124755-19-7

Basic information

• Product Name: 6-tert-butyl-2-(hydroxy-tert-butyl)-4-methylene-2,5-cyclohedanedienone
• Synonyms: 6-tert-butyl-2-(hydroxy-tert-butyl)-4-methylene-2,5-cyclohedanedienone;QM-OH;6-TERT-BUTYL-2-(HYDROXY-TERT-BUTYL)-4-METHYLENE-2,5-CYCLOHEXADIENONE
• CAS NO: 124755-19-7
• Molecular Formula: C₁₅H₂₂O₂
• Molecular Weight: 234.33
• Mol File: 124755-19-7.mol

Chemical Properties

• Boiling Point: 353.3°Cat760mmHg
• Flash Point: 150.6°C
• Appearance: /
• Density: 1g/cm³
• Vapor Pressure: 2.11E-06mmHg at 25°C
• Refractive Index: 1.509
• PKA: 14.73±0.10(Predicted)
• CAS DataBase Reference: 6-tert-butyl-2-(hydroxy-tert-butyl)-4-methylene-2,5-cyclohedanedienone(CAS DataBase Reference)
• NIST Chemistry Reference: 6-tert-butyl-2-(hydroxy-tert-butyl)-4-methylene-2,5-cyclohedanedienone(124755-19-7)
• EPA Substance Registry System: 6-tert-butyl-2-(hydroxy-tert-butyl)-4-methylene-2,5-cyclohedanedienone(124755-19-7)

Safety Data

• Hazardous Substances Data: 124755-19-7(Hazardous Substances Data)

Usage

InChI:InChI=1/C15H22O2/c1-10-7-11(14(2,3)4)13(17)12(8-10)15(5,6)9-16/h7-8,16H,1,9H2,2-6H3

Upstream product

• 112700-14-8 6-tert-butyl-2-(2'-hydroxy-1',1'-dimethylethyl)-4-methylphenol 

Relevant articles and documents

Alkylation of 2'-deoxynucleosides and DNA by quinone methides derived from 2,6-Di-tert-butyl-4-methylphenol

4-Alkylphenols, such as the antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT), exhibit toxicities that appear to be mediated by their oxidative metabolism to electrophilic quinone methides. Reactions of these Michael acceptors with simple nucleophiles and proteins have been reported, but little information is available on quinone methide binding to the competing nucleophilic sites in DNA. In the present investigation, 2'-deoxynucleoside adducts generated in vitro with two BHT-derived quinone methides, 2,6-di- tert-butyl-4-methylenecyclohexa-2,5-dienone and 6-tert-butyl-2-(2'-hydroxy- 1',1'-dimethylethyl)-4-methylenecyclohexa-2,5-dienone (BHTOH-QM) were isolated and identified. Both quinone methides produced adducts at the 1- and N2-positions of deoxyguanosine (dG) and the N6-position of deoxyadenosine (dA). In addition, a labile adduct formed at the 7-position of dG, which degraded to the corresponding 7-alkylguanine derivative. Additional work was conducted with BHTOH-QM, the more reactive of the two quinone methides. This species also formed stable adducts at the N4-position of deoxycytosine (dC) and the 3-position of thymidine and formed a labile adduct at the 3-position of dC that underwent hydrolytic cleavage to regenerate dC. In mixtures of deoxynucleosides treated with [14C]BHTOH-QM, alkylation occurred primarily at the N2- and 7-positions of dG and the N6-position of dA and occurred secondarily at the 1-position of dG. Treatment of calf thymus DNA with this quinone methide yielded N6-dA and N2-dG adducts with the former predominating. The unstable 7-dG adduct was detected by analysis of the 7- alkylguanine product from depurination. These results demonstrate that quinone methides are most likely to damage DNA through alkylation of the exocyclic amino groups of purine residues and possibly also by attack at the 7-position of dG followed by depurination.

Lung toxicity and tumor promotion by hydroxylated derivatives of 2,6-di-tert-butyl-4-methylphenol (BHT) and 2-tert-butyl-4-methyl-6-iso-propylphenol: correlation with quinone methide reactivity.

Acute pulmonary toxicity and tumor promotion by the food additive 2,6-di-tert-butyl-4-methylphenol (BHT) in mice are well documented. These effects have been attributed to either of two quinone methides, 2,6-di-tert-butyl-4-methylenecyclohexa-2,5-dienone (BHT-QM) formed through direct oxidation of BHT by pulmonary cytochrome P450 or a quinone methide formed by hydroxylation of a tert-butyl group of BHT (to form BHTOH) followed by oxidation of this metabolite to BHTOH-QM. BHTOH-QM is a more reactive electrophile compared to BHT-QM due to intramolecular interactions of the side-chain hydroxyl with the carbonyl oxygen. To further examine this bioactivation pathway, an analogue of BHTOH was prepared, 2-tert-butyl-6-(1'-hydroxy-1'-methyl)ethyl-4-methylphenol (BPPOH), that is structurally very similar to BHTOH but forms a quinone methide (BPPOH-QM) capable of more efficient intramolecular hydrogen bonding and, therefore, higher electrophilicity than BHTOH-QM. BPPOH-QM was synthesized and its reactivity with water, methanol, and glutathione determined to be >10-fold higher than that of BHTOH-QM. The conversions of BPPOH and BHTOH to quinone methides in lung microsomes from male BALB/cByJ mice were quantitatively similar, but in vivo the former was pneumotoxic at one-half of the dose required for the latter and one-eighth of the dose required for BHT, as determined by increased lung weight:body weight ratios following a single i.p. injection. Similar differences were found in the doses of BHT, BHTOH, or BPPOH required for tumor promotion after a single initiating dose of 3-methylcholanthrene followed by three weekly injections of the phenol. The downregulaton of calpain II, previously shown to accompany lung tumor promotion by BHT and BHTOH, also occurred with BPPOH. The correlation between biologic activities of these phenols and the reactivities of their corresponding quinone methides provides additional support for the role of BHTOH-QM as the principal metabolite responsible for the effects of BHT on mouse lung.