Molecules 27 01176 sch005
Molecules 27 01176 g003 550
Figure 3. Electronic absorption spectrum in CH2Cl2 (left) and ERP spectrum in benzene (right) for Ia.
Figure 3. Electronic absorption spectrum in CH2Cl2 (left) and ERP spectrum in benzene (right) for Ia.
Molecules 27 01176 g003
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Kapuściński, S.; Anand, B.; Bartos, P.; Garcia Fernandez, J.M.; Kaszyński, P. Tethered Blatter Radical for Molecular Grafting: Synthesis of 6-Hydroxyhexyloxy, Hydroxymethyl, and Bis(hydroxymethyl) Derivatives and Their Functionalization. Molecules 2022, 27, 1176. https://doi.org/10.3390/molecules27041176

AMA Style

Kapuściński S, Anand B, Bartos P, Garcia Fernandez JM, Kaszyński P. Tethered Blatter Radical for Molecular Grafting: Synthesis of 6-Hydroxyhexyloxy, Hydroxymethyl, and Bis(hydroxymethyl) Derivatives and Their Functionalization. Molecules. 2022; 27(4):1176. https://doi.org/10.3390/molecules27041176

Chicago/Turabian Style

Kapuściński, Szymon, Bindushree Anand, Paulina Bartos, Jose M. Garcia Fernandez, and Piotr Kaszyński. 2022. "Tethered Blatter Radical for Molecular Grafting: Synthesis of 6-Hydroxyhexyloxy, Hydroxymethyl, and Bis(hydroxymethyl) Derivatives and Their Functionalization" Molecules 27, no. 4: 1176. https://doi.org/10.3390/molecules27041176

Article Metrics

Back to TopTop