Electrophilic Fluorination with 1-Fluoro-2,4,6
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Organic and Medicinal Chemistry International Journal ISSN 2474-7610 Research Article Organic & Medicinal Chem IJ Volume 3 Issue 4 - September 2017 Copyright © All rights are reserved by SunitaBhagat DOI: 10.19080/OMCIJ.2017.03.555620 Electrophilic Fluorination with 1-Fluoro-2,4,6- trimethylpyridinium tetrafluoroborate and NFSI (N-Fluorobenzenesulfonimide) reagents directed towards the synthesis of heterocycles ; Current Trends Pankaj Sharma, Nutan Sharma, Amit Kumar and SunitaBhagat* Department of Chemistry, ARSD College, University of Delhi, India Submission: September 06, 2017; Published: September 19, 2017 *Corresponding author: SunitaBhagat, Department of Chemistry, ARSD College, University of Delhi, Dhaula Kuan, New Delhi-110021, Indias Abstract Landolphiaowariensis The phytochemical screening and the antidiarrhoeal activities of the crude extracts from Landolphiaowariensisthe leaves were carried out using standard methods. The results of the phytochemical screening showed thatLandolphiawariensis the plant contained alkaloids, saponins, tannins, flavonoids and glycosides. The results of the antidiarrhoeal screening of the crude extracts showed that exhibited zone of inhibition ranging from 15 mm to 35 mm against test microbes.Salmonella Ethyl-acetate Typhi, Shigelladysentriaeand extract of the Escherichaia Colirespectively being the most active fraction was subjected to column chromatography,1 leading13 to the isolation of single compound that showed a high activities (zone of inhibition from 8mm to 32mm) HNMR, CNMR against these causative agents of diarrhoea (Landolphiaowariensis ). Spectroscopic analysis of the isolated compound using , IR and GCMS showed that the compound was Cis-9-Octadecenoic acid. The result of this works therefore showed that the extract from the leaves of could be used for the treatment of diarrhoea and other diseases caused by targetedKeywords: microorganisms. Antidiarrheal; Landolphiaowariensis ; Isolation; Cis-9-Octadecenoic Acid Introduction located at a specific site, or often it is desirable to introduce The development of fluorination chemistry began more the element directly in order to obtain the desired chemical than 100 years ago with the first examples of nucleophilic and composition [12,13]. Electrophilic fluorination is one of the electrophilic fluorination reactions being reported in the second most direct methods for selective introduction of fluorine into half of the 19th century [1,2]. Fluorinated molecules plays a organic compounds [14]. In this respect, various reagents for significant role in pharmaceutical/medicinal [3,4] agrochemical electrophilic fluorination have been developed till now as shown [5,6] and material sciences [7] due to the unique properties in (Figure 1). Elemental fluorine itself is one of the most powerful of fluorine atom [8]. The introduction of fluorine atom can reagents [15]. modulate the properties of biologically active compounds, since 3 3 this may lead to changes in lipophilicity, chemical reactivity, However, fluoroxcompounds3 13 [16], such as CF OF, CF C(O) solubility, conformation, ability of hydrogen-bonding [9]. As a OF, CsSO4F, and CH C(O)OF some of which are generated result, 30-40% of agrochemicals and 20-25% of pharmaceuticals in situ, are exciting reagents for the introduction of fluorine on the market are estimated to contain fluorine [10]. electrophilically into a wide variety of organic compounds [17,18]. Most electrophilic fluorinating reagents are ultimately The efficacy of agrochemicals and pharmaceuticals derived from fluorine gas, the strongest elemental oxidant oftenly enhanced or it is due to the presence of fluorine atom known, which is synthesized by electrolysis of potassium in the structure [11]. Frequently, these type of compounds difluoride in hydrogen fluoride [19]. Electrophilic fluorination can be synthesized from small moieties in which fluorine is reactions with highly oxidizing fluorinating reagents [20] such Organic & Medicinal Chem IJ 3(4): OMCIJ.MS.ID.555620 (2017) 001 Organic and Medicinal Chemistry International Journal as fluorine gas, hypofluorites, fluoroxysulfates, and perchloryl was crucial for the development of selective, functional-group- N+ fluoride are challenging to perform due to the high reactivity of tolerant fluorination methods. Another class of2 electrophilic3 the reagents. Xenon difluoride was developed as a more stable fluorinating reagents with the general structure R N-F or R -F electrophilic fluorination source, but its high oxidation potential began to gain popularity. In comparison to the previous reagents, still limits the tolerance of this reagent to functional groups [21]. these compounds were stable, safer, milder and less expensive N to produce. Furthermore, some of these compounds proved The development of crystalline, benchtop-stable fluorinating to be as reactive as established reagents in some cases, which reagents such as -fluorobis (phenyl) sulfonimide (NFSI) were also capable of a degree of selectivity that was previously [19] and related analogues [22,23], N-fluoropyridinium salts unattainable [26]. Efforts by Umemoto et al. led to the first [24], and 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo-[2.2.2] isolatable N-fluoropyridinium salts, which had good activity and octane bis(tetrafluoroborate) (Selectfluor, F-TEDABF4) [25] F were amenable to commercial production [27] (Figure 1). F O O F Xe O Cl O F N F F F O F OTf trifluoromethyl hypofluorite difluoroxenon hypofluorous perchloric 1-fluoroquinuclidin anhydride -1-ium Cl N N F N F S N S O2N O O O O F 2BF4 2-fluoro-3,3-dimethyl-2,3- 2-fluoro-3,3-dimethyl-6-nitro-2,3- Seletfluor dihydrobenzo[d]isothiazole 1,1- dihydrobenzo[d]isothiazole 1,1-dioxide dioxide F O O O O O N S S S S N F3C N CF3 O O O F BF4 F N,1,1,1-tetrafluoro-N- 1-fluoro-2,4,6-trimeth l ridin N-fluoro-N-(phenylsulfonyl) y py ((trifluoromethyl)sulfonyl)met benzenesulfonamide -1-ium tetrafluoroborate hanesulfonamide Figure 1: Electrophilic fluorinating reagents. Electrophilic Fluorinating Reagents The important role of the counter anion, which influences N-Fluoropyridinium tetrafluoroborate: (Scheme 1) the reactivity, selectivity, and stability of the reagent, was also N F demonstrated [28]. Des Marteau and co-workers later reported N the discovery of -fluorobis [(trifluoromethyl) sulfonyl] imide, BF4 accessed by the reaction of bis [(trifluoromethyl) ulfonyl]-imide F with fluorine gas [29,30]. The synthesis of this compound, which MgX LiCl 2 R R is still one of the most powerful sources of electrophilic fluorine, heptane, 1.5 h, 00C 3 1 was a step forward in the identification of a stable source of 30-83 % Yield electrophilic fluorine with desirable physical properties. One Scheme 1: Synthesis of aryl fluoride from Grignard reagents. major drawback is that it is not commercially available, so that the use of fluorine gas for its preparation in the laboratory is ultimately required. N O More recently, the development of the reagent NFSI O O F BF4 O presented a major advance for electrophilic fluorination, as it is a O THF, 00C, 30 min. F O 5 reliable, mild, stable, and effective source of electrophilic fluorine 4 rt, 48 h 58 %, 67 % ee that lends itself to large-scale synthesis and is commercially available. A number of reagents, each with its advantages and Scheme 2: Fluorination using N-Fluoropyridinium tetrafluoroborate. disadvantages, currently exist for the electrophilic incorporation of fluorine and have been the subject of several reviews [31-34]. In the present review, we give a comprehensive overview of the In (Scheme 1), Lagow and co. workers used literature reports emphasizing on two potential electrophilic N N-Fluoropyridinium tetrafluoroborate as fluorinating reagent fluorinating reagents 1-Fluoro-2,4,6-trimethylpyridinium among the N-fluoropyridinium salt series and can react as tetrafluoroborate and NFSI ( -Fluorobenzenesulfonimide). How to cite this article: Pankaj S, Nutan S, Amit K, SunitaB. Electrophilic Fluorination with 1-Fluoro-2,4,6-trimethylpyridinium tetrafluoroborate and 002 NFSI (N-Fluorobenzenesulfonimide) reagents directed towards the synthesis of heterocycles ; Current Trends. Organic & Medicinal Chem IJ. 2017; 3(4): 555620. DOI: 10.19080/OMCIJ.2017.03.555620. Organic and Medicinal Chemistry International Journal ortho an electrophilic fluorine source. Exhibiting almost the same of organic molecules. The C-H activation/oxidative fluorination reactivity as other related N-fluoropyridinium salts, albeit with a process allows -fluorination of the aryl ring under kg somewhat−1 lower solubility, it has a high fluorine content (103 g microwave irradiation [38] (Scheme 4). ) [35] (Scheme 2). N (1.5 eq) BF4 CF N F 3 CF3 F BF4 N N 0 10 mol % Pd(OAc)2, C6H6, 110 C, 18 h 9 N 8 H F Pd OAC , ACN, PhCF N ( )2 3 82% 6 − 300 F µ wave ( W) 7 0 150 C, 2 h, 75 % Scheme 4: Palladium-catalyzed fluorination of Scheme 3: Palladium catalyzed fluorination of carbon-hydrogen 8-methylquinoline. bonds. Tomita, K. and Co workers used N In Scheme 4, Sanford and co workers used Palladium- -Fluoropyridinium catalyzed fluorination of 8-methylquinoline.2 Initial investigations tetrafluoroborate as fluorinating reagent as shown in (Scheme 2). focused on the Pd (OAc) -catalyzed benzylic fluorination of In this case of fluorination of 1-(trimethylsilyloxy) cyclohexene, 8-methylquinoline. This substrate was selected because it the yields and/or rates of reaction are not satisfactory, compared undergoes facile quinoline-directed C-H activation at Pd(II) to Cl to