Nitration of trifluoromethyl benzene puts the nitro group mainly in the meta position with high. Electrophilic aromatic substitution the most characteristic reaction of aromatic compounds is electrophilic aromatic substitution, in which one of the ring hydrogens is substituted by a halogen, nitro group, sulfonic acid group, alkyl or acyl group. The resonance hybrid model explains these properties of benzene. Synthesis and properties of fluorinated alkynylbenzenes. Reactions of aromatic compounds rutgers university. Meta substitution means a 1,3 arrangement on a benzene ring. Notice that either of the oxygens can accept the electron pair. An analogous addition reaction between benzene and bromine would be. Step 3 loss of a proton from the carbocation to give a new aromatic compound. Aromatic substitution reactions electrophilic nucleophilic. Copper catalysed synthesis of trifluoromethylhetero. Benzene and benzene based molecules are part of many popular medications used to relieve pain, alleviate cold and flu symptoms, and as a weightloss aid. S1 cuimediated 18ftrifluoromethylationsupporting information of arenes. The deamination reaction of the invention refers to a deamination reaction on an intermediate and nitrous acid.
Chapter reactions of arenes electrophilic aromatic. The alkyl groups activate the ring of benzene, however, the acetyl groups deactivate the benzene as electron withdraw groups. Nitration of methyl benzene toluene takes place 25 times faster than benzene, and thus it is said to be activated toward electrophilic aromatic substitution. Carbon dioxide is a weak electrophile and normally does not react with aromatic compounds. The rest of the mechanism proceeds as a general electrophilic aromatic substitution reaction. Synthesis of trifluoromethyl substituted bi and terphenyls by siteselective suzukimiyaura reactions of various dihalogenated trifluoromethyl benzene derivatives. Trifluoromethylbenzene an overview sciencedirect topics. An oxidationreduction process of trifluoromethylcontaining compounds is thought to be involved in many recently tested catalytic trifluoromethylation reactions. S1 synthesis of trans2 trifluoromethylcyclopropanes via suzuki reactions with an n methyliminodiacetic acid mida boronate matthew a. An electron donating group edg or electron releasing group erg, z in structural formulas is an atom or functional group that donates some of its electron density. Benzotrifluoride btf, trifluoromethylbenzene, a,a,atrifluorotoluene. Onepot synthesis of nprotected amino trifluoromethyl ketones as hydrated hydrochloride salts via the csfcatalyzed reactions of trifluoromethyl trimethylsilane with nprotected amino esters. Trifluoromethylation reactions are important transformations in the research and development of drugs, agrochemicals and functional materials. Heats of reaction of cobaltic fluoride with hydrogen and with bis trifluoromethyl benzene a,a,a,a,a,a hexafl uoroxy lene by ralph s.
We begin our discussion of benzene reactions with processes that take place not on the ring itself, but at the. A preparation method of 4bromine2nitro trifluoromethyl benzene. The tbutylchloride reacts with the lewis acid to generate the tbutyl carbocation. Substituded derivatives of benzene and their nomenclature. Trifluoromethyl ethers synthesis and properties of an. Based on steric effects, we see that there is steric hinderance of the methyl. Predicted data is generated using the us environmental protection agencys episuite.
Trifluoromethyl arene synthesis by trifluoromethylation. Alkyl trifluoromethyl ethers, still a rarity, have so far been prepared by the reaction of alkyl fluoroformates with sulfur tetrafluoride, the trifluoromethyl transfer from o trifluoromethyl dibenzofuranium hexafluoroantimonate 4 and the addition of trifluoromethyl hypofluorite focf 3 to olefins. The dashed lines inside the hexagon in the resonance hybrid of benzene. Common reactions that proceed by electrophilic aromatic substitution include the nitration and sulfonation of benzene, hydration of benzene, friedelcrafts acylation and friedelcrafts alkylation. The second reaction is interesting in that it further demonstrates the delocalization of charge that occurs in the phenolate anion. Chapter 16 the chemistry of benzene and its derivatives.
A raw material of mtrifluoromethylphenyl chloride is treated with four steps of nitration, ammonification, bromination and deamidation to obtain the 4bromine2nitro trifluoromethyl benzene. Synthesis of trans 2trifluoromethylcyclopropanes via. The rate determining step in an electrophilic aromatic substitution is the formation of a resonance stabilized radical. Pdf siteselective sonogashira reactions of 1,4dibromo. Propargyl is removed by its direct reaction with molecular oxygen whose rate was measured by slagel and gutman 1986. Some fluoro arenes, such as 1iodo2 trifluoromethyl benzene, also react with imidazolederived ions to give the corresponding 4fluorinatedaryl imidazole analogues scheme 109. Would you expect trifluoromethyl benzene to be more reactive or less reactive than toluene towards electrophilic substitution. King chapter 18 electrophilic aromatic substitution i. The journal of organic chemistry 2002, 67 9, 31563159.
Benzene does not undergo addition reactions readily like alkenes. Although the electrons are in a stable aromatic system, they are still available for reaction with strong electrophiles. In an electrophilic aromatic substitution reaction, existing substituent groups on the aromatic ring influence the overall reaction rate or have a directing effect on positional isomer of the products that are formed. Riss contents materials 2 general 2 syntheses and nonradioactive control experiments 2. This is followed by loss of a proton, giving tbutyl benzene as the product. Pcbtf is used as an intermediate in the synthesis of dyes, pharmaceuticals, pesticides, insecticides, and herbicides, and as a solvent, mainly in paint and coating formulations. The results, according to the theoretical calculations of energy minima, show the monometallation regiochemistry is directed by the sulphur atom. Occupational exposure to pcbtf can occur through inhalation and dermal contact during its production and use. Literature 2 trifluoromethyl cyclopropyl derivatives attached to cyclic structures the following substructure search was conducted within scifinder between 28 th february and 16 th march 20 to ascertain the number of 2 trifluoromethyl cyclopropyl derivatives attached to cyclic structures that are described in the literature. The tbutyl carbocation acts as the electrophile, and forms a sigma complex. Halogenation of benzene, nitration of benzene, sulfonation of benzene and alkylation and acylation of benzene are some various chemical reactions of benzene. Siteselective sonogashira reactions of 1,4dibromo2 trifluoromethylbenzene.
Examples of electrophilic aromatic substitution reactions s. Catalytic trifluoromethylation of aryl and vinylboronic acids by 2cyclopropyl1 trifluoromethyl benzobthiophenium proceeded in good yields for various substrates in the presence of a catalytic amount of cuoac and 2,4,6collidine in ethyl acetate under mild reaction conditions at room temperature. Copper catalysed synthesis of trifluoromethylhetero arenes from. Several of these reactions form 1,3 butadiene, which is removed by three reactions reported by vaughn, howard, and longwell 1991. The reaction is triggered by dissociative electron transfer and, therefore, does not involving the intermediacy of the anion radical of the substrate. Benzene is a colorless liquid that was first discovered by michael faraday in 1825. Heat of fluorination of cobaltous fluoride, and the heats.
Reactions of aromatic trifluoromethyl compounds with. Convenient synthesis of 3,3,3trifluoropropenyl compounds from aromatic aldehydes by means of the tbafmediated horner reaction. Application 1iodo3,5bis trifluorom ethyl benzene may be used in the preparation of bistrifluoroacetoxyiod operfluoroalkanes. Hgcf 3 2, prepared by decarboxylation of the trifluoroacetate, has proven useful for the trifluoromethylation of other metals. Organic chemistry specific name reactions class xii sandmeyer reaction the cl, br and cn nucleophiles can easily be introduced in the benzene ring of benzene diazonium salt in the presence of cui ion. Representative electrophilic aromatic substitution. Nitration is the usual way that nitro groups are introduced. Chemical information profile for 1chloro4 trifluoromethyl benzene cas no. Wechsler 1 calorimetric measurements of the heats of the following reactions have been made, with the results indicated. Covid19 is an emerging, rapidly evolving situation. The metallation reactions of trifluoromethyl alkylthiobenzenes with organolithium reagents and with the butyllithiumpotassium tertbutoxide superbasic mixture are here described.
Pdf synthesis of trifluoromethylsubstituted bi and. Benzene undergoes substitution reactions instead of addition. The structure of benzene in the resonance hybrid, the six electrons from the three. These reagents are generated in situ by reaction of cf 3 i with copper powder in polar solvents. A novel lactate dehydrogenase inhibitor, 1phenylseleno.
We know that benzene is a human carcinogen with a unique electromagnetic potential that enables it to insert itself into human dna. Redox potentials of trifluoromethylcontaining compounds. A substituent x is said to be an meta director if it directs an incoming electrophile to position meta to itself. All the above information and example problems are taken from lecture, chemistry 14d thinkbook by steven hardinger for winter 2006, organic chemistry by paula yurkanis bruice, 4th edition, and the electrophilic aromatic substitution. Lithiation reaction of 1,3bis trifluoromethyl benzene has been investigated. A method is provided for forming 3trifluoromethylphenylacetonitrile through the intermediate. General description lithiation reaction of 1,3bis trifluoromethyl benzene has been investigated. Use of the information, documents and data from the echa website is subject to the terms and conditions of this legal notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the echa website may be reproduced, distributed andor used, totally or in part, for noncommercial purposes provided. This intermediate is formed by selective chlorination of. This section is on the general mechanism of how an electrophilic atom becomes a part of a benzene ring through the substitution of a hydrogen. National institute of environmental health sciences. Birch reduction reaction conditions involve sodium metal, in an alcoholic solution of ammonia. The journal of organic chemistry 2000, 65 10, 324243. Benzotrifluoride, reaction solvent, organic synthesis, fluorous synthesis, green.