Synthesis and Characterization of New Bis-Schiff Bases Linked to Various Imide Cycles

This research includes the synthesis of new bis-Schiff bases linked to different imide cycles. There were some steps involved in the synthesis of the novel Schiff bases with succinimide, phthalimide, tetrachlorophthalimide, and tetrabromophthalimide cycles. The first step involved the preparation of 4,4`-bis[(4-aminophenyl) methyl benzylidene]tolidine ( 1 ) via the condensation reaction of 3,3'- dimethyl-(1,1'-biphenyl)-4,4'-diamine with 4-amino acetophenone. In the second step, compound 1 reacted with various cyclic anhydrides, affording bis-amic acid Schiff bases 2 - 5 . In the third step, the products 2-5 were dehydrated using the fusion method to produce the target bis-imidyl Schiff bases 6 - 9 . This work also involved the synthesis of bis-imidyl Schiff base 10 directly by fusion of compound 1 with 1,8-naphthalic anhydride. The prepared compounds were characterized depending on their FT-IR, 1 H NMR, and 13 C NMR spectra. The newly synthesized target compounds are expected to be very active biologically since their molecules are essential components of two active groups (imine and imide)


Introduction
A lot of interest has been paid to Schiff's base compounds that contain (carbon-nitrogen) double bonds because of their ease of synthesis and various applications [1][2].These important compounds are usually formed via the condensation of primary amines with carbonyl compounds (aldehyde or ketone) [3].The presence of imine linkage (-C=N-) in the Schiff base molecules is essential for exhibiting these compounds' wide spectrum of biological applications like analgesic, antimicrobial, antioxidant, antiviral, anticancer, and anti-inflammatory activities [4][5][6][7][8]. 1 Besides, Schiff bases have various applications in many fields, including analytical chemistry, corrosion inhibitors, dyes, and ligands for metal complexes [9][10][11].However, cyclic imides are organic compounds because they have biological activity, such as antibacterial, anticancer, analgesic, anti-inflammatory, and antimicrobial activities [12][13][14][15].Moreover, cyclic imides are essential building blocks for the synthesis of pharmaceuticals, natural products, polymers, and drugs [16][17].Depending on all the above facts, we believe it is very worthwhile to synthesize new molecules that combine these two active biological components (Schiff base and imide cycle) since they exhibit various biological activities.

Experimental part
The melting points of synthesized compounds were measured on the Thomas Hoover melting point apparatus and on the Shimadzu FTIR-8400 Fourier Transform Infrared spectrophotometer using KBr pellets.While their 1 H NMR and 13 C NMR were recorded in DMSO-d 6 on the Bruker 400MHZ instrument, the internal standard is TMS.

Synthesis of bis-(amic acid Schiff bases) 2-5
A solution of compound 1 (2.23 g, 5 mmol) in acetone was added dropwise through a dropping funnel to succinic, phthalic, tetrachlorophthalic, or tetrabromophthalic anhydride (10 mmol) in acetone (20 mL), with stirring and cooling [18].After the completion of the addition, the reaction mixture was stirred for 2 hours.The solid-crude material was then filtered, dried, and recrystallized using a suitable solvent to afford the desired products 2-5.

Synthesis of bis-imidyl Schiff bases 6-9
Bis-amic acid Schiff bases 2-5 were heated in a sand-bath until complete fusion, and then the temperature was raised to many degrees above the melting and held there for 2 hours [12].The solid-crude material that resulted was recrystallized from a suitable solvent to yield the title products 6-9.(10) Following the same process employed in the synthesis of compounds 6-9, a mixture of compound 1 (2.23 g, 5 mmol) and naphthalic anhydride (1.98 g, 10 mol) was grinded and combined before being heated in a sand-bath for 2 hours.The resulting solid-crude material was recrystallized from ethanol to give the desired product 10.

Result and discussion
The primary aim of this research is to develop novel compounds by combining these two active components (Schiff bases and cyclic imides) into a single molecule, followed by testing their antibacterial activity.Schiff bases and cyclic imides are both well-known, significant classes of organic compounds that exhibit various biological activities.Since the target compounds were just produced and have already been built with biologically active components, it is expected that they will have strong anti-bacterial activity.Many steps were performed to synthesize the target compounds, which are presented in Scheme 1.In the first step of preparing 4,4-bis[(4-aminophenyl)methylbenzylidene]tolidine (1), 3,3'-dimethyl-[1,1'biphenyl]-4,4'-diamine (one equivalent) and 4-aminoacetophenone (two equivalents) were combined in a condensation reaction with glacial acetic acid as a catalyst and absolute ethanol as a solvent for 12 hours [12].Compound 1 represents the key material in our work since it contains two imine groups (Schiff bases) and two amino groups ready for introduction in subsequent reactions.Thus, in the second step, compound 1 was introduced in the reaction with different cyclic anhydrides, including succinic, phthalic, tetrachlorophthalic, and tetrabromophthalic anhydrides in acetone, producing the corresponding bis-amic acids 2-5 [18].The third step includes the dehydration of compounds 2-5 using a fusion technique, giving the title products 6-9.In addition, the fusion of compound 1 with 1,8-naphthalic anhydride affords bis-naphthalimidyl Schiff base 10.The physical characteristics of compound 1 are reported in Table 1, whereas those of compounds 2-5 and 6-10 are shown in Tables 2 and 3, respectively.

Scheme 1 -Synthesis of bis-imidyl Schiff bases
Based on the data from their FT-IR, 13 C NMR, and 1 H NMR spectra, the chemical structure of the synthesized compounds was identified.The FT-IR spectral data of compound 1 showed absorption bands at 3463-3334 cm -1 related to ν(NH 2 ) and other absorption bands at 1645 cm - 1 , and at 1591 and 1560 cm -1 belonging to ν(C=N) and ν(C=C) aromatic, respectively [19].The 1 H NMR spectrum of compound 1 presented chemical shifts at 2.50 and 2.43 ppm attributed to the three protons of the two CH 3 groups.Other signals appeared at 4.75 ppm and from 6.03 to 7.69 ppm, which are due to NH 2 protons and aromatic protons, respectively [19].Details of FT-IR and 1 H NMR spectral data for compound 1 are reported in Table 4.The FT-IR spectra of bis-amic acid Schiff bases 2-5 revealed distinct absorption bands at 3402-3463 cm -1 and 3228-3359 cm -1 , which correspond to ν(O-H) carboxylic and ν(N-H) amide, respectively.Other stretching bands are found at 1695-1720 cm -1 , 1650-1970 cm -1 , 1639-1656 cm -1 and 1554-1595 cm -1 for v(C=O) carboxylic, v(C=O) amide, ν(C=N) and ν(C=C), respectively [19].On the other hand, FT-IR spectra of bis-imide Schiff base 6-10 showed the disappearance of ν(O-H) and v(N-H) absorption bands and the appearance of two absorption bands at 1772-1782 cm -1 and 1701-1739 cm -1 , which are related to asymmetric ν(C=O) imides and symmetric ν(C=O) imides, respectively.These two points provide strong support for producing bis-imides 6-10.Other absorption bands are associated with ν(C=N), ν(C=C), and v(C-N) imides, which appear at 1604-1640 cm -1 , 1556-1575 cm -1 , and 1359-1390 cm -1 .The 1 H NMR and 13 C NMR spectra were used to confirm the structures of the prepared compounds.Thus, the 1 H NMR spectra of bis-amic acids 3 and 4 showed signals at 1.08-2.34ppm, 6.07-7.72 ppm, 9.34-10.23ppm and 10.32-10.49ppm, which are related to CH 3 protons, aromatic protons, NH protons, and OH protons, respectively.It is noticeable that signals of NH and OH did not appear in the 1 H NMR spectra of bis-imides 6 and 7, which proves the success of bis-imide formation.The 1 H NMR spectra of compounds 6, 7, and 10 showed clear signals at 2.08-2.38 ppm, 7.57-8.56ppm, which are related to CH 3 protons and aromatic protons, respectively.Compound 6's 1H NMR spectrum revealed signals between 2.6 and 2.9 ppm related to -CH 2 CH 2 -protons in the succinimide ring.The 13 C NMR data of bis-amic acid Schiff bases 3 and 4 are 18.1-27.6ppm and belong to the CH 3 groups, while signals at 115.2-138.5 ppm belong to the aromatic rings.Other signals appeared at 139.0-158.1 ppm, 162.1-163.9ppm and 165.3-166.7 ppm, which are related to C=N imines, C=O amides, and C=O carboxylic acids, respectively.The 13 C NMR spectra of bis-imides 6 and 7 showed signals at 17.8-18.1 ppm, 112.9-137.4ppm, 140.5-140.7 ppm, and 167.5-177.4ppm, which are related to CH 3 groups, aromatic rings, C=N imines, and C=O imides [19].Other signals in the 13C NMR spectrum of compound 6 range from 29.0 to 29.1 ppm, and are related to -CH 2 CH 2groups in succinimide rings.All details of FT-IR spectral data for compounds 2-5 and 6-10 are shown in Tables 5 and 6, while 1 H NMR and 13 C NMR spectral data for compounds 3, 4, 6, 7, and 10 are listed in Tables 7 and 8.

Table 1 :
Physical characteristics of compound 1

Table 4 :
FT-IR and 1 H NMR spectral data of compound 1