Synthesis and Characterization Benzimidazole Ring by using O-Phenylinediamine with Different Compounds and using Mannich Reaction to Preparation some of Derivatives

Introduction

Benzimidazole is heterocyclic compound found in many natural and non-natura1 products, such as some vitamins⁽¹⁾.Therefore, benzimidazole substitutes tooks the attention of differents research groups, especially as compensation or replacement in the position 1,2 is very important sites in the impact of drug effective⁽²⁾. In This study reported some of the ways to prepare benzimidazole 2-substitution, for the importance of this compound in the field of antibiotics,such as cancer,angiotensin-II receptor antegonests and antimicrobial properties⁽³⁾antifungal, antiparkinson,…etc⁽⁴⁾.The NH group compounds are able to entering into N-alkylation and N-acylation according to Mannich and Michael reaction as in isatin compounds⁽⁵⁾, which are similar with benzimidazoles. Mannich reaction  very important reaction by converting some of the prepared compounds into other compounds are more important than in the biological field,⁽⁶⁾.

Materials and Methods

Melting points were determined by using Melting PointSMP3 apparatus.

F.T.I.R. spectra were recorded by using Fourier Transform Infrared Spectrophotometer (F.T.I.R) 8400 S Shimadzu apparatus.

NMR Spectrometer 400 MHz, Avance III 400 Bruker, Germany.

Experimental Section

Synthesis 1,3-dihydro-benzimidazol-2-subsititution  (A and B)

A mixture of o-phenylenediamine with urea to yield (A) and with thiourea to yield (B)  in existence of HCl in equal concentrations was heated at 130c⁰ under reflux in alcohol solution until the evolution of ammonia ceased,⁽⁷⁾.

Synthesis 2-Phenol-1H-benzimidazol (C)

A mixture of equal concentration (0.01mol) of o-phenylenediamine and Salicylic acid in 4N HCl (20 ml) was refluxed for 30 min. then cooled, filtered and recrystallized  from absolute alcohol ⁽³⁾.

General Procedure for Synthesis of Compounds (A1) (B1) (C1)

A mixture of alcoholic solution with (A) , with (B) , with (C) (0.01 mol) and formaldehyde (15 ml, 40 %) was added slowly on alcoholic solution of (4-chloro-aniline ) (0.01 mol) the reaction mixture was stirred for three hours at room temperature and kept full night in the fridge. The solid obtained was filtered ,washed with cold ethanol, dried and crystallized form aqueous ethanol to give compounds (A1), (B1), (C1)⁽⁸⁾.

General Procedure for the Synthesis of Compounds (A2) (B2) (C2)

A mixture equimolar of (A), (B), (C) with Diallylamine in presence  formaldehyde were carried out 0-5C^O by stirring with magnetic stirrer⁽⁹⁾.

Table 1: show physical properties of compounds

Compound	Molecular formula	Solvent	Yield %	m.p. Cº	Color
A	C7H6N2O	Ethanol	94	275-279	Yellow
B	C7H6N2S	Ethanol	66	114-118	Violet
C	C13H10N2O	Ethanol	72	155-161	Violet
A1	C21H18N4OCl	Ethanol	63	Oil	Yellow
B1	C14H12N3ClS	Ethanol	62	Oil	Nutty
C1	C20H16N3ClO	Ethanol	64	Oil	Nutty
A2	C21H28N4O	Ethanol	70	Oil	Yellow
B2	C14H17N3S	Ethanol	73	Oil	Nutty
C2	C20H21N3O	Ethanol	76	Oil	Nutty

 

Scheme 1 Click here to View scheme

 

Scheme 2 Click here to View scheme

 

Scheme 3 Click here to View shceme

 

Result and Discussion

The aim of the research is to synthesis mannich bases from different Benzimidazole rings with primary and secondary amines by using formaldehyde as catalyst.

1H-benzimidazole-2-ol (A)

Infrared spectroscopy of this compound showed a broadband at 3348-3433 cm^-1 refers to O-H group, as well as the emergence of weak peak  at 1739 cm^-1 indicate that O-H group turn to C=O group by resonance between O-H and N atom , the spectroscopy showed too other peaks at 3132-3178cm^-1 refers to N-H group and at 3024 cm^-1 to C-H aromatic. Table (2) shows other peaks to this compound. ¹HNMR (400 MHz , DMSO) δ(ppm) Ar(6.97 Hz 1H),OH(5.45 Hz 1H),NH(5.45 Hz 1H)

1-{[(4-chlorophenyl)amino]methyl}-1H-benzimidazol-2-ol (A1)

Infrared spectroscopy showed  overlap of (O-H) peak with (N-H) peaks at 3261-3481 cm^-1 after substitution (H) atom by compound (4-chloro aniline), also emergence absorption peak at 2921-2979 cm^-1 refers to (C-H) aliphatic . Table (2) shows the other peaks for this compound. ¹HNMR (400 MHz , DMSO) δ(ppm) Ar (7.09,7.10 Hz and 7.25) , OH(5.24Hz) , CH2(5.77-5.81Hz), NH(3.84-3.88Hz).

1-[(diallyl-amino)methyl]- 1H-benzimidazol-2-ol (A2)

Infrared measurements of this compound showed disappearance (N-H) peak duo to substitution H atom by compound (diallyl amine) and emergence new peak at 2908-2958 cm^-1 refers to (C-H) and (CH=CH) respectively in addition to (O-H) group in 3355-3394 cm^-1. Table (2) shows other peaks to this compound. ¹HNMR (400 MHz , DMSO) δ(ppm) Ar (7.18,7.19 Hz and 7.32 Hz), OH(4.89 Hz), CH₂ (4.76 Hz), CH=(5.87 Hz) , CH2  (3.41 Hz), =CH2(5.30 and 5.43 Hz).

1H-Benzimidazole-2-thiol (B)

Infrared spectrum for this compound showed absorption peaks sharp at 3379 cm^-1 indicate to (N-H) group, also appearance absorption peak at 2360 cm^-1 indicate to (S-H) group. Table (2) shows other absorption peaks for this compound. ¹HNMR (400 MHz , DMSO) δ(ppm) Ar (broad 7.19-7.28Hz 2H) and (broad 7.64-7.73 Hz 2H),

1-{[(4-chlorophenyl)amino]methyl}-Benzimidazole-2-thiol (B1)

Infrared spectrum showed stay of absorption peaks of (N-H) group at 3224 cm^-1 after substitution of (H) atom by compound (4-chloroaniline ) and emergence absorption peak at 2923 cm^-1 indicate to (C-H) aliphatic. Table (2) shows other absorption peaks for this compound.

1-[(diprop-2-en-1-ylamino)methyl]-1H-benzimidazole-2-thiol (B2)

Infrared spectrum showed disappearance absorption peak of (N-H) after substitution of (H) atom by compound (Diallylamine) and appearance absorption peak at 2950 cm^-1  indicated to (C-H) aliphatic. Table (2) shows other absorption peaks for this compound. ¹HNMR (400 MHz , DMSO) δ(ppm) Ar(7.27,7.31 and 7.72 Hz ), SH(2.54 Hz 1H), CH2(4.70 2H), CH2-CH= (3.51-3.52 Hz 4H),  CH= (5.07 Hz 2H) , =CH2(4.85-4.95Hz 4H).

2-(2-hydroxyphenyl)-1H-Benzimidazol (C)

Infrared spectrum showed broadband at 3402-3421cm^-1 indicated to (OH) group and absorption peak at 3236 cm^-1 indicated to (NH) group. Table (1) shows other absorption peaks for this compound. ¹HNMR (400 MHz , DMSO) δ(ppm) Ar(7.23,7.24  and 7.77 Hz ) and (6.77, 6.89 and 7.05) , OH(6.74Hz ), NH(6.77Hz ).

2-(2-hydroxyphenyl)-1-{[(4-chlorophenyl)amino]methyl}-1H-Benzimidazol (C1)

Infrared spectrum showed appearance broadband at 3317-3417 cm^-1 indicated to (OH) group and absorption peak at 3186 cm^-1 indicated to (NH) group and new absorption peak at 2981cm^-1 indicated to (C-H) aliphatic. Table (1) shows other absorption peaks for this compound. ¹HNMR (400 MHz , DMSO) δ(ppm) Ar (7.03),(7.19-7.21) ,(7.76, 7.39) and (6.76, 6.86Hz) , OH(4.97Hz 1H), CH2 (5.49 Hz), NH(4.14 – 4.17Hz 1H).

2-(2-hydroxyphenyl)-1-[(diprop-2-enamino)methyl]-1H-Benzimidazol (C2)

Infrared spectrum showed survival of broadband for (OH) group at 3398 cm^-1 and disappearance absorption peak of (N-H) for Benzimidazole ring duo to substitution hydrogen atom by formaldehyde and secondary amine and new absorption peaks at 2800-2977 cm^-1 indicated to C-H aliphatic in propene  . Table (1) shows other absorption peaks for this compound. ¹HNMR (400 MHz , DMSO) δ(ppm) Ar(7.25-7.29Hz) and (7.32,7.44 , 7.70 , 7.79Hz ), OH(4.79Hz) , CH2(4.68Hz) , =CH(5.49-5.55Hz) , CH2-CH= (3.67-369Hz), =CH2(5.16-5.18 Hz).

Figure 1: F.T.I.R Spectroscopy of Compound (A) Click here to View figure

 

Figure 2: F.T.I.R Spectroscopy of Compound (A1) Click here to View figure

 

Figure 3: F.T.I.R Spectroscopy of compound (A2) Click here to View figure

 

Figure 4: F.T.I.R Spectroscopy of compound (B)  Click here to View figure

 

Figure 5: F.T.I.R Spectroscopy of compound (B1) Click here to View figure

 

Figure 6: H-NMR Spectroscopy of compound (B2) Click here to View figure

 

Figure 7: F.T.I.R Spectroscopy of compound (C) Click here to View figure

 

Figure 8: F.T.I.R Spectroscopy of compound (C1) Click here to View figure

 

Figure 9: F.T.I.R Spectroscopy of compound (C2) Click here to View figure

 

Table 2: show F.T.I.R absorption packs of compounds Click here to View table

 

Acknowledgements

The author gratefully acknowledges Chemistry department, University of Qadissiah, Iraq for providing lab facilities to carry out this work.

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This work is licensed under a Creative Commons Attribution 4.0 International License.