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. 2024 Nov 21;9(48):47532–47542. doi: 10.1021/acsomega.4c06250

Clean and Efficient Green Protocol of N,N′-Bis(2-(arylazo)-2-(aroyl)vinyl)ethane-1,2-diamines in Aqueous Medium without Catalyst: Synthesis and Photophysical Characterization

Abdulrahman M Alazemi †,*, Kamal M Dawood ‡,*, Hamad M Al-Matar †, Wael M Tohamy †
PMCID: PMC11618421  PMID: 39651086

Abstract

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An interesting platform for the construction of novel N,N′-bis(2-(arylazo)-2-(aroyl)vinyl)ethane-1,2-diamines is reported in this work. These bis-arylazo compounds were assembled based on the reaction of ethylenediamine with various 2-arylhydrazono-3-oxopropanals in aqueous conditions under both conventional stirring and microwave conditions at ambient temperature. The factors affecting the optimization conditions were intensively practiced. The structures of the new products were established from their spectroscopic analyses and X-ray single crystals. The photophysical behavior of the bis-arylazo derivatives was examined. The UV–vis spectra showed maximum absorption band in the range of 348–383 nm with molar extinction coefficients ranging from 0.89 × 104 to 4.02 × 104 M–1 cm–1. The highest molar absorptivity coefficient (∼45 × 103 M–1 cm–1) was observed in CHCl3 solvent. The fluorescence properties showed that some compounds were interesting fluorophore materials with high Stokes shifts. The photoluminescence study of some compounds was promising, with maximal emission peaks ranging between 417–436 nm.

1. Introduction

Substituted amines are important pharmacophores in a wide range of biologically active compounds. Several amine derivatives are presented to have potent analgesic, antiparasitic, antifungal, and antibacterial activities.1,2 They also behaved as promising electronic materials with semiconductive and piezoelectric properties.3−5 Bis-amines are good substrates for the synthesis of carbon fiber reinforced composite materials,6 with highly promising biological applications, such as antimicrobial7,8 and anticancer9−14 activities. On the other side, bis-enaminones are versatile multifunctional substrates with wide applications in combinatorial chemistry and are employed as precursors in synthesizing several heterocyclic systems.15−17 They are also involved as ligands in the synthesis of liquid crystalline metallocomplexes and polymer materials.18,19

The reaction of 1,3-dicarbonyl compounds with diaminoalkanes can produce various products based on the reaction conditions. For example, the reaction of 1,3-diketones and diamines can either result in N,N′-ethylene-bis(1,3-aminovinyl ketones)20,21 or 1,4-diazepine derivatives.22−24 In the presence of nickel(II), 1,3-diketones and ethylenediamine reacted together to yield the nickel chelates of N,N′-bis(2-(arylazo)-2-(aroyl)vinyl)ethane-1,2-diamines.25,26

Direct condensation of amines with dicarbonyl compounds at reflux under azeotropic water removal conditions resulted in the formation of enaminoketones.27 This reaction was conducted using a number of catalysts such as Zn(ClO4)2·6H2O,28 β-cyclodextrin in water,29 metal salts,30−33 VO(acac)2,34 metal triflates,35−38 metal oxides,39,40 Bi(TFA)3,33 solid supported reagents,41−44 ceric ammonium nitrate,45 trimethylsilyl trifluoromethanesulfonate (TMSTf),46 [(PPh3)AuCl]/AgOTf,47 formic acid,48 ionic liquids,49 tris(hydrogensulfato)boron or trichloroacetic acid,50 K-10/ultrasound,51 microwave (MW)-assisted,52,53 and phosphomolybdic acid (PMA).54 However, some of such approaches have synthetic drawbacks, such as longer reaction times, use of toxic solvents, low yields, use of excess amounts of catalyst, use of toxic metal catalysts, lack of selectivity, and, in some cases, catalyst preparation requires tedious workup procedures.

Therefore, the current study aims to find alternative conditions for the synthesis of N,N′-bis(2-(arylazo)-2-(aroyl)vinyl)ethane-1,2-diamines with the achievement of the following goals: (1) milder reaction conditions, (2) high product yield, (3) shorter reaction time, and (4) encourage cost-effective and green experimental procedures. These goals were accomplished by carrying out the reaction under MW and environmentally favorable water solvent, where water is the most proper solvent for a green environment.55−57 In addition, utilizing MW energy speeds up organic reactions, resulting in cleaner products, higher yields, and better time management.58−66 In continuation of our research projects involving various green conditions (water, ultrasonic, MW irradiation, and metal catalysts) for the functionalization of several ketohydrazonals and various reactive substrates,67−74 we herein carry out a green synthetic protocol for the construction of various N,N′-bis(2-(arylazo)-2-(aroyl)vinyl)ethane-1,2-diamines via reaction of 3-ketohydrazonals with ethylenediamine under aqueous conditions.

2. Results and Discussion

2.1. Chemistry

The highly reactive substrates: 2-arylhydrazono-3-oxopropanals 1a–o were assembled following the previously reported procedures in the literature.75,76 Afterward, a demonstrative reaction example was carried out by treating ethylenediamine 2 with two equivalents of 2-(4-chlorophenyl)hydrazono-3-oxopropanal 1a. The variation of reaction solvents and heating modes on the reaction productivity was thoroughly examined (Table 1 and Scheme 1). The reaction was followed by thin-layer chromatography (TLC). Conducting the reaction in solvents such as DMF, acetic acid, toluene, cyclohexane, chloroform, or 1,4-dioxane at room temperature (rt) for 90 min (entries 1–6, Table 1), afforded low yields of the bis-arylazo derivative 3a of 12 to 35%. When the same reaction conditions were performed under MW irradiation, the isolated yields increased to 25 to 45%. Later, when the reaction was conducted in water, the isolated product yield increased to 66 and 76% under thermal and MW conditions at rt, respectively (entry 7, Table 1). Repeating the same reaction using propanol, isobutanol, ethanol, or methanol solvents resulted in the formation of compound 3a in 50–69% under thermal condition at rt, compared with 61–80% yields under MW (entries 8–11, Table 1). However, methanol/H2O mixed solvent (2:1) was found to be the optimal reaction solvent in both thermal and MW conditions at rt, where the formation of 3a was accomplished in 80 and 92% yield, respectively (entry 12, Table 1). It was reported that polar solvents facilitate reactions to proceed faster under MW conditions where they absorb MW energy faster than thermal mode. When the same reaction was repeated at 100 °C, the isolated product of 3a decreased to 65 and 75% under thermal and MW conditions, respectively (entry 13, Table 1). Also, when further lowering the temperature to 50 °C, compound 3a yielded 68 and 79% under thermal and MW conditions, respectively (entry 14, Table 1). Changing the ratio of methanol/water to (1:1) led to the formation of the bis-arylazo derivative 3a to 74 and 85% yields under thermal and MW conditions, respectively (entry 15, Table 1). Finally, repeating the same reaction conditions using a methanol/water (1:2) aqueous solvent dropped the yield of compound 3a to 72 and 83% under thermal and MW conditions, respectively (entry 16, Table 1). The structure of product 3a was established from its elemental and spectroscopic analyses (IR, 1H- and 13C NMR, MS, and HRMS).

Table 1. Optimization of the Condensation Reaction Condition of 1a with 2a.

entry solvent temp. °C conventional (90 min) MW (15 min)
      yield (%) yield (%)
1 DMF rt 16 25
2 acetic rt 18 28
3 toluene rt 25 36
4 cyclohexane rt 22 32
5 chloroform rt 28 37
6 1,4 dioxane rt 35 45
7 H2O rt 66 76
8 propanol rt 50 61
9 isobutanol rt 64 75
10 ethanol rt 60 70
11 methanol rt 69 80
12 methanol/H2O(2:1) rt 80 92
13 methanol/H2O (2:1) 100 65 75
14 methanol/H2O (2:1) 50 68 79
15 methanol/H2O (1:1) rt 74 85
16 methanol/H2O (1:2) rt 72 83
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a

Reaction conditions: 1a (1 mmol), 2 (0.5 mmol), and solvent (9 mL); stirrer for 90 min at rt, for 15 min MW irradiation (200 W) at 25 °C.

Scheme 1. Reaction of the Arylhydrazonopropanal 1a with Ethylenediamine 2.

Scheme 1

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From the above results, decreasing the yield with an increasing temperature can be attributed to both thermodynamic and kinetic factors influencing the reaction. At elevated temperatures, reactants or intermediates involved in the condensation reaction may undergo decomposition or give undesired side products, leading to a decrease in the product yields. Such thermal degradation is common in reactions involving sensitive organic compounds, where optimal yields are often achieved at lower temperatures. This agrees with the observed significant drop in the yield of compound 3a at 100 °C compared to rt, suggesting that higher temperatures promote undesired reactions or decompose intermediates, thereby reducing the efficiency of the desired products.

The optimal reaction conditions obtained from Table 1 were utilized to construct a library of the bis-arylazo derivatives 3a–o (Table 2). Thus, treatment of various 2-(aryl)hydrazono-3-oxopropanal 1a–o with ethylenediamine 2 in a 2:1 molar ratio in methanol/H2O mixed solvent (2:1 v/v) was carried out at rt under both conventional stirring and MW irradiating conditions (Scheme 2). Conducting the reaction under MW conditions resulted in an increase in the production yields of compounds 3a–o compared to conventional stirring. The conventional condition yields varied between 50 and 80%, but the yields increased under MW conditions to be ranged between 59 to 92%. Studying the effect of variation of the electronic behaviors of the 2-(aryl)hydrazono-3-oxopropanal 1a–o substrates was also achieved. It was found that substrate 1 having highly electron-withdrawing substituents such as NO2 and Cl (where Ar = 4-ClC6H4 and R = 4-NO2C6H4) provided the highest yield under both conventional stirring and MW irradiation conditions. The lowest yields were obtained for substrates 1 having electron-releasing substituents, such as methyl or methoxy groups. All structures of the obtained pure products were fully characterized using spectral analyses as well as X-ray single crystals of a demonstrative compound 3k (Figure 1).77 A suggested reaction mechanism for the formation of a demonstrative example of the bis-arylazo derivatives 3a–o is described in Scheme 3.

Table 2. Synthesis of the Bis(arylazo) Derivatives 3a–o under Conventional and MW Conditionsa.

entry products R Ar conv. (90 min) MW (10 min)
        yieldsb yieldsb
1 3a 4-NO2C6H4 4-ClC6H4 80 92
2 3b 4-NO2C6H4 4-BrC6H4 75 88
3 3c 4-NO2C6H4 C6H5 68 75
4 3d 4-ClC6H4 C6H5 70 82
5 3e 4-ClC6H4 4-BrC6H4 72 80
6 3f 4-BrC6H4 4-ClC6H4 62 73
7 3g 4-FC6H4 4-ClC6H4 74 85
8 3h 4-FC6H4 4-BrC6H4 72 82
9 3i 4-OMeC6H4 4-BrC6H4 53 63
10 3j 4-OMeC6H4 4-ClC6H4 54 63
11 3k C6H5 4-ClC6H4 57 66
12 3l C6H5 4-BrC6H4 55 66
13 3m C6H5 o-NO2C6H4 50 59
14 3n 2-thienyl 4-CH3C6H4 67 76
15 3o 2-thienyl C6H5 69 78
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a

Reaction condition: 1a–o (1 mmol) and ethylenediamine (2) (0.5 mmol), in MeOH/H2O (2:1) (9 mL), stirrer at rt for 90 min, MW irradiation (200 W) at 25 °C for 15 min.

b

Isolated yields.

Scheme 2. Reaction of Arylhydrazonopropanals 1a–o with Ethylenediamine 2.

Scheme 2

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Figure 1.

Figure 1

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X-ray single crystals of compound 3k obtained from diffraction data.

Scheme 3. Proposed Reaction Mechanism for the Formation of 3a.

Scheme 3

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2.2. Photophysical Studies

The photophysical behavior of the bis-diamine derivatives 3a–o presented in Table 3, showing the variation of electronic behavior of the substituents, has been studied. As shown in Figure 2a, the UV–vis spectrum of the dichloromethane solution of 3a–o showed the maximum absorption band (λmax) in the range of 348–383 nm. This can be attributed to n → π* and/or π → π* electronic transitions of azo chromophores with molar extinction coefficients ranging from 0.89 × 104 to 4.02 × 104 M–1 cm–1. Meanwhile, the measured molar extinction coefficient (εmax/abs) for 3h is ∼3.69 × 104 M–1 cm–1 at 378 nm, which appeared to be higher than the corresponding values for 3b (εmax/abs ∼ 1.28 × 104 M–1 cm–1 at 375 nm) and 3i (εmax/abs ∼ 3.01 × 104 M–1 cm–1 at 383 nm) (Table 4).2.2.

Table 3. Molecular Structures of the Bis-Arylazo Derivatives 3a–o.

entry bis-arylazo compds R Ar
1 3a 4-NO2C6H4 4-ClC6H4
2 3b 4-NO2C6H4 4-BrC6H4
3 3c 4-NO2C6H4 C6H5
4 3d 4-ClC6H4 C6H5
5 3e 4-ClC6H4 4-BrC6H4
6 3f 4-BrC6H4 4-ClC6H4
7 3g 4-FC6H4 4-ClC6H4
8 3h 4-FC6H4 4-BrC6H4
9 3i 4-OMeC6H4 4-BrC6H4
10 3j 4-OMeC6H4 4-ClC6H4
11 3k C6H5 4-ClC6H4
12 3l C6H5 4-BrC6H4
13 3m C6H5 o-NO2C6H4
14 3n 2-thienyl 4-CH3C6H4
15 3o 2-thienyl C6H5
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Figure 2.

Figure 2

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(a) UV–vis spectra of the bis-arylazo derivatives 3a–o recorded in DMSO. (b) Emission spectra of the bis-arylazo derivatives 3a–o recorded in DMSO.

Table 4. Photophysical Properties of the Synthesized Bis-Arylazo Derivatives 3a–o.

bis-arylazo compds. absorptiona λmax/abs (nm) εmax/abs M–1 cm–1 emissionb λmax/em (nm) Stokes shiftsc (nm)
3a 377 40,212 424 47
3b 375 12,744 421 46
3c 373 27,971 420 47
3d 370 16,276 415 45
3e 375 36,684 435 60
3f 381 20,073 422 41
3g 376 40,485 441 65
3h 378 36,928 426 48
3i 383 30,076 432 49
3j 380 38,358 429 49
3k 377 37,128 424 47
3l 353 29,172 434 81
3m 348 8955 389 41
3n 376 58,403 424 48
3o 373 55,504 437 64
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a

Determined in DMSO at rt when the concentration of each compound is 1.0 × 10–5 M.

b

Excited at the longest wavelength of the absorption maxima.

c

Stokes shifts are provided as wavelength differences, Δλmax = λmax(em) – λmax(ex).

The UV–vis absorption spectra of all of the prepared bis-arylazo derivatives are shown in Figure 2a. The derivatives that have varied substitutions R at the 1-prop-2-enone moiety (3b, 3e, 3h, 3i, and 3l) have band range 353–383 nm (Table 4), 3i (383 nm) > 3h (378 nm) > 3b, 3e (375 nm) > 3l (353 nm). When the electron-donating substituent (methoxy group) was introduced at the phenyl group of the 1-prop-2-enone (3i), the absorption spectra gave a considerable redshift (383 nm).

The fluorescence properties of 3a–o in DMSO were also studied (Figure 2b). We found that the emission maximum emerges in the visible region, which appeared in the 389–441 nm range. This may be attributed to the azo forms of the synthesized bis-arylazo derivatives (Table 4). It was found that the emission maximum wavelength was little affected by the nature of the substituent R in the derivatives 3a–e. Bathochromic shift was evoked more effectively by the electron-withdrawing substituents than by the electron-donating substituents. The highest bathochromic shift was observed for the derivative 3i with a methoxy substituent.

The Stokes shifts of the bis-arylazo compounds 3a–o were evaluated and found to range between 41 and 81 nm (Table 4), indicating promising fluorescence characteristics that make them suitable candidates for photonic device applications. Notably, compound 3l, featuring a bromo substituent on the phenyl ring of the 1-prop-2-enone moiety, exhibited the largest Stokes shift of 81 nm and demonstrated an absorption maximum at 353 nm. In contrast, compound 3m, bearing a nitro group at the ortho position of the aryl ring, displayed the smallest Stokes shift of 41 nm with an absorption peak at 349 nm.

The absorption properties of compound 3g were measured in eight solvents; methanol (protic solvent), ethyl acetate (EtOAc), tetrahydrofuran (THF), chloroform, toluene, acetone, acetonitrile, and dimethyl sulfoxide (DMSO) (polar aprotic solvents), as presented in Figure 3. The UV–vis absorption maxima and extinction coefficients are given in Table 5. The absorption spectra of compound 3 (Figure 3) showed maximum absorption in the range of 370–385 nm. This could be related to the azo group and demonstrate apparent solvatochromic performance. Generally, the absorption maximum of 3g was slightly blue-shifted when dissolved in more polar solvents, for example, CHCl3 (385 nm) > THF (379 nm) > acetone (376 nm) > DMSO (375 nm). However, a slight blue shift of 15 nm was observed for the protic solvent MeOH.

Figure 3.

Figure 3

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Absorption spectra of the bis-arylazo derivative 3g in different organic solvents (DMSO, MeOH, CH3CN, acetone, EtOAc, THF, CHCl3, and toluene).

Table 5. UV–Vis Absorption and Emission Spectra of Compound 3g in Solvents of Varied Polaritya.

solvent absorption λmax/abs εmax/abs M–1 cm–1 emissionb λmax/em
DMSO 375 40,485 424
MeOH 370 31,657 417
CH3CN 374 42,244 422
acetone 376 46,316 424
EtOAc 377 42,524 425
THF 379 40,287 429
CHCl3 385 47,574 436
toluene 384 43,080 434
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a

Concentration of 3g 1.0 × 10–5 M in different solvents.

b

Excitations were executed at or near the wavelength position of absorption maxima.

Additionally, the highest molar absorptivity coefficients (∼45 × 103 M–1 cm–1) were found in CHCl3, acetone, and toluene; however, the median absorptivity coefficients (∼42 × 103 M–1 cm–1) were observed in acetonitrile and EtOAc. The lowest absorptivity coefficient (∼32 × 103 M–1 cm–1) was noted in DMSO, methanol, and THF (Table 5).

The photoluminescence (PL) study of compound 3g in different solvents is shown in Figure 4. Herein, it was observed that the solvent effect was more pronounced in the maximal emission peak range between 417 and 436 nm: for example, toluene (434 nm), CHCl3 (436 nm), THF (429 nm), EtOAc (425 nm), and acetone (424 nm) (Table 5). However, in the polar aprotic solvents: CH3CN (422 nm) and DMSO (424 nm) and, in the polar protic solvent, MeOH (417 nm). Compound 3g displayed an increasing blue shift as the polarity of the solvent increased. This could be caused by many reasons, one of which is (1) change in the nature of the emitting state induced by the solvent; (2) dipole–dipole interactions between solute and the solvent; and (3) specific solute–solvent interactions, such as H-bonding.

Figure 4.

Figure 4

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Effect of the solvent polarity of DMSO, MeOH, CH3CN, acetone, EtOAc, THF, CHCl3, and toluene on the emission spectra of the bis-arylazo compound 3g.

Thus, the spectroscopic data indicated a correlation between the nature of the substituents on the bis-arylazo derivatives and their photophysical properties. Specifically, a systematic trend was observed, where electron-withdrawing groups, such as (NO2) and (Cl), consistently resulted in a red shift in both absorption and emission wavelengths. This red shift was attributed to the reduction in the energy gap between the excited and ground states. For example, compound 3a (4-NO2C6H4/4-ClC6H4) exhibited absorption and emission maxima at 377 and 424 nm, respectively, while compound 3b (4-NO2C6H4/4-BrC6H4) showed absorption at 375 nm and emission at 421 nm.

Conversely, electron-donating groups like methoxy (OCH3) and methyl (CH3) induce a blueshift, reflecting a higher energy transition due to an increased energy gap. For instance, compound 3i (4-OMeC6H4/4-BrC6H4) displayed an absorption maximum at 383 nm and an emission maximum at 432 nm, while compound 3n (4-CH3C6H4/2-thienyl) had absorption and emission maxima at 376 and 424 nm, respectively.

In summary, the substituents’ electronic properties significantly affected the absorption and emission spectra, with electron-withdrawing groups causing red shifts and electron-donating groups leading to blue shifts. These systematic trends provide a clear understanding of how substituent variations influence the photophysical behavior of the synthesized compounds.

3. Experimental Section

3.1. Materials and Methods

All fine chemicals were highly pure and were purchased from Sigma-Aldrich. The Griffin apparatus was used for measuring the melting points, and they were uncorrected. TLC was established using Polygram SIL G/UV 254 TLC plates, and visualization was performed under UV light at 254 and 365 nm. IR spectra were conducted using KBr disks in a PerkinElmer System 2000 FTIR spectrophotometer. 1H- and 13C NMR spectra were recorded at 600 and 150 MHz, respectively, on a Bruker DPX 400 or 600 superconducting NMR spectrometer, at ambient temperature using DMSO-d6 as a deuterated solvent and TMS as the internal standard (with chemical shifts given in parts per million (ppm)). Low-resolution electron impact mass spectrometry [MS (EI)] and high-resolution [MS (EI)] [HRMS (EI)] were carried out using a high-resolution thermos spectrometer [GC–MS (DFS)] and a magnetic sector mass analyzer at 70.1 eV. MW experiments were conducted using a Discover LabMate CEM MV instrument (300 W with CHEMDRIVER software; Matthews, NC). MW irradiation reactions were carried out in equipped closed-pressured Pyrex tubes. The X-ray single-crystal data were performed, involving a Bruker X8 Prospector and a Rigaku RAXISRAPID diffractometer, and the single-crystal data collection was conducted using Cu Kα radiation at ambient temperature. Solving and refining the structures were performed using the Bruker SHELXTL software package (refinement program-SHELXL97 and structure solution program-SHELXS-97). UV–vis experiments were carried out on a Varian Cary 5 spectrometer from Agilent. Fluorescence assessments were conducted with the Horiba Jobin Yvon-Fluoromax-4 equipped with a time-correlated single-photon counting (TCSPC) module. The 3-oxo-2-arylhydrazonopropanal derivatives 1a–o were synthesized using the procedures reported in the literature.53,54

3.1.1. Synthesis of the N,N′-Bis(2-(arylazo)-2-(aroyl)vinyl)ethane-1,2-diamine Derivatives 3a–o

3.1.1.1. General Method A

Ethylenediamine 2 (0.5 mmol) was added dropwise to a solution of the arylhydrazonopropanals 1a–o (1 mmol) in methanol/H2O (2:1) (9 mL), and the reaction mixture was mixed thoroughly in a process glass vial. The vial was capped properly and irradiated in a MW synthesis system (200 W) for 15 min at rt, and then volatiles were removed in a vacuum to dryness. The crude product was crystallized from ethanol/DMF to afford the corresponding N,N′-ethylene-bis(arylazo) derivatives 3a–o as pure products.

3.1.1.2. General Method B

Ethylenediamine 2 (0.5 mmol) was added dropwise to a solution of arylhydrazonopropanals 1a–o (1 mmol) in methanol/H2O (2:1) (9 mL). The reaction mixture was stirred for 90 min at rt, and then volatiles were removed in a vacuum to dryness. The crude product was crystallized from ethanol/DMF to afford the corresponding N,N′-ethylene-bis(arylazo) derivatives 3a–o as pure products.

3.1.1.3. N,N′-Bis(2-((4-chlorophenyl)azo)-2-(4-nitrobenzoyl)vinyl)ethane-1,2-diamine (3a)

Yellow crystals, mp 260–261 °C; IR (KBr) ν/cm–1: 3435, 3098, 2930, 1647, 1599, 1540, 1492, 1437, 1277; 1H NMR (DMSO-d6): δ 3.90 (s, 2H, CH2), 3.97 (s, 2H, CH2), 6.81–6.82 (m, 2H, Ar–H, and CH=N), 7.19–7.37 (m, 2H, Ar–H), 7.42–7.45 (m, 2H, Ar–H), 7.46–7.52 (m, 4H, Ar–H), 8.05–8.08 (m, 4H, Ar–H), 8.22–8.30 (m, 4H, CH=N, Ar–H), 12.33 (b, 2H, NH); 13C NMR (DMSO-d6): δ 60.81, 119.38, 121.96, 122.59, 122.64, 122.99, 123.02, 128.52, 128.84, 128.97, 129.09, 130.11, 130.46, 131.29, 131.63, 131.75, 136.27, 136.41, 141.87, 148.08, 148.43, 149.11, 150.49, 162.29 (Ar–C), 187.99, 189.09 (CO). MS (EI): 685.58 [M]+. HRMS: calcd for C32H24Cl2N8O6, 686.1195; found, 686.1190.

3.1.1.4. N,N′-Bis(2-((4-bromophenyl)azo)-2-(4-nitrobenzoyl)vinyl)ethane-1,2-diamine (3b)

Yellow crystals, mp 257–258 °C; IR (KBr) ν/cm–1: 3101, 3079, 2924, 1656, 1601, 1540, 1486, 1352, 1299; 1H NMR (DMSO-d6): δ 3.91 (s, 2H, CH2), 3.98 (s, 2H, CH2), 6.83–6.85 (m, 2H, Ar–H, and CH=N), 7.17–7.39 (m, 2H, Ar–H), 7.20–7.32 (m, 2H, Ar–H), 7.46–7.60 (m, 3H, Ar–H), 7.81–7.84 (m, 3H, Ar–H), 7.93–8.06 (m, 4H, Ar–H), 8.28–8.29 (m, 2H, CH=N, Ar–H), 12.36 (b, 2H, NH); 13C NMR (DMSO-d6): δ 60.72, 61.39 (−CH2−), 116.63, 120.17, 122.27, 122.62, 127.97, 131.75, 131.85, 131.96, 131.99, 136.29, 142.25, 142.37, 145.61, 146.04, 148.06, 148.11, 148.20, 148.49, 148.98, 149.10, 162.27 (Ar–C), 187.96, 189.24 (CO). MS (EI): 744.40 [M]+. HRMS: calcd for C32H24Br2N8O6, 774.0185; found, 774.0183.

3.1.1.5. N,N′-Bis(2-(phenylazo)-2-(4-nitrobenzoyl)vinyl)ethane-1,2-diamine (3c)

Orange crystals, mp 268–270 °C; IR (KBr) ν/cm–1: 3098, 3043, 2940, 1645, 1601, 1586, 1459, 1426, 1278; 1H NMR (DMSO-d6): δ 3.91 (s, 2H, CH2), 4.00 (s, 2H, CH2), 6.85–6.88 (m, 2H, Ar–H, and CH=N), 7.13–7.26 (m, 4H, Ar–H), 7.49–7.51 (m, 2H, Ar–H), 7.84–7.95 (m,, 4H, Ar–H), 8.07–8.08 (m, 3H, Ar–H), 8.31–8.33 (m, 5H, Ar–H, and CH=N), 12.53 (b, 2H, 2NH); 13C NMR (DMSO-d6): δ 60.39, 61.27 (−CH2−), 116.45, 119.37, 121.18, 122.12, 122.99, 123.38, 123.57, 128.03, 128.45, 129.36, 129.98, 130.46, 131.29, 136.26, 141.86, 142.40, 144.70, 148.43, 148.60, 151.89, 152.02, 156.30, 156.36 (Ar–C), 185.10, 187.99 (CO). MS (EI): 617.82 [M]+. HRMS: calcd for C32H26N8O6, 618.1975; found, 618.1974.

3.1.1.6. N,N′-Bis(2-(phenylazo)-2-(4-chlorobenzoyl)vinyl)ethane-1,2-diamine (3d)

Yellow crystals, mp 230–231 °C; IR (KBr) ν/cm–1: 3066, 3044, 2929, 1641, 1600, 1540, 1487, 1427, 1277; 1H NMR (DMSO-d6): δ 3.89 (s, 2H, CH2), 4.00 (s, 2H, CH2), 6.84 (s, 2H, Ar–H, and CH=N), 7.18–7.19 (m, 2H, Ar–H), 7.38–7.58 (m, 4H, Ar–H), 7.79–7.80 (m, 4H, Ar–H), 7.81–7.91 (m, 5H, Ar–H), 8.22–8.28 (m, 3H, CH=N, Ar–H), 12.70 (b, 1H, NH), 12.92 (b, 1H, NH); 13C NMR (DMSO-d6): δ 61.09 (−CH2−), 61.70, 117.87, 117.95, 120.56, 120.94, 124.54, 127.87, 127.95, 128.57, 129.39, 129.63, 129.72, 132.02, 136.12, 136.19, 136.47, 138.36, 143.65, 143.80, 155.04 (Ar–C), 188.57, 188.75 (CO). MS (EI): 596.82 [M]+. HRMS: calcd for C32H26Cl2N6O2, 596.1494; found, 596.1483.

3.1.1.7. N,N′-Bis(2-(4-bromophenylazo)-2-(4-chlorobenzoyl)vinyl)ethane-1,2-diamine (3e)

Yellow crystals, mp 144–145 °C; IR (KBr) ν/cm–1: 3208, 2927, 1633, 1580, 1475, 1269; 1H NMR (DMSO-d6): δ 3.87 (s, 2H, CH2), 3.96 (s, 2H, CH2), 6.79–6.81 (m, 2H, Ar–H, and CH = N), 7.22–7.24 (m, 2H, Ar–H), 7.47–7.62 (m, 8H, Ar–H), 7.77–7.78 (m, 2H, Ar–H), 7.87–7.88 (m, 2H, Ar–H), 8.20–8.23 (m, 2H, CH=N, Ar–H), 12.49 (b, 2H, NH); 13C NMR (DMSO-d6): δ 60.52, 61.15 (−CH2−), 116.13, 116.22, 119.35, 119.88, 122.05, 122.41, 127.48, 128.18, 128.44, 131.51, 131.94, 135.20, 135.37, 135.47, 136.41, 137.15, 138.28, 142.35, 142.53, 148.10, 148.46, 150.66, 151.28 (Ar–C), 187.99, 189.28 (CO). MS (EI): 751.54 [M]+. HRMS: calcd for C32H24Br2Cl2N6O2, 751.9704; found, 751.9699.

3.1.1.8. N,N′-Bis(2-(4-chlorophenylazo)-2-(4-bromobenzoyl)vinyl)ethane-1,2-diamine (3f)

Orange crystals, mp 219–220 °C; IR (KBr) ν/cm–1: 3416, 1642, 1585, 1531, 1489, 1257; 1H NMR (DMSO-d6): δ 3.86 (s, 2H, CH2), 3.95 (s, 2H, CH2), 6.80–7.08 (m, 1H, CH=N), 7.19 (d, J = 8.40 Hz, 2H, Ar–H), 7.28 (d, J = 8.40 Hz, 2H, Ar–H), 7.35 (d, J = 8.40 Hz, 1H, Ar–H), 7.45–7.63 (m, 11H, Ar–H), 8.17–8.21 (m, 1H, CH=N), 12.44 (b, 2H, NH); 13C NMR (DMSO-d6): δ 60.83 (−CH2−), 119.04, 119.08, 121.75, 122.09, 126.28, 128.15, 128.85, 128.94, 129.10, 130.42, 131.05, 131.38, 131.69, 131.73, 132.12, 135.74, 136.37, 141.96, 148.09, 150.02, 151.30 (Ar–C), 188.16, 188.37 (CO). MS (EI): 472.10 [M]+. HRMS: calcd for C32H24Br2Cl2N6O2, 751.9704; found, 751.9707.

3.1.1.9. N,N′-Bis(2-(4-chlorophenylazo)-2-(4-fluorobenzoyl)vinyl)ethane-1,2-diamine (3g)

Yellow crystals, mp 197–198 °C; IR (KBr) ν/cm–1: 3053, 2924, 1648, 1597, 1540, 1434, 1272; 1H NMR (DMSO-d6): δ 3.88 (s, 2H, CH2), 3.97 (s, 2H, CH2), 6.80 (d, J = 7.20 Hz, 2H, Ar–H, and CH=N), 7.27–7.45 (m, 5H, Ar–H), 7.46–7.54 (m, 3H, Ar–H), 7.56–7.76 (m, 5H, Ar–H), 8.15–8.22 (m, 3H, CH=N, Ar–H), 12.56 (b, 1H, NH), 12.60 (b, 1H, NH); 13C NMR (DMSO-d6): δ 60.55, 61.17 (−CH2−), 114.25, 114.39, 114.98, 115.12, 122.03, 127.94, 128.04, 128.83, 129.04, 132.26, 136.50, 136.74, 141.99, 142.17, 148.01, 148.42, 150.32, 150.95, 163.60, 165.26 (Ar–C), 187.80, 188.00 (CO). MS (EI): 631.91 [M]+. HRMS: calcd for C32H24Cl2F2N6O2, 632.1305; found, 632.1300.

3.1.1.10. N,N′-Bis(2-(4-bromophenylazo)-2-(4-fluorobenzoyl)vinyl)ethane-1,2-diamine (3h)

Yellow crystals, mp 178–180 °C; IR (KBr) ν/cm–1: 3057, 2899, 1647, 1597, 1542, 1490, 1440, 1270; 1H NMR (DMSO-d6): δ 3.88 (s, 2H, 2CH2), 3.97 (s, 2H, CH2), 6.80 (d, J = 7.20 Hz, 4H, Ar–H, and CH=N), 7.27–7.49 (m, 6H, Ar–H), 7.75–7.85 (m, 5H, Ar–H), 8.21–8.22 (m, 3H, CH=N, Ar–H), 12.61(b, 2H, NH); 13C NMR (DMSO-d6): δ 60.49, 61.11 (−CH2−), 114.25, 114.39, 114.98, 115.12, 116.03, 119.31, 121.99, 122.36, 128.25, 131.80, 132.96, 133.02, 136.53, 136.78, 142.56, 148.08, 151.26, 163.60, 165.26 (Ar–C), 187.77, 187.97 (CO). MS (EI): 721.66 [M]+. HRMS: calcd for C32H24Br2F2N6O2, 722.0295; found, 722.0277.

3.1.1.11. N,N′-Bis(2-(4-bromophenylazo)-2-(4-methoxybenzoyl)vinyl)ethane-1,2-diamine (3i)

Yellow crystals, mp 207–208 °C; IR (KBr) ν/cm–1: 3003, 2927, 1634, 1601, 1541, 1487, 1438, 1258; 1H NMR (DMSO-d6): δ 3.84 (s, 6H, 2-OCH3), 3.85 (s, 2H, CH2), 3.97 (s, 2H, CH2), 6.76–6.77 (m, 2H, Ar–H, and CH=N), 7.25–7.39 (m, 2H, Ar–H), 7.60–7.62 (m, 4H, Ar–H), 7.73–7.75 (m, 2H, Ar–H), 7.88–7.91 (m, 5H, Ar–H), 8.18–8.21 (m, 3H, CH=N, Ar–H), 12.72 (b, 1H, NH), 12.89 (b, 1H, NH); 13C NMR (DMSO-d6): δ 55.27, 55.44 (−OCH3), 60.46, 61.06 (−CH2−), 112.73, 113.44, 113.47, 115.66, 115.75, 119.00, 119.07, 122.18, 129.02, 129.09, 132.47, 136.99, 137.30, 142.52, 142.67, 148.07, 148.70, 150.32, 151.14, 161.34, 161.44 (Ar–C), 187.57, 187.77 (CO). MS (EI): 743.71 [M]+. HRMS: calcd for C34H30Br2N6O4, 744.0695; found, 744.0690.

3.1.1.12. N,N′-Bis(2-(4-chlorophenylazo)-2-(4-methoxybenzoyl)vinyl)ethane-1,2-diamine (3j)

Yellow crystals, mp 190–191 °C; IR (KBr) ν/cm–1: 3250, 2894, 1634, 1602, 1575, 1540, 1492, 1438, 1307; 1H NMR (DMSO-d6): δ 3.84 (s, 6H, 2OCH3), 3.85 (s, 2H, CH2), 3.97 (s, 2H, CH2), 6.78 (s, 1H, CH=N), 6.87–7.05 (m, 3H, Ar–H), 7.20–7.36 (m, 8H, Ar–H), 7.45–7.68 (m, 2H, Ar–H), 7.81–7.90 (m, 2H, Ar–H), 8.16–8.21 (m, 2H, Ar–H, and CH=N), 12.85 (b, 2H, 2NH); 13C NMR (DMSO-d6): δ 55.27, 55.44 (−OCH3), 60.53, 61.12 (−CH2−), 112.72, 113.47, 118.72, 121.41, 121.84, 127.60, 127.69, 129.04, 130.85, 131.26, 132.04, 132.46, 136.97, 137.26, 142.12, 142.27, 147.99, 148.59, 150.04, 150.83, 161.43, 162.71 (Ar–C), 187.59, 187.79 (CO). MS (EI): 656.95 [M]+. HRMS: calcd for C34H30Cl2N6O4, 656.1705; found, 656.1700.

3.1.1.13. N,N′-Bis(2-(4-chlorophenylazo)-2-(benzoyl)vinyl)ethane-1,2-diamine (3k)

Orange crystals, mp 196–197 °C; IR (KBr) ν/cm–1: 3085, 3060, 2937, 1637, 1586, 1560, 1479, 1446, 1320; 1H NMR (DMSO-d6): δ 3.97 (s, 4H, 2CH2), 7.17–7.19 (m, 1H, CH=N), 7.28–7.54 (m, 10H, Ar–H), 7.65–7.68 (m, 6H, Ar–H), 7.82–7.84 (m,, 1H, Ar–H), 8.20–8.23 (m, 2H, Ar–H, and CH=N), 12.66 (b, 2H, 2NH); 13C NMR (DMSO-d6): δ 60.59, 61.21(−CH2−), 118.91, 121.96, 127.36, 127.99, 128.80, 128.89, 129.04, 129.60, 130.04, 130.48, 132.30, 136.78, 136.86, 142.02 (Ar–C), 189.35 (CO). MS (EI): 595.73 [M]+. HRMS: calcd for C32H26Cl2N6O2, 596.1494; found, 596.1492. Crystal data: C32H26Cl2N6O2, monoclinic, a = 11.0544 Å, b = 11.452 Å, c = 12.0243 Å, a = 90°, b = 100.751(7)°, g = 90°, V = 1495.5 Å3, T = 296 K, space group: P21/c, Z = 4, calculated density = 1.327 g cm–3, no. of refection measured 2621, theta (max) = 67.005, R1 = 0.0642.77

3.1.1.14. N,N′-Bis(2-(4-bromophenylazo)-2-(benzoyl)vinyl)ethane-1,2-diamine (3l)

Orange crystals, mp 211–212 °C; IR (KBr) ν/cm–1: 3067, 2924, 1637, 1597, 1597, 1486, 1446, 1262; 1H NMR (DMSO-d6): δ 3.80 (s, 2H, CH2), 3.88 (s, 2H, CH2), 6.80 (s, 4H, Ar–H, and CH=N), 7.21–7.31 (m, 9H, Ar–H), 7.75–7.85 (m, 5H, Ar–H), 8.21–8.22 (m, 2H, CH=N, Ar–H), 12.58 (b, 2H, NH); 13C NMR (DMSO-d6): δ 60.53, 61.15 (−CH2−), 115.98, 116.06, 119.25, 119.62, 119.72, 121.92, 127.36, 128.01, 128.66, 129.61, 130.49, 130.63, 131.72, 131.90, 132.30, 142.42, 142.58, 148.45, 150.60, 162.27 (Ar–C), 189.32, 190.55 (CO). MS (EI): 684.32 [M]+. HRMS: calcd for C32H26Br81 Br N6O2, 684.0483; found, 684.0446.

3.1.1.15. N,N′-Bis(2-(2-nitrophenylazo)-2-(benzoyl)vinyl)ethane-1,2-diamine (3m)

Yellow crystals, mp 235–236 °C; IR (KBr) ν/cm–1: 3098, 3072, 2918, 1642, 1607, 1576, 1446, 1419, 1277; 1H NMR (DMSO-d6): δ 3.87 (s, 2H, CH2), 3.96 (s, 2H, CH2), 6.79 (s, 1H, CH=N), 7.19–7.21 (m, 1H, Ar–H), 7.29–7.31 (m, 1H, Ar–H), 7.35–7.38 (m, 4H, Ar–H), 7.41–7.47 (m, 4H, Ar–H), 7.61–7.71 (m, 5H, CH=N, Ar–H), 7.79 (d, 2H, CH=N, Ar–H), 8.18–8.22 (m, 2H, CH=N, Ar–H), 12.51 (b, 2H, NH); 13C NMR (DMSO-d6): δ 60.61, 61.23(−CH2−), 119.03, 121.73, 122.07, 124.14, 124.30, 126.20, 128.05, 128.38, 128.84, 129.05, 130.40, 131.03, 131.67, 132.11, 135.73, 136.36, 136.59, 138.31, 138.67, 141.95, 142.12, 148.04, 148.37, 150.35, 150.94, 157.34 (Ar–C), 188.15, 189.23 (CO). MS (EI): 618.01 [M]+. HRMS: calcd for C32H26N8O6, 618.1975; found, 618.1977.

3.1.1.16. N,N′-Bis(2-(4-tolylazo)-2-(2-thienoyl)vinyl)ethane-1,2-diamine (3n)

Yellow crystals, mp 158–160 °C; IR (KBr) ν/cm–1: 3082, 3063, 2927, 1615, 1592, 1547, 1433, 1277; 1H NMR (DMSO-d6): δ 2.29 (s, 6H, 2CH3), 3.96 (s, 4H, 2CH2), 7.15–7.21 (m, 4H, Ar–H and CH=N), 7.58 (d, 2H, J = 9.60 Hz, Ar–H), 7.93–7.94 (m, 4H, Ar–H), 7.99–8.00 (m, 4H, Ar–H), 8.24–8.27 (m, 2H, Ar–H and CH=N), 12.73 (b, 1H, NH), 12.76 (b, 1H, NH); 13C NMR (DMSO-d6): δ 51.98 (−OCH3), 61.45 (−CH2−), 118.36, 120.40, 120.72, 121.10, 126.87, 126.96, 127.81, 128.31, 129.56, 129.63, 133.52, 133.79, 134.69, 134.69, 135.96, 136.83, 137.07, 138.56, 140.10, 141.28, 148.40, 148.78 (Ar–C), 178.91, 179.70 (CO). MS (EI): 567.99 [M]+. HRMS: calcd for C30H28N6O2S2, 568.1715; found, 568.1710.

3.1.1.17. N,N′-Bis(2-(phenylazo)-2-(2-thienoyl)vinyl)ethane-1,2-diamine (3o)

Yellow crystals, mp 263–264 °C; IR (KBr) ν/cm–1: 3101, 3072, 2897, 1629, 1597, 1547, 1465, 1414, 1274; 1H NMR (DMSO-d6): δ 3.99 (s, 4H, 2CH2), 6.82 (s, 1H, CH=N), 7.18–7.24 (m, 6H, Ar–H), 7.43–7.53 (m, 3H, Ar–H), 7.66 (d, J = 7.80 Hz, 3H, Ar–H), 7.92–8.05 (m, 3H, Ar–H), 8.32 (d, J = 9.60 Hz, 2H, Ar–H), 12.97 (b, 2H, NH); 13C NMR (DMSO-d6): δ 61.20, 61.85 (−CH2−), 118.01, 118.17, 120.67, 121.08, 124.19, 126.92, 127.76, 128.88, 129.28, 133.66, 134.80, 136.70, 138.50, 140.18, 140.39, 143.51, 147.63, 148.01, 151.19 (Ar–C), 179.05, 179.20 (CO). MS (EI): 540.10 [M]+. HRMS: calcd for C28H24N6O2S2, 540.1402; found, 540.1404.

4. Conclusions

Due to the involvement of bis-amines in a wide-array of highly promising biologically active candidates, this work describes an interesting platform for the construction of novel N,N′-bis(2-(arylazo)-2-(aroyl)vinyl)ethane-1,2-diamines. These targets were assembled based on the reaction of ethylenediamine with various 2-arylhydrazono-3-oxopropanals in aqueous conditions under both conventional stirring and MW conditions at ambient temperature. The optimal reaction condition was found to be a mixture of methanol/H2O (2:1). The structures of the new products were established from their elemental and spectroscopic analyses as well as X-ray single crystals of a demonstrative compound. The photophysical behavior of the bis-arylazo derivatives, having various substituents of different electronic behaviors, was studied. The UV–vis spectra in dichloromethane solution showed the maximum absorption band in the range of 348–383 nm due to n → π* and/or π → π* electronic transitions of azo chromophores with molar extinction coefficients ranging from 0.89 × 104 to 4.02 × 104 M–1 cm–1. The highest molar absorptivity coefficient (∼45 × 103 M–1 cm–1) was observed in CHCl3 solvent. The fluorescence properties in DMSO showed that the emission maximum emerges in the visible region in the 389–441 nm range. Some compounds were considered interesting fluorophore materials by showing high Stokes shifts. The PL study of some compounds was promising, with maximal emission peaks ranging between 417–436 nm.

Acknowledgments

The RSP unit general facilities of the Faculty of Science GFS supported by research grants GS01/05, GS01/03, GS03/01, GS02/01, and GS03/08 are greatly appreciated. This research work was funded by Kuwait University, grant no. (SC01/22).

Data Availability Statement

The data supporting this article have been included as part of the Supporting Information.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.4c06250.

  • 1H NMR; 13C NMR; HRMS; and MS of compounds (PDF)

Author Contributions

A.A. conceived the project and directed the research. A.A., K.D., and M.H. designed the experiments. W.T. conducted the experiments. A.A., K.D., and W.T. analyzed the data and wrote the manuscript. A.A., K.W., and H.M. discussed the results and edited the manuscript.

The authors declare no competing financial interest.

Supplementary Material

ao4c06250_si_001.pdf (3.5MB, pdf)

References

  1. Salvatore R. N.; Yoon C. H.; Jung K. W. Synthesis of secondary amines. Tetrahedron 2001, 57, 7785–7811. 10.1016/S0040-4020(01)00722-0. [DOI] [Google Scholar]
  2. Bisceglia J. Á.; Díaz J. E.; Torres R. A.; Orelli L. R. 1,n-Diamines. Part 3: Microwave-assisted synthesis of N-acyl-N′-arylhexahydropyrimidines and hexahydro-1,3-diazepines. Tetrahedron Lett. 2011, 52, 5238–5240. 10.1016/j.tetlet.2011.07.131. [DOI] [Google Scholar]
  3. Murata T.; Miyazaki E.; Nakasuji K.; Morita Y. Nucleobase-functionalized 1, 6-dithiapyrene-type electron-donors: supramolecular assemblies by complementary hydrogen-bonds and π-stacks. Cryst. Growth Des. 2012, 12, 5815–5822. 10.1021/cg301414s. [DOI] [Google Scholar]
  4. Patel M.; Patil S. Physicochemical investigation on a chelate polymer. J. Macromol. Sci., Part A: Chem. 1981, 16, 1429–1440. 10.1080/00222338108063246. [DOI] [Google Scholar]
  5. Suematsu K.; Nakamura K.; Takeda J. Piezoelectricity in polyimine derivatives. Yakugaku Zasshi 1983, 103, 250–253. 10.1248/yakushi1947.103.2_250. [DOI] [PubMed] [Google Scholar]
  6. Telatin T.; De la Flor S.; Montané X.; Serra À. Chemically degradable vitrimers based on divanillin imine diepoxymonomer and aliphatic diamines for enhanced carbon fiber composite applications. Polymers 2024, 16, 2754. 10.3390/polym16192754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dawood K. M.; Abu-Deif H. K.-A. Synthesis and antimicrobial evaluation of some new 1, 2-bis-(2-(N-arylimino)-1, 3-thiazolidin-3-yl) ethane derivatives. Chem. Pharm. Bull. 2014, 62, 439–445. 10.1248/cpb.c14-00031. [DOI] [PubMed] [Google Scholar]
  8. Dawood K. M.; Abu-Deif H. K.-A. Synthesis and antimicrobial activity of some new 1,2-bis-[1,3-thiazolidin-3-yl]ethane derivatives. Eur. J. Chem. 2013, 4, 277–284. 10.5155/eurjchem.4.3.277-284.837. [DOI] [PubMed] [Google Scholar]
  9. Coulibaly W. K.; Paquin L.; Bénie A.; Bekro Y.-A.; Durieu E.; Meijer L.; Bazureau J. P. Synthesis of N,N′-bis (5-arylidene-4-oxo-3, 5-dihydro-4H-imidazole-2-yl) diamines bearing various linkers and biological evaluation as potential inhibitors of kinases. Eur. J. Med. Chem. 2012, 58, 581–590. 10.1016/j.ejmech.2012.08.044. [DOI] [PubMed] [Google Scholar]
  10. Chen W.; Zhang G.; Guo L.; Fan W.; Ma Q.; Zhang X.; Du R.; Cao R. Synthesis and biological evaluation of novel alkyl diamine linked bivalent β-carbolines as angiogenesis inhibitors. Eur. J. Med. Chem. 2016, 124, 249–261. 10.1016/j.ejmech.2016.08.050. [DOI] [PubMed] [Google Scholar]
  11. Dawood K. M.; Raslan M. A.; Abbas A. A.; Mohamed B. E.; Abdellattif M. H.; Nafie M. S.; Hassan M. K. Novel bis-thiazole derivatives: synthesis and potential cytotoxic activity through apoptosis with molecular docking approaches. Front. Chem. 2021, 9, 694870. 10.3389/fchem.2021.694870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Thabet F. M.; Dawood K. M.; Ragab E. A.; Nafie M. S.; Abbas A. A. Design and synthesis of new bis (1, 2, 4-triazolo [3, 4-b] [1, 3, 4] thiadiazines) and bis ((quinoxalin-2-yl) phenoxy) alkanes as anti-breast cancer agents through dual PARP-1 and EGFR targets inhibition. RSC Adv. 2022, 12, 23644–23660. 10.1039/D2RA03549A. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dawood K. M.; Raslan M. A.; Abbas A. A.; Mohamed B. E.; Nafie M. S. Novel bis-amide-based bis-thiazoles as anti-colorectal cancer agents through Bcl-2 inhibition: synthesis, in vitro, and in vivo studies. Anti-Cancer Agents Med. Chem. 2023, 23, 328–345. 10.2174/1871520622666220615140239. [DOI] [PubMed] [Google Scholar]
  14. Salem M. E.; Mahrous E. M.; Ragab E. A.; Nafie M. S.; Dawood K. M. Synthesis and anti-breast cancer potency of mono-and bis-(pyrazolyl [1, 2, 4] triazolo [3, 4-b] [1, 3, 4] thiadiazine) derivatives as EGFR/CDK-2 target inhibitors. ACS Omega 2023, 8, 35359–35369. 10.1021/acsomega.3c05309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Shawali A. S. Bis-enaminones as versatile precursors for terheterocycles: synthesis and reactions. Arkivoc 2012, 2012 (1), 383–431. 10.3998/ark.5550190.0013.110. [DOI] [Google Scholar]
  16. Baskovc J.; Bevk D.; Stanovnik B.; Svete J. Bis-enaminone based parallel solution-phase synthesis of 1,4-dihydropyridine derivatives. J. Comb. Chem. 2009, 11, 500–507. 10.1021/cc900032c. [DOI] [PubMed] [Google Scholar]
  17. Elwahy A. H. M.; Darweesh A. F.; Shaaban M. R. Microwave-assisted synthesis of bis(enaminoketones): versatile precursors for novel bis(pyrazoles) via regioselective 1,3-dipolar cycloaddition with nitrileimines. J. Heterocycl. Chem. 2012, 49, 1120–1125. 10.1002/jhet.952. [DOI] [Google Scholar]
  18. Kadkin O. N.; Kim E. H.; Kim S. Y.; Choi M.-G. Synthesis and liquid crystal properties of copper(II) and palladium(II) chelates with new ferrocene-containing enaminoketones. Polyhedron 2009, 28, 1301–1307. 10.1016/j.poly.2009.01.045. [DOI] [Google Scholar]
  19. Xue M.; Lei L.; Ren S.; Li T.; You Q.; Xie G. Significant cooperative effects in binuclear titanium complexes based on trifluoromethyl substituted bis-β-carbonylenamine ligands for ethylene (co)polymerization. Polymer 2023, 277, 125995. 10.1016/j.polymer.2023.125995. [DOI] [Google Scholar]
  20. McCarthy P. J.; Hovey R. J.; Ueno K.; Martell A. E. Inner complex chelates. I. Analogs of bisacetylacetoneethylenediimine and its metal chelates. J. Am. Chem. Soc. 1955, 77, 5820–5824. 10.1021/ja01627a011. [DOI] [Google Scholar]
  21. Crookes M. J.; Roy P.; Williams D. L. H. Nitrosation of acetylacetone (pentane-2, 4-dione) and some of its fluorinated derivatives. J. Chem. Soc., Perkin Trans. 1989, 2, 1015–1019. 10.1039/p29890001015. [DOI] [Google Scholar]
  22. Burgart Y. V.; Skryabina Z.; Saloutin V. Template reactions of fluorine-containing 1, 3-diketones with ethylenediamine. Bull. Acad. Sci. USSR 1991, 40, 1849–1853. 10.1007/BF00960416. [DOI] [Google Scholar]
  23. Skryabina Z.; Burgart Y. V.; Saloutin V. Cyclization of fluoroalkyl-containing 1, 3-dicarbonyl compounds with ethylenediamine hydroperchlorate to 1, 4-diazepines. Bull. Acad. Sci. USSR Div. Chem. Sci. 1991, 40, 788–794. 10.1007/BF00958575. [DOI] [Google Scholar]
  24. Gorringe A. M.; Lloyd D.; Marshall D. Diazepines. Part VI. Condensation products from benzoylacetone and ethylenediamine. J. Chem. Soc. C 1967, 2340–2341. 10.1039/j39670002340. [DOI] [Google Scholar]
  25. Holm R.; Everett G.; Chakravorty A. Metal complexes of schiff bases and β-ketoamines. Prog. Inorg. Chem. 1966, 7, 83–214. 10.1002/9780470166086.ch3. [DOI] [Google Scholar]
  26. Olszewski E.; Boucher L.; Oehmke R.; Bailar J. C. Jr.; Martin D. F. Amine-catalyzed condensation of β-diketones using a metal-chelate template. Inorg. Chem. 1963, 2, 661–662. 10.1021/ic50007a072. [DOI] [Google Scholar]
  27. Zhang Z. H.; Yin L.; Wang Y. M. A general and efficient method for the preparation of β-enamino ketones and esters catalyzed by indium tribromide. Adv. Synth. Catal. 2006, 348, 184–190. 10.1002/adsc.200505268. [DOI] [Google Scholar]
  28. Bartoli G.; Bosco M.; Locatelli M.; Marcantoni E.; Melchiorre P.; Sambri L. Zn(ClO4)2·6H2O as a powerful catalyst for the conversion of β-ketoesters into β-enamino esters. Synlett 2004, 0239–0242. 10.1055/s-2003-44974. [DOI] [Google Scholar]
  29. Khodaei M.; Khosropour A.; Cardel C. Enamination of β-dicarbonyl compounds with amines. J. Chin. Chem. Soc. 2008, 55, 217–221. 10.1002/jccs.200800032. [DOI] [Google Scholar]
  30. Zhang Z.-H.; Hu J.-Y. Cobalt (II) chloride-mediated synthesis of beta-enamino compounds under solvent-free conditions. J. Braz. Chem. Soc. 2006, 17, 1447–1451. 10.1590/S0103-50532006000700038. [DOI] [Google Scholar]
  31. Zhang Z.-H.; Ma Z.-C.; Mo L.-P. Enamination of 1,3-dicarbonyl compounds catalyzed by tin tetrachloride. Indian J. Chem. 2007, 46B, 535. [Google Scholar]
  32. Lin J.; Zhang L.-F. ZrCl 4-catalyzed efficient synthesis of enaminones and enamino esters under solvent-free conditions. Monatsh. Chem. 2007, 138, 77–81. 10.1007/s00706-006-0565-2. [DOI] [Google Scholar]
  33. Khosropour A. R.; Khodaei M. M.; Kookhazadeh M. A mild, efficient and environmentally friendly method for the regio-and chemoselective synthesis of enaminones using Bi (TFA) 3 as a reusable catalyst in aqueous media. Tetrahedron Lett. 2004, 45, 1725–1728. 10.1016/j.tetlet.2003.12.093. [DOI] [Google Scholar]
  34. Laskar R. A.; Begum N. A.; Mir M. H.; Ali S.; Khan A. T. Vanadium (IV) acetylacetonate catalyzed stereoselective synthesis of β-enaminoesters and β-enaminones. Tetrahedron Lett. 2013, 54, 436–440. 10.1016/j.tetlet.2012.11.051. [DOI] [Google Scholar]
  35. Yadav J.; Kumar V. N.; Rao R. S.; Priyadarshini A. D.; Rao P. P.; Reddy B.; Nagaiah K. Sc(OTf)3 catalyzed highly rapid and efficient synthesis of β-enamino compounds under solvent-free conditions. J. Mol. Catal. A: Chem. 2006, 256, 234–237. 10.1016/j.molcata.2006.04.065. [DOI] [Google Scholar]
  36. Epifano F.; Genovese S.; Curini M. Ytterbium triflate catalyzed synthesis of β-enaminones. Tetrahedron Lett. 2007, 48, 2717–2720. 10.1016/j.tetlet.2007.02.064. [DOI] [Google Scholar]
  37. Dalpozzo R.; De Nino A.; Nardi M.; Russo B.; Procopio A. Erbium (III) triflate: a valuable catalyst for the synthesis of aldimines, ketimines, and enaminones. Synthesis 2006, 1127–1132. 10.1055/s-2006-926378. [DOI] [Google Scholar]
  38. Feng C.-L.; Chu N.-N.; Zhang S.-G.; Cai J.; Chen J.-Q.; Hu H.-Y.; Ji M. Solvent-free synthesis of β-enamino ketones and esters catalysed by recyclable iron(III) triflate. Chem. Pap. 2014, 68, 1097–1103. 10.2478/s11696-014-0544-8. [DOI] [Google Scholar]
  39. Shendage S.; Nagarkar J. Ultrasound assisted synthesis of enaminones using nickel oxide. Curr. Chem. Lett. 2013, 2, 145–152. 10.5267/j.ccl.2013.05.002. [DOI] [Google Scholar]
  40. Chen J.-X.; Zhang C.-F.; Gao W.-X.; Jin H.-L.; Ding J.-C.; Wu H.-Y. B2O3/Al2O3 as a new, highly efficient and reusable heterogeneous catalyst for the selective synthesis of β-enamino ketones and esters under solvent-free conditions. J. Braz. Chem. Soc. 2010, 21, 1552–1556. 10.1590/S0103-50532010000800021. [DOI] [Google Scholar]
  41. Mohammadizadeh M. R.; Hasaninejad A.; Bahramzadeh M.; Khanjarlou Z. S. P2O5/SiO2 as a new, efficient, and reusable catalyst for preparation of β-enaminones under solvent-free conditions. Synth. Commun. 2009, 39, 1152–1165. 10.1080/00397910802513052. [DOI] [Google Scholar]
  42. Eshghi H.; Seyedi S. M.; Safaei E.; Vakili M.; Farhadipour A.; Bayat-Mokhtari M. Silica supported Fe(HSO4)3 as an efficient, heterogeneous and recyclable catalyst for synthesis of β-enaminones and β-enamino esters. J. Mol. Catal. A: Chem. 2012, 363–364, 430–436. 10.1016/j.molcata.2012.07.021. [DOI] [Google Scholar]
  43. Sun J.; Dong Z.; Li P.; Zhang F.; Wei S.; Shi Z.; Li R. Ag nanoparticles in hollow magnetic mesoporous spheres: a highly efficient and magnetically separable catalyst for synthesis of β-enaminones. Mater. Chem. Phys. 2013, 140, 1–6. 10.1016/j.matchemphys.2013.03.030. [DOI] [Google Scholar]
  44. Kulkarni P.; Jadhav A. An Efficient Synthesis of β-Enaminoketone/Ester Under Grinding Condition Using Calcium Bromide as Solid Support Catalyst. Der Pharma Chem. 2017, 9, 55–58. [Google Scholar]
  45. Paira M.; Misra R.; Roy S. C. Ceric (IV) ammonium nitrate catalyzed synthesis of β-enaminones. Indian J. Chem. 2008, 966–969. [Google Scholar]
  46. Cartaya-Marin C. P.; Henderson D. G.; Soeder R. W.; Zapata A. J. Synthesis of enaminones using trimethylsilyl trifluoromethanesulfonate as an activator. Synth. Commun. 1997, 27, 4275–4283. 10.1080/00397919708005051. [DOI] [Google Scholar]
  47. Zhang M.; Abdukader A.; Fu Y.; Zhu C. Efficient synthesis of β-enaminones and β-enaminoesters catalyzed by gold (I)/silver (I) under solvent-free conditions. Molecules 2012, 17, 2812–2822. 10.3390/molecules17032812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Patil S. A.; Medina P. A.; Gonzalez-Flores D.; Vohs J. K.; Dever S.; Pineda L. W.; Montero M. L.; Fahlman B. D. Formic acid: a low-cost, mild, ecofriendly, and highly efficient catalyst for the rapid synthesis of β-enaminones. Synth. Commun. 2013, 43, 2349–2364. 10.1080/00397911.2012.708467. [DOI] [Google Scholar]
  49. Singh A.; Gupta N.; Sharma M.; Singh J. Ionic liquid promoted synthesis of β-enamino ketones and esters under microwave irradiation. Indian J. Chem. 2014, 53B, 900–906. [Google Scholar]
  50. Karimi-Jaberi Z.; Takmilifard Z. Efficient synthesis of β-enaminones and β-enamino esters using tris (hydrogensulfato) boron or trichloroacetic acid as catalysts. Eur. Chem. Bull. 2013, 2, 211–213. [Google Scholar]
  51. Valduga C. J. The use of K-10/ultrasound in the selective synthesis of unsymmetrical β-enamino ketones. Synthesis 1998, 1998, 1019–1022. 10.1055/s-1998-2107. [DOI] [Google Scholar]
  52. Sharma D.; Bandna; Reddy C. B.; Kumar S.; Shil A. K.; Guha N. R.; Das P. Microwave assisted solvent and catalyst free method for novel classes of β-enaminoester and acridinedione synthesis. RSC Adv. 2013, 3, 10335–10340. 10.1039/c3ra23484c. [DOI] [Google Scholar]
  53. Braibante H. T.; Braibante M. E.; Rosso G. B.; Oriques D. A. Preparation of beta-enamino carbonylic compounds using microwave radiation/K-10. J. Braz. Chem. Soc. 2003, 14, 994–997. 10.1590/S0103-50532003000600016. [DOI] [Google Scholar]
  54. Nagaiah K.; Purnima K.; Sreenu D.; Jhansi S.; Srinivasa Rao R.; Yadav J. Phosphomolybdic acid (PMA) catalyzed highly efficient and rapid synthesis of β-enaminones. Synth. Commun. 2012, 42, 461–468. 10.1080/00397911.2010.524339. [DOI] [Google Scholar]
  55. Grieco P.. Organic Synthesis in Water; Blackie Academic & Professional, Springer Dordrecht: London, 1998. [Google Scholar]
  56. Minakata S.; Komatsu M. Organic reactions on silica in water. Chem. Rev. 2009, 109, 711–724. 10.1021/cr8003955. [DOI] [PubMed] [Google Scholar]
  57. Li C.-J.; Chan T.-H.. Organic Reactions in Aqueous Media; John Wiley & Sons: New York, 1997. [Google Scholar]
  58. Prajapati D.; Gohain M.; Thakur A. J. Regiospecific one-pot synthesis of pyrimido[4, 5-d]pyrimidine derivatives in the solid state under microwave irradiations. Bioorg. Med. Chem. Lett. 2006, 16, 3537–3540. 10.1016/j.bmcl.2006.03.088. [DOI] [PubMed] [Google Scholar]
  59. Prajapati D.; Thakur A. J. Studies on 6-[(dimethylamino) methylene] aminouracil: a facile one-pot synthesis of novel pyrimido[4,5-d]pyrimidine derivatives. Tetrahedron Lett. 2005, 46, 1433–1436. 10.1016/j.tetlet.2005.01.047. [DOI] [Google Scholar]
  60. Caddick S. Microwave assisted organic reactions. Tetrahedron 1995, 51, 10403–10432. 10.1016/0040-4020(95)00662-R. [DOI] [Google Scholar]
  61. Loupy A.; Petit A.; Hamelin J.; Texier-Boullet F.; Jacquault P.; Mathe D. New solvent-free organic synthesis using focused microwaves. Synthesis 1998, 1998, 1213–1234. 10.1055/s-1998-6083. [DOI] [Google Scholar]
  62. Galema S. A. Microwave chemistry. Chem. Soc. Rev. 1997, 26, 233–238. 10.1039/cs9972600233. [DOI] [Google Scholar]
  63. Satyanarayana V. S. V.; Sreevani P.; Sivakumar A.; Vijayakumar V. Synthesis and antimicrobial activity of new schiff bases containing coumarin moiety and their spectral characterization. Arkivoc 2009, 2008, 221–233. 10.3998/ark.5550190.0009.h21. [DOI] [Google Scholar]
  64. Ali P.; Ramakanth P.; Meshram J. Exploring microwave synthesis for co-ordination: synthesis, spectral characterization and comparative study of transition metal complexes with binuclear core derived from 4-amino-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one. J. Coord. Chem. 2010, 63, 323–329. 10.1080/00958970903305437. [DOI] [Google Scholar]
  65. Tanaka K.; Shiraishi R.; Toda F. A new method for stereoselective bromination of stilbene and chalcone in a water suspension medium. J. Chem. Soc., Perkin Trans. 1999, 1, 3069–3070. 10.1039/a906967d. [DOI] [Google Scholar]
  66. Polshettiwar V.; Varma R. S. Microwave-assisted organic synthesis and transformations using benign reaction media. Acc. Chem. Res. 2008, 41, 629–639. 10.1021/ar700238s. [DOI] [PubMed] [Google Scholar]
  67. Alazemi A. M.; Dawood K. M.; Al-Matar H. M.; Tohamy W. M. Microwave-assisted chemoselective synthesis and photophysical properties of 2-arylazo-biphenyl-4-carboxamides from hydrazonals. RSC Adv. 2023, 13, 25054–25068. 10.1039/D3RA04558G. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Alazemi A. M.; Dawood K. M.; Al-Matar H. M.; Tohamy W. M. Efficient and recyclable solid-supported Pd (II) catalyst for microwave-assisted suzuki cross-coupling in aqueous medium. ACS Omega 2022, 7, 28831–28848. 10.1021/acsomega.2c01809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Al-Matar H. M.; Dawood K. M.; Tohamy W. M.; Shalaby M. A. Facile assembling of novel 2, 3, 6, 7, 9-pentaazabicyclo-[3.3. 1] nona-3, 7-diene derivatives under microwave and ultrasound platforms. Molecules 2019, 24, 1110. 10.3390/molecules24061110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Al-Matar H. M.; Dawood K. M.; Tohamy W. M. Tandem one-pot synthesis of 2-arylcinnolin-6-one derivatives from arylhydrazonopropanals and acetoacetanilides using sustainable ultrasound and microwave platforms. RSC Adv. 2018, 8, 34459–34467. 10.1039/C8RA06494F. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Dawood K. M.; Alaasar M. Transition-metal-catalyzed heteroannulation reactions in aqueous medium. Asian J. Org. Chem. 2022, 11, e202200331 10.1002/ajoc.202200331. [DOI] [Google Scholar]
  72. Dawood K. M.; Elamin M. B.; Farag A. M. Microwave-assisted synthesis of arylated pyrrolo[2,1-a]isoquinoline derivatives via sequential[3 + 2]cycloadditions and Suzuki-Miyaura cross-couplings in aqueous medium. J. Heterocycl. Chem. 2016, 53, 1928–1934. 10.1002/jhet.2508. [DOI] [Google Scholar]
  73. Dawood K. M.; El-Deftar M. M. Microwave-assisted synthesis of 2-substituted 4-biarylyl-1,3-thiazoles by carbon-carbon cross-coupling in water. Synthesis 2010, 2010, 1030–1038. 10.1055/s-0029-1218662. [DOI] [Google Scholar]
  74. Dawood K. M.; Elamin M. B.; Faraga A. M. Microwave-assisted synthesis of 2-acetyl-5-arylthiophenes and 4-(5-arylthiophen-2-yl) thiazoles via Suzuki coupling in water. Arkivoc 2015, 2015, 50–62. 10.3998/ark.5550190.p009.018. [DOI] [Google Scholar]
  75. Al-Shiekh M. A.; Medrassi H. Y.; Elnagdi M. H.; Hafez E. A. Substituted hydrazonals as building blocks in heterocyclic synthesis: a new route to arylhydrazonocinnolines. J. Chem. Res. 2007, 2007, 432–436. 10.3184/030823407X234617. [DOI] [Google Scholar]
  76. Hassaneen H. M.; Abdelhamid I. A. Acetylacetaldehyde dimethyl acetal as versatile precursors for the synthesis of arylazonicotinic acid derivatives: green multicomponent syntheses of bioactive poly-heteroaromatic compounds. J. Heterocycl. Chem. 2017, 54, 1048–1053. 10.1002/jhet.2673. [DOI] [Google Scholar]
  77. The Crystallographic Data for compound 3k (ref CCDC 2225513).

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