Benzodiazepines constitute an impotant class of biologically active. compounds and their synthesis has been receiving much attention in

Transcription

1 CHPATER-III Synthesis of 1,5-benzodiazepine and its derivatives using silica gel supported sulfuric acid and cage type mesoporous aluminosilicate catalysts 3.1. Introduction: Benzodiazepines constitute an impotant class of biologically active compounds and their synthesis has been receiving much attention in the field of medicinal and pharmaceutical chemistry owing to their application as anticonvulsant, anti-inflammatory, analgesic, sedative agents,and hypnotic activity. 1 6 The derivatives of 1,5-benzodiazepines are also used as dyes for acrylic fibers in photography. 7 In addition, benzodiazepines are the useful precursors for the synthesis of other fused ring compounds such as oxadiazolo-, oxazino- and triazolo-, or furano-benzodiazepines Benzodiazepines are generally synthesized by the condensation of o-phenylenediamine (OPDA) with α,βunsaturated carbonyl compounds, β-haloketones or with ketones 12 using acidic catalysts which are critical to enhance the condensation process. Different reagents such as BF 3-etherate, polyphosphoric acid, abh4, MgO/POCl3, Yb(OTf)3, Ga(OTf)3, lead nitrate, L-proline, acetic acid under microwave conditions, molecular iodine, and ionic liquids have also been used for the synthesis of benzodiazepines Recently the synthesis of benzodiazepines was also reported using different solid acid catalysts such as sulfated zirconia, Al2O3/P2O5, Ag 3PW 12O 40, PVP-FeCl 3, and zeolite catalysts Unfortunately, many of these catalysts suffer from one or more limitations such as drastic

2 reaction conditions, long reaction times, occurrence of several side reactions, tedious work-up procedure and low yields. In addition, the solid acid catalyst used previously had poor textural parameters such as low surface area and pore volume which do not support a better performance in the synthesis of benzodiazepines. In recent years, ordered mesoporous silica materials have received considerable importance because of their unique structures with organized porosity, high specific surface area and pore volume, and well-ordered mesopores that are considerably larger than zeolites and zeotype molecular sieves, and find potential applications mainly in the field of catalysis, adsorption, separation, sensors, and fuel cells These materials can be prepared by using either a cationic or an anionic or a neutral surfactant as a structure directing agent. There are numerous reports which deal with the preparation of various types of one and three dimensional mesoporous materials, such as MCM- 41, MCM-48, SBA-1, SBA-15, AMS, HMS, and MSU etc. 37 Among the various materials, materials with three-dimensional cage type pore arrangements are more resistant to pore blocking, allow faster diffusion of reactants, and provide more adsorption sites, which can be easily accessible through three dimensional pore channels. In spite of these interesting features, surprisingly, the majority of studies published so for deal with phases having a one-dimensional pore system, viz. MCM-41 and SBA-15.

3 Despite these interesting features, the KIT-5 materials have several disadvantages including neutral framework, poor stability, weak acidity, and low ion exchange capacity, which limit their applications, especially in catalysis and adsorption. These problems can be overcome by introducing the hetero-atoms in the silica framework of KIT-5 materials. Moreover, the content of the heteroatoms in the silica framework is a major factor, which determines the properties of the catalysts such as acidity and catalytic reactivity. However, it is highly difficult to incorporate the metal atoms in the silica framework of KIT-5 because the preparation of the materials requires highly acidic medium where the solubility of the metal source is very high. Moreover, at highly acidic medium, the hetero-atoms exist only in the cationic forms rather than their corresponding oxo species which suppress the contact between the hetero-atoms and the silica species. Therefore, particular interest was focused on the design and fabrication of highly ordered mesoporous materials with threedimensional (3D) pore structures such as SBA-1 and KIT-5 as they are believed to be more advantageous for catalytic applications than phases having a 1D array of pores Moreover, these materials can offer more resistant to pore locking and allow faster diffusion of reactants which are highly necessary to obtain a stable and a high catalytic activity. Recently, Vinu et al. reported the preparation of various mesoporous metallosilicate catalytic materials with 3D cage

4 type structure and investigated their catalytic activity in the alkylation and acylation of aromatics. 34,36,37,38 They found that the activity of the 3D mesoporous catalysts is much better than the catalysts with unidimensional mesoporous structure. Among the 3D metallosilicate catalysts, aluminium supported mesoporous KIT-5 material (AlKIT-5) was found to be interesting as it possesses 3D mesostructure with Fm3m symmetry and large cage type pores, a high acidity which mainly comes from the Brönsted acid sites on the surface of the catalyst, and a large pore diameter. 37 These features are clearly reflected in its high catalytic activity towards various acid catalyzed reactions. 37,38 The activity of the AlKIT-5 catalyst has been studied on the acetylation of veratrole by acetic anhydride and it has been found that the AlKIT-5(10) shows 37 higher activity than that of the zeolites, such as ZSM-5, HY, mordenite, and Hb. Although these materials possess interesting textural and catalytic properties, unfortunately, with the best of our knoeledge, there has been no publication available on the synthesis of benzodiazepines using such materials as catalysts in the open literature so far. Here we are expressing first time for the synthesis of 1,5- benzodiazepine using AlKIT-5 as the catalyst through a condensation reaction between OPDA and ketones in acetonitrile. The effect of the aluminium content of the catalyst and the catalyst concentration on the above process has also been investigated in detail. We also

5 demonstrate the preparation of various derivatives of 1,5- benzodiazepine using substituted OPDAs and various ketones Present work: Initially we focused on the synthesis of 1,5-benzodiazepines using 10 mol% silica gel supported sulfuric acid 39 and the results are presented in Table 3.3. However, mesoporous AlKIT-5(10) 40 catalyst gave the better yields and recoverability than the previous catalyst. Since AlKIT-5 is better choice, we focused our synthesis using this catalyst. Thus, condensation of OPDA or substituted OPDA 1 with various ketones 2 in acetonitrile at room temperature gave the products 3(a-t) in good yields (Scheme 1). R O H 2 + R 1 R 2 SiO 2 -H 2 SO 4 / AlKIT-5 C CH 2 H 2 CH 3 C, R.T R (a-t) R = H, Cl R 1 = Alkyl, Phenyl R 2 = H, Alkyl H R 1 R 2 CH 2 R 1 Scheme1: Synthesis of 1,5-benzodiazepines at R.T The role and activity of the catalyst in this transformation was shown in Table.3.1. The role of the Brönsted acid site of the AlKIT-5 catalyst in the formation of 1,5-benzodiazepines and the reaction mechanism are clearly depicted in scheme 2.

6 H -H + R R R O=C CH3 R C CH 3 OH H O O O Si Al O O O O H 2 H 2 H 2 H -H 2 O R H H R R R + O=C CH3 -H + H 2 R H CH 3 C R H CH 3 C R H + -H 2 O H C CH 2 R C CH 3 R Scheme 2: A plausible mechanism for the synthesis of 1,5- benzodiazepines using AlKIT-5 catalyst at R.T Table 3.1 shows the textural parameters and the acidity of the AlKIT-5 samples with different Al content. All the materials possess well-ordered 3D mesostructure with cage type pores, high surface area and large pore diameter. It can be seen from Table 3.1 that the acidity, surface area, pore volume and pore diameter of the materials increase with increasing the Al content in the AlKIT-5. The specific surface area, pore volume, pore diameter, cage diameter and the acidity of the AlKIT-5(10) is found to be 989 m 2 /g, 0.68 cm 3 /g, 6 nm, 12 nm, and 0.51 mmol of H 3/g, respectively. These features make this material special among other metal substituted mesoporous materials. As the detailed characterization of the materials can be found in earlier reports. 37,38 Here, the acidity and the catalytic activity of the novel AlKIT-5 materials were investigated. This suggests that the amount of

7 tetrahedral Al incorporation in AlKIT-5 materials increases remarkably with decreasing the nsi/nal ratio. Moreover, the catalytic activity of the AlKIT-5 materials with different ratios on the BDPs synthesis was investigated and the results are compared with silica gel supported sulfuric acid (Table 3.3). Interestingly, among the catalysts examined under the optimized reaction conditions, the AlKIT-5(10) shows much higher activity. The silica and AlKIT-5 structures are given below. O O O O O O O O O Si Si Si Si Si Si Si O O O O O O O O O O O O O Structure 1: Silica structure O O H O O O H O O O H O Si Al Si Al Si Si Al O O O O O O O O O O O O O Structure 2: AlKIT-5 structure The prepared 3D mesoporous aluminosilicate nanocage in a Highly Acidic Media will give high Al content upto n Si/n Al = 10. From the above structures, 3D silica is neutral in charge and AlKIT-5 is acidic as per the charge shown on the structure. Therefore, the conversion is superior over other catalysts 37 such as AlKIT-5 catalysts with the n Si/n Al ratio lower than 10, mordenite, zeolite HY, zeolite Hb, and ZSM-5. The higher activity of the AlKIT-5(10) could be due to the

8 fact that the sample exhibits three dimensional cage type porous networks with a high surface area and comparable acidity, which enhance the diffusion of the reactant molecules and allows the easy access to all the active sites. These catalytic results also confirm that the AlKIT-5(10) material indeed possesses more amount of tetrahedral Al, which provides the Bronsted acid sites. The promising catalytic activity of the materials encouraged us to discover these catalysts in the synthesis of benzodiazepine and its derivatives (Scheme 1).

9 Table: 3.1. Textural parameters, acidity and the catalytic activity of the AlKIT-5 catalysts with different Al content S.o. Catalyst a 0 (nm) n Si/n Al S BET (m 2 /g) Gel Product V p (cm 3 /g) Dp BJH (nm) Cage diameter (nm) Acidity (mmol/g) Yield (%) 1 AlKIT-5(10) AlKIT-5(28) AlKIT-5(44) SiO 2-H 2SO 4 (10 mol %) a o unit cell constant; S BET specific surface area; V p specific pore volume; Dp pore diameter; Reaction conditions: substrate = OPDA and acetone, weight of the catalyst = 100 mg, reaction temperature = RT, solvent = acetonitrile.

10 Initially we have focused on the synthesis of 1,5-benzodiazepines from o-phenylenediamines and ketones. Thus, OPDA was treated with acetone in the presence of mesoporous AlKIT-5(10) in acetonitrile at room temperature and the outcome results are also presented in Table 3.1. The catalyst was found to be highly active, affording 97% isolated yield of 1,5-benzodiazepine in 30 min. In order to understand the role of acidity ofalkit-5 on the yield of the final product, we carried out the reaction using AlKIT-5 with different Al content. Among the catalysts studied, AlKIT-5(10) was found to be highly active and selective. It must also be noted that when the reaction was conducted without any catalyst, the reaction was not occurred. These outcome results indicate that the role and activity of the catalyst in this transformation and dictate the activity of the catalyst. As AlKIT- 5(10) showed a much higher activity than other catalysts used in this transformation under the optimized reaction conditions, we have used AlKIT-5(10) for the remaining reactions. The synthesis of 1,5-benzodiazepines was also carried out over different amounts of AlKIT-5(10) at room temperature for 30 min and the outcome results are given in Table.3.2. Theweight of the catalyst was increased between 25 and 150 mg. It was found that the yield increases from 24% to 97% with increasing the weight of the catalyst from 25 to 100 mg, respectively. This could be mainly due to the availability of huge acidic sites on the porous surface of the aluminosilicate catalysts as the weight of the catalyst is increased. It must be noted that the yield of the product is remain constant with

11 the further increase of the weight of the catalyst from 100 to 150 mg. Hence, we used the weight of the catalyst was 100 mg for the rest of the studies. Table: 3.2. Effect of the weight of AlKIT-5(10) on the synthesis of 1,5- benzodiazepine S.o. Weight of AlKIT-5(10) (mg) Reaction time (min) Yield (%) Reaction conditions: substrate = OPDA and acetone, reaction temperature = RT, solvent = acetonitrile. The effect of solvents on the synthesis of BDPs was also investigated. Among various solvents like methylene chloride (87%), tetrahydrofuran (THF) (89%), acetonitrile and methanol studied, methanol and acetonitrile (97%) were found to be the excellent solvents for this synthesis (Table 3.3, entry 1).

12 Table: 3.3. Synthesis of 1,5-benzodiazepines and its derivatives using silica gel supported sulfuric acid and AlKIT- 5(10) through a condensation reaction between a series of OPDA and various ketones Entry Diamine (1) Ketone (2) Product (3) Time a (min) Yield b (%) Time c (min) Yield d (%) 1 H 2 H 2 Acetone 3a H H 2 H 2 2-butatone 3b H H 2 H 2 2-pentatone 3c H H 2 H 2 Methyl Iso Butyl Ketone 3d H

13 5 H 2 H 2 Acetophenone 3e H H 2 H 2 4-methyl Acetophenone 3f H CH 3 CH H 2 H 2 4- Chloro Acetophenone 3g H Cl Cl H 2 Cyclopentanone H H 2 3h 9 H 2 H 2 2-Acetyl thiophene 3i H S S

14 10 H 2 H 2 3-Acetyl thiophene 3j H S S Cl H 2 H 2 Acetone Cl 3l H Cl H 2 H 2 2-butatone Cl 3k H Cl H 2 H 2 2-pentatone Cl 3m H Cl H 2 H 2 Methyl Iso Butyl Ketone Cl 3n H

15 15 Cl H 2 H 2 Acetophenone Cl 3o H Cl H 2 H 2 4-methyl Acetophenone Cl 3p H CH 3 CH Cl H 2 H 2 4- Chloro Acetophenone Cl 3q H Cl Cl Cl H 2 H 2 Cyclopentanone Cl 3r H Cl H 2 H 2 2-Acetyl thiophene Cl 3s H S S

16 20 Cl H 2 H 2 3-Acetyl thiophene Cl 3t H S S a Reaction time for the BDPs with silica gel supported sulfuric acid b Isolated yields for the BDPs with silica gel supported sulfuric acid c Reaction time for the BDPs with AlKIT-5 d Isolated yields for the BDPs with AlKIT-5

17 The excellent catalytic performance of the AlKIT-5(10) in the synthesis of 1,5-benzodiazepine stimulated us to extend this process for the synthesis of various derivatives of benzodiazepines using various substituted OPDAs and a series of symmetrical and unsymmetrical ketones and the results are shown in Table 3.3. In all cases, the reactions are highly selective and are completed within h. The catalyst showed excellent activity in all the cases, affording 85 97% isolated yield of the corresponding derivatives of 1,5- benzodiazepine. It was found that the catalyst showed superior performance with high yields in a relatively shorter reaction time than Ersorb-4 (E4), a clinoptylolite-type zeolite catalyst reported previously. 28 Furthermore, E4 needed a high temperature and a longer reaction time to achieve high isolated yield of the final product whereas AlKIT-5(10) was active even at room temperature. These findings reveal the superior nature of our catalyst in this transformation. Chloro-substituted OPDA and substituted ketones were also used with similar success to provide the corresponding benzodiazepines in high yields, which are also of much interest with regard to biological activity. Chloro-substituted benzodiazepines were prepared easily in good yields by using this catalyst. Especially, chloro-substituted OPDA and acetyl thiophenes were used to obtain the corresponding thiophene derivatives of benzodiazepines. It was reported previously that thiophene derivatives of 1,5-benzodiazepines possess good biological activities. 41 Cyclopentanone also worked well with chloro-

18 substituted OPDA. It is also significant to note down the work-up of the reaction mixture is very simple. The catalyst can be filtered out easily and the solvent was evaporated. Recycling experiments were conducted to find out the stability of the catalyst after the reaction. The catalyst was easily separated by centrifuge and reused after activation at C for h. The efficiency of the recovered catalyst was verified with the reaction of OPDA and acetone (Entry 1). Using the fresh catalyst, the yield of product (3a) was 97%, while the recovered catalyst in the three subsequent recyclization gave the yields of 95%, 93% and 90%, respectively. The small reduction in the catalytic activity after three cycles can be mainly due to the loss of the catalyst or catalyst structure during the recovery process. These results reveal that the catalyst can be recycled several times without lacking its activity. The AlKIT-5 with 3D structure having better recyclable nature than silica gel supported sulfuric acid. Structural assignments of compounds (Table 3.3, 3a-3t) were made based on IR, 1 H MR and MALDI-MS spectral data. The compound 4a IR spectrum (Fig.5.1) showed the absorption peaks at 3295, 2964, 1633, 1475 and 770 cm -1. The peak at 3295 cm 1 indicates the occurrence of H group in diazepine ring, peak at 2964 cm 1 indicates CH stretching, peak at 1633 cm -1 indicates the presence of >C=, peak at 1475 cm -1 indicates the presence of conjugated >C=C< stretching, peak at 770 cm -1 assigns the aromatic CH bending and these peaks are confirmed the formation of diazepine.

19 The 1 H MR spectrum (300 MHz, CDCl3) for compound 3a (Fig.3.4) showed the signals at δ 1.25 (s, 6H, 2CH3) was assigned to two methyl groups on 4 th position of benzodiazepine ring and signal at δ 2.14 (s, 2H, -CH 2-) was assigned to -CH 2- group in diazepine ring, and signal at δ 2.28 (s, 3H, -CH 3) indicates the methyl protons at 2 nd position in diazepine ring, and signal at δ 3.40 (brs, 1H, -H) indicates the presence of -H proton in diazepine ring. The remaining signals at δ 6.65 (d, 1H, J = 8.2 Hz, Ar-H), (m, 2H, J = 3.2 Hz, Ar-H), 7.05 (d, 1H, J = 8.2 Hz, Ar-H) confirms the presence of aromatic protons. MALDI-MS spectrum (Fig.3.5) for compound 3a showed molecular ion peak at m/z [M + ] =188, corresponds to molecular formula C12H162 and which is equal to calculated mass g/mol. All other compounds spectral data results are presented in experimental section Conclusions: BDPs are synthesized by using silica gel supported sulfuric acid and AlKIT-5 catalysts. These two catalysts are heterogeneous and additional to the present existing procedures. We designed and synthesized some biologically active chloro and thiophene derivatives of BDPs. We have established for the first time the synthesis of 1,5- benzodiazepine using silica gel supported sulfuric acid and AlKIT-5 catalysts through a condensation reaction between substituted OPDA and a series of symmetrical and unsymmetrical ketones at room

20 temperature in acetonitrile solvent. But AlKIT-5 showed better performance in terms of yields and recyclability. The AlKIT-5 catalyst was found to be highly active and selective, recyclable, affording a high yield of benzodiazepines. The effect of the Al content of the catalyst and the catalyst concentration on the above process was investigated. The catalyst was also successfully employed for the preparation of various derivatives of 1,5-benzodiazepine using substituted OPDAs and various ketones. In all cases, the reactions are highly selective and are completed within h. The catalyst showed excellent activity in all the cases, affording 85 97% isolated yield of the corresponding derivatives of 1,5-benzodiazepine. The high activity of the catalyst is mainly due to its high acidity; excellent textural parameters such as high surface area, large pore volume and cage type 3D porous structure. This method is quite simple and selective. The catalyst gave high isolated yield of the derivatives of 1,5-benzodiazepine in a shorter reaction time at room temperature and can be recycled several times. We strongly hope that the highly stable AlKIT-5 catalyst could pave the way for the production of 1,5-benzodiazepine and its derivatives and create the platform for the commercialization of the process by replacing the existing homogenous catalysts which suffered from various drawbacks such as corrosion, toxicity, waste production, and a high cost.

21 3.4. Experimental: General procedure for the synthesis of 1,5-benzodiazepines: A mixture of OPDA (1) (1 mmol), ketone (2) (2.5 mmol) and AlKIT-5 (100 mg) was stirred in acetonitrile (4 ml) at room temperature until thin layer chromatography indicated the reaction was completed. Ethyl acetate (10%) in hexane was used as the mobile phase and both the reactant and the final product were spotted on the TLC plate. The product retention factor (Rf) was observed at around The disappearance of the reactant spot on the TLC plate indicates the completion of the reaction. After completion of the reaction, ethyl acetate (20 ml) was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate-n-hexane (1:9) as eluent to afford the desired product (3). The spectral data of entry 1, 2, 4, 5, 8 and 11, 42 entry 9, 10, 43 and entry 6, 7 and in Table 3.3 are in full agreement with the reported literature and the spectral data of all the compounds are described in the following sections. Entry 1: 2,2,4-Trimethyl-2,3-duhydro-1H-1,5-benzodiazepine (3a): To a mixture of o-phenylenediamine (0.108 g, 1 mmol), acetone (0.145 g, 2.5 mmol) and AlKIT-5 (0.100 g) was stirred at room temperature for 30 min under 4 ml of acetonitrile solvent. The completion of reaction was monitored by TLC. After completion of the reaction, 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated and

22 the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired product 3a as yellow solid crystals (0.182 g, 97% yield): m.p C. IR (KBr): νmax 3295, 2964, 1633, 1591, 1475, 770 cm 1 (Fig.3.3). 1 HMR (300 MHz, CDCl3): δ 1.25 (s, 6H, 2CH3), 2.14 (s, 2H, - CH 2-), 2.28 (s, 3H, -CH 3), 3.40 (brs, 1H, -H), 6.65 (d, 1H, J = 8.2 Hz, Ar-H), 6.90 (d, 2H, J = 3.2 Hz, Ar-H) 7.05 (d, 1H, J = 8.2 Hz, Ar-H) ppm (Fig.3.4). MALDI-MS: m/z [M + ] = 188 (Fig.3.5). M.F. C12H162. Entry 2: 2,4-Diethyl-2-methyl -2,3-dihydro-1H-1,5-benzo diazepine (3b): To a solution of o-phenylenediamine (0.108 g, 1 mmol), 2-butanone (0.180 g, 2.5 mmol), and AlKIT-5 (0.100 g) in 4 ml of acetonitrile was added. The resulting mixture was stirred for 60 min at room temperature. The completion of the reaction was monitored by TLC. 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The mixture was extracted from ethyl acetate, washed with water, brine and dried over magnesium sulfate. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired benzodiazepine 3b as a yellow solid (0.205 g, 95% yield): m.p C. IR (KBr): νmax 3341, 2966, 1592, 1375, 750 cm 1 (Fig.3.6). 1 HMR (300 MHz, CDCl3): δ 0.95 (t, 3H, J = 3.5 Hz, -CH3), (m, 6H, 2CH3), (m, 2H, -CH 2-), (m, 2H, -CH 2-), (m, 2H, - CH3), 3.57 (brs, 1H), (m, 1H, Ar-H), (m, 2H, Ar-H), (m, 1H, Ar-H) ppm (Fig.3.7). MALDI-MS: m/z [M + ] = 216

23 (Fig.3.8). M.F. C14H202. Entry 3: 2-methyl-2,4-dipropyl -2,3-dihydro-1H-1,5-benzo diazepine (3c): This compound was prepared as described in general procedure from a solution of o-phenylenediamine (0.108 g, 1mmol), and 2-pentanone (0.215 g, 2.5 mmol) in acetonitrile (4 ml) and AlKIT- 5 (0.100 g) were added. The reaction mixture was stirred at room temperature for 60 min. The completion of reaction was monitored by TLC. The catalyst was filtered off and phases were separated and the aqueous layer was extracted with EtOAc (3x15 ml). The combined organic phase was dried over MgSO 4 and concentrated. The residue was chromatographed using silica gel, eluting with n-hexane-etoac (9:1), to give the desired product 3c as a yellow solid (0.227 g, 93% yield): m.p C. IR (KBr): ν max 3341, 3060, 1589, 1371, 687 cm 1 (Fig.3.9). 1 HMR (300 MHz, CDCl3): δ (m, 6H, 2CH3), 1.13 (s, 3H, -CH3), (m, 4H, 2CH2), (m, 1H, -CH a ), (m, 1H, -CH b ), (m, 4H, 2CH 2), 3.05 (brs, 1H, -H), (m, 1H, Ar-H), (m, 2H, Ar-H), (m, 1H, Ar-H) ppm (Fig.3.10). MALDI-MS: m/z [M + ] = 244 (Fig.3.11). Anal. Calcd. for C 16H 24 2: C, 78.64; H, 9.90;, Found: C, 78.50; H, 9.85;, 11. Entry 4: 2,4-diisobutyl -2methyl- -2,3-dihydro-1H-1,5-benzo diazepine (3d): This compound was prepared according to the gereal procedure, from o-phenylenediamine (0.108 g, 1 mmol) and methyl isobutyl ketone (MIBK) (0.250 g, 2.5 mmol), was dissolved in acetonitrile (4 ml) and AlKIT-5 (0.100 g) were added. The reaction

24 mixture was allowed to stir at room temperature for 60 min. The completion of the reaction was monitored by TLC. 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford resulting benzodiazepine 3d yellow solid (0.250 g, 92% yield): mp C. IR (KBr): νmax 3403, 2955, 2353, 1674, 1464, 750 cm 1 (Fig.3.12). 1HMR (300 MHz, CDCl 3): δ (m, 12H, 4CH 3), 1.32 (s, 3H, - CH 3), (m, 2H, 2CH of MIBK), (m, 2H,-CH 2-), (m, 2H,-CH2-), (m, 2H,-CH2-), 3.13 (brs, 1H, -H), (m, 1H, Ar-H), (m, 2H, Ar-H), (m, 1H, Ar-H) ppm (Fig.3.13). MALDI-MS: m/z[m+] = 272 (Fig.3.14). M.F. C18H282. Entry 5: 2-Methyl-2,4-diphenyl -2,3-dihydro-1H -1,5-benzo diazepine (3e): To the 4 ml of acetonitrile, o-phenylenediamine (0.108 g, 1 mmol), acetophenone (0.300 g, 2.5 mmol) and AlKIT-5 (0.100 g) were combined in a 100 ml round-bottom flask. The reaction mixture was stirred for 60 min at room temperature. After completion of reaction, 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired product 3e yellow crystalline solid. (0.299 g, 96% yield): m.p C. IR (KBr): νmax 3278, 2960, 1634, 1466, 749 cm 1

25 (Fig.3.15). 1 HMR (300 MHz, CDCl3): δ 1.31 (s, 3H, -CH3), 2.29 (d, 1H, J = 12.8 Hz, -CH a ), 2.58 (d, 1H, J = 12.8 Hz, -CH b ), 3.34 (brs, 1H, - H), (m, 3H, Ar-H), (m, 4H, Ar-H), (m, 4H, Ar-H), (m, 3H, Ar-H) ppm (Fig.3.16). MALDI-MS: m/z [M + ] = 312 (Fig.3.17). M.F. C22H202. Entry 6: 2-Methyl-2,4-ditoluyl -2,3-dihydro-1H-1,5-benzo diazepine (3f): The title compound was prepared using o-phenylenediamine (0.108 g, 1 mmol), 4-methyl acetophenone (0.335 g, 2.5 mmol), catalyst AlKIT-5 (0.100 g) and 4 ml of acetonitrile were combined in a 100mL round-bottom flask. The reaction mixture was stirred at room temperature for 60 min. The completion of reaction was monitored by TLC. 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to give desired product 3f as a pale yellow crystalline solid (0.326 g, 96% yield): m.p C. IR(KBr): ν max 3307, 2974, 1603, 1471, 759 cm 1 (Fig.3.18). 1 HMR (300 MHz, CDCl3): δ 1.32 (s, 6H, - CH 3 of 4-methyl acetophenone), 2.40 (s, 3H, -CH 3), (s, 2H, - CH 2-), 3.05 (brs, 1H, -H), (m, 1H, Ar-H), (m, 3H, Ar-H), (m, 5H, Ar-H), (m, 3H, Ar-H) ppm (Fig.3.19). MALDI-MS: m/z [M + ] = 340 (Fig.3.20). M.F. C24H242. Entry 7: 2,4-bis(4-chlorophenyl) -2-methyl-2,3-dihydro -1H-1,5- benzodiazepine (3g): To a mixture of o-phenylenediamine (0.108 g, 1

26 mmol), 4-chloroacetophenone (0.385 g, 2.5 mmol) and AlKIT-5 (0.100 g) was stirred for 60 min at room temperature under 4 ml of acetonitrile solvent. The completion of reaction was monitored by TLC. After completion of reaction, 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated, dried over MgSO 4 and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired product 3g as pale yellow crystalline solid (0.361 g, 95% yield): m.p C. IR (KBr): ν max 3332, 2974, 1607, 1468, 762 cm 1 (Fig.3.21). 1 HMR (300 MHz, CDCl3): δ 1.73 (s, 3H, -CH3), 2.86 (d, 1H, J = 13.3 Hz, -CH a ), 3.04 (d, 1H, J = 13.3 Hz, -CH b ), 3.42 (brs, -H), (m, 1H, Ar- H), (m, 2H, Ar-H), (m, 4H, Ar-H), (m, 1H, Ar-H), (m, 4H, Ar-H) ppm (Fig.3.22). MALDI-MS: m/z [M + ] = 380 (Fig.3.23). M.F. C22H18Cl22. Entry 8: 10-Spirocyclopentane -1, 2, 3, 9, 10, 10a -hexahydro benzo [b] cyclopenta [e][1,4]-diazepine (3h): To a solution of o- phenylenediamine (0.108 g, 1 mool), cyclopentanone (0.210 g, 2.5 mmol) and AlKIT-5 (0.100 g) in 4 ml of acetonitrile was added. The resulting mixture was stirred for 60 min at room temperature. The completion of reaction was monitored by TLC. 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was extracted with ethyl acetate, concentrated and dried over magnesium sulphate. The crude product

27 was purified by silica gel column chromatography using ethyl acetaten-hexane (1:9) as eluent to yield desired benzodiazepine 3h as a yellow solid (0.220 g, 92% yield): m.p C. IR (KBr) ν max 3326, 2950, 1629, 1371, 676 cm 1 (Fig.3.24). 1 HMR (300 MHz, CDCl3): δ 1.25 (s, 1H, -CH of diazepine ring), (m, 14H, 7CH2), 2.78 (brs, 1H, - H), (m, 1H, Ar-H), 7.25 (dd, J = 1.4 Hz, 7.2 Hz, 2H, Ar-H), 7.85 (d, J = 7.2 Hz, 1H, Ar-H) ppm (Fig.3.25). MALDI-MS: m/z [M + ] = 240 (Fig.3.26). M.F. C16H202. Entry 9: 2-Methyl -2,4-di(thiophen-2-yl) -2,3-dihydro-1H-1,5- benzodiazepines (3i): To a solution of o-phenylenediamine (0.108 g, 1 mmol) and 2-acetyl thiophene (0.315 g, 2.5 mmol) in acetonitrile (4 ml) and AlKIT-5 (0.100 g) were added. The reaction mixture was stirred at room temperature for 120 min. The completion of reaction was monitored by TLC. The catalyst was filtered off and phases were separated and the aqueous layer was extracted with EtOAc (3x15 ml). The combined organic phase was dried over MgSO 4 and concentrated. The residue was chromatographed using silica gel, eluting with hexane-etoac (9:1), to give the desired product 3i as a brown solid (0.278 g, 86% yield): m.p C. IR (KBr): ν max 3373, 3106, 1615, 1487, 760 cm 1 (Fig.3.27). 1 HMR (300 MHz, CDCl3): δ 1.60 (s,1h, - CH2 a ), 2.16 (s, 1H,- CH2 b ), 2.33 (s, 3H, -CH3), 3.73 (brs, 1H, -H), (m, 2H, thiophenyl-h), (m, 4H, thiophenyl-h), (m, 1H, Ar-H), (m, 1H, Ar-H), (m, 2H,

28 Ar-H) ppm (Fig.3.28). MALDI-MS: m/z [M + ] = 324. M.F (Fig.3.29). C18H162S2. Entry 10: 2-Methyl -2,4-di(thiophen-3-yl) -2,3-dihydro-1H -1,5- benzodiazepine (3j): o-phenylenediamine (0.108 g, 1 mmol) and 3- acetyl thiophene (0.315 g, 2.5 mmol) was dissolved in acetonitrile (4 ml) and AlKIT-5 (0.100 g) were added. The reaction mixture was allowed to stir for 120 min at room temperature. The completion of reaction was monitored by TLC. 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired product 3j light yellow solid (0.265 g, 82% yield): m.p C. IR (KBr) ν max 3303, 2920, 1600, 1468, 763 cm 1 (Fig.3.30). 1 HMR (300 MHz, CDCl3): δ 1.65 (s, 1H, -CH a ), 1.74 (s, 1H, -CH b ), 2.54 (s, 3H, -CH 3), 3.46 (brs, 1H, -H), (m, 6H, thiophenyl-h), (m, 4H, Ar-H) ppm (Fig.3.31). MALDI-MS: m/z [M + ] = 324 (Fig.3.32). M.F. C18H162S2. Entry 11: 2,2,4-Trimethyl -2,3-dihydro-7-chloro-1H-1,5-benzo diazepine (3k): To a mixture of 4-chloro-1,2-phenylenediamine (0.142 g, 1 mmol), acetone (0.145 g, 2.5 mmol) and AlKIT-5 (0.100 g) was stirred at room temperature for 60 min under 4 ml of acetonitrile solvent. The completion of reaction was monitored bt TLC. After completion of the reaction, 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The

29 mixture was extracted from ethyl acetate, washed with water, brine and dried over magnesium sulfate. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired product 3k as a yellow solid (0.209 g, 94%): m.p C. IR (KBr): ν max 3282, 2962, 1630, 1453, 750 cm 1 (Fig.3.33). 1 HMR (300 MHz, CDCl 3): δ 1.33 (m, 6H, 2CH 3), 2.22 (t, 2H, -CH 2-), 2.34 (s, 3H, -CH3), 3.01 (brs, 1H, -H), (m, 1H,Ar-H), (m, 1H, Ar-H), (m, 1H, Ar-H) ppm (Fig.3.35). MALDI-MS: m/z [M + ] = 222 (Fig.3.36). M.F. C 12H 15Cl 2. Entry 12: 7-chloro -2,4-diethyl- 2-methyl -2,3-dihydro-1H-1,5- diazepine (3l): This compound was prepared as described in general procedure from a solution of 4-chloro-1,2-phenylenediamine (0.142 g, 1 mmol), 2-butanone (0.180 g, 2.5 mmol) and AlKIT-5 (0.100 g) in 4 ml of acetonitrile was added. The resulting mixture was stirred for 60 min at room temperature. The completion of reaction was monitored by TLC. 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired product 3l as a yellow solid (0.230 g, 92% yield): m.p C. IR (KBr): ν max 3424, 2971, 1596, 1499, 798 cm -1 (Fig.3.36). 1HMR (300 MHz, CDCl 3): δ 0.93 (t, J = 6.7 Hz, 3H, -CH 3), (m, 6H, 2CH3), (m, 2H, -CH2-), 2.22 (m, 2H, -CH2-), 2.59 (q,

30 2H, J = 3.2 Hz, -CH2-), 3.10 (brs,1h, -H), (m, 1H, Ar-H), (m, 1H, Ar-H), (m, 1H, Ar-H) ppm (Fig.3.37). MALDI-MS: m/z [M + ] = 250 (Fig.3.38). Anal. Calcd. for C 14H 19Cl 2: C, 67.05; H, 7.64;, Found: C, 67.00; H, 7.54;, Entry 13: 7-chloro-2-methyl -2,4-dipropyl -2,3-dihydro-1H-1,5- benzodiazepine (3m): To a solution of 4-choloro-1,2-phenylene diamine (0.142 g, 1 mmol) and 2-pentanone (0.215 g, 2.5 mmol) in acetonitrile (4 ml) and AlKIT-5 (0.100 g) were added. The reaction mixture was stirred at room temperature for 120 min. The completion of reaction was monitored by TLC. The catalyst was filtered off and phases were separated and the aqueous layer was extracted with EtOAc (3X15 ml). The combined organic phase was dried over MgSO 4 and concentrated. The residue was chromatographed using silica gel, eluting with hexane-etoac (9:1), to give the desired product 3m as a reddish yellow solid (0.244 g, 88% yield): m.p C. IR (KBr): ν max 3338, 2959, 1638, 1468, 806 cm -1 (Fig.3.39). 1 HMR (300 MHz, CDCl3): δ (m, 6H, 2CH3), 1.15 (s, 3H, -CH3), (m, 4H, 2CH2), (m, 2H, -CH2-), (m, 2H, -CH2-), (m, 2H, -CH 2-), 3.10 (brs, 1H, -H), (m, 1H, Ar-H), (m, 1H, Ar-H), (m, 1H, Ar-H) ppm (Fig.3.40). MALDI-MS: m/z [M + ] = 278 (Fig.3.41). Anal. Calcd. for C16H23Cl2: C, 68.92; H, 8.31;, Found: C, 68.83; H, 8.21;, Entry 14: 7-chloro-2,4-diisobutyl -2-methyl -2,3-dihydro-1H-1,5- benzodiazepine (3n): This compound was prepared according to the

31 general procedure, 4-chloro-1,2-phenylenediamine (0.142 g, 1 mmol) and methyl isobutyl ketone (0.250 g, 2.5 mmol) was dissolved in acetonitrile (4 ml) and AlKIT-5 (0.100 g) were added. The reaction mixture was allowed to stir at room temperature for 120 min. The completion of reaction was monitored by TLC. 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The mixture was extracted from ethyl acetate, washed with water, brine and dried over magnesium sulfate. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired product 3n as light yellow solid (0.269 g, 88% yield): m.p C. IR (KBr): νmax 3196, 2959, 1589, 1496, 817 cm -1. (Fig.3.42). 1 HMR (300 MHz, CDCl 3): δ (m, 12H, 4CH 3), 1.25 (m, 2H, 2CH), 1.32 (s, 3H, -CH3), (m, 2H, -CH2-), (m, 2H, -CH2-), (m, 2H, -CH2-), 3.50 (brs, 1H, -H), (m, 1H, Ar-H), (m, 1H, Ar-H), (m, 1H, Ar-H) ppm (Fig.3.43). MALDI-MS: m/z [M + ] = 306 (Fig.3.44). Anal. Calcd. for C18H27Cl2: C, 70.45; H, 8.87;, Found: C, 70.35; H, 8.76;, Entry 15: 7-chloro-2-methyl -2,4-diphenyl-2,3-dihydro-1H-1,5- benzodiazepine (3o): To the 4 ml of acetonitrile, 4-chloro-1,2- phenylenediamine (0.142 g, 1 mmol), acetophenone (0.300 g, 2.5 mmol) and AlKIT-5 (0.100 g) were combined in a 100mL round-bottom flask. The reaction was stirred at room temperature for 120 min. After

32 completion of reaction, 20 ml of ethylacetate was added to the reaction mixture and the catalyst was recovered by fitration. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired product 3o yellow solid. (0.318 g, 92% yield): m.p C. IR (KBr): ν max 3352, 3066, 1584, 1457, 835 cm -1 (Fig.3.45). 1 HMR (300 MHz, CDCl 3): δ 1.76 (s, 3H, -CH 3), (d, 1H, J = 12.8 Hz, -CH a ), (d, 1H, J = 12.8 Hz, -CH b ), 3.59 (brs, 1H, -H), (m, 1H, Ar-H), (m, 1H, Ar-H), (m, 8H, Ar-H), (m, 4H, Ar-H) ppm (Fig.3.46). MALDI-MS: m/z [M + ]=346 (Fig.3.47). M.F. C22H19Cl2. Entry 16: 7-chloro-2methyl -2,4-dip-toluyl -2,3-dihydro-1H-1,5- benzodiazepine (3p): The title compound was prepared using 4- chloro-1,2-phenylenediamine (0.142 g, 1 mmol), 4-methylacetophenone (0.335 g, 2.5 mmol), catalyst AlKIT-5 (0.100 g) and 4 ml of acetonitrile were combined in 100 ml round-bottom flask. The reaction mixture was stirred at room temperature for 120 min. The completion of reaction was monitored by TLC. 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired product 3p as a pale yellow solid (0.336 g, 90% yield): m.p C, IR(KBr): ν max 3318, 2955, 1604, 1444, 817 cm -1 (Fig.3.48). 1 HMR (300 MHz, CDCl3): δ

33 1.72 (s, 3H, -CH3), 2.17 (s, 2H, -CH2-), 2.33 (s, 6H, 2CH3 of 4-methyl acetophenone), 3.00 (brs, 1H, -H), (m, 1H, Ar-H), (m, 5H, Ar-H), (m, 5H, Ar-H) ppm (Fig.3.49). MALDI- MS: m/z [M + ] = 374 (Fig.3.50). Anal. Calcd. for C24H23Cl2: C, 76.89; H, 6.18;, Found: C, 76.79; H,6.08;, Entry 17: 7-chloro-2,4-bis(4-chlorophenyl)-2-methyl -2,3-dihydro- 1H-1,5-benzodiazepine (3q): To a mixture of 4-chloro-1,2-phenylene diamine (0.142 g, 1 mmol), 4-chloro acetophenone (0.385 g, 2.5 mmol) and AlKIT-5 (0.100 g) was stirred for 120 min at room temperature under 4 ml of acetonitrile solvent. The completion of reaction was monitored by TLC. After completion of reaction, 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired product 3q as a yellow solid (0.356 g, 86% yield): m.p C, IR (KBr): ν max 3265, 2967, 1588, 1475, 829 cm -1 (Fig.3.51). 1 HMR (300 MHz, CDCl 3): δ 1.75 (s, 3H, -CH3), 2.86 (d, 1H, J = 12.8 Hz, -CH2-), 3.14 (d, 1H, J = 12.8 Hz, - CH 2-), 3.50 (brs, 1H, -H), (m, 1H, Ar-H), (m, 1H, Ar-H), (m, 4H, Ar-H), (m, 5H, Ar-H) ppm (Fig.3.52). MALDI-MS: m/z [M + ] = 415 (Fig.3.53). Anal. Calcd. for C22H17Cl32: C ; H, 4.12;, Found: C, 63.46; H, 4.06;, 6.64.

34 Entry 18: 7-chloro-10-Spirocyclopentane -1, 2, 3, 9, 10, 10a pentahydrobenzo [b] cyclopenta [e] [1,4]-diazepine (3r): To a solution of 4-chloro-1,2-phenylenediamine (0.142 g, 1mmol), cyclopentanone (0.210 g, 2.5 mmol), and AlKIT-5 (0.100 g) in 4 ml of acetonitrile was added. The resulting mixture was stirred for 120 min at room temperature. The completion of reaction was monitored by TLC. 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired product 3r as a yellow solid (0.235 g, 86% yield): m.p C. IR (KBr): νmax 3342, 2959, 1650, 1499, 837 cm -1 (Fig.3.54). 1 HMR (300 MHz, CDCl 3): δ (m, 12H, 6CH 2), (d, J = 13.2 Hz, 1H, -CH), (m, 2H, -CH2-), 3.05 (brs, 1H, -H), (m, 1H, Ar-H), (m, 1H, Ar-H), (m, 1H, Ar-H) ppm (Fig.3.55). MALDI-MS: m/z [M + ] = 274 (Fig.3.56). Anal. Calcd. for C 16H 19Cl 2: C, 69.93; H, 6.97;, Found: C, 69.83; H, 6.87;, Entry 19: 7-chloro -2-methyl -2,4-di(thiophen-2-yl) -2,3-dihydro- 1H-1,5-benzodiazepine (3s): To a solution of 4-chloro-1,2- phenylenediamine (0.142 g, 1 mmol) and 2-acetyl thiophene (0.315 g, 2.5 mmol) in acetonitrile (4 ml) and AlKIT-5(0.100 g) were added. The reaction mixture was stirred at room temperature for 150 min. The completion of reaction was monitored by TLC. The catalyst was filtered

35 off and phases were separated and the aqueous layer was extracted with EtOAc (3X15 ml). The combined organic phase was dried over MgSO 4 and concentrated. The residue was chromatographed using silica gel, eluting with n-hexane EtOAc (9:1), to give the desired product 3s as a yellow solid (0.304 g, 85% yield): m.p C, IR (KBr): ν max 3303, 2967, 1577, 1471, 705 cm -1 (Fig.3.57). 1 HMR (300 MHz, CDCl 3): δ 1.83 (s, 3H, -CH 3), 2.99 (d, 1H, J = 13.2 Hz, -CH 2-), 3.08 (d, 1H, J = 13.2 Hz, -CH2-), 3.58 (brs, 1H, -H), (m, 1H, Ar-H), (m, 2H, Ar-H), (m, 4H, Ar-H), (m, 1H, Ar-H), (m, 1H, Ar-H) ppm (Fig.3.58). MALDI- MS: m/z [M + ] = 358 (Fig.3.59). Anal. Calcd. for C18H15Cl2S2: C, 60.24; H, 4.21;, Found: C, 60.14; H, 4.15;, Entry 20: 7-chloro-2-methyl -2,4-di(thiophen-3-yl) -2,3-dihydro- 1H-1,5-benzodiazepine (3t): 4-chloro-1,2-phenylenediamine (0.142 g, 1 mmol) and 3-acetyl thiophene (0.315 g, 2.5 mmol) was dissolved in acetonitrile (4 ml) and AlKIT-5 (0.100 g) were added. The reaction mixture was allowed to stir for 150 min at ambient temperature. The completion of reaction was monitored by TLC. 20 ml of ethyl acetate was added to the reaction mixture and the catalyst was recovered by filtration. The organic layer was concentrated and the crude product was purified by silica gel column chromatography using ethyl acetate n-hexane (1:9) as eluent to afford the desired benzodiazepine 3t as light yellow crystalline solid (0.304 g, 85% yield): m.p C, IR (KBr): νmax 3394, 2962, 1592, 1469, 781 cm -1 (Fig.3.60). 1 HMR (300

36 MHz, CDCl3): δ 1.73 (s, 3H, -CH3), 2.86 (d, 1H, J = 13.2 Hz, CH2), 2.93 (d, 1H, J = 13.2 Hz, -CH2-), 3.43 (brs, 1H, -H), (m, 1H, Ar-H), (m, 2H, Ar-H), (m, 1H, Ar-H), (m, 5H, Ar-H) ppm (Fig.3.61). MALDI-MS: m/z [M + ] = 358 (Fig.3.62). Anal. Calcd. for C18H15Cl2S2: C, 60.24; H, 4.21;, Found: C, 60.14; H, 4.15;, 7.71.

37 Fig: H MR spectrum of o-phenylenediamine Fig: H MR spectrum of 4-Chloro-1,2-phenylenediamine

38 Fig: 3.3. IR spectrum of 2,2,4-Trimethyl-2,3-dihydro-1H-1,5- benzodiazepine (3a) Fig: H MR spectrum of 2,2,4-Trimethyl-2,3-dihydro-1H-1,5- benzodiazepine (3a)

39 Fig: 3.5. Mass spectrum of 2,2,4-Trimethyl-2,3-dihydro-1H-1,5- benzodiazepine (3a) (MW=188) Fig: 3.6. IR spectrum of 2,4-Diethyl-2-methyl-2,3-dihydro-1H-1,5- benzodiazepine (3b)

40 Fig: H MR spectrum of 2,4-diethyl-2-methyl-2,3-dihydro-1H- 1,5-benzodiazepine (3b) Fig: 3.8. Mass spectrum of 2,4-Diethyl-2-methyl-2,3-dihydro-1H-1,5- benzodiazepine (3b) (MW=216)

41 Fig: 3.9. IR spectrum of 2-methyl-2,4-dipropyl-2,3-dihydro-1H-1,5- benzodiazepine (3c) Fig: H MR spectrum of 2-methyl-2,4-dipropyl-2,3-dihydro-1H- 1,5-benzodiazepine (3c)

42 Fig: Mass spectrum of 2-methyl-2,4-dipropyl-2,3-dihydro-1H- 1,5-benzodiazepine (3c) (MW=244) Fig: IR spectrum of 2,4-diisobutyl-2-methyl-2,3-dihydro-1H-1,5- benzodiazepine (3d)

43 Fig: H MR spectrum of 2,4-diisobutyl-2-methyl-2,3-dihydro- 1H-1,5-benzodiazepine (3d) Fig: Mass spectrum of 2,4-diisobutyl-2-methyl-2,3-dihydro -1H- 1,5-benzodiazepine (3d) (MW=272)

44 Fig: IR spectrum of 2-Methyl-2,4-diphenyl-2,3-dihydro-1H-1,5- benzodiazepine (3e) Fig: H MR spectrum of 2-Methyl-2,4-diphenyl-2,3-dihydro-1H- 1,5-benzodiazepine (3e)

45 Fig: Mass spectrum of 2-Methyl-2,4-diphenyl-2,3-dihydro-1H- 1,5-benzodiazepine (3e) (MW=312) Fig: IR spectrum of 2-Methyl-2,4-ditoluyl-2,3-dihydro-1H-1,5- benzodiazepine (3f)

46 Fig: H MR spectrum of 2-Methyl-2,4-ditoluyl-2,3-dihydro-1H- 1,5-benzodiazepine (3f) Fig: Mass spectrum of 2-Methyl-2,4-ditoluyl-2,3-dihydro-1H-1,5- benzodiazepine (3f) (MW=340)

47 Fig: IR spectrum of 2,4-bis(4-chlorophenyl)-2-methyl-2,3- dihydro-1h-1,5-benzodiazepine (3g) Fig: H MR spectrum of 2,4-bis(4-chlorophenyl)-2-methyl-2,3- dihydro-1h-1,5-benzodiazepine (3g)

48 Fig: Mass spectrum of 2,4-bis(4-chlorophenyl)-2-methyl-2,3- dihydro-1h-1,5-benzodiazepine (3g) (MW=380) Fig: IR spectrum of 10-Spirocyclopentane-1, 2, 3, 9, 10, 10ahexahydrobenzo[b] cyclopenta [e][1,4]-diazepine (3h)

49 Fig: H MR spectrum of 10-Spirocyclopentane-1, 2, 3, 9, 10, 10a-hexahydrobenzo[b]cyclopenta[e][1,4]-diazepine (3h) Fig: Mass spectrum of 10-Spirocyclopentane-1, 2, 3, 9, 10, 10ahexahydrobenzo[b]cyclopenta[e][1,4]-diazepine(3h)(MW=240)

50 Fig: IR spectrum of 2-Methyl-2,4-di(thiophen-2-yl)-2,3-dihydro- 1H-1,5-benzodiazepine (3i) Fig: H MR spectrum of 2-Methyl-2,4-di(thiophen-2-yl)-2,3- dihydro-1h-1,5-benzodiazepine (3i)

51 Fig: Mass spectrum of 2-Methyl-2,4-di(thiophen-2-yl)-2,3- dihydro-1h-1,5-benzodiazepine (3i) (MW=324(2T)) Fig: IR spectrum of 2-methyl-2,4-di(thiophen-3-yl)-2,3-dihydro- 1H-1,5-benzodiazepine (3j)

52 Fig: H MR spectrum of 2-Methyl-2,4-di(thiophen-3-yl)-2,3- dihydro-1h-1,5-benzodiazepine (3j) Fig: Mass spectrum of 2-Methyl-2,4-di(thiophen-3-yl)-2,3- dihydro-1h-1,5-benzodiazepine (3j) (MW=324(3T))

53 Fig: IR spectrum of 2,2,4-Trimethyl-2,3-dihydro-7-chloro-1H- 1,5-benzodiazepine (3k) Fig: H MR spectrum of 2, 2, 4-Trimethyl-2,3-dihydro-7-chloro- 1H-1,5-benzodiazepine (3k)

54 Fig: Mass spectrum of 2,2,4-Trimethyl-2,3-dihydro-7-chloro-1H- 1,5-benzodiazepine (3k) (MW=222) Fig: IR spectrum of 7-chloro-2,4-diethyl-2-methyl-2,3-dihydro- 1H-1,5-benzodiazepine (3l)

55 Fig: H MR spectrum of 7-chloro-2,4-diethyl-2-methyl-2,3- dihydro-1h-1,5-benzodiazepine (3l) Fig: Mass spectrum of 7-chloro-2,4-diethyl-2-methyl-2,3- dihydro-1h-1,5-benzodiazepine (3l) (MW=250)

56 Fig: IR spectrum of 7-chloro-2-methyl-2,4-dipropyl-2,3-dihydro- 1H-1,5-benzodiazepine (3m) Fig: H MR spectrum of 7-chloro-2-methyl-2,4-dipropyl-2,3- dihydro-1h-1,5-benzodiazepine (3m)

57 Fig: Mass spectrum of 7-chloro-2-methyl-2,4-dipropyl-2,3- dihydro-1h-1,5-benzodiazepine (3m) (MW=278) Fig: IR spectrum of 7-chloro-2,4-diisobutyl-2-methyl-2,3- dihydro-1h-1,5-benzodiazepine (3n)

58 Fig: H MR spectrum of 7-chloro-2,4-diisobutyl-2-methyl-2,3- dihydro-1h-1,5-benzodiazepine (3n) Fig: Mass spectrum of 7-chloro-2,4-diisobutyl-2-methyl-2,3- dihydro-1h-1,5-benzodiazepine (3n) (MW=306)

59 Fig: IR spectrum of 7-chloro-2-methyl-2,4-diphenyl-2,3-dihydro- 1H-1,5-benzodiazepine (3o) Fig: H MR spectrum of 7-chloro-2-methyl-2,4-diphenyl-2,3- dihydro-1h-1,5-benzodiazepine (3o)

60 Fig: Mass spectrum of 7-chloro-2-methyl-2,4-diphenyl-2,3- dihydro-1h-1,5-benzodiazepine (3o) (MW=346) Fig: IR spectrum of 7-chloro-2-methyl-2,4-di-p-tolyl-2,3-dihydro- 1H-1,5-benzodiazepine (3p)

61 Fig: H MR spectrum of 7-chloro-2-methyl-2,4-di-p-tolyl-2,3- dihydro-1h-1,5-benzodiazepine (3p) Fig: Mass spectrum of 7-chloro-2-methyl-2,4-di-p-tolyl-2,3- dihydro-1h-1,5-benzodiazepine (3p) (MW=374)

62 Fig: IR spectrum of 7-chloro-2,4-bis (4-chlorophenyl)-2-methyl- 2,3-dihydro-1H-1,5-benzodiazepine (3q) Fig: H MR spectrum of 7-chloro-2,4-bis(4-chlorophenyl)-2- methyl-2,3-dihydro-1h-1,5-benzodiazepine (3q)