405-50-5

Usage

Uses

Used in Pharmaceutical Industry:
4-Fluorophenylacetic acid is used as an intermediate for the production of fluorinated anesthetics, which are essential in the medical field for their anesthetic and analgesic properties during surgeries and medical procedures.
Used in Chemical Synthesis:
Due to its unique chemical structure, 4-Fluorophenylacetic acid can also be utilized as a building block in the synthesis of various organic compounds, contributing to the development of new pharmaceuticals, agrochemicals, and other specialty chemicals.

Synthesis Reference(s)

Journal of the American Chemical Society, 78, p. 6037, 1956 DOI: 10.1021/ja01604a023

Purification Methods

Crystallise it from heptane, but it is best purified by distillation at high vacuum. [Bergmann et al. J Am Chem Soc 78 6037 1956, Beilstein 9 III 2261, 9 IV 1672.]

InChI:InChI=1/C8H7FO2/c9-7-3-1-6(2-4-7)5-8(10)11/h1-4H,5H2,(H,10,11)/p-1

Upstream product

• 1197-55-3 4-aminophenylacetic acid 
• 352-34-1 4-fluoro-1-iodobenzene 
• 34837-84-8 4-fluorobenzeneacetic acid methyl ester 
• 321547-57-3 4-(2-methoxy-3-triisopropylsilanyloxy-benzoyl)-piperidine 
• 459-04-1 4-Fluorophenylacetyl chloride 
• 124-38-9 carbon dioxide 
• 352-11-4 1-chloromethyl-4-fluorobenzene 
• 64-19-7 acetic acid 
• 702-11-4 4-fluoro-N,N-dimethylbenzylamine 
• 243145-83-7 2-[(4-fluorophenyl)methyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 
• 797755-07-8 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetic acid 
• 201230-82-2 carbon monoxide 
• 459-46-1 4-Fluorobenzyl bromide 
• 352-32-9 p-fluorotoluene 

Downstream Products

• 587-88-2 ethyl 2-(4-fluorophenyl)acetate 
• 2967-95-5 2-(4-fluorophenyl)-3-hydroxypropanoic acid 
• 459-04-1 4-Fluorophenylacetyl chloride 
• 143033-77-6 Acetic acid 6-(4-fluoro-phenyl)-7-oxo-7H-dibenzo[a,c]cyclohepten-5-yl ester 
• 35567-36-3 3-(4'-fluorophenyl)-2-oxo-2H-pyrano<2,3-b>pyridine 
• 127035-59-0 4-[(E)-2-(4-Fluoro-phenyl)-vinyl]-2,6-diisopropyl-phenol 
• 125722-16-9 enofelast 
• 459-03-0 4-fluorophenyl acetone 
• 93668-67-8 4-Fluoro-N-[3-(1H-imidazol-1-yl)propyl]benzeneacetamide 
• 130311-20-5 C₂₆H₂₁ClFN₅OS 
• 73442-36-1 2,5-Bis(4-fluorphenyl)-4-phenyl-4-cyclopenten-1,3-dion 
• 116376-70-6 2,6-Di-tert-butyl-4-[(E)-2-(4-fluoro-phenyl)-vinyl]-phenol 
• 2194-09-4 p-fluorobenzyl radical 
• 29270-33-5 2-bromo-2-(4-fluorophenyl)acetic acid 

Relevant academic research and scientific papers

Potential proinsecticides of fluorinated carboxylic acids and β-ethanolamines. IV. Evaluation of the Δ2-oxazoline-1,3 structure by 19F NMR monitoring of the in vitro metabolism in locust tissues

The enzymatic effect of locust tissues upon hydrolysis of the fluorinated Δ2-oxazoline-1,3 Ia was elucidated using 19F[1H] NMR monitoring. In a phosphate buffer at pH = 7.4 (mean physiological pH of locust tissues), the substrate Ia hydrolyses slowly into the corresponding fluorinated hydroxylamide VIa. If diluted, locust haemolymph (12.5% in phosphate buffer) catalyses slightly this hydrolytic pathway, it overall triggers the unmasking of carboxylate IIIa, corresponding to the expected proinsecticide behaviour of Ia. This behaviour is spectacularly almost the unique reaction observed during in vitro assays in concentrated fat body and mesenteron. Inasmuch as β-hydroxylamide VIa is not hydrolysed into carboxylate IIIa during such conditions, it must be concluded that carboxylate formation exclusively results from hydration and hydrolysis of substrate Ia via the aminoester Va. The formation of this intermediate aminoester is demonstrated by complementary assays. The enzymes supposed to intervene are of the α-chymotrypsine type for the first step (hydration) and of the esterase type for subsequent hydrolysis of intermediate aminoester Va. Thus, this work constitutes the first example of a Δ2-oxazoline-1,3 structure exploited for elaborating proinsecticides of carboxylates III and/or β-ethanolamines II based on enzymatic activation in insects.

Visible-Light-Enabled Carboxylation of Benzyl Alcohol Derivatives with CO2 Using a Palladium/Iridium Dual Catalyst

A highly efficient carboxylation of benzyl alcohol derivatives with CO2 using a palladium/iridium dual catalyst under visible-light irradiation was developed. A wide range of benzyl alcohol derivatives could be employed to provide benzylic carboxylic acids in moderate to high yields. Mechanistic studies indicated that the oxidative addition of benzyl alcohol derivatives was possibly the rate-determining-step. It was also found that a switchable site-selective carboxylation between benzylic C?O and aryl C?Cl moieties could be achieved simply by changing the palladium catalyst.

Desulfonylative Electrocarboxylation with Carbon Dioxide

Electrocarboxylation of organic halides is one of the most investigated electrochemical approaches for converting thermodynamically inert carbon dioxide (CO2) into value-added carboxylic acids. By converting organic halides into their sulfone derivatives, we have developed a highly efficient electrochemical desulfonylative carboxylation protocol. Such a strategy takes advantage of CO2as the abundant C1 building block for the facile preparation of multifunctionalized carboxylic acids, including the nonsteroidal anti-inflammatory drug ibuprofen, under mild reaction conditions.

BF3·OEt2-promoted tandem Meinwald rearrangement and nucleophilic substitution of oxiranecarbonitriles

Tandem Meinwald rearrangement and nucleophilic substitution of oxiranenitriles was realized. Arylacetic acid derivatives were readily synthesized from 3-aryloxirane-2-carbonitriles with amines, alcohols, or water in the presence of boron trifluoride under microwave irradiation, and the designed synthetic strategy includes introducing a cyano leaving group into arylepoxides and capturing the in situ generated toxic cyanide with boron trifluoride, making the reaction efficient, safe, and environmentally benign. The reaction occurs through an acid-promoted Meinwald rearrangement, producing arylacetyl cyanides, followed by an addition-elimination process with nitrogen or oxygen-containing nucleophilic amines, alcohols or water. The current method provides a new application of the tandem Meinwald rearrangement.

Oxidation of Alkynyl Boronates to Carboxylic Acids, Esters, and Amides

A general efficient protocol was developed for the synthesis of carboxylic acids, esters, and amides through oxidation of alkynyl boronates, generated directly from terminal alkynes. This protocol represents the first example of C(sp)?B bond oxidation. This approach displays a broad substrate scope, including aryl and alkyl alkynes, and exhibits excellent functional group tolerance. Water, primary and secondary alcohols, and amines are suitable nucleophiles for this transformation. Notably, amino acids and peptides can be used as nucleophiles, providing an efficient method for the synthesis and modification of peptides. The practicability of this methodology was further highlighted by the preparation of pharmaceutical molecules.

Method for converting benzyl borate compounds into phenylacetic acid and derivatives thereof by carbon dioxide

The invention discloses a method for converting benzyl borate compounds into phenylacetic acid and derivatives thereof by carbon dioxide. The method comprises the steps: dissolving the benzyl borate compounds and an alkali in an organic solvent in the absence of a metal catalyst, introducing carbon dioxide into the reaction system, carrying out a reaction at the temperature of 50-150 DEG C for 3-72 hours, and acidifying to obtain phenylacetic acid or the derivatives thereof. The method is a green, simple and efficient method for synthesizing phenylacetic acid and the derivatives thereof, greenhouse gas carbon dioxide is used as a carbon source in the reaction, no transition metal catalyst is used, and the method is environmentally friendly, economical and high in efficiency.

Pd(OH)2/C, a Practical and Efficient Catalyst for the Carboxylation of Benzylic Bromides with Carbon Monoxide

A simple, efficient, cheap, and broadly applicable system for the carboxylation of benzylic bromides with carbon monoxide and water is reported. Upon simple reaction with only 2.5 wt % of Pearlman's catalyst and 10 mol % of tetrabutylammonium bromide in tetrahydrofuran at 110 °C for 4 h, a range of benzylic bromides can be smoothly converted to the corresponding arylacetic acids in good to excellent yields after simple extraction and acid-base wash. The reaction was found to be broadly applicable, scalable, and could be successfully extended to the use of ex situ-generated carbon monoxide and applied to the synthesis of the nonsteroidal anti-inflammatory drug diclofenac.

Design and evolution of an enzyme with a non-canonical organocatalytic mechanism

The combination of computational design and laboratory evolution is a powerful and potentially versatile strategy for the development of enzymes with new functions1–4. However, the limited functionality presented by the genetic code restricts the range of catalytic mechanisms that are accessible in designed active sites. Inspired by mechanistic strategies from small-molecule organocatalysis5, here we report the generation of a hydrolytic enzyme that uses Nδ-methylhistidine as a non-canonical catalytic nucleophile. Histidine methylation is essential for catalytic function because it prevents the formation of unreactive acyl-enzyme intermediates, which has been a long-standing challenge when using canonical nucleophiles in enzyme design6–10. Enzyme performance was optimized using directed evolution protocols adapted to an expanded genetic code, affording a biocatalyst capable of accelerating ester hydrolysis with greater than 9,000-fold increased efficiency over free Nδ-methylhistidine in solution. Crystallographic snapshots along the evolutionary trajectory highlight the catalytic devices that are responsible for this increase in efficiency. Nδ-methylhistidine can be considered to be a genetically encodable surrogate of the widely employed nucleophilic catalyst dimethylaminopyridine11, and its use will create opportunities to design and engineer enzymes for a wealth of valuable chemical transformations.

Synthesis and biological evaluation of 3-arylcoumarin derivatives as potential anti-diabetic agents

A variety of substituted 3-arylcoumarin derivatives were synthesised through microwave radiation heating. The method has characteristics of environmental friendliness, economy, simple separation, and purification process, less by-products and high reaction yield. Those 3-arylcoumarin derivatives were screened for antioxidant, α-glucosidase inhibitory and advanced glycation end-products (AGEs) formation inhibitory. Most compounds exhibited significant antioxidant and AGEs formation inhibitory activities. Anti-diabetic activity studies showed that compounds 11 and 17 were equipotent to the standard drug glibenclamide in vivo. According to the experimental results, the target compound 35 can be used as a lead compound for the development of new anti-diabetic drugs. The whole experiment showed that anti-diabetic activity is prevalent in 3-arylcoumarins, which added a new natural skeleton to the development of anti-diabetic active drugs.

Synthesis and biological evaluation of 3-arylcoumarins as potential anti-Alzheimer's disease agents

Alzheimer's disease, a neurodegenerative illness, has the extremely complex pathogenesis. Accumulating evidence indicates there is a close relationship between several enzymes and Alzheimer's disease. Various substituted 3-arylcoumarin derivatives were synthesised, and their in vitro activity, including cholinesterase inhibitory activity, monoamine oxidase inhibitory activity, and antioxidant activity were investigated. Most of the compounds exhibited high activity; therefore 3-arylcoumarin compounds have the potential as drug candidates for the treatment of Alzheimer's disease.