1.                   Introduction

Benzothiazoles bearing substituent at C₂ position are of great interest as these structural frameworks have proved to be an important class of privileged bicyclic substructures owing to their potent utility as imaging agents for β-amyloid, antituberculotic, antitumour, antiparasitics, chemiluminescent agents, calcium channel antagonists and photosensitizers[1-7].

Numerous classical methods have been reported for the synthesis of benzothiazoles. The commonly used methods involve the condensation of 2-aminothiophenol with substituted nitriles, carboxylic acids, aldehydes, acyl chlorides or esters[8]. A number of catalysts e.g. (pmlm)Br, I₂, ZrOCl₂.8H₂O, TMSCl, H₂O, PCC, Cu, Pd, Fe, P₂O_5, Lewis acid and CAN have been used in the cyclocondensation of 2-aminothiophenol and aldehydes[9-32]. The other route is based on Jacobson’s cyclization of thiobenzanilides[33-37]. But these routes require multistep reaction sequence. Many of these methods have several disadvantages such as drastic reaction conditions, tedious work-up, and possibility of side reactions and generation of acidic/metallic wastes.

To overcome these disadvantages of above methodologies[38-42]. There report a simple andefficient method for the synthesis of benzothiazoles using PEG as a recoverable catalyst.

PEG is non-toxic, thermally stable, recyclable, inexpensive, low volatile non-ionic liquid medium and also a phase transfer catalyst[25-32]. PEG is a biologically acceptable polymer used extensively in drug delivery and in bio-conjugates as tool for diagnostics. It has not only been used as a solvent medium but also as a support for various organic transformations. Many organic reactions have been carried out in PEG like Heck asymmetric dehydroxylation, Baylis-Hillman, Biginelli, Michael addition, Stille cross-coupling, Wacker and asymmetric aldol reaction[38-42]. Development of efficient, selective and eco-friendly methods for complex organic preparations is the ultimate goal of several research groups, so in accordance to this, an eco-friendly synthesis of substituted benzothiazoles by cyclocodensation of 2-aminothiophenol and substituted aromatic aldehydes assisted by PEG-400 is reported.

In order to standardize the reaction 2-chlorobenzaldehyde (4 mmol) and 2-aminothiophenol (4.5 mmol) were heated at 115˚C for 30 minutes in PEG-400 (0.1 mL) (Scheme 1. The results of the study of this model reaction for its optimization are summarized in Table 1. We find that the reaction proceeded smoothly and better results were obtained with 0.1 mL of PEG-400 for 4mmol of 2-chlorobenzaldehyde. Using more than 0.1 mL of PEG-400 did not improve the yield of the product. At the same time there is no conversion took place in the absence of PEG-400 even after 40 hrs. Since only catalytic amount i.e. 0.1 mL of PEG-400 is used so it acts as a promoter for the reaction rather than a solvent. No formation of benzothiazole took place under argon atmosphere (the reaction stopped at the imine stage) indicating that the aerial oxygen is absolutely necessary for the oxidation step. We investigated our protocol with various PEGs with molecular weights 200, 400, 4000, 6000 (0.1 mL each) for our model reaction with 2-chlorobenzaldehyde and 2-amino-5-methylthiophenol. The reaction occurred giving excellent yields of the product (84-95%) with low as well as high molecular weight PEGs.

Table 1: Synthesis of 2-(2-chlorophenyl)-6-methylbenzothiazole under various conditions (entry 3 gives the optimum condition)

^aIsolated yield

To generalize our methodology, we have synthesized several 2-aryl-6-substituted-benzothiazoles by reaction of various aldehydes and 2-amino-5-substitutedthiophenol using PEG-400 (Scheme 1, Table 2). A variety of aldehydes containing electron releasing and electron withdrawing groups were successfully employed to prepare corresponding benzothiazoles. In all cases, yields were excellent and no significant substituent effect was observed on the yields of the products (Table 2). All the products were characterized by comparing their physical and spectral (¹H NMR, ¹³C NMR & HRMS) data with those of authentic samples reported in literature. PEG-400 used during reaction is recycled and reused for three times and it was observed that yield was almost same in each case.

There was no reaction observed in the absence of PEG. Thus, probably the formation of substituted benzothiazole by employing PEG-400 as reaction medium may be due to the hydrogen bonding between the ethereal oxygen and hydrogen attached to sulphur of thio group which makes S-H bond weaker, enhancing the nucleophilicity of sulphur for nucleophilic addition. The electron deficiency of carbonyl carbon of aldehydes may be enhanced by hydrogen bonding with hydroxy group of PEG-400. Moreover, since PEG-400 contains many hydroxy groups, extensive hydrogen bonding occurs between PEG-400, 2-aminothiophenol and aldehyde. Therefore, nearness effect may be produced which facilitate the reaction.

In summary, polyethylenene glycol with water offers a convenient, inexpensive, green, non-toxic and recyclable catalyst to access a wide variety of substituted benzothiazoles in good yields. This protocol offers a rapid and clear alternative to reduce reaction time. The recyclability of PEG makes reaction economically and potentially viable for commercial applications

Table 2: Synthesis of 2-substituted benzothiazole derivatives in PEG 400- H₂O catalytic system at room temperature

^a Isolated yields.

2.                   Experimental

General procedure for 2-substituted benzothiazole synthesis:

A mixture of an aldehyde (4 mmol), 2-amino-substituted-thiophenol (4.5 mmol) and PEG-400 (0.1 mL) and water (10 mL) were taken in a dry 25 mL round bottom flask. The reaction mixture was stirred at room temperature for 30-90 minutes.  The progress of the reaction was monitored by thin layer chromatography. The reaction mass was poured in ice water on completion of reaction and then extracted with ether. The ethereal extract was evaporated and obtained crude product was purified by silica gel column chromatography. All the compounds were characterized by comparing their melting points and ¹H NMR, ¹³C NMR and HRMS data with those of the reported compounds[43-50].

3.       Result and Discussion

Spectral data for synthesized compounds:

Compound 3a: m.p. 113-114˚C; ¹H NMR (400 MHz, CDCl₃) δ: 7.35 (dt, J = 1.2, 8.2 Hz, 1H), 7.45-7.50 (m, 4H), 7.87 (d, J = 7.8 Hz, 1H), 8.05-8.09 (m, 3H); ¹³C NMR (100 M Hz, CDCl₃) δ: 121.5, 123.1, 125.1, 126.2, 127.5, 128.9, 130.9, 133.5, 134.9, 154.1, 167.9; HRMS calcd for C₁₃H₉NS: 211.04; found: 211.04; elemental anal calcd C, 73.90; H, 4.29; N, 6.63; found C, 73.84; H, 4.32; N, 6.59.

Compound 3b: m.p. 119-120˚C; ¹H NMR (400 MHz, CDCl₃) δ: 3.84 (s, 3H), 6.97 (d, J  =  8.8  Hz, 2H), 7.33 (t, J = 7.4  Hz, 1H), 7.45 (t, J = 7.8  Hz, 1H), 7.85 (d, J  =  7.8  Hz, 1H), 8.01 (d, J  =  8.4  Hz, 2H), 8.02 (d, J = 8.8  Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 55.3, 114.2, 121.4, 122.7, 124.7, 126.1, 126.3, 129.0, 134.7, 154.1, 161.8, 167.8; HRMS calcd for C₁₄H₁₁NOS: 241.06; found: 241.05; elemental anal calcd C, 69.68; H, 4.59; N, 5.80; found C, 69.66; H, 4.61; N, 5.84.

Compound 3c: m.p. 68-70˚C; ¹H NMR (400 MHz, CDCl₃) δ: 2.43 (s, 3H), 7.28 (d, J = 7.2 Hz, 1H), 7.35 (t, J = 8.2 Hz, 2H), 7.47 (t, J = 8.2 Hz,1H), 7.86 (t, J = 7.8  Hz, 2H), 7.93 (s, 1H), 8.07 (d, J = 8.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 21.3, 121.5, 123.1, 124.8, 125.0, 126.2, 127.9, 128.8, 131.7, 133.4, 134.9, 138.8, 154.0, 168.2; HRMS calcd for C₁₄H₁₁NS: 225.06; found: 225.05; elemental anal calcd C, 74.63; H, 4.92; N, 6.22; found C, 74.52; H, 4.95; N, 6.20.

Compound 3d: m.p. 101-102˚C; ¹H NMR (400 MHz, CDCl₃) δ: 4.01 (s, 3H), 7.03 (d, J = 8.2 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.35 (t, J = 6.8 Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.47 (t, J = 8.2 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 8.09 (d, J = 8.2 Hz, 1H), 8.53 (dd, J = 1.6,7.8  Hz, 1H). ¹³C NMR (100MHz, CDCl₃) δ: 55.6, 111.6, 121.0, 122.2, 122.7, 124.5, 125.8, 129.4, 131.7, 136.0, 152.1, 157.1, 163.1; HRMS calcd for C₁₄H₁₁NOS: 241.05; found: 241.05; elemental anal calcd C, 69.68; H, 4.59; N, 5.80; found C, 69.62; H, 4.68; N, 5.62.

Compound 3e: m.p. 144-149˚C; ¹H NMR (400 MHz, CDCl₃) δ: 7.44(t, J = 7.8 Hz, 1H), 7.54 (t, J = 7.4 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.97 (s, 1H), 8.11(d, J = 8.4 Hz, 1H), 8.50(s, 2H). ¹³C NMR (100 MHz, CDCl₃) δ: 121.8, 122.9 (d, J = 271.6 Hz), 123.8, 124.0, 126.2, 126.9, 127.2, 132.5 (q, J = 33.6 Hz), 135.1, 135.5, 153.8, 164.0; HRMS calcd for C₁₅H₈F₆NS: 347.03; found: 347.02; elemental anal calcd C, 51.88; H, 2.03; N, 4.03; found C, 51.92; H, 2.13; N, 4.01.

 Compound 3f: m.p. 84-85˚C; ¹H NMR (400 MHz, CDCl₃) δ: 7.54-7.71 (m, 5H), 8.18-8.26 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 122.6, 123.6, 126.3, 127.2, 128.3, 131.4, 131.8, 139.9, 132.1, 132.5, 135.8, 152.4, 163.8; HRMS calcd for C₁₃H₈ClNS: 245.01; found: 245.00; elemental anal calcd C, 63.54; H, 3.28; N, 5.70; found C, 63.50; H, 3.32; N, 5.67.

Compound 3g: m.p. 103-104˚C; ¹H NMR (400 MHz, CDCl₃) δ: 6.57 (dd, J  =  1.6, 7.4 Hz, 1H), 7.17 (d, J  =  6.8 Hz, 1H), 7.35 (dt, J = 1.0, 8.4 Hz, 1H), 7.47 (dt, J = 1.0, 8.4 Hz, 1H), 7.55-7.59 (m, 1H), 8.04 (d, J = 8.4 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 111.3, 112.4, 121.4, 123.0, 125.1, 126.4, 134.1, 144.6, 148.6, 153.6, 157.4; HRMS calcd for C₁₁H₇NOS: 201.02; found: 201.01; elemental anal calcd C, 65.65; H, 3.51; N, 6.96; found C, 65.63; H, 3.49; N, 6.97.

Compound 3h: m.p. 87-88˚C; ¹H NMR (400 MHz, CDCl₃) δ: 2.83(s, 3H), 7.33(t, J = 7.8 Hz, 1H), 7.43(t, J = 8.0 Hz, 1H), 7.81(d, J = 7.8 Hz, 1H) 7.95(d, J = 7.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 20.1,, 121.3, 122.3, 124.6, 125.8, 135.5, 153.3, 166.9; HRMS calcd for C₈H₇NS: 149.02; found: 149.02; elemental anal calcd C, 64.39; H, 4.73; N, 9.39; found C, 64.45; H, 4.71; N, 9.35.

Compound 3i: m.p. 130-131˚C; ¹H NMR (400 MHz, CDCl₃) δ: 2.47 (s, 3H), 7.28 (dd, J = 1.6, 8.4 Hz, 1H), 7.44-7.48 (m, 3H), 7.65 (s, 1H), 7.94 (d, J = 8.4 Hz, 1H), 8.04-8.07 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 21.5, 121.3, 122.6, 127.3, 127.8, 128.9, 130.7, 133.7, 135.1, 135.3, 152.2, 166.9; HRMS calcd for C₁₄H₁₁NS: 225.06; found: 225.03; elemental anal calcd C, 74.63; H, 4.92; N, 6.22; found C, 74.54; H, 4.88; N, 6.14.

Compound 3j: m.p. 137-139˚C; ¹H NMR (400 MHz, CDCl₃) δ: 2.47 (s, 3H), 3.85 (s, 3H), 6.97(d, J = 8.8 Hz, 2H), 7.26(d, J = 9.0 Hz, 1H), 7.63 (s, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.99 (d, J = 8.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 21.4, 55.4, 114.2, 121.2, 122.2, 126.5, 127.7, 128.9, 134.8, 134.9, 152.2, 161.6, 161.7; HRMS calcd for C₁₅H₁₃NOS: 255.07; found: 255.07; elemental anal calcd C, 70.56; H, 5.13; N, 5.49; found C, 70.52; H, 5.10; N, 5.51.

Compound 3k: Syrup; ¹H NMR (400 MHz, CDCl₃) δ: 2.42 (s, 3H), 2.46 (s, 3H), 7.24-7.28 (m, 2H), 7.34 (t, J = 7.82 Hz, 1H), 7.63 (s, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.90 (s, 1H), 7.93 (d, J = 8.4 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 21.2, 21.4, 121.2, 122.5, 124.6, 127.7, 127.8, 128.8, 131.5, 133.5, 135.1, 135.2, 138.7, 152.1, 167.1; HRMS calcd for C₁₅H₁₄NS: 239.08; found: 239.06; elemental anal calcd C, 75.28; H, 5.47; N, 5.85; found C, 75.20; H, 5.50; N, 5.88.

Compound 3l: Syrup; ¹H NMR (400 MHz, CDCl₃) δ: 2.50 (s, 3H), 7.33(dd, J = 1.6, 8.4 Hz, 1H), 7.69 (s, 1H), 7.94 (s, 1H), 7.96 (d, J = 8.8 Hz, 1H), 8.47 (s, 2H); ¹³C NMR (100 MHz, CDCl₃)

δ: 121.5 ,123.0 (q, J = 271.7 Hz), 123.2, 123.7, 127.1, 128.6, 132.5 (q, J = 34.3 Hz), 135.3, 135.7, 136.6, 151.9, 162.9; HRMS calcd for C₁₆H₉F₆NS^: 361.04; found: 361.03; elemental anal calcd C, 53.19; H, 2.51; N, 3.88; found C,53.25; H, 2.48; N,3.88.

Compound 3m: Syrup; ¹H NMR (400 MHz, CDCl₃) δ: 2.46 (s, 3H), 6.56 (dd, J = 2.0, 7.4 Hz, 1H), 7.13 (d, J = 7.4 Hz, 1H), 7.27 (d, J = 8.8 Hz, 1H), 7.56 (s, 1H), 7.63 (s, 1H), 7.90 (d, J = 8.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 21.4, 110.9, 112.3, 121.2, 122.5, 127.9, 134.3, 135.3, 144.3, 148.7, 151.7, 156.4; HRMS calcd for C₁₂H₉NOS: 215.04; found: 215.03; elemental anal calcd C, 66.95; H, 4.21; N, 6.51; found C, 66.98; H, 4.24; N, 6.49.

Compound 3n: m.p. 127-129˚C; ¹H NMR (400 MHz, CDCl₃) δ: 7.20 (dt, J = 2.4, 8.8 Hz, 1H), 7.44-7.51 (m, 3H), 7.54 (dd, J = 2.4, 8.4 Hz, 1H), 7.97-8.05 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ:107.8 (d, J = 26.7), 114.9 (d, J = 24.8), 124.0, 127.3, 129.0, 130.9, 133.2, 133.9, 150.7, 160.4 (d, J = 244.1 Hz), 167.7; HRMS calcd for C₁₃H₈FNS: 229.04; found: 229.03; elemental anal calcd C, 68.10; H, 3.52; N, 6.11; found C, 68.02; H, 3.47; N, 6.24.

Compound 3o: m.p. 125-126˚C; ¹H NMR (400 MHz, CDCl₃) δ: 3.84 (s, 3h), 6.96 (d, J = 8.8 Hz, 2H), 7.28 (dt, J = 2.4, 8.8 Hz, 1H), 7.51 (dd, J = 2.4, 8.4 Hz, 1H), 7.93-7.96 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 55.3, 107.7 (d, J = 26.7), 114.3, 114.6 (d, J = 24.8 Hz), 123.5 (d, J = 8.6 Hz), 126.0, 128.9, 135.7 (d, J = 10.5 Hz), 150.7, 161.1 (d, J = 240.8 Hz), 168.8, 167.5; HRMS calcd for C₁₄H₁₀FNOS: 259.05; found: 259.04; elemental anal calcd C, 64.85; H, 3.89; N, 5.40; found C, 64.82; H, 3.87; N, 5.34.

Compound 3p: m.p. 112-114˚C; ¹H NMR (400 MHz, CDCl₃) δ: 2.42 (s, 3H), 7.20 (dt, J = 2.4, 8.8 Hz, 1H), 7.28 (d, J = 7.8 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.53 (dd, J = 2.4,7.8 Hz, 1H), 7.79 (d, J = 7.4 Hz, 1H), 7.87 (s, 1H), 7.98 (dd, J = 4.4, 8.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 21.2, 107.7 (d, J = 25.0 Hz), 114.8 (d, J = 25.2 Hz), 124.0, 124.6, 127.7, 128.9, 131.8, 133.1, 135.9, 138.8, 150.6, 160.3 (d, J = 241 Hz), 167.9; HRMS calcd for C₁₄H₁₀FNS: 243.06; found: 243.05; elemental anal calcd C, 69.11; H, 4.14; N, 5.76; found C, 69.04; H, 4.17; N, 5.81.

Compound 3q: m.p. 145-147˚C; ¹H NMR (400 MHz, CDCl₃) δ: 7.27 (dt, J = 2.8, 8.2 Hz, 1H), 7.60 (dd, J = 2.4, 7.8 Hz, 1H), 7.97 (s, 1H), 8.04 (dd, J = 4.8, 8.8 Hz, 1H), 8.46 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 108.0 (d, J = 26.7 Hz), 115.8 (sd, J = 24.4 Hz), 129.9 (q, J = 270.9 Hz), 124.0, 124.9 (d, J = 9.1 Hz), 127.1, 132.6 (q, J = 33.6), 135.2, 136.1 (d, J = 11.4 Hz), 150.4, 161.0 [d, J = 246.5 Hz], 163.7; HRMS calcd for C₁₅H₆F₇NS: 365.01; found 365.02; elemental anal calcd C, 49.32; H, 1.66; N, 3.83; found C, 49.20; H, 1.70; N,3.88.

Compound 3r: m.p. 115-117˚C; ¹H NMR (400 MHz, CDCl₃) δ: 6.58 (dd, J = 1.4, 7.4 Hz, 1H), 7.15 (d, J = 7.4 Hz, 1H), 7.20 (dt, J = 2.4, 8.8 Hz, 1H), 7.54 (dd, J = 2.4, 8.4 Hz, 1H), 7.57-7.60 (m, 1H), 7.96 (dd, J = 4.4, 8.4 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 107.8 (d, J = 26.7 Hz), 111.3, 112.5, 115.1 (d, J = 24.8 Hz), 123.9, 135.2, 144.7, 148.3, 150.3, 157.2, 160.3 (d, J = 245.0 Hz); ; HRMS calcd for C₁₁H₇FNOS: 309.05; found: 309.04; elemental anal calcd C, 60.26; H, 2.76; N, 6.39; found C, 6.17; H, 2.73; N, 6.42.

Compound 3s: m.p. 137-140˚C; ¹H NMR (400 MHz, CDCl₃) δ: 1.46-7.52 (m, 3H), 7.71 (dd,  J = 1.0, 8.4 Hz, 1H), 8.05-8.10 (m, 2H), 8.12 (d, J = 8.8 Hz, 1H), 8.16 (s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 119.2, 123.2, 123.4, 124.1 (q, J = 269.8 Hz), 127.2 (q, J = 32.4 Hz), 127.7, 129.1, 131.6, 132.9, 135.0, 156.0, 171.0; HRMS calcd for C₁₄H₈F₃NS: 279.04; found: 279.04; elemental anal calcd C, 60.21; H, 2.89; N, 5.02; found C, 60.14; H, 2.86; N, 5.08.

Compound 3t: m.p. 134-136˚C ¹H NMR (400 MHz, CDCl₃) δ: 3.85 (s, 3H), 6.97 (d, J = 8.8 Hz, 2H), 7.67 (dd, J = 1.6, 8.8 Hz, 1H), 7.99 (d, J = 8.8 Hz, 2H), 8.05 (d, J =  8.8 Hz,, 1H), 8.11 (s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 55.4, 114.4, 119.0, 122.9, 123.1, 124.2 (q, J = 271.2 Hz), 125.7, 126.7 (q, J = 32.4 Hz), 129.3, 134.85, 156.1, 162.4, 170.8; HRMS calcd for C₁₅H₁₀F₃NOS: 309.05; found: 309.05 elemental anal calcd C, 58.25; H, 3.26; N, 4.53; found C, 58.25; H, 3.22; N, 4.59.

Compound 3u: m.p. 156-158˚C; ¹H NMR (400 MHz, CDCl₃) δ: 7.78 (d, J = 8.4 Hz, 1H), 8.01 (s, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.24 (s, 1H), 8.52 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 119.6, 122.8 (q, J = 271.7 Hz), 123.8 (q, J = 270.8 Hz), 123.9, 124.2, 124.7, 127.5, 128.4 (q, J = 32.4 Hz), 132.8 (q, J = 34.3 Hz), 135.0 (d, J = 19.0 Hz), 155.6, 167.1; HRMS calcd for C₁₆H₆F₉NS: 415.01; found 415.01; elemental anal calcd C, 46.28; H, 1.46; N, 3.37; found C, 46.17; H, 1.49; N, 3.40.

The synthesized compounds (3a–3u) were successfully characterized using melting point determination, ^1H NMR, 13C NMR, high-resolution mass spectrometry (HRMS), and elemental analysis, all of which confirmed their proposed structures. The melting points were sharp, indicating good purity of the compounds; derivatives such as 3e, 3q, and 3u exhibited relatively higher melting points, likely due to stronger intermolecular interactions arising from electron-withdrawing substituents like fluorine, whereas compounds such as 3c and 3f showed lower melting points, suggesting comparatively weaker interactions. The 1H NMR spectra of all compounds displayed characteristic aromatic proton signals in the range of δ 6.5–8.5 ppm, confirming the presence of aromatic systems. Singlet peaks observed around δ 2.4–2.8 ppm in compounds such as 3c, 3h, 3i, 3j, 3k, 3m, and 3p were attributed to methyl groups, while methoxy-substituted derivatives (3b, 3d, 3j, 3o, 3t) showed singlets near δ 3.8–4.0 ppm corresponding to –OCH₃ groups. The observed splitting patterns and coupling constants (J ≈ 7–9 Hz) indicated ortho- and meta-coupled aromatic protons, supporting substituted benzene frameworks. Downfield signals around δ 8.4–8.5 ppm in certain compounds (e.g., 3e, 3l, 3q, 3u) suggested deshielding effects due to strong electron-withdrawing groups. The ^13C NMR spectra further supported the structures, with aromatic carbons appearing in the range δ 110–140 ppm and signals around δ 150–170 ppm assigned to carbonyl or imine-type carbons. Methoxy carbons were observed near δ ~55 ppm, while methyl carbons appeared around δ ~20–22 ppm. Notably, fluorinated compounds exhibited characteristic carbon–fluorine coupling with large coupling constants (~240–270 Hz), confirming the presence of CF₃ or related groups. The HRMS data showed molecular ion peaks that were in excellent agreement with calculated values for all compounds, confirming their molecular formulas. Additionally, elemental analysis data (C, H, N) closely matched theoretical values, indicating high purity and correct composition. Overall, the combined spectral and analytical data strongly support the successful synthesis and structural confirmation of compounds 3a–3u.

4.       Conclusion

In conclusion, a series of compounds (3a–3u) were successfully synthesized and thoroughly characterized using melting point determination, ^1H NMR, ^13C NMR, HRMS, and elemental analysis techniques. The spectral data obtained for all compounds were in excellent agreement with the proposed molecular structures, confirming their successful formation. The presence of characteristic functional groups, including aromatic rings, methyl, methoxy, and fluorinated substituents, was clearly evidenced from the NMR studies, while HRMS and elemental analysis further validated the molecular composition and purity of the synthesized derivatives. Variations in spectral features and melting points among the compounds were attributed to the influence of different substituents, particularly electron-donating and electron-withdrawing groups, on the electronic environment and intermolecular interactions. Overall, the study demonstrates an efficient synthesis and reliable structural confirmation of the target compounds, providing a strong foundation for further investigations and potential applications.

Acknowledgement:

            The authors are grateful to Govt. D B Girls’ P G College to support finically and providing basic facilities for this research work.