456-06-4

Basic information

• Product Name: 4-Fluorobenzhydrazide
• Synonyms: ASISCHEM R36621;BUTTPARK 35\03-73;4-FLUOROBENZENECARBOHYDRAZIDE;4-FLUOROBENZOYLHYDRAZINE HYDRATE;4-FLUOROBENZHYDRAZIDE;4-FLUOROBENZOHYDRAZIDE HYDRATE;4-FLUOROBENZOIC HYDRAZIDE;4-FLUOROBENZOIC HYDRAZIDE HYDRATE
• CAS NO: 456-06-4
• Molecular Formula: C₇H₇FN₂O
• Molecular Weight: 154.14
• EINECS: 207-258-5
• Product Categories: Fluorobenzene;Phenyls & Phenyl-Het;Benzenes;Fluorine Compounds;Phenyls & Phenyl-Het;Carbonyl Compounds;Hydrazides;Organic Building Blocks
• Mol File: 456-06-4.mol

Chemical Properties

• Melting Point: 162-166 °C(lit.)
• Boiling Point: 299.8 °C at 760 mmHg
• Flash Point: 135.1 °C
• Appearance: Orange to light brown/Crystalline Powder
• Density: 1.272 g/cm³
• Vapor Pressure: 0.392mmHg at 25°C
• Refractive Index: 1.524
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: Soluble in methanol.
• PKA: 12.17±0.10(Predicted)
• CAS DataBase Reference: 4-Fluorobenzhydrazide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Fluorobenzhydrazide(456-06-4)
• EPA Substance Registry System: 4-Fluorobenzhydrazide(456-06-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: DH1310000
• HazardClass: IRRITANT
• Hazardous Substances Data: 456-06-4(Hazardous Substances Data)

Usage

Uses

Used in the Synthesis of Fluorinated Polymers:
4-Fluorobenzhydrazide is used as a key intermediate in the synthesis of fluorinated poly(1,3,4-oxadiazole-ether-imide). This polymer is a high-performance material with excellent thermal stability, mechanical properties, and chemical resistance, making it suitable for various applications, such as aerospace, automotive, and electronics industries.
In the synthesis process, 4-Fluorobenzhydrazide serves as a solvent for the reaction between N-(3,5-dinitrobenzoyl)-N'-(4-fluorobenzoyl)-hydrazine and itself in N-methyl-2-pyrrolidone (NMP). This reaction leads to the formation of the desired fluorinated poly(1,3,4-oxadiazole-ether-imide), which exhibits improved properties compared to non-fluorinated counterparts.
While the provided materials do not explicitly mention other applications, 4-Fluorobenzhydrazide may also have potential uses in the pharmaceutical industry, given its structural similarity to other hydrazide compounds that have been studied for their biological activities. Further research and development could reveal additional applications for this versatile compound.

preparation

The synthesized ester (12.5ml) was taken into a round ?bottom flask (250ml), 50ml of absolute ethanol & ?37.5ml of hydrazine hydrate was added in the flask. ?The ester, ethanol & hydrazine hydrate for the synthesis of hydrazide must be in following ratio: Ester: Absolute ethanol: Hydrazine hydrate 1 : 4 : 3 ?Then round bottom flask was covered with aluminium ?foil, placed on hot plate & allowed to stir it for almost ?12-15 hrs. As the solid product appeared, reaction ?completion was checked by performing TLC using n-hexane, ethyl acetate & TLC cards & observed under ?UV lamp. After completion of reaction n-hexane was added. ?Solution filtered as needle like crystals appeared. ?Allowed it to dry & a shiny off white product was ?obtained that was hydrazide & product was calculated ?(79%).

InChI:InChI=1/C7H5Cl2F/c8-7(9)5-1-3-6(10)4-2-5/h1-4,7H

Upstream product

• 451-46-7 4-fluorobenzoic acid ethyl ester 
• 403-33-8 methyl 4-flurobenzoate 
• 2714-90-1 phenyl 4-fluorobenzoate 
• 403-43-0 4-fluorobenzoyl chloride 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 90172-63-7 1-(p-fluorophenylcarbonyl)imidazole 
• 459-57-4 4-fluorobenzaldehyde 
• 403-42-9 1-(4-fluorophenyl)ethanone 
• 456-22-4 4-Fluorobenzoic acid 

Downstream Products

• 16113-34-1 1-(4-Fluor-benzoylhydrazono)-1-(5-fluor-2-hydroxy-phenyl)-ethan 
• 16113-35-2 1-(4-Fluor-benzoylhydrazono)-1-(5-fluor-2-hydroxy-phenyl)-propan 
• 16113-36-3 1-(4-Fluor-benzoylhydrazono)-1-(5-fluor-2-hydroxy-phenyl)-butan 
• 84919-26-6 4-Fluoro-benzoic acid [5-methyl-2-oxo-1,2-dihydro-indol-(3Z)-ylidene]-hydrazide 
• 84919-28-8 4-Fluoro-benzoic acid [5-bromo-2-oxo-1,2-dihydro-indol-(3Z)-ylidene]-hydrazide 
• 84919-25-5 N’-(2-oxo-1,2-dihydro-indol-3-ylidene)-4-fluorobenzohydrazide 
• 116114-19-3 4-fluoro-N-[(methylcarbamoyl)amino]benzamide 
• 154106-08-8 1-(4-fluorobenzoyl)-4-methylthiosemicarbazide 
• 41421-13-0 5-(4-fluorophenyl)-2,3-dihydro-1,3,4-oxadiazole-2-thione 
• 41421-13-0 2-mercapto-5-(4-fluorophenyl)-1,3,4-oxadiazole 
• 29527-12-6 1-(4-fluorobenzoyl)-4-ethylthiosemicarbazide 
• 205806-25-3 C₁₁H₁₄FN₃OS 
• 205806-29-7 C₁₄H₁₂FN₃OS 
• 831-38-9 2-(4-fluorobenzoyl)hydrazinecarbothioamide 

Relevant articles and documents

Synthesis, spectral analysis, antibacterial, antifungal, antioxidant and hemolytic activity studies of some new 2,5-disubstituted-1,3,4-oxadiazoles

Series of 1,3,4-oxadiazole derivatives (5a–5g and 5h, 5i) were synthesized and characterized by FT-IR, 1H NMR, 13C NMR and HR-MS spectral analysis. All the target compounds were screened for their in vitro antibacterial activity against two Gram-negative bacterial strains namely Escherichia coli (MTCC 405) and Salmonella typhi (MTCC 3224) and two Gram-positive bacterial strains namely Bacillus subtilis (MTCC 1790) and Bacillus megaterium (MTCC 1684) and antifungal activity against Aspergillus niger (MTCC 282), Rhizopus oryzae (MTCC 262), Penicillium chrysogenum (MTCC 974), and Candida albicans (MTCC 183) fungal strains. The synthesized compounds exhibited significant antibacterial and antifungal potential. Three compounds (5e, 5f and 5g) have shown higher antibacterial activity with very low MIC values comparable to streptomycin. According to the SAR study, the antibacterial efficacy can be intensified by substituting fluoro and methyl substituents at the para position in acid hydrazide. The synthesized compounds were also screened for % radical scavenging activity by OH and DPPH assay and found to be good antioxidant agents. Besides, the hemolytic study revealed that the synthesized 1,3,4-oxadiazoles possessed negligible cytotoxicity compared with the standard.

N-Amino-1,8-Naphthalimide is a Regenerated Protecting Group for Selective Synthesis of Mono-N-Substituted Hydrazines and Hydrazides

A new route to synthesis of various mono-N-substituted hydrazines and hydrazides by involving in a new C?N bond formation by using N-amino-1,8-naphthalimide as a regenerated precursor was invented. Aniline and phenylhydrazines are reproduced upon reacting these individually with 1,8-naphthalic anhydride followed by hydrazinolysis. The practicality and simplicity of this C?N dihalo alkanes; developed a synthon for bond formation protocol was exemplified to various hydrazines and hydrazides. N-amino-1,8-naphthalimide is suitable synthon for transformation for selective formation of mono-substituted hydrazine and hydrazide derivatives. Those are selective mono-amidation of hydrazine with acid halides; mono-N-substituted hydrazones from aldehydes; synthesis of N-aminoazacycloalkanes from acetohydrazide scaffold and inserted to hydroxy derivatives; distinct synthesis of N,N-dibenzylhydrazines and N-benzylhydrazines from benzyl halides; synthesis of N-amino-amino acids from α-halo esters. Ecofriendly reagent N-amino-1,8-naphthalimide was regenerated with good yields by the hydrazinolysis in all procedures.

Design, Synthesis, and Study of the Insecticidal Activity of Novel Steroidal 1,3,4-Oxadiazoles

A series of novel steroidal derivatives with a substituted 1,3,4-oxadiazole structure was designed and synthesized, and the target compounds were evaluated for their insecticidal activity against five aphid species. Most of the tested compounds exhibited potent insecticidal activity against Eriosoma lanigerum (Hausmann), Myzus persicae, and Aphis citricola. Compounds 20g and 24g displayed the highest activity against E. lanigerum, showing LC50 values of 27.6 and 30.4 μg/mL, respectively. Ultrastructural changes in the midgut cells of E. lanigerum were detected by transmission electron microscopy, indicating that these steroidal oxazole derivatives might exert their insecticidal activity by destroying the mitochondria and nuclear membranes in insect midgut cells. Furthermore, a field trial showed that compound 20g exhibited effects similar to those of the positive controls chlorpyrifos and thiamethoxam against E. lanigerum, reaching a control rate of 89.5% at a dose of 200 μg/mL after 21 days. We also investigated the hydrolysis and metabolism of the target compounds in E. lanigerum by assaying the activities of three insecticide-detoxifying enzymes. Compound 20g at 50 μg/mL exhibited inhibitory action on carboxylesterase similar to the known inhibitor triphenyl phosphate. The above results demonstrate the potential of these steroidal oxazole derivatives to be developed as novel pesticides.

Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof

The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.

Oxazole ring-containing honokiol thioether derivative and preparation method and application thereof

The invention discloses an oxazole ring-containing honokiol thioether derivative, a preparation method thereof and application of the oxazole ring-containing honokiol thioether derivative as an alpha-glucosidase inhibitor, the chemical structure of the oxazole ring-containing honokiol thioether derivative is shown as a general formula (I), and R is selected from non-substituted or substituted phenyl. Compared with the prior art, the invention provides the novel honokiol thioether derivative containing the oxazole ring, and the honokiol thioether derivative containing the oxazole ring has good inhibitory activity on alpha-glucosidase, provides more possibilities for treating diabetes, and is expected to be used for preparing novel candidate drug molecules for treating diabetes. In addition, the preparation process is simple, the cost is low, and the yield is high.

Phosphine-free ruthenium complex-catalyzed synthesis of mono- Or dialkylated acyl hydrazides via the borrowing hydrogen strategy

Herein, we report a diaminocyclopentadienone ruthenium tricarbonyl complex-catalyzed synthesis of mono- or dialkylated acyl hydrazide compounds using the borrowing hydrogen strategy in the presence of various substituted primary and secondary alcohols as alkylating reagents. Deuterium labeling experiments confirm that the alcohols were the hydride source in this cascade process. Density functional theory (DFT) calculations unveil the origin and the threshold between the mono- and dialkylation.

Antibacterial and Antiviral Activities of 1,3,4-Oxadiazole Thioether 4H-Chromen-4-one Derivatives

Various 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives were conceived. The title compounds demonstrated striking inhibitory effects againstXac,Psa, andXoo. EC50data exhibited that A8 (19.7 μg/mL) had better antibacterial activity againstXoothan myricetin, BT, and TC. Simultaneously, the mechanism of action of A8 had been verified by SEM. The results of anti-tobacco mosaic virus indicated that A9 had the bestin vivoantiviral effect compared with ningnanmycin. From the data of MST, it could be seen that A9 (0.003 ± 0.001 μmol/L) exhibited a strong binding capacity, which was far superior to ningnanmycin (2.726 ± 1.301 μmol/L). This study shows that the 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives may become agricultural drugs with great potential.

Ruthenium-Catalyzed Three-Component Alkylation: A Tandem Approach to the Synthesis of Nonsymmetric N,N-Dialkyl Acyl Hydrazides with Alcohols

The borrowing hydrogen strategy has been applied in the synthesis of nonsymmetric N,N-dialkylated acyl hydrazides via a tandem three-component reaction catalyzed by a phosphine free diaminocyclopentadienone ruthenium tricarbonyl complex. This strategy represents the first direct one-pot approach to nonsymmetric functionalized acyl hydrazides. Different aromatic acyl hydrazides underwent dialkylation with a variety of primary or secondary alcohols and methanol or ethanol as alkylating agents in mild reaction conditions and good yields. Deuterium labelling experiments suggested that the primary or secondary alcohol was the hydrogen source in this tandem process. DFT calculations show that the combination of the tandem mixed product cannot be perfectly explained neither structurally nor electronically, but might be dependent of the physical state of the aldehyde or ketone intermediate (gaz vs. liquid) at the reaction temperature. (Figure presented.).

Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker

A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85–110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log10 CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔGb = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.

Synthesis and biological evaluation of honokiol derivatives bearing 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3h)-ones as potential viral entry inhibitors against sars-cov-2

The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from Magnoliae officinalis Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, 6a and 6p demonstrated antiviral entry effect with IC50 values of 29.23 and 9.82 μM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC50 value more than 50 μM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that 6p binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of 6p on SARS-CoV-2 spike RBD’s binding with ACE2. Importantly, 6a and 6p (TC50 > 100 μM) also had higher biological safety for host cells than honokiol (TC50 of 48.23 μM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although 6p’s antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.