2161-90-2

Usage

Uses

Used in Pharmaceutical Synthesis:
1-Methoxy-1,3-cyclohexadiene is used as a key intermediate in the synthesis of tetracyclic polyhydroxyquinones, which are important for the development of novel pharmaceutical compounds with potential therapeutic applications.
Used in Organic Synthesis:
1-Methoxy-1,3-cyclohexadiene is used as a reactant in the synthesis of tetra-ortho-substituted biaryls via Diels-Alder reactions. These biaryl compounds are valuable building blocks in organic chemistry and can be utilized in the creation of various complex organic molecules.
Used in Natural Product Synthesis:
In the field of natural product synthesis, 1-Methoxy-1,3-cyclohexadiene is used as a precursor for the synthesis of optically active forms of specific compounds, such as the dihydroisocoumarin fragment of the gastroprotective natural product AI-77-B. This is achieved through a regiospecific Diels-Alder reaction with an acetylenic ester derivative, showcasing its utility in the development of bioactive natural products.
Overall, 1-Methoxy-1,3-cyclohexadiene is a significant compound in various chemical and pharmaceutical applications, particularly in the synthesis of complex organic molecules and the development of new pharmaceutical agents.

Synthesis Reference(s)

Tetrahedron Letters, 13, p. 4195, 1972 DOI: 10.1016/S0040-4039(01)94273-X

InChI:InChI=1/C7H10O/c1-8-7-5-3-2-4-6-7/h2-3,5H,4,6H2,1H3

Upstream product

• 2886-59-1 1-methoxycyclohexa-1,4-diene 
• 30979-68-1 2-methoxy-1,3-cyclohexadiene 
• 1728-18-3 dimethylacetal of cyclohexenone 
• 60-29-7 diethyl ether 
• 7664-41-7 ammonia 
• 100-66-3 methoxybenzene 
• 75-04-7 ethylamine 
• 930-68-7 cyclohexenone 

Downstream Products

• 931-57-7 1-methoxy-cyclohex-1-ene 
• 56051-94-6 4-(2-oxopropyl)-2-cyclohexen-1-one 
• 33553-25-2 2-(2-oxopropyl)cyclohex-2-en-1-one 
• 24673-17-4 1-methoxy-3-phenyl-2-oxa-3-azabicyclo[2.2.2]oct-5-ene 
• 109770-48-1 (1R,4S,6S)-6-(3,4-Dimethoxy-phenyl)-1-methoxy-bicyclo[2.2.2]oct-2-ene 
• 109770-48-1 (1R,4S,6R)-6-(3,4-Dimethoxy-phenyl)-1-methoxy-bicyclo[2.2.2]oct-2-ene 
• 58785-57-2 1,4,4a,8a-tetrahydro-1,7-dimethoxy-1,4-ethanonaphthalene-5,8-dione 
• 3300-25-2 8-O-methylchrysophanol 
• 76695-93-7 1-hydroxy-5-methoxy-3-methyl-9,10 dihydroanthracene 9,10-dione 
• 94371-37-6 (1R,6R)-6-Benzenesulfonyl-1-methoxy-5-methylene-bicyclo[2.2.2]oct-2-ene 
• 94371-37-6 (1R,6S)-6-Benzenesulfonyl-1-methoxy-5-methylene-bicyclo[2.2.2]oct-2-ene 
• 144079-72-1 1-Methoxy-3-exo-(p-toluenesulfonyl)bicyclo<2.2.2>oct-5-ene-2-endo-carbaldehyde 
• 144079-72-1 1-Methoxy-3-endo-(p-toluenesulfonyl)bicyclo<2.2.2>oct-5-ene-2-exo-carbaldehyde 
• 74827-79-5 1,4,4a,9,9a,10-hexahydro-8-hydroxy-1-methoxy-9,10-dioxo-1,4-ethanoanthracen-5-yl(4-nitrophenyl)methyl carbonate 

Relevant academic research and scientific papers

Hetero-diels-alder reaction of ethyl 2-nitrosoacrylate and cyclohexadienes, and bromine induced diene isomerization

Bicyclic 8a-methoxy-1,2-oxazine (3a) and bicyclic 7-methoxy-1,2-oxazine (3b) were prepared via Hetero-Diels-Alder reaction between 1-methoxy-1,4-cyclohexadiene (2a) and ethyl 2-nitrosoacrylate generated in situ from ethyl bromopyruvate oxime (1). The formation of 3b was ascribed to bromine, released from 1, which induced transformation of 2a to 1-methoxy-1,3-cyclohexadiene (2b). 3b could be easily transformed to oxazinone (3c) in CHCl3, or other organic solvents in the presence of a trace amount of acid.{A figure is presented}.

Preparation of 1-Alkoxy-1,3-cyclohexadienes via Iron Complexation/Decomplexation

A synthetic method for the preparation of 1-alkoxy-1,3-cyclohexadienes is presented. Iron complexation/decomplexation is used to produce and purify the desired compound without contamination of isomeric by products.

Reductions with lithium in low molecular weight amines and ethylenediamine

Reductions of several types of compounds with lithium and ethylenediamine using low molecular weight amines as solvent are described. In all cases 1 mol of ethylenediamine or N,N'-dimethylethylenediamine per gram-atom of lithium was used. In some cases it was beneficial to add an alcohol as a proton donor. These reaction conditions were applied to the debenzylation of N-benzylamide and lactams which are refractory to hydrogenolysis with hydrogen and a catalyst. N-Benzylpilolactam 2, synthesized from pilocarpine hydrochloride in refluxing benzylamine, was debenzylated in good yield using 10 gram-atoms of lithium per mole (10 Li/mol) of 2 in n-propylamine. The debenzylation of N-benzyl-N-methyldecanoic acid amide, 4 (6 Li/mol), in t-butylamine/N,N'-dimethylethylenediamine gave N-methyldecanoic acid amide 6 in 70% yield. Alternatively, reduction of 4 (7 Li/mol) in t-butanol/n-propylamine/ethylenediamine gave n-decanal 12 in 36% yield. Using the same conditions, thioanisole, 1-adamantane-p-toluenesulfonamide, and 1-adamantane methyl p-toluenesulfonate were reduced with 3, 7, and 7.2 Li/mol of compound to give thiophenol (74%), adamantamine (91%), and 1-adamantane methanol (75%), respectively. In this solvent system naphthalene and 3-methyl-2-cyclohexene-1-one were reduced to isotetralin (74%) and 3-methyl cyclohexanone (quantitative) with 5 and 2.2 Li/mol of starting compound, respectively. Oximes and O-methyloximes were reduced to their corresponding amines using 5 and 8 Li/mol of compound, respectively. Anisole was also reduced to 1-methoxy-1,4-cyclohexadiene with 2.5 Li/mol of anisole. Undecanenitrile was reduced to undecylamine with 8.6 Li/mol. Additionally, a base-catalyzed formation of imidazolines from a nitrile and ethylenediamine was also explored.

Olefin Radical Cation Cycloadditions

Radical-cation cyclodimerizations of electron-rich cyclic 1,3-dienes and radical-cation Diels-Alder reactions of these dienes with several electron-rich olefins have been investigated.In some cases the efficiency of the electron transfer could be increased if the electron acceptors were combined with LiClO4 (special salt effect).The dimerization of 1,3-cyclohexadiene (7a) , as well as 1-acetoxy- and 1-methoxy-1,3-cyclohexadiene (7b, 7c) with several electron acceptors yielded endo-selectively the Diels-Alder dimers.The formation of the Diels-Alder products via radical-ion intermediates could be demonstrated by quenching experiments.In addition, cyclobutane dimers were also formed, mostly through triplet-reaction channels., Only in the case of 1-acetoxy-1,3-cyclohexadiene (7b) photochemically induced electron transfer is involved as well, as shown by quenching experiments.Some of these Diels-Alder dimerizations are indicated by a characteristic concentration dependence, i.e. the endo dimers were preferably formed at low diene concentrations, whereas high diene concentrations favored the exo adducts.In the reaction sensitized by 1,4-dicyanonaphthalene (2) these concentration effects could be emphasized by differently strong quenching of the different products.Concentration and quenching effects indicate the involvement of different radical-ion intermediates.Crossed Diels-Alder reactions usually ran endo-selectively.Here, quenching of product formation with 1,2,4-trimethoxybenzene (TMB) indicated the involvement of radical intermediates as well.

Thermodynamics of Vinyl Ethers. 31. Isomer Equilibria in Some Six- and Seven-Membered Cyclic Dienes

The relative thermodynamic stabilities of 1,3-cyclohexadiene and 1,4-cyclohexadiene, together with a number of their alkoxy and other derivatives and some related seven-membered cyclic dienes, have been determined by chemical equilibration in Me2SO and cyclohexane solution at various temperatures.The values of the thermodynamic parameters ΣG, ΔH, and ΔS for the isomerization processes involved are discussed and show clearly that the apparently conjugated diene system of 1,3-cyclohexadiene is devoid of conjugation, contrary to that of 1,3-cycloheptadiene.

Two New Syntheses of the Pyranojuglone Pigment α-Caryopterone

By a simple process, 3-methoxyjuglone ( = 8-hydroxy-2-methoxy-1,4-naphthoquinone; 9) has been synthesized from 1,2,4-trimethoxybenzene (5) and converted, after prenylation, to α-caryopterone (1; Scheme 1), a pyranojuglone pigment from Caryopteris clandonensis.On the other hand, juglone ( = 5-hydroxy-1,4-naphthoquinone; 12) was regioselectively prenylated at C(2) via its 1-methoxy-cyclohexa-1,3-diene adduct 15 (Scheme 2).The 2-prenyljuglone (4) thus formed led to 1 after oxidation and other reactions.

Synthesis of daunomycinone and the derivatives thereof

Regio- and stereospecific method for the preparation of daunomycinone and derivatives thereof utilizing the p-nitrobenzyloxy carbonyl group as a blocking group.

Strategic Synthesis based on Cyclohexadienes: Preparation of 2-, 2,3- and 2,4-Substituted Cyclohexenones; Synthesis of (Z)-Heneicosa-6-en-11-one

The mesomeric anions, generated from 1-methoxycyclohexa-1,4-diene, 1-methoxy-5-methylcyclohexa-1,4-diene, and 1-methoxy-4-methylcyclohexa-1,4-diene with potassium amide in liquid ammonia, have been readily alkylated and the resulting dienes were hydrolysed to yield 2-alkyl-, 2,3-dialkyl- and 2,4-dialkyl-cyclohex-2-enones in good yield.Arylation of the above mesomeric anions followed by hydrolysis afforded 2-arylcyclohex-2-enones in addition to substituted biphenyls.A new and efficient synthesis of the male sex attractant of the Douglas Fir Tussock Moth, (Z)-heneicosa-6-en-11-one is described using the above methodology.