Abstract:Abstract2,4,6-Trialkyl substituted phenols were selectively transformed in high yield to para-quinols or para-quinol ethers by reaction with the N-fluoro-1,4-diazoniabicyclo[2.2.2]octane salt analogues Selectfluor TM F-TEDA-BF 4 or Accufluor TM NFTh in acetonitrile in the presence of water or alcohols. At low temperature 2,4,6-tri-tert-butylphenol in pure acetonitrile gave 2-fluoro and 4-fluoro substituted cyclohexadienone products with both reagents, while at elevated temperature 2-fluoro-4,6-di-tert-butylphe… Show more
“…Alkyl pentamethylbenzyl ether 6 is transformed after formation of a cation-radical, nucleophilic attack of methanol, and a second electron transfer to cationic intermediate 6 α, while further deprotonation of the neighboring methyl group gave 6 β, which following further attack of methanol gave the ortho dimethoxy derivative 11a . Similar ipso attack of water or alcohols has already been observed in F-TEDA-BF 4 -mediated functionalizations of sterically hindered phenols, but deprotonation of the hydroxyl group was the dominant process there, and dienone derivatives were thus formed , path B ), where deprotonation of cation-radical is followed by one-electron transfer thus giving the cationic intermediate 1 δ, which could further collapse with methanol resulting in the formation of 6a or 6e , 6f , or 5 if acetic acid, trifluoroacetic acid or acetonitrile were the source of the nucleophile, respectively.…”
Various N-F reagents reacted with hexamethylbenzene (1) forming side chain substituted alkoxides or esters in protic solvents, Ritter type side chain functionalization was observed in acetonitrile in the presence of trifluoroacetic acid, while in aqueous acetonitrile solution phenyl ring transformation took place, starting with ipso attack of water and further rearrangement of the methyl group as the main process. Rearranged 2,3,4,5,6,6-hexamethylcyclohexa-2,4-dienone (7) was transformed to 5-fluoro-2,3,5,6,6-pentamethyl-4-methylenecyclohex-2-en-1-one (8) or 5-hydroxy-2,3,5,6,6-pentamethyl-4-methylenecyclohex-2-en-1-one (9). 1,2,3,4,5,6-Hexamethyl-bicyclo[2.2.0]hexa-2,5-diene reacted with F-TEDA-BF4 in the presence of water and 7 was formed in high yield. Durene (12) followed similar ipso attack of water as 1, but on the other hand 1,2,3,4-tetramethylbenzene displayed different regioselectivity and 2,3,4,5-tetramethylphenol was formed, further transforming to 4-fluoro-2,3,4,5-tetramethylcyclohexa-2,5-dienone. The functionalizations of methylbenzenes obeyed a second-order rate equation v = d[N-F]/dt = k2[N-F][substrate], and DeltaG# values between 77 and 94 kJ/mol were determined. The presence of water did not significantly influence DeltaG# but considerably affected DeltaS# and positive values were found where methyl group migration was the dominant process (9.1 J/(mol K) for 1 and 0.5 J/(mol K) for 12). A higher reactivity of durene than mesitylene (k2(MES)/k2(DUR) = 0.23) was found, supporting the assumption that single electron transfer (SET) is the dominant process in the functionalizations of methyl-substituted benzene derivatives with F-TEDA-BF4.
“…Alkyl pentamethylbenzyl ether 6 is transformed after formation of a cation-radical, nucleophilic attack of methanol, and a second electron transfer to cationic intermediate 6 α, while further deprotonation of the neighboring methyl group gave 6 β, which following further attack of methanol gave the ortho dimethoxy derivative 11a . Similar ipso attack of water or alcohols has already been observed in F-TEDA-BF 4 -mediated functionalizations of sterically hindered phenols, but deprotonation of the hydroxyl group was the dominant process there, and dienone derivatives were thus formed , path B ), where deprotonation of cation-radical is followed by one-electron transfer thus giving the cationic intermediate 1 δ, which could further collapse with methanol resulting in the formation of 6a or 6e , 6f , or 5 if acetic acid, trifluoroacetic acid or acetonitrile were the source of the nucleophile, respectively.…”
Various N-F reagents reacted with hexamethylbenzene (1) forming side chain substituted alkoxides or esters in protic solvents, Ritter type side chain functionalization was observed in acetonitrile in the presence of trifluoroacetic acid, while in aqueous acetonitrile solution phenyl ring transformation took place, starting with ipso attack of water and further rearrangement of the methyl group as the main process. Rearranged 2,3,4,5,6,6-hexamethylcyclohexa-2,4-dienone (7) was transformed to 5-fluoro-2,3,5,6,6-pentamethyl-4-methylenecyclohex-2-en-1-one (8) or 5-hydroxy-2,3,5,6,6-pentamethyl-4-methylenecyclohex-2-en-1-one (9). 1,2,3,4,5,6-Hexamethyl-bicyclo[2.2.0]hexa-2,5-diene reacted with F-TEDA-BF4 in the presence of water and 7 was formed in high yield. Durene (12) followed similar ipso attack of water as 1, but on the other hand 1,2,3,4-tetramethylbenzene displayed different regioselectivity and 2,3,4,5-tetramethylphenol was formed, further transforming to 4-fluoro-2,3,4,5-tetramethylcyclohexa-2,5-dienone. The functionalizations of methylbenzenes obeyed a second-order rate equation v = d[N-F]/dt = k2[N-F][substrate], and DeltaG# values between 77 and 94 kJ/mol were determined. The presence of water did not significantly influence DeltaG# but considerably affected DeltaS# and positive values were found where methyl group migration was the dominant process (9.1 J/(mol K) for 1 and 0.5 J/(mol K) for 12). A higher reactivity of durene than mesitylene (k2(MES)/k2(DUR) = 0.23) was found, supporting the assumption that single electron transfer (SET) is the dominant process in the functionalizations of methyl-substituted benzene derivatives with F-TEDA-BF4.
“…Aminofluorothiophenes are possible precursors that can be used in the synthesis of fluoroquinolone antibiotics . Although 1 has shown reasonable reactivity for the fluorination of acetanilide, it was incompatible with acetamidothiophene, and the fluorinated derivatives were obtained in very low yields . Two possible routes to 2,2-difluoro-1-keto-5-tosylbenzazepine using 1 are available…”
Section: Fluorination Reactions Using Selectfluormentioning
confidence: 99%
“…Stavber has utilized 1 in the high-yield, direct synthesis of 4-fluorocyclohexa-2,5-dienone derivatives. Estrogen steroids were also readily converted to 10β-fluoro-1,4-estradiene-3-one derivatives in good yields (Table ) 22b 9 10 11 12 13 14
3 Reaction of Vinylsilane Derivatives with 1
…”
Section: Fluorination Reactions Using Selectfluormentioning
confidence: 99%
“…Hindered 2,4,6-trialkyl-substituted phenols were also selectively converted to p -quinols in high yield by reaction with 1 . The effects of temperature and the presence of different external nucleophiles have been studied (Scheme ) 22c. Reactions of hindered phenols with 1 require well-defined conditions in order to ensure the selectivity of the course of reaction.…”
Section: Fluorination Reactions Using Selectfluormentioning
Synthetic and structural aspects of organofluorine compounds continue to be the focal points of vigorous research activities, as evidenced by the appearance of a large number of publications. Among the various useful methodologies for the introduction of fluorine into organic molecules, electrophilic fluorination is a promising and exciting area of research. While a variety of electrophilic fluorinating reagents are available, currently 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) provides a remarkably straightforward and effective route. The breadth of applications realizable from this reagent in its role as a key electrophilic fluorinating reagent is highlighted here. This Account covers the literature for electrophilic fluorination reactions that employ Selectfluor during the period January 1999-January 2003.
“…[22] Thus, Selectfluor® has quickly become a commercial chemical produced on a multi-ton scale and has become one of the most popular NÀ F reagents. [23] It has been widely used in the fluorination of heterocycles, [24] such as the fluorination of various indoles, [25][26][27] phenols, [28,29] benzazepine, [30] thiazolidinone, [31] and stilbene. [32] Monofluorination with Selectfluor® has been reported to produce high yields, such as monofluorination of 3fluorooxindoles [25] and aryl-substituted imidazo[1,2-α]pyridines, [33] which result in yields of over 70 %.…”
Caffeine is a naturally occurring central nervous system (CNS) stimulant found in many drinks and foods. Many interesting biological activities of caffeine, and some of its derivatives, have been reported. Therefore, this study aims to conduct chemical transformations of caffeine. The method used is direct fluorination of caffeine using Selectfluor® in acetonitrile at room temperature, followed by purification to obtain 8‐fluorocaffeine. This reaction can be done on a multigram scale. Subsequently, 8‐fluorocaffeine was further modified by a nucleophilic substitution reaction with amines and alcohols as the nucleophiles under reflux conditions in an appropriate solvent to form fifteen 8‐substituted caffeine derivatives, with yields ranging from moderate to high. Of these derivatives, four are novel compounds, which are 8‐(3‐chloro‐4‐fluorophenyl)aminocaffeine, 8‐(3‐aminophenyl)amino‐caffeine, 8‐(azetidin‐1‐yl)‐caffeine, and 8‐(tetrahydrofuran‐3‐yl)oxycaffeine.
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