1083-27-8

Usage

Uses

Used in Pharmaceutical Industry:
Hexyl 4-Hydroxybenzoate is used as a solubility enhancer and stabilizer in the preparation of Propranolol Hydrochloride cubic liquid crystal gel. This application is particularly important for improving the bioavailability and effectiveness of the drug, as well as ensuring its stability during storage and use.
In the preparation method of Propranolol Hydrochloride cubic liquid crystal gel, Hexyl 4-Hydroxybenzoate plays a crucial role in enhancing the solubility of the active pharmaceutical ingredient, Propranolol Hydrochloride. This allows for the development of a more effective and stable liquid crystal gel formulation, which can be easily applied and absorbed by the skin. The use of Hexyl 4-Hydroxybenzoate in this context demonstrates its potential as a valuable component in the pharmaceutical industry for improving drug delivery and performance.

InChI:InChI=1/C13H18O3/c1-2-3-4-5-10-16-13(15)11-6-8-12(14)9-7-11/h6-9,14H,2-5,10H2,1H3

Synthetic route

4-Hydroxyacetophenone (99-93-4) + hexan-1-ol (111-27-3) → hexyl paraben (1083-27-8)

Conditions	Yield
With iron(III) chloride; ammonium persulfate In tetrachloromethane; 1,2-dichloro-ethane at 120℃; for 15h;	76%

4-hydroxy-benzaldehyde (123-08-0) + 1-(tert-butyldimethylsilyl)oxyhexane (80033-60-9) → hexyl paraben (1083-27-8)

Conditions	Yield
With [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate; Selectfluor In acetonitrile at 20℃; for 7h; Inert atmosphere; Irradiation;	73%

hexan-1-ol (111-27-3) + 4-hydroxy-benzoic acid (99-96-7) → hexyl paraben (1083-27-8)

Conditions	Yield
With dicyclohexyl-carbodiimide In tetrahydrofuran for 20h;	66%
With sulfuric acid In toluene for 4h; Heating;	53.2%
With hydrogenchloride at 150℃;

(E)-1,3-diethyl-2-(hexyltriaz-2-en-1-ylidene)-2,3-dihydro-1H-imidazole + 4-hydroxy-benzoic acid (99-96-7) → n-hexyl 4-(hexyloxy)benzoate (111222-69-6) + hexyl paraben (1083-27-8) + C7H13N3

Conditions	Yield
In methanol; dichloromethane at 20℃; for 4h; Inert atmosphere;	A 12% B 51% C n/a

1-bromo-hexane (111-25-1) + 4-hydroxy-benzoic acid (99-96-7) → para-hexyloxybenzoic acid (1142-39-8) + hexyl paraben (1083-27-8)

Conditions	Yield
With PEG 200; potassium hydroxide at 80℃; for 2h; Title compound not separated from byproducts;	A 83 % Spectr. B 7 % Spectr.
With PEG 200; potassium hydroxide In 1,4-dioxane at 80℃; for 2h; Title compound not separated from byproducts;	A 73 % Spectr. B 11 % Spectr.

1-bromo-hexane (111-25-1) → hexyl paraben (1083-27-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: durch 6-taegiges Kochen 2: hydrogen chloride / 150 °C View Scheme
Multi-step reaction with 2 steps 2: hydrogen chloride / 150 °C View Scheme

1,2,4-tris(4-chloroformylphenyloxycarbonyl)benzene + hexyl paraben (1083-27-8) → C69H66O18 (1194090-79-3)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 5h;	88%
With triethylamine In dichloromethane at 20℃; for 5h;

hexyl paraben (1083-27-8) → hexyl 4-[(aminosulphonyl)oxy]benzoate

Conditions	Yield
With sulphamoyl chloride; sodium hydride In N,N-dimethyl-formamide; toluene for 10h; Heating;	35.4%
Stage #1: hexyl paraben With sodium hydride In N,N-dimethyl-formamide at 0℃; Stage #2: With sulphamoyl chloride In N,N-dimethyl-formamide; toluene
Stage #1: hexyl paraben With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: With sulphamoyl chloride In N,N-dimethyl-formamide; toluene for 10h;

hexyl paraben (1083-27-8) → phosphoric acid tris-(4-hexyloxycarbonyl-phenyl ester)

Conditions	Yield
With trichlorophosphate

hexyl paraben (1083-27-8) + 2-(diethylamino)ethyl chloride (100-35-6) → 4-(2-diethylamino-ethoxy)-benzoic acid hexyl ester

4-iodobenzoic acid (619-58-9) + hexyl paraben (1083-27-8) → 4-(n-Hexyloxycarbonyl)phenyl 4'-iodobenzoate

Conditions	Yield
With dicyclohexyl-carbodiimide; 4-pyrrolidin-1-ylpyridine In diethyl ether Ambient temperature;

hexyl paraben (1083-27-8) + benzyl chloride (100-44-7) → p-Benzyloxybenzoesaeure-n-hexylester (56441-76-0)

Conditions	Yield
With sodium ethanolate

3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-1-decanol (678-39-7) + hexyl paraben (1083-27-8) → 4-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-decyloxy)-benzoic acid hexyl ester

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; Mitsunobu reaction;

(E)-3-(4-methoxyphenyl)propenoyl chloride (34446-64-5, 42996-84-9) + hexyl paraben (1083-27-8) → 4-[(E)-3-(4-Methoxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + trans-p-ethoxycinnamoyl chloride (77251-75-3) → 4-[(E)-3-(4-Ethoxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + (E)-4-propoxycinnamic acid chloride (77251-76-4) → 4-[(E)-3-(4-Propoxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + (E)-4-butoxycinnamic acid chloride (77251-77-5) → 4-[(E)-3-(4-Butoxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + trans-p-pentyloxycinnamoyl chloride (77251-78-6) → 4-[(E)-3-(4-Pentyloxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + trans-hexyloxycinnamoyl chloride (77251-79-7) → 4-[(E)-3-(4-Hexyloxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + trans-p-heptyloxycinnamoyl chloride (77251-80-0) → 4-[(E)-3-(4-Heptyloxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + trans-octyloxycinnamoyl chloride (77251-81-1) → 4-[(E)-3-(4-Octyloxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + trans-decyloxycinnamoyl chloride (77251-82-2) → 4-[(E)-3-(4-Decyloxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + 4-dodecyloxycinnamoyl chloride (77251-83-3) → 4-[(E)-3-(4-Dodecyloxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + 4-n-tetradecyloxycinnamoyl chloride (130286-00-9) → 4-[(E)-3-(4-Tetradecyloxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + 4-hexadecyloxycinnamoyl chloride (77251-84-4) → 4-[(E)-3-(4-Hexadecyloxy-phenyl)-acryloyloxy]-benzoic acid hexyl ester

Conditions	Yield
With pyridine for 0.166667h;

hexyl paraben (1083-27-8) + 1,3-phenylene bis(methyliminobenzoic acid) → C48H48N2O8

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;

hexyl paraben (1083-27-8) → 4'-(n-Hexyloxycarbonyl)phenyl 4''-<(4-(S)-2'-methylbutoxy-2,3,5,6-tetrafluorophenyl)ethynyl>benzoate

Conditions	Yield
Multi-step reaction with 2 steps 1: DCC / 4-pyrrolidinopyridine / diethyl ether / Ambient temperature 2: Et3N / bis(triphenylphosphine)palladium dichloride, copper(I) iodide / Heating View Scheme

sulphur dichloride + zinc chloride anhydrate + hexyl paraben (1083-27-8) → 3,3'-thiobis(hexyl p-hydroxybenzoate) (107490-77-7)

Conditions	Yield
In chloroform

hexyl paraben (1083-27-8) + 4,5-dichlorophthalonitrile (139152-08-2) → 4,5-bis[(4-hexyloxycarbonyl)phenoxy]phthalonitrile

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 65℃; for 24h;	2.2 g

Upstream product

• 111-25-1 1-bromo-hexane 
• 99-96-7 4-hydroxy-benzoic acid 
• 99-93-4 4-Hydroxyacetophenone 
• 111-27-3 hexan-1-ol 
• 123-08-0 4-hydroxy-benzaldehyde 
• 80033-60-9 tert-butyldimethyl(n-hexyloxy)silane 

Downstream Products

• 107490-77-7 3,3'-thiobis(hexyl p-hydroxybenzoate) 
• 1194090-79-3 C₆₉H₆₆O₁₈ 
• 56441-76-0 p-Benzyloxybenzoesaeure-n-hexylester 

Relevant academic research and scientific papers

Inhibition of estrone sulfatase (ES) by alkyl and cycloalkyl ester derivatives of 4-[(aminosulfonyl)oxy] benzoic acid

In our search for potent inhibitors of the enzyme estrone sulfatase (ES), we have undertaken the synthesis and biochemical evaluation of a range of esters of 4-[(aminosulfonyl)oxy] benzoic acid. The results of the study show that the synthesised compounds possess potent inhibitory activity, indeed the cyclooctyl derivative was found to be more potent than 667-COUMATE, which is currently undergoing clinical trials.

Synthesis and biochemical evaluation of some novel benzoic acid based esters as potential inhibitors of oestrone sulphatase

Oestrone sulphatase is an important target in the fight against hormone-dependent breast cancer. In an effort to investigate the reported definitive pharmacophore for oestrone sulphatase and continue our search for potent inhibitors of this enzyme, we have undertaken extensive synthesis, biochemical evaluation and physicochemical property determination of a range of benzoic acid based esters. Here, we report the initial results of our study into a series of straight chain alkyl esters of 4-sulphonylbenzoic acid. Using these compounds, we have investigated the involvement of two physicochemical properties, namely logP and pKa. The results of this study show that there was a strong correlation between the inhibitory activity and the logP of the parent compound. Within the series of compounds studied, hydrophobicity appears to be a more important factor than pKa in determining the overall inhibitory activity. In a previous report, we showed that pKa plays an important role in stabilizing the phenoxide ion resulting from the hydrolysis of the sulphamate group. Here, we propose that although pKa is an important factor in determining the overall inhibitory activity when a wide range of compounds are considered, both hydrophobicity and pKa need to be considered in the design of potential inhibitors of oestrone sulphatase.

Iron-catalyzed C[sbnd]C bond activation/C[sbnd]O bond formation: Direct conversion of ketones to esters

The iron-catalyzed oxidative activation of the (O)C[sbnd]C bond in ketones has been developed. This method enables direct synthesis of esters by the reaction between ketones and alcohols via conversion of the (O)C[sbnd]C bond to the (O)C[sbnd]O bond. The

Inhibition of estrone sulfatase (ES) by derivatives of 4-[(aminosulfonyl)oxy] benzoic acid

In our search for potent inhibitors of the enzyme estrone sulfatase (ES), we have undertaken the synthesis and biochemical evaluation of a range of straight chain alkyl esters of 4-[(aminosulfonyl)oxy] benzoic acid. The results of the study show that the synthesised compounds possess greater inhibitory activity when compared to COUMATE, although they were all found to possess lower inhibitory activity with respect to EMATE. Furthermore, the data suggest a strong correlation between logP and IC50 and therefore adds further support to our previous report where we suggested a link between inhibitory activity and hydrophobicity.

Insect repellents (by machine translation)

[Problem] excellent safety, provides effective insect repellent insect repellent. (1) Formula [solution]4 - Hydroxybenzoic acid hexyl represented comprises an insect repellent. [Drawing] no (by machine translation)

Single-Step Dual Functionalization: One-Pot Bromination-Cross-Dehydrogenative Esterification of Hydroxy Benzaldehydes with CCl 3 Br - A Comparison with Selectfluor

Bromination of phenolic compounds without directly using molecular bromine possesses much importance. In this article an Ir III /CCl 3 Br-assisted single-step double functionalization of hydroxy benzaldehydes is reported. It involves simultaneous esterification of the aldehyde group and bromination of the aryl ring of phenolic aldehydes in one-pot. The reaction proceeds under mild conditions in the presence of 445 nm blue LED light to obtain highly functionalized bromo hydroxy benzoates in moderate to good yields. In comparison, Selectfluor as an oxidant gives only non-bromo phenolic esters.

METHOD FOR PRODUCING HEXYL 4-HYDROXYBENZOATE

PROBLEM TO BE SOLVED: To provide a production method that makes it possible to obtain hexyl 4-hydroxybenzoate with excellent productivity, reduced by-products, and high yield, and a production method that makes it possible to obtain high-purity hexyl 4-hydroxybenzoate. SOLUTION: The present invention provides a method for producing hexyl 4-hydroxybenzoate represented by formula (1), including the step of making a reaction occur between hexyl 4-hydroxybenzoate of 1 molar equivalent and 1-hexanol of 0.8-3.0 molar equivalents in the presence of an acid catalyst. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

Hexyl triazabutadiene as a potent alkylating agent

Alkyl diazonium ions are among the most reactive alkylating agents in the synthetic chemists’ arsenal. That said, there are precious few methods by which one can selectively and safely utilize this chemistry. Herein, we show the use of a bench stable hexyl triazabutadiene as a source of reactive diazonium ions that undergo substitution chemistry with weak nucleophiles, such as carboxylates and even sulfonates. In the absence of a nucleophile, elimination was observed to occur. To overcome issues stemming from side-product inhibition of the reaction, we show that the triazabutadiene can be pre-activated with tosyl isocyanate.

Dipole architecture of molecules and mesomorphic behavior of liquid crystals with rigid T-shaped mesogenic fragment

A number of liquid crystalline polyesters having a rigid T-shaped mesogenic fragment and differing in dipole architecture were synthesized and examined by polarizing optical microscopy, differential scanning calorimetry, and IR and 1H NMR spectroscopy. The thermal stability of the mesophase in the given series of compounds was shown to increase with extension of arms in the T-shaped mesogenic fragment, as well as on replacement of the terminal ester groups (COOAlk) therein by ether moieties (OAlk). Such replacement also enhances smectogenic properties.

Molecular design of antifungal agents

In a rational approach to the design of antifungal agents against Saccharomyces cerevisiae, a series of alkyl gallates (3,4,5-trihydroxybenzoates) were synthesized and assayed. Nonyl gallate (1) was found to be the most effective with a minimum fungicidal concentration (MFC) of 12.5 μg/mL (42 μM), followed by octyl gallate (2) with an MFC of 25 μg/mL (89 μM). These MFCs are little influenced by pH values. A time-kill curve study indicates that nonyl gallate exhibits fungicidal activity against S. cerevisiae at any growing stage. The antifungal activity of nonyl gallate is due primarily to its ability to act as a nonionic surface-active agent (surfactant). The length of the alkyl group is not a major contributor but plays a role in eliciting the activity to a large extent. As far as alkyl gallates are concerned, their antimicrobial spectra and potency depend largely on the hydrophobic portion of the molecules.