Synthesis of Novel Symmetrical and Unsymmetrical o-Phthalic Acid Diamides

Praveen Kumar, Padam; Dathu Reddy, Yervala; Reddy, Chittireddy Venkata Ramana; Devi, Bhoomireddy Rama; Dubey, Pramod Kumar

doi:https://doi.org/10.1155/2014/576715

Organic Chemistry International

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Research Article | Open Access

Volume 2014 | Article ID 576715 | https://doi.org/10.1155/2014/576715

Synthesis of Novel Symmetrical and Unsymmetrical o-Phthalic Acid Diamides

Padam Praveen Kumar,¹Yervala Dathu Reddy,¹Chittireddy Venkata Ramana Reddy,¹Bhoomireddy Rama Devi,¹and Pramod Kumar Dubey¹

Academic Editor: Joseph E. Saavedra

Received23 Jan 2014

Revised26 Mar 2014

Accepted27 Mar 2014

Published05 May 2014

Abstract

Phthalic anhydride was treated with secondary amines in acetic acid yielding 2-(diethyl (or) 4-alkylpiperazine or morpholine-1-carbonyl) benzoic acids. The latter were reacted, again, with secondary amines and arylamines by using the coupling reagent HATU and Et₃N as a base in DMF giving the novel symmetrical o-phthalic acid diamides , unsymmetrical o-phthalic acid diamides , and primary amidic-secondary amidic containing unsymmetrical o-phthalic acid diamides , respectively.

1. Introduction

Phthalic anhydride is used in the manufacture of dialkylphthalates [1, 2] which find application as plasticisers for polymers like polyvinyl chloride (PVC) and polyvinylacetate (PVA). It is used in the manufacture of phenolphthalein indicator [3, 4], anthraquinone [5] (a versatile, raw materials in the dye industry [6]), and metal phthalocyanines [7]. Phthalocyanine compounds are used in a variety of applications [7] in addition to their use as pigments, in paints [8] and in many types of dyestuffs [7]. Phthalic anhydride derivatives have been widely reported to possess beneficial pharmaceutical effects, like analgesic [9], anti-inflammatory [10] and antiviral effects [11].

Dunlap and Cummer reported [12] the preparation of symmetrical o-phthalic acid diamides [o-ArNHCOC₆H₄CONHAr] by the reaction of phthaloyl dichloride with two moles of aniline in ether at RT. Dann et al. reported [13] the preparation of symmetrical o-phthalic acid diamides by the reaction of phthaloyl dichloride with two moles of aniline in the presence of sodium fluoride in benzene under reflux for 1 h. de Toranzo and Brieux reported [14] the synthesis of unsymmetrical diamides [ArNHCOC₆H₄CONHAr¹] by the reaction of phthalphenylisoimide with anilines in ether at RT. Reynolds reported [15] that unsymmetrical diamides [ArNHCOC₆H₄CONHAr¹] can be made by the reaction of N-arylphthalamic acid with the sodium salt of o- or p-methylaniline in an atmosphere of nitrogen for 1 h at 75°C. However, these methods suffer from drawbacks such as long reaction times, excess use of organic solvents, harsh refluxing conditions, and preparation of difficult starting materials from phthalic anhydride by the reaction with primary amines in the presence of trifluoroacetic anhydride. Keeping these facts in mind, we wish to report our results on reactions of phthalic anhydride with primary and secondary amines using HATU as a coupling reagent. Probably, this appears to be the first ever case of facile preparation of symmetrical and unsymmetrical o-phthalic acid diamides. The use of HATU as a coupling agent has been reported in the literature for reactions such as amide bond formation in solid phase synthesis [16–18] and peptides synthesis [19]. However, its use in the preparation of diamides from phthalic anhydride with amines has probably not been reported so far.

2. Results and Discussion

Phthalic anhydride 1 was treated with the secondary amines 2a–2e in acetic acid at RT for 10–15 min resulting in the formation of 2-(diethyl (or) 4-alkylpiperazine (or) morpholine-1-carbonyl)benzoic acid 3a–3e. Reaction of 3a with the piperazine 2b in the presence of o-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU) and Et₃N at 0–5°C for 40–45 min in DMF gave 5a. Alternatively, this compound was prepared by treating 2-(piperazine-1-carbonyl)benzoic acid 3b withdiethylamine 2a by HATU and Et₃N at 0–5°C for 40–45 min in DMF to form N,N-diethyl-2-(piperazine-1-carbonyl)benzamide 5a. This reaction was examined by carrying out the condensation of 2-(diethylcarbonyl)benzoic acid 3a (1 mmol) with piperazine 2b (1 mmol) in the presence different coupling reagents (HATU, EDC.HCl/HOBt (1-hydroxybenzotriazole), DCC (N,N′-dicyclohexylcarbodiimide), HBTU and PTSA (4-methylbenzenesulfonic acid)) and tertiary bases (Et₃N and DBU (2, 3, 4, 6, 7, 8, 9, 10-octahydropyrimido azepine) at different temperatures in DMF as a solvent (Table 1) with a view to study the generalisation of condensation between 3 and 2. However, coupling of 3a with 2b in the presence of HATU and Et₃N at 0–5°C for 40–45 min in DMF was found to be the best method giving 5a in quality and yield (≥80%) (Table 1, entry 1).

Using the above-stated optimised conditions, 3a–3e were condensed into 2a–2e using HATU and Et₃N at 0–5°C for 40–65 min in DMF yielding 4a–4e and 5a–5j (Scheme 1) (Tables 2 and 3) in excellent yield. The structures of the products have been established on the basis of their spectral and analytical data. (Please see experimental section)

Condensation of 3a–3e with arylamines 6a–6e in the presence of HATU and Et₃N at 0–5°C for 40–55 min in DMF gave primary amidic-secondary amidic containing unsymmetrical o-phthalic acid diamides [o-R₁R₁NCOC₆H₄CONHAr] 7a–7y (Scheme 2) (Table 4). The structures of the products have been established on the basis of their spectral and analytical data. An alternate protocol was attemptedto synthesize 7a–7y by treatment of 1 with aniline 6a in acetic acid at 0–5°C for 10–15 min which gave 2-(phenylcarbamoyl)benzoic acid 8a¹⁸ and subsequent reaction of 8a with diethylamine 2a in the presence of HATU and Et₃N at RT for 20–25 min in DMF which resulted in the formation of 2-phenylisoindoline-1, 3-dione 9a¹⁸.

3. Conclusion

In conclusion, we have developed novel syntheses of symmetrical 4a–4e and unsymmetrical 5a–5j and 7a–7y o-phthalic acid diamides. This approach presents a simple and useful synthetic process which requires a few minutes of reaction time, easily available starting materials and straight forward and easy workup procedure. Probably, this appears to be the first ever case of facile preparation of symmetrical and unsymmetrical o-phthalic acid diamides. The use of HATU as a coupling agent has been reported in the literature for reactions such as amide bond formation in solid phase synthesis and peptides synthesis. However, its use in the preparation of diamides from phthalic anhydride with amines has probably not been reported so far. The overall yields of these compounds are very good.

4. Materials and Methods

Melting points are uncorrected and were determined in open capillary tubes in sulphuric acid bath, TLC was run on silica gel-G, visualization was done using iodine or UV light, and IR spectra were recorded using PerkinElmer 1000 instrument in KBr pellets. 1HNMR spectra were recorded in DMSO-d₆ using TMS as internal standard using 400 MHz spectrometer. Mass spectra were recorded on Agilent-LCMS instrument under CI conditions and given by values only. Starting 1, 2, and 6 were obtained from commercial sources and used as such.

4.1. Preparation of 3a–3e

A mixture of 1a (10 mM), 2a–2e (10 Mm) and CH₃COOH (20 mL) was stirred at RT for 10–20 min. A colourless solid separated out from reaction mixture which was filtered, washed with hexane (10 mL), and dried. The crude product was recrystallized from suitable solvent to obtain 3a–3e.

4.2. Preparation of 4a–4e & 5a–5j

A mixture of 3a–3e (10 mM), 2a–2e (10 mM) HATU (10 mM), Et₃N (10 mM), and DMF (15 mL) was stirred at 0–5°C for 40–65 min. Then, ice-cold water (50 mL) was added to the reaction mixture. The separated solid was filtered, washed with water (10 mL), and dried. The product was recrystallized from a suitable solvent to obtain 4a–4e and 5a–5j.

4.3. Preparation of 7a–7y

A mixture of 3a–3e (10 mM), 6a–6e (10 mM), HATU (10 mM), Et₃N (10 mM), and DMF (15 mL) was stirred at 0–5°C for 40–55 min. Then, ice-cold water (50 mL) was added to the reaction mixture. The separated solid was filtered, washed with water (10 mL), and dried. The product was recrystallized from a suitable solvent to obtain 7a–7y.

5. Supporting Information

3a: IR (KBr): 3100–3400 (broad medium, –NH and –OH groups put together), 1720 (sharp, strong, –CO– of acid group), 1655 (sharp, storng, –CO– of amide group); ¹H-NMR: 0.8 (t, 3H, –CH₃), 1.2 (t, 3H, –CH₃), 3.0 (q, 2H, –CH₂), 3.6 (q, 2H, –CH₂), 7.0–8.0 (m, 4H, Ar-H), 13.00 (s, 1H, –COOH, D2O exchangeable), 10.12 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 12.3, 41.4, 123.1, 128.5, 129.3, 129.5, 160.2, 165.5. Ms: = 222 (M^+. + 1).

3b: IR (KBr): 3100–3400 (broad medium, –NH and –OH groups put together), 1725 (sharp, strong, –CO– of acid group), 1670 (sharp, storng, –CO– of amide group); ¹H-NMR: 2.2 (s, 1H, –NH), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 4H, Ar-H), 13.00 (s, 1H, –COOH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 49.4, 50.1, 51.4, 51.9, 124.1, 125.5, 127.3, 128.5, 161.2, 164.8. Ms: = 235 (M^+. + 1).

3c: IR (KBr): 3100–3400 (broad medium, –NH and –OH groups put together), 1730 (sharp, strong, –CO– of acid group), 1655 (sharp, storng, –CO– of amide group); ¹H-NMR: 1.2 (t, 3H, –CH₃), 2.6 (q, 2H, –CH₂), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 4H, Ar-H), 13.2 (s, 1H, –COOH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 12.5, 49.4, 50.1, 50.9, 51.9, 52.2, 123.1, 124.5, 125.3, 127.5, 163.2, 164.8. Ms: = 263 (M^+. + 1).

3d: IR (KBr): 3100–3400 (broad medium, –NH and –OH groups put together), 1720 (sharp, strong, –CO– of acid group), 1660 (sharp, storng, –CO– of amide group); ¹H-NMR: 1.6 (t, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 4H, Ar-H), 13.1 (s, 1H, –COOH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 39.4, 55.1, 55.9, 55.9, 55.2, 126.1, 127.5, 128.3, 129.5, 160.2, 165.8. Ms: = 249 (M^+. + 1).

3e: IR (KBr): 3100–3400 (broad medium, –NH and –OH groups put together), 1720 (sharp, strong, –CO– of acid group), 1655 (sharp, storng, –CO– of amide group); ¹H-NMR: 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 4H, Ar-H), 13.1 (s, 1H, –COOH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 50.2, 50.6, 71.9, 72.2, 125.1, 125.5, 126.3, 127.5, 162.2, 164.8. Ms: = 236 (M^+. + 1).

4a: IR (KBr): 3100–3400 (broad medium, –NH–), 1680 (sharp, strong, –CO– of amide group), 1665 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.2 (t, 6H, –CH₃, –CH₃), 1.4 (t, 6H, –CH₃, –CH₃), 2.8 (q, 4H, –CH₂, –CH₂) 3.2 (q, 4H, –CH₂, –CH₂), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 12.9, 14.1, 31.6, 36.7, 39.1, 43.5, 125.3, 126.5, 127.1, 129.3, 163.6, 169.6. Ms: = 277 (M^+. + 1).

4b: IR (KBr): 3100–3400 (broad medium, –NH–), 1685 (sharp, strong, –CO– of amide group), 1665 (sharp, strong, –CO– of amide group); ¹H-NMR: 2.2 (s, 2H, –NH, –NH), 3.0 (t, 8H, Four –CH₂ groups), 3.4 (t, 8H, Four –CH₂ groups), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 47.4, 48.6, 49.7, 50.9, 51.5, 52.4, 125.3, 125.5, 127.1, 128.6, 164.3, 167.6. Ms: = 303 (M^+. + 1).

4c: IR (KBr): 3100–3400 (broad medium, –NH–), 1660 (sharp, strong, –CO– of amide group), 1665 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.3 (t, 6H, –CH₃, –CH₃), 2.8 (q, 4H, –CH₂, –CH₂), 3.2 (t, 8H, Four –CH₂ groups), 3.2 (t, 8H, Four –CH₂ groups), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 12.3, 16.1, 46.4, 47.6, 48.7, 49.1, 50.5, 51.4, 123.3, 124.5, 128.1, 128.9, 164.6, 168.6. Ms: = 359 (M^+. + 1).

4d: IR (KBr): 3100–3400 (broad medium, –NH–), 1670 (sharp, strong, –CO– of amide group), 1665 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.4 (t, 6H, –CH₃, –CH₃), 3.0 (t, 8H, Four –CH₂ groups), 3.2 (t, 8H, Four –CH₂ groups), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 32.3, 33.4, 48.4, 48.9, 49.7, 50.5, 52.4, 55.3, 125.3, 125.6, 128.3, 129.9, 165.2, 169.3. Ms: = 331 (M^+. + 1).

4e: IR (KBr): 3100–3400 (broad medium, –NH–), 1675 (sharp, strong, –CO– of amide group), 1665 (sharp, strong, –CO– of amide group); ¹H-NMR: 3.0 (t, 8H, Four –CH₂ groups), 3.2 (t, 8H, Four –CH₂ groups), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 49.3, 49.9, 50.7, 52.8, 55.9, 56.8, 125.4, 126.3, 127.4, 128.9, 164.2, 167.3. Ms: = 305 (M^+. + 1).

5a: IR (KBr): 3100–3400 (broad medium, –NH–), 1690 (sharp, strong, –CO– of amide group), 1660 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.0–1.2 (t, 6H, –CH₃, –CH₃), 2.2 (s, 1H, –NH), 3.0 (t, 4H, –CH₂, –CH₂), 3.2 (t, 4H, –CH₂, –CH₂), 3.4 (q, 2H, –CH₂), 3.6 (q, 2H, –CH₂, –CH₂), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 12.9, 31.7, 43.5, 44.6, 51.1, 52.5, 123.1, 124.3, 128.3, 129.6, 161.7, 165.5. Ms: = 290 (M^+. + 1).

5b: IR (KBr): 3100–3400 (broad medium, –NH–), 1680 (sharp, strong, –CO– of amide group), 1650 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.0–1.2 (t, 6H, –CH₃, –CH₃), 1.4 (t, 3H, –CH₃), 2.2 (q, 2H, –CH₂), 3.0 (t, 4H, –CH₂, –CH₂), 3.2 (t, 4H, –CH₂, –CH₂), 3.4 (q, 2H, –CH₂), 3.6 (q, 2H, –CH₂, –CH₂), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 12.9, 13.6, 31.5, 44.5, 45.6, 48.6, 54.1, 55.5, 123.6, 125.3, 128.3, 129.6, 162.7, 165.4. Ms: = 318 (M^+. + 1).

5c: IR (KBr): 3100–3400 (broad medium, –NH–), 1695 (sharp, strong, –CO– of amide group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.0–1.2 (t, 6H, –CH₃, –CH₃), 1.8 (t, 3H, –CH₃), 3.0 (t, 4H, –CH₂, –CH₂), 3.2 (t, 4H, –CH₂, –CH₂), 3.4 (q, 2H, –CH₂), 3.6 (q, 2H, –CH₂, –CH₂), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 13.9, 32.7, 41.5, 44.6, 45.5, 53.1, 54.5, 122.3, 125.3, 129.2, 129.9, 164.7, 166.4. Ms: = 304 (M^+. + 1).

5d: IR (KBr): 3100–3400 (broad medium, –NH–), 1680 (sharp, strong, –CO– of amide group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.0–1.2 (t, 6H, –CH₃, –CH₃), 3.0 (t, 4H, –CH₂, –CH₂), 3.2 (t, 4H, –CH₂, –CH₂), 3.4 (q, 2H, –CH₂), 3.6 (q, 2H, –CH₂, –CH₂), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 13.2, 33.4, 44.3, 45.2, 50.1, 52.4, 124.2, 123.5, 125.4, 125.7, 160.3, 165.6. Ms: = 291 (M^+. + 1).

5e: IR (KBr): 3100–3400 (broad medium, –NH–), 1690 (sharp, strong, –CO– of amide group), 1665 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.4 (t, 3H, –CH₃), 2.2 (q, 2H, –CH₂), 2.2 (s, 1H, –NH), 2.8–3.6 (t, 16H, eight –CH₂ groups), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 12.4, 29.4, 30.2, 31.7, 33.4, 34.3, 42.5, 43.6, 50.2, 51.2, 124.1, 125.2, 127.3, 129.3, 160.3, 164.2. Ms: = 331 (M^+. + 1).

5f: IR (KBr): 3100–3400 (broad medium, –NH–), 1690 (sharp, strong, –CO– of amide group), 1650 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.6 (t, 3H, –CH₃), 2.2 (s, 1H, –NH), 2.8–3.6 (t, 16H, eight –CH₂ groups), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 28.4, 31.4, 32.5, 33.3, 35.4, 41.4, 42.4, 51.4, 52.3, 125.2, 126.1, 128.3, 129.2, 161.6, 165.1. Ms: = 317 (M^+. + 1).

5g: IR (KBr): 3100–3400 (broad medium, –NH–), 1680 (sharp, strong, –CO– of amide group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 2.2 (s, 1H, –NH), 2.8–3.6 (t, 16H, eight –CH₂ groups), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 30.1, 31.3, 33.5, 34.2, 42.6, 43.8, 50.1, 51.4, 123.2, 125.1, 128.2, 129.3, 160.3, 165.3. Ms: = 304 (M^+. + 1).

5h: IR (KBr): 3100–3400 (broad medium, –NH–), 1690 (sharp, strong, –CO– of amide group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.4 (t, 3H, –CH₃), 1.8 (t, 3H, –CH₃), 2.2 (q, 2H, –CH₂), 2.8–3.6 (t, 16H, eight –CH₂ groups), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 13.2, 28.6, 29.5, 32.2, 33.7, 34.5, 35.4, 43.5, 44.5, 53.5, 54.6, 125.5, 126.4, 126.9, 129.5, 161.3, 165.9. Ms: = 345 (M^+. + 1).

5i: IR (KBr): 3100–3400 (broad medium, –NH–), 1680 (sharp, strong, –CO– of amide group), 1650 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.4 (t, 3H, –CH₃), 2.2 (q, 2H, –CH₂), 2.8–3.6 (t, 16H, eight –CH₂ groups), 7.0–8.0 (m, 4H, Ar-H). ¹³C NMR (DMSO-d₆, 400 MHz): 13.2, 29.4, 31.2, 32.2, 33.2, 34.5, 42.7, 44.8, 50.9, 51.9, 124.3, 125.9, 127.8, 129.0, 160.7, 168.9. Ms: = 332 (M^+. + 1).

5j: IR (KBr): 3100–3400 (broad medium, –NH–), 1670 (sharp, strong, –CO– of amide group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.6 (t, 3H, –CH₃), 2.8–3.6 (t, 16H, Eight –CH₂ groups), 7.0–8.0 (m, 4H, Ar-H).¹³C NMR (DMSO-d₆, 400 MHz): 28.4, 33.2, 34.7, 35.4, 39.3, 44.5, 47.6, 53.2, 55.2, 127.1, 128.2, 129.3, 129.9, 163.3, 169.4. Ms: = 318 (M^+. + 1).

7a: IR (KBr): 3100–3400 (broad medium, –NH–), 1680 (sharp, strong, –CO– of acid group), 1645 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.0 (t, 6H, –CH₃, –CH₃), 3.2 (q, 2H, –CH₂), 3.4 (q, 2H, –CH₂), 7.0–8.0 (m, 9H, Ar-H), 10.6 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 12.2, 13.4, 37.9, 42.5, 123.4, 126.2, 127.8, 128.1, 128.5, 130.3, 134.1, 137.4, 139.1, 165.8, 169.2. Ms: = 297 (M^+. + 1).

7b: IR (KBr): 3100–3400 (broad medium, –NH–), 1680 (sharp, strong, –CO– of acid group), 1645 (sharp, strong, –CO– of amide group); ¹H-NMR: 2.2 (s, 1H, –NH), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 9H, Ar-H), 10.4 (s, 1H, –NH, D2O exchangeable).¹³C NMR (DMSO-d₆, 400 MHz): 49.3, 50.3, 51.5, 51.3, 124.3, 124.5, 125.5, 126.4, 127.3, 128.5, 129.5, 129.9, 131.5, 163.2, 164.5. Ms: = 310 (M^+. + 1).

7c: IR (KBr): 3100–3400 (broad medium, –NH–), 1690 (sharp, strong, –CO– of acid group), 1645 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.2 (t, 3H, –CH₃), 2.6 (q, 2H, –CH₂), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 9H, Ar-H), 10.4 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 12.6, 44.5, 47.3, 48.5, 50.5, 51.3, 120.3, 122.7, 125.4, 126.3, 127.7, 128.3, 129.2, 130.9, 131.4, 160.6, 164.9. Ms: = 338 (M^+. + 1).

7d: IR (KBr): 3100–3400 (broad medium, –NH–), 1690 (sharp, strong, –CO– of acid group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.6 (t, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 9H, Ar-H), 13.00 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 34.5, 46.4, 47.2, 48.6, 50.2, 121.2, 123.4, 123.9, 124.6, 125.6, 126.3, 128.2, 131.9, 132.4, 164.2, 169.2. Ms: = 324 (M^+. + 1).

7e: IR (KBr): 3100–3400 (broad medium, –NH–), 1680 (sharp, strong, –CO– of acid group), 1660 (sharp, strong, –CO– of amide group); ¹H-NMR: 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 13.00 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 50.3, 51.3, 71.5, 72.3, 120.3, 121.2, 124.2, 125.6, 128.1, 128.9, 129.1, 129.9, 131.4, 165.1, 166.3. Ms: = 311 (M^+. + 1).

7f: IR (KBr): 3100–3400 (broad medium, –NH–), 1680 (sharp, strong, –CO– of acid group), 1644 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.0 (t, 6H, –CH₃, –CH₃), 2.4 (s, 3H, –CH₃), 3.2 (q, 2H, –CH₂), 3.4 (q, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 10.6 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 12.6, 13.8, 19.4, 39.9, 43.6, 123.6, 124.6, 125.2, 126.6, 127.6, 129.8, 131.2, 133.5, 136.5, 166.7, 168.3. Ms: = 311 (M^+. + 1).

7g: IR (KBr): 3100–3400 (broad medium, –NH–), 1685 (sharp, strong, –CO– of acid group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 2.2 (s, 1H, –NH), 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 10.6 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 20.5, 44.5, 49.3, 50.5, 51.5, 120.2, 122.4, 123.4, 124.5, 125.3, 126.6, 128.5, 130.1, 133.5, 163.7, 166.6. Ms: = 324 (M^+. + 1).

7h: IR (KBr): 3100–3400 (broad medium, –NH–), 1695 (sharp, strong, –CO– of acid group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.2 (t, 3H, –CH₃), 2.4 (s, 3H, –CH₃), 2.6 (q, 2H, –CH₂), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 10.6 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 12.2, 19.3, 44.2, 47.6, 48.3, 51.2, 52.2, 119.3, 121.3, 124.2, 124.9, 126.2, 127.1, 130.4, 131.3, 132.3, 161.1, 165.1. Ms: = 352 (M^+. + 1).

7i: IR (KBr): 3100–3400 (broad medium, –NH–), 1680 (sharp, strong, –CO– of acid group), 1650 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.6 (t, 3H, –CH₃), 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 13.00 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 18.4, 35.4, 45.4, 46.3, 47.3, 51.3, 120.1, 122.2, 122.6, 124.5, 124.7, 127.4, 128.6, 131.0, 132.8, 164.6, 169.9. Ms: = 338 (M^+. + 1).

7j: IR (KBr): 3100–3400 (broad medium, –NH–), 1685 (sharp, strong, –CO– of acid group), 1650 (sharp, strong, –CO– of amide group); ¹H-NMR: 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 13.00 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 17.9, 51.2, 52.0, 70.2, 72.4, 121.2, 122.4, 125.3, 126.0, 126.9, 127.0, 129.6, 130.1, 131.5, 160.4, 166.7. Ms: = 325 (M^+. + 1).

7k: IR (KBr): 3100–3400 (broad medium, –NH–), 1685 (sharp, strong, –CO– of acid group), 1645 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.1 (t, 6H, –CH₃, –CH₃), 2.6 (s, 3H, –CH₃), 3.2 (q, 2H, –CH₂), 3.4 (q, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 10.6 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 12.4, 13.5, 19.6, 40.9, 43.5, 124.6, 125.6, 126.7, 128.6, 129.4, 130.6, 131.2, 136.5, 135.5, 166.9, 168.7. Ms: = 311 (M^+. + 1).

7l: IR (KBr): 3100–3400 (broad medium, –NH–), 1685 (sharp, strong, –CO– of acid group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 2.4 (s, 1H, –NH), 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 10.6 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 19.5, 43.4, 45.5, 52.5, 53.4, 119.3, 123.4, 123.9, 124.9, 125.5, 127.6, 128.7, 130.2, 132.5, 161.3, 166.5. Ms: = 324 (M^+. + 1).

7m: IR (KBr): 3100–3400 (broad medium, –NH–), 1695 (sharp, strong, –CO– of acid group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.4 (t, 3H, –CH₃), 2.4 (s, 3H, –CH₃), 2.6 (q, 2H, –CH₂), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 10.4 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 11.23, 18.2, 42.1, 43.4, 45.2, 50.8, 51.3, 119.5, 120.4, 124.5, 126.9, 127.4, 126.1, 130.6, 131.3, 132.6, 160.1, 165.6. Ms: = 352 (M^+. + 1).

7n: IR (KBr): 3100–3400 (broad medium, –NH–), 1683 (sharp, strong, –CO– of acid group), 1650 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.6 (t, 3H, –CH₃), 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 13.00 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 18.3, 36.3, 43.5, 45.2, 46.2, 50.2, 121.2, 121.1, 122.4, 124.4, 125.6, 126.3, 127.2, 130.0, 131.4, 162.6, 166.8. Ms: = 338 (M^+. + 1).

7o: IR (KBr): 3100–3400 (broad medium, –NH–), 1685 (sharp, strong, –CO– of acid group), 1650 (sharp, strong, –CO– of amide group); ¹H-NMR: 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 13.00 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 18.5, 50.1, 51.6, 73.5, 74.3, 119.2, 120.2, 121.2, 122.1, 123.4, 124.1, 125.3, 127.3, 128.3, 163.5, 167.4. Ms: = 325 (M^+. + 1).

7p: IR (KBr): 3100–3400 (broad medium, –NH–), 1670 (sharp, strong, –CO– of acid group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.0 (t, 6H, –CH₃, –CH₃), 2.4 (s, 3H, –CH₃), 3.2 (q, 2H, –CH₂), 3.4 (q, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 10.6 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 12.4, 14.4, 32.9, 40.5, 121.4, 125.8, 126.8, 129.1, 130.3, 131.4, 134.6, 138.4, 139.9, 163.6, 169.9. Ms: = 331 (M^+. + 1).

7q: IR (KBr): 3100–3400 (broad medium, –NH–), 1684 (sharp, strong, –CO– of acid group), 1650 (sharp, strong, –CO– of amide group); ¹H-NMR: 2.2 (s, 1H, –NH), 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 10.4 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 44.5, 44.9, 53.2, 54.2, 119.6, 120.5, 121.9, 122.9, 127.5, 128.5, 129.6, 130.2, 131.3, 162.4, 164.2. Ms: = 344 (M^+. + 1).

7r: IR (KBr): 3100–3400 (broad medium, –NH–), 1650 (sharp, strong, –CO– of acid group), 1640 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.2 (t, 3H, –CH₃), 2.4 (s, 3H, –CH₃), 2.6 (q, 2H, –CH₂), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 10.4 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 12.8, 44.2, 45.4, 46.2, 51.8, 52.4, 119.6, 121.5, 124.5, 125.6, 127.3, 125.6, 130.2, 132.4, 135.7, 160.7, 165.9. Ms: = 372 (M^+. + 1).

7s: IR (KBr): 3100–3400 (broad medium, –NH–), 1640 (sharp, strong, –CO– of acid group), 1635 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.6 (t, 3H, –CH₃), 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 13.00 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 38.3, 45.6, 46.2, 47.5, 50.6, 123.2, 126.6, 127.3, 128.3, 129.1, 129.9, 130.2, 131.4, 132.4, 160.3, 166.4. Ms: = 358 (M^+. + 1).

7t: IR (KBr): 3100–3400 (broad medium, –NH–), 1690 (sharp, strong, –CO– of acid group), 1650 (sharp, strong, –CO– of amide group); ¹H-NMR: 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 8H, Ar-H), 13.00 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 48.1, 50.6, 72.5, 73.1, 119.5, 120.6, 122.3, 122.9, 123.5, 124.3, 125.7, 126.3, 129.3, 165.7, 169.4. Ms: = 345 (M^+. + 1).

7u: IR (KBr): 3100–3400 (broad medium, –NH–), 1680 (sharp, strong, –CO– of acid group), 1650 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.0 (t, 6H, –CH₃, –CH₃), 2.4 (s, 3H, –CH₃), 3.2 (q, 2H, –CH₂), 3.4 (q, 2H, –CH₂), 7.0–8.0 (m, 9H, Ar-H), 10.6 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 12.5, 15.4, 37.9, 43.5, 125.4, 126.5, 126.8, 129.6, 131.2, 131.3, 135.6, 138.6, 139.3, 164.6, 169.8. Ms: = 375 (M^+. + 1).

7v: IR (KBr): 3100–3400 (broad medium, –NH–), 1687 (sharp, strong, –CO– of acid group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 2.2 (s, 1H, –NH), 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 9H, Ar-H), 13.00 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 41.5, 45.9, 52.3, 54.5, 118.4, 121.3, 125.9, 126.9, 127.7, 128.4, 129.7, 131.4, 133.5, 165.4, 167.7. Ms: = 388 (M^+. + 1).

7w: IR (KBr): 3100–3400 (broad medium, –NH–), 1681 (sharp, strong, –CO– of acid group), 1655 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.2 (t, 3H, –CH₃), 2.4 (s, 3H, –CH₃), 2.6 (q, 2H, –CH₂), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 9H, Ar-H), 10.4 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 12.4, 43.5, 45.7, 47.3, 52.9, 53.4, 118.4, 121.6, 124.7, 125.5, 128.3, 129.5, 130.5, 131.3, 135.4, 164.5, 165.9. Ms: = 416 (M^+. + 1).

7x: IR (KBr): 3100–3400 (broad medium, –NH–), 1690 (sharp, strong, –CO– of acid group), 1658 (sharp, strong, –CO– of amide group); ¹H-NMR: 1.6 (t, 3H, –CH₃), 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 9H, Ar-H), 13.00 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 39.2, 46.4, 47.3, 48.4, 49.5, 121.2, 124.3, 124.9, 125.7, 126.4, 128.3, 130.6, 131.1, 131.3, 166.1, 169.3. Ms: = 402 (M^+. + 1).

7y: IR (KBr): 3100–3400 (broad medium, –NH–), 1675 (sharp, strong, –CO– of acid group), 1635 (sharp, strong, –CO– of amide group); ¹H-NMR: 2.4 (s, 3H, –CH₃), 3.0 (t, 2H, –CH₂), 3.2 (t, 2H, –CH₂), 3.4 (t, 2H, –CH₂), 3.8 (t, 2H, –CH₂), 7.0–8.0 (m, 9H, Ar-H), 13.00 (s, 1H, –NH, D2O exchangeable). ¹³C NMR (DMSO-d₆, 400 MHz): 48.9, 51.4, 73.5, 74.5, 119.6, 121.4, 122.5, 123.8, 124.7, 125.7, 126.4, 127.3, 129.3, 165.8, 169.3. Ms: = 389 (M^+. + 1).

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Acknowledgment

The authors are thankful to the authorities of Jawaharlal Nehru Technological University Hyderabad for providing laboratory facilities and for financial support to two of the authors (Padam Praveen Kumar and Yervala Dathu Reddy).

Supplementary Materials

1. ¹H NMR scanned copies of 3a, 4a, 5a and 7a

2. ¹³C NMR scanned copies of 4a and 7a

3. HRMS scanned copies of 3a, 4a, 5a and 7a

Supplementary Material

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Copyright © 2014 Padam Praveen Kumar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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