395-33-5

Usage

Uses

Used in Pharmaceutical Synthesis:
4-Fluoromandelic acid is utilized as an intermediate in the pharmaceutical industry for the synthesis of various drugs and organic compounds. Its unique structure allows for the creation of new molecules with potential therapeutic applications.
Used as a Chiral Resolving Agent in Analytical Chemistry:
In the field of analytical chemistry, 4-Fluoromandelic acid serves as a chiral resolving agent. It aids in the separation of enantiomers, which is crucial for the development and analysis of chiral drugs, as different enantiomers can have distinct biological activities.
Used as a Precursor in the Synthesis of Complex Molecules:
4-Fluoromandelic acid also acts as a precursor in the synthesis of more complex molecules, contributing to the advancement of organic chemistry and the creation of new compounds with specific properties and applications.
Used in Research and Development:
Due to its distinctive chemical and physical properties, 4-Fluoromandelic acid is employed in research and development settings to explore new chemical reactions, investigate the effects of fluorination on molecular behavior, and develop innovative applications in various industries.

InChI:InChI=1/C8H7FO3/c9-6-3-1-5(2-4-6)7(10)8(11)12/h1-4,7,10H,(H,11,12)/p-1/t7-/m1/s1

Upstream product

• 70122-98-4 [2,2,2-Trichloro-1-(4-fluoro-phenyl)-ethyl]-carbamic acid methyl ester 
• 75-77-4 chloro-trimethyl-silane 
• 151-50-8 potassium cyanide 
• 459-57-4 4-fluorobenzaldehyde 
• 403-42-9 1-(4-fluorophenyl)ethanone 
• 134219-54-8 4-Chloro-N-[2,2,2-trichloro-1-(4-fluoro-phenyl)-ethyl]-benzamide 
• 82128-66-3 2-(4-fluorophenyl)-2-(trimethylsilyloxy)acetonitrile 
• 133721-87-6 2-(4-fluorophenyl)-2-hydroxyacetonitrile 
• 124-38-9 carbon dioxide 
• 768-33-2 phenyldimethylsilyl chloride 
• 1504663-20-0 [dimethylphenylsilyl(4-fluorophenyl)methoxy]trimethylsilane 
• 2251-76-5 2-(4-fluorophenyl)-2-oxoacetic acid 
• 77429-21-1 1-methoxycarbonylamino-1-(4-fluorophenyl)-2,2-dichloroethane 
• 1424934-11-1 C₁₅H₁₇FOSi 

Downstream Products

• 127709-19-7 methyl 4-fluoro-α-hydroxyphenylacetate 
• 459-57-4 4-fluorobenzaldehyde 
• 182308-89-0 5-(4-fluorophenyl)-2,2-dimethyl-1,3-dioxolan-4-one 
• 456-22-4 4-Fluorobenzoic acid 
• 7550-03-0 ethyl 2-(4-fluorophenyl)-2-hydroxyacetate 
• 1301601-25-1 methyl 2-(allyloxy)-2-(4-fluorophenyl)acetate 
• 1301601-27-3 C₁₃H₁₅FO₅ 
• 1301601-41-1 methyl 2-(4-fluorophenyl)-2-(4-oxo-4-(pyrrolidin-1-yl)butoxy)acetate 
• 1301601-52-4 C₁₃H₁₃FO₄ 
• 1629-26-1 2-(4-fluorophenyl)-benzothiazole 
• 824-75-9 p-fluorobenzamide 
• 1201686-45-4 (5S)-N-[5-chloro-2-(1H-tetrazol-1-yl)benzyl]-1-[(2R)-2-(4-fluorophenyl)-2-hydroxyacetyl]-4,5-dihydro-1H-pyrazole-5-carboxamide 

Relevant academic research and scientific papers

Preparation and reactions of certain racemic and optically active cyanohydrins derived from 2-chlorobenzaldehyde, 4-fluorobenzaldehyde, benzo[d][1,3]-dioxole-5-carbaldehyde and 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde. Antimicrobial and in vitro antitumor evaluation of the products

THE CHEMOENZYMATIC reaction of selected aldehydes, namely 2-chlorobenzaldehyde (1a), 4-fluorobenzaldehyde (1b), benzo[d][1,3]dioxole-5-carbaldehyde (1c) and/or 2,3-dihydrobenzo [b] [1,4] dioxine-6-carbaldehyde (1d) with hydrogen cyanide in presence of (R)-oxynitrilase (R)-Pa HNL [EC 4.1.2.10] from almonds, as a chiral catalyst, gave the optically active cyanohydrin enantiomers ( R)-2a-c, respectively. Acetone cyanohydrin (3), was also used, as a transcyanating agent, to give the same products. The racemic cyanohydrins (R,S)-2a-d have been synthesized, as well, by treating compounds 1a-d with aqueous potassium cyanide solution in presence of a saturated solution of sodium metabisulphite (Na2S2O5). The optical purity of cyanohydrins (R)-2a-c was determined through their derivatization with (S)-naproxen chloride (S)-5 to the respective diastereomers (R,2S)-6a-c which were obtained in diastereomeric excess (de) values up to 93 % (1H NMR). Heating compounds (R)-2a,b and / or their racemic analogues (R,S)-2a-c with concentrated hydrochloric acid gave the respective α-hydroxycarboxylic acids 7a-c. Moreover, reduction of cyanohydrins (R,S)-2b,c under different conditions resulted in a hydrodecyanation giving the respective primary alcohols 8a,b. Structures and configurations of the new compounds were confirmed with compatible elementary microanalyses and spectroscopic (IR, 1H NMR, 13C NMR, MS and single crystal X-ray crystallography) measurements. The antimicrobial activity of derivatives 6a-d against four bacterial species (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) and two fungi (Aspergillus flavus and Candida albicans) were undertaken. Moreover, compounds (R,2S)-6b, (R,2S)(S,2S)-6b and (R,2S)-6c were screened for their in virto antitumor activity against three human solid cancer cell lines (HCT 116, HepG2 and MCF-7). In general, the tested compounds were found inactive or showed weak activities in comparison with the standard drugs.

The Synthesis of Chiral α-Aryl α-Hydroxy Carboxylic Acids via RuPHOX-Ru Catalyzed Asymmetric Hydrogenation

A ruthenocenyl phosphino-oxazoline-ruthenium complex (RuPHOX?Ru) catalyzed asymmetric hydrogenation of α-aryl keto acids has been successfully developed, affording the corresponding chiral α-aryl α-hydroxy carboxylic acids in high yields and with up to 97% ee. The reaction could be performed on a gram scale with a relatively low catalyst loading (up to 5000 S/C) and the resulting products can be transformed to several chiral building blocks, biologically active compounds and chiral drugs. (Figure presented.).

Solid phase behavior in the chiral systems of various 2-hydroxy-2-phenylacetic acid (mandelic acid) derivatives

The solid phase behavior of a series of monosubstituted F-, Cl-, Br-, I-, and CH3- and two 2,4-halogen-disubstituted 2-hydroxy-2-phenylacetic acid (mandelic acid) derivatives was investigated. The study includes detailed information about melting temperature, melting enthalpy, X-ray diffraction data, as well as selected binary phase diagrams of the respective chiral systems. Aside from the known metastable conglomerate 2-chloromandelic acid, evidence for two more metastable conglomerates was found.

Carboxylation with CO2 via brook rearrangement: Preparation of α-hydroxy acid derivatives

In the presence of CsF, a wide range of α-substituted α-siloxy silanes were carboxylated under a CO2 atmosphere (1 atm) via Brook rearrangement. A variety of α-substituents including aryl, alkenyl, and alkyl groups were tolerated to afford α-hydroxy acids in moderate-to-high yields. One-pot synthesis from aldehydes using PhMe2SiLi and CO 2 was also possible, providing α-hydroxy acids without the isolation of an α-hydroxy silane.

Kinetic resolution of mandelate esters via stereoselective acylation catalyzed by lipase PS-30

By using lipase PS-30 as catalyst, the kinetic resolution of a series of racemic mandelate esters has been achieved via stereoselective acylation. The value of kinetic enantiomeric ratio (E) reached up to 197.5. Substituent effect is briefly discussed.

Relationships between the racemic structures of substituted mandelic acids containing 8- and 10-membered hydrogen bonded dimer rings

The structures of 27 monosubstituted mandelic acids, including several of their polymorphs, plus unsubstituted mandelic acid itself (two polymorphs) are investigated for structural similarity. The results, presented pictorially as a structural relationship plot, show that rather more structures are built up from the carboxyl-chain hydroxyl hydrogen bonded dimer than from the conventional carboxylic acid dimer. The results show how all the structures are related and, based on the two types of dimer, the degree of similarity that they possess. Some structures with Z′ > 1 contain both sorts of dimers and there are many examples of isostructural sets within the structures so far determined. We also present an example where analysing similarity in related families of structures highlights a structure that should be present and which has indeed then proceeded to be synthesised and determined.

Structures of Racemic Monofluoro-Substituted Mandelic Acids, Their Relation to the Thermochemical Properties and an Analysis of Short Intermolecular Fluorine-Carbon Contacts

The structures of the three monofluoro-substituted mandelic acids (C8H7FO3, Mr=170.14) have been determined from low-temperature X-ray diffraction data . o-Fluoromandelic acid, monoclinic, P21/c, a=8.4238 (12), b=5.4766 (7), c=15.959 (2) Angstroem, β=95.962 (11)o, V=732.3 (3) Angstroem3, Z=4, Dx=1.543 g cm-3, μ=11.25 cm-1, F(000)=352, R=0.040 for 1357 contributing reflections, m.p. 388.3 (5) K. m-Fluoromandelic acid (metastable modification), monoclinic, P21/a, a=10.8657 (14), b=9.2663 (10), c=15.722 (2) Angstroem, β=107.474 (10)o, V=1509.9 (6) Angstroem3, Z=8, Dx=1.497 g cm-3, μ=10.92 cm-1, F(000)=704, R=0.048 for 2977 contributing reflections, m.p. 368.4 (5) K. p-Fluoromandelic acid, orthorhombic, Pbca, a=9.4685 (9), b=16.497 (2), c=9.7677 (8) Angstroem, V=1525.7 (5) Angstroem3, Z=8, Dx=1.481 g cm-3, μ=10.80 cm-1, F(000)=704, R=0.042 for 1489 contributing reflections, m.p. 408.9 (5) K.The results obtained from the structure determination are related to their physico-chemical properties examined by differential scanning calorimetry (DSC).The DSC measurements showed that m-fluoromandelic acid is prepared as a metastable modification.The distortions of the angles of the benzene rings observed in the three acids are identical, within experimental error, to those predicted from the sum of the substituent effects.Hydrogen bonds are important for the crystal packing in all these structures, and in addition very short distances are observed in the ortho- and para-substituted acids between the F atom and the C atom of the carboxylic acid group.Semi-empirical calculations indicated that these short distances correspond to attractive electrostatic interactions.The carbon-fluorine interactions were also elucidated by a search in the Cambridge Structural Database. m-Fluoromandelic acid has the lowest melting enthalpy and entropy.This is consistent with the lack of C...F interactions and the presence of two molecules per asymmetric unit in this compound.The ortho and para acids which have similar intermolecular interactions have similar melting enthalpies and entropies, which are higher than those observed in m-fluoromandelic acid.

Reduction of manganate(VI) by mandelic acid and its significance to development of a general mechanism for oxidation of organic compounds by high-valent transition metal oxides

Results obtained from a study of the oxidation of mandelic acid and cyclobutanol by manganate(VI) indicate that reaction mechanisms traditionally applied to oxidations of this type (i.e., hydrogen atom or hydride ion transfers) may not be correct. Instead it appears that the reaction may be initiated by a 2 + 2 addition of the α-C-H bond to a manganese oxo double bond. This interpretation may be useful in the development of a general mechanism for the oxidation of organic compounds by high-valent transition metal oxides including more common oxidants such as permanganate, ruthenium tetroxide, and chromic acid.

The Oxidation of Alcohols by Permanganate. A Comparison with Other High-Valent Transition-Metal Oxidants

The results obtained from a study of the oxidation of mandelic acid and cyclobutanol by permanganate in 1.0 M KOH are best accomodated by a mechanism in which the initial reaction is the addition of a manganese-oxo bond to the α-C-H bond of the alcohol, followed by homolytic cleavage of the resulting Mn-C bond to give free-radical intermediates.A comparison with other high-valent transition-metal oxidants suggests that it is possible to systematically classify the way in which these reagents react with alcohols on the basis of the initial reaction (C-H or O-H addition) and the cleavage mode of the metal-oxygen or metal-carbon bond (homolytic or heterolytic).The approach provides a framework for understanding these reactions that is less chaotic than the current situation where distinctive mechanisms have been proposed for each individual oxidant.

N-(1-ARYL-2,2,2-TRIHALOGENOETHYL)CARBOXAMIDES

The readily obtained products from the condensation of trihalogenoacetaldehydes with carboxamides react with benzene and its homologs in the presence of concentrated sulfuric acid with the formation of N-(1-aryl-2,2,2-trihalogenoethyl)carboxamides.The latter were used for the production of 1-aryl-2,2,2-trihalogenoethylamines and 1-acylimino-1-aryl-2,2,2-trihalogenoethanes.