Thiophenol → 4,4-Dimethyl-7-bromo-1-phenylthio-3,4-dihydronaphthalene

HRID 24557

Reaction equation

HRID 24557 reaction equation
C1C2C(=CC=CC=2)C=CC1.C1(=O)C2C(CC=CC=2)CCC1.[Br:22][C:23]1[CH:32]=[C:31]2[C:26]([C:27]([CH3:35])([CH3:34])[CH2:28][CH2:29][C:30]2=O)=[CH:25][CH:24]=1.[C:36]1([SH:42])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>O1CCCC1.[Ti](Cl)(Cl)(Cl)Cl.C(N(CC)CC)C>[CH3:34][C:27]1([CH3:35])[C:26]2[C:31](=[CH:32][C:23]([Br:22])=[CH:24][CH:25]=2)[C:30]([S:42][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[CH:29][CH2:28]1

Participants

8

Reactant 4

HCID 7969ThiophenolHCID 99381,2-DihydronaphthaleneHCID 107533577-Bromo-4,4-dimethyl-1,2,3,4-tetrahydronaphthalen-1-one2×HCID 14148769Tetrahydronaphthalene-one

Product 1

HCID 158960184,4-Dimethyl-7-bromo-1-phenylthio-3,4-dihydronaphthalene

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

Reaction Scheme 3 provides further examples for the synthesis of compounds within the scope of Formula S where the linking group between the dihydronaphthalene moiety and the Y group is —CH═CH—. In the sequence of reactions described here the oxo function of a starting tetrahydronaphthalene-one moiety is modified before a Heck coupling reaction is performed. Specifically, in the example shown in the reaction scheme, 7-bromo-3,4-dihydro-4,4-dimethylnaphthalen-1(2H)-one (Compound G) is reacted with thiophenol in the presence of titanium tetrachloride and triethylamine in tetrahydrofuran (THF), to provide the intermediate 4,4-dimethyl-7-bromo-1-phenylthio-3,4-dihydronaphthalene (Compound A35). A similar reaction can be performed with ethanethiol as a reagent instead of thiophenol, to yield 2-bromo-5,6-dihydro-5,5-dimethyl-8-ethylthio-naphthalene (Compound A36) and other analogous compounds which are not shown in the reaction scheme. Compound A35 is reacted in the Heck reaction to yield ethyl (E)-4-[2-(5,6-dihydro-5,5-dimethyl-8-phenylthio'naphthalenyl)ethenyl] benzoate (Compound A16). Compound A16 is saponified to yield the carboxylic acid, (E)-4-[2-(5,6-dihydro-5,5-dimethyl-8-(phenylthio)-naphthalen-2-yl)ethenyl] benzoic acid (Compound A18), and is oxidized with m-chloroperoxybenzoic acid (MCPBA) to provide the corresponding phenylsulfonyl compound, ethyl (E)-4-[-2-(5,6-dihydro-5,5-dimethyl-8-(phenylsulfonyl)-naphthalenyl)ethenyl]benzoate (Compound A17). Compound A18 can also be oxidized under similar conditions to provide the free carboxylic acid (or salt thereof) of the phenylsulfonyl compound, (E)-4-[-2-(5,6-dihydro-5,5-dimethyl-8-phenylsulfonyl-naphthalenyl)ethenyl]benzoic acid (Compound A19).

Workup

  1. customReaction Scheme 3
  2. customprovides further examples
  3. customis modified before a Heck coupling reaction

Sources & evidence

ORD record
ord-26c6d571296041708a639572976e5d97
Source dataset
uspto-grants-2005_02
Patent number
US06855832B2

Linked notes

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