View of IMPLEMENTATION ON N1-ALKYL BENZOTRIAZOLES USING INTERMOLECULAR CYCLIZATION

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ACCENT JOURNAL OF ECONOMICS ECOLOGY & ENGINEERING

Peer Reviewed and Refereed Journal IMPACT FACTOR: 7.98 (INTERNATIONAL JOURNAL) UGC APPROVED NO. 48767

Vol.03, Issue 04, April 2018, Available Online: www.ajeee.co.in/index.php/AJEEE

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IMPLEMENTATION ON N1-ALKYL BENZOTRIAZOLES USING INTERMOLECULAR CYCLIZATION

Dr. Ramesh Kumar N Patel Associate Professor

Muni Arts & Science College Mahesana, India

Abstract:-Those drawbacks connected with normal engineered methodologies for N1- substituted benzotraizoles similar to inclusion about flimsy benzene intermediate, low response yields, strictly anhydrous states and Also the unsafe nature from claiming low sub-atomic weight asides provoked us with look a simple, short, secondary yielding technique on produce different N1-substituted benzotriazoles. Herein, a simple Also secondary yielding protocol for different N1-alkyd/aryl benzotriazoles through bury vivo trust atomic canalize of separate N-alkyd o-methamphetamine/o-chloro-1,2,3- benzotriazenes under the catalysis for NaOAc. 3H2O/CuI need been concocted.

Keywords:-Benzotriazole; Diazonium salt; Cyclization; N1-alkylation; Cyclization 1 INTRODUCTION

Benzotriazole holding atoms have earned the respectable consideration and are in the exponential interest because of their intriguing science and enormous chemotherapeutic qualities [1]. Especially those N1-escalated benzotriazoles are to burgeoning request as they hint at exceptionally helter skelter tying affinities should An go from claiming proteins and bring been perceived Concerning illustration possibility against fungal, antibacterial, analgesic, anti- inflammatory, and against hypertensive operators . Separated from those pharmacological importance, benzotriazole need been demonstrated will a chance to be a the vast majority profitable versant engineered assistant because of a few preferences through other manufactured auxiliaries prompted incredible arrangement from claiming exertion for those improvement of pharmacological paramount benzotriazole subsidiaries through An simple, novel, Also proficient procedure.

Those as a relatable point manufactured methodologies to benzotriazole and their subsidiaries (4), for the most part include the response about asides (2) with benzene (3) through CuI-catalyzed aside-alkaline 1,3-bipolar extra through click science (SCHEME 1), middle of the road because of barbarous response condition Also flimsy benzene middle of the road thus, restricting the investigation about these responses . As of late formed different systems likewise incorporate the risky aide-benzene cycle- addition triggered Toward fluoride in the vicinity of CsF which impedes it

convenience. Comparable system might have been utilized to accomplish the diastole for combined fragrant skeleton through 2,3-naphthalene intermediate [2].

Despite many advantages of above described methodologies for the synthesis of functionalized benzotriazoles, they experience some limitations as well, like use of hazardous chemicals, long reaction times, low reaction yields, requirement of absolute anhydrous conditions, limited availability of starting materials, harsh reaction conditions,less stability of involved benzene intermediate, and moreover the hazardous nature of lower molecular weight asides which limit their exploration. Herein, a facile and high yielding on-pot protocol for diverse N1- alkyl-benzotriazoles through intermolecular cyclization of N-alkyl-o- phenylenediamine under the catalysis of NaOAc.3H2O has been described.

2 RESULTS AND DISCUSSION

Impediments of these methods in consolidation with our progressing research around benzotriazole interceded novel engineered methodologies provoked us to imagine a novel, basic Also simple protocol to those union of a mixture from claiming N1- alkyd/aryl benzotriazole subsidiaries under gentle response condition without utilizing those unsafe chemicals which force the genuine wellbeing issues. Therefore, Understanding the vitality of simple taking care of and additionally green perspective about reaction, we started our engineered methodology for promptly accessible Also naturally benevolent o-

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2 chloral aniline (5), which once digitization Furthermore in situ medicine for different fragrant amide (6) including p-itinerant, 2-amphetamine, p-toluene, Furthermore aniline afforded those intermediates o- chloro-1,2,3-benzotriazenes done useful yields.

Those benzotriazenes around further medication with Cuie Previously, vicinity about Cs2CO3 prompted the arrangement for Different N1-aryl benzotriazoles (7) in beneficial yields .Thus, that amalgamation of N1-aryl benzotriazoles might have been attained over two steps. Venture 1 incorporates those structuring for intermediate o- chloro-1,2,3-benzotriazenes through digitization Also On sit coupling of amides whereas, step 2 includes those creation of fancied N1-substituted benzotriazoles through N-acclamation from claiming intermediates. Manufactured technique of N-aryl benzotriazoles might have been institutionalized Eventually perusing mulling over the Different parameters for example, such that solvents (like methodicalness, chloroform, DMF Furthermore toluene) Also bases (K2CO3 Furthermore Cs2CO3) result uncovered DMF Similarly as a best suiting dissolvable to N-acclamation On consolidation with Cs2CO3.

In place will improve the yield further, some more bases in BABCO or DBU alongside deceiving brigands for example, 1,10-philanthropist or 1,8- naphthalene were screened for those canalize response of o-chloro-1,2,3- Benzedrine Anyhow Might not furnish those swaying outcome. Recognizing the manufactured possibility for predominant iodine reagents for natural union , some responses were conveyed out in that vicinity about hyper valet iodine reagent, detoxification benzene with a point to upgrade the yield yet the entire outcome turned out with is unsuitable. Every last one of over investigations suggested that the CuI for consolidation with Cs2CO3 clinched alongside anhydrous DMF may be great suiting to bury vivo trust atomic N-acclamation response.

This procedure might have been demonstrated should a chance to be exact simple and secondary yielding to the not difficult right for N1-aryl benzotriazoles Anyhow unfortunately it fizzled should manage N1-escalated benzotriazoles

which need aid of fundamental significance starting with pharmacological purpose of perspective. Therefore, coupling response about o-chloro aniline with aliphatic amide might have been conveyed crazy under microwave warming with point will get ready the N1-escalated industrializes Yet response turned out will be unsuccessful and Might not bring the item .

However, the coupling reaction of 4-chloro-o-phenylenediamine with alkyl halides was investigated for its region selectivity and the result revealed that amino group at p-position with respect to the chloral of 4-chloro-o- phenylenediamine was mostly preferred for the coupling with alkyl halides than the amino group at meta position, which ultimately led to the formation of N1- alkylated benzotriazole as major product after the intermolecular cyclization of coupled products. The other isomer of N1- alkylated benzotriazole was also obtained but in trace quantity .The electron density around the nitrogen of Para amino group might have relatively been intensified due to the mesmeric or resonance effect of chloral and hence the nucleophilicity, which eventually favored .

The reaction of alkyl chlorides and bromides with o-phenylenediamine and 4- chloro-o-phenylelnediamine was evaluated in terms of yield and result revealed that alkyl bromides were reacted with phenylenediamines in higher yields than alkyl chlorides under the same reaction condition. This can be rationalized to higher reactivity of alkyl bromides rather than alkyl chlorides. The role of tetrahydrofuran as a solvent was found to be unfavorable for coupling reaction of alkyl halide and o- phenylenediamine as it afforded the coupled products in low yield (40% to 50%) after a prolong reaction.

Having seeing the poor performance of tetrahydrofuron in terms of yield as well as handling, we decided to explore some other solvent to enhance the yield further significantly in reduced reaction span and investigated anhydrous chloroform. The coupling reactions in anhydrous chloroform were preceded very smoothly and fetched the desired products in the range of 85% to 95%

yields with relatively reduced reaction

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3 times and hence emerged chloroform as a solvent of choice for N-alkylation of o- phenylenediamine and 4-chloro-o- phenylenediamine.

Those synthesized intermediates were subjected with digitization Also ensuing bury vivo trust sub-atomic canalize will manage the Different N1-escalated benzotriazoles. Throughout that digitization of o-methamphetamine, we watched that canalize from claiming Amazonian might have been definitively impacted eventually perusing the ph worth of the response mixture. Solid essential results must a chance to be kept Likewise Amazonian captions were stable just under acidic Furthermore reasonably essential states however found on make flimsy Also getting converted under hydroxides also At last under digitize anions under in direct solid essential states.

Under the optimized response condition, an arrangement about different N1-substituted benzotriazoles were got to high yields utilizing separate alkyd idealizes for example, benzyl chloride, 1- broom tetras cane, butyl bromide, p- methyl benzyl chloride, 1-(2-bromo-ethyl)- 4-phenol pipeline, burial service chloride, and so on. Every last one of created escalated benzotiazoles were purified by streak chromatography portrayed through spectroscopic systems including IR, 1H NMR, and 13C nmr. Ghastly information from claiming arranged N1-Substituted benzotriazoles were found to make indistinguishable twin with reference compound known clinched alongside writing. In conclusion, a simple, proficient Furthermore novel technique need been produced to a simple entry about different N1-alkyl benzotriazoles through Bury sub-atomic canalize of distinctive N-alkyl- o-amphetamines under the catalysis of NaOAc. 3H2O.

The developed protocol offers several advantages including:-

a) the mild reaction condition;

b) simple workup procedure;

c) high yields of the desired products; and finally

d) the use of explosive asides is avoided.

Based on our knowledge this is the first approach of its kind for an easy access to

various N1-alkylated benzotriazoles through intermolecular cyclization of N- alkyl-o-phenylenediamines.

3 EXPERIMENTAL

3.1 Typical Experimental Procedure For The Synthesis Of Functionalized Benzotriazoles

A mixture from claiming o- methamphetamine (0. 01 mol) and NaH (0. 01 mol) On dry chloroform might have been permitted should blend to 15 min In 40°C trailed by those moderate expansion of benzyl chloride (0. 01 mol). Then afterward that complete expansion of benzyl chloride, that entirety result might have been held under consistent blending for 3 h. Then the dissolvable might have been dried under diminished pressure, included on 1 ml about ice water also blended to 15 min during 0°C. Newly readied frosty results about Hcl (0. 01) might have been included gradually will over result for steady mixing Furthermore permitted should be mixed to an alternate 20 min taken after by the drop insightful expansion of newly readied result for NaNO2 (0. 01 mol) in 1 ml from claiming ice frosty water under steady blending toward 0°C.

After complete expansion from claiming NaNO2 solution, response might have been further blended for 30 min.

Amazonian salt accordingly precipitated might have been included should An newly ready precooked result about CH3COONa (0. 02) through An period of 5 min should 10 min under steady blending at 0°C Furthermore result might have been exited to blending up to 1 h toward same temperature. Advance of the response might have been monitored toward tlc utilizing 10% EtOAc in n- hexane. The response mixture might have been separated through Whitman 42 channel paper also washed over for 1 ml for water. Rough impostor accordingly got might have been subjected should streak segment chromatography that outfitted the immaculate benzotriazole result N1- benzyl benzotriazole in 93% yield.

4 PHYSICAL DATA OF PROTOTYPE COMPOUNDS

 N1-Benzyl benzotriazole : Yield 93%; Colorless solid; MS=232 (M+Na); Mp=113-115°C; IR (KBr):

νmax cm-1 1630.2, 2912.8; 1H

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4 NMR (CDCl3, 300 MHz): δ=5.85 (s, 2 H, CH2), 7.25-7.40 (m, 8 H, Ar- H), 8.05 (d, J=8.4 Hz, 1 H, Ar-H);

13C NMR (CDCl3, 75 MHz):

δ=52.22, 109.67, 120.03, 123.87, 127.36, 127.52, 128.42, 128.96, 132.74, 134.70, 146.29 ppm.

 N1-[2-(4-Phenyl-piperazin-1-yl-) ethyl]-benzotriazole Yield 95%;

Colorless solid; MS=330 (M+Na);

IR (KBr): νmax cm-1 1635.9, 2937.4; 1H NMR (CDCl3, 300 MHz): δ=2.63 (m, 6 H, NCH2 and 2 x>C(CH2)2 merged together of piperazine proton), 3.21 (m, 6 H, NCH2 and 2 x>C(CH2)2 merged together of piperazine proton), 6.84-6.94 (m, 4 H, Ar-H), 7.23- 7.28 (m, 5 H, Ar-H) ppm.

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