Tetrahydrobenzoic acid

It is therefore orf/io-valeryl-.J -tetrahydrobenzoic acid. The anhydride is formed by the elimination of a molecule of water from the two side chains. 

Tetrahydrobenzoic Acid. This material, also known as 3-cyclohex-ene-l-carboxylic acid, has been evaluated in numerous screening tests... 

Ethyl-2-thenoyl)-3,4,5,6-tetrahydrobenzoic acid (69) gave 4-(5-ethylthien-2-yl)-5,6,7,8-tetrahydro-l(2fl)-phthalazinone (70) (H2NNH2 H2O, EtOH,... 

Diethoxybenzoyl)-l,2,3,6-tetrahydrobenzoic acid (83) with p-hydrazino-benzoic acid gave 2-p-carboxyphenyl-4-(3,4-diethoxyphenyl)-4a,5,8,8a-tetra-... 

Dihalo- and dinitropyromellitic acids undergo cyclization when reacted with sulfur tetrafluoride and hydrogen fluoride to give high yields of 4,8-dihalo- and 4,8-dmitro-l,l,3,3,5,5,7,7-octafluoro-l,3,5,7-tetrahydrobenzo[l,2-c 4,5-c 5]difurans, respectively [218, 219, 220] (equation 112). 

When the 7,8-hydroxyl groups are missing, epoxide introduction occurs from both sides of the pyrene ring. Thus 7,8-dihydrobenzo(a)-pyrene is cooxidized by PGH synthase to a potent mutagen that is identified by product and nucleic acid binding studies as 9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (Equation 3) (32). The structures... 

Substituted derivatives of l-(tetrahydrobenzo[b]thiophen-2-yl-3-carboxylate)-5-phenyl-6-thio-l,2,4-triazin-4-one have been synthesized by heterocyclization reactions of different hydrazones obtained from 2-amino-tetrahydrobenzo[b]thiophene-3-carboxylate with phenyl isothiocyanate <00PS275>. Reaction of 5-methyl isothiosemicarbazide with a-amino acid vicinal tricarbonyl reactive substrates 1 and 2 yields 1,2,4-triazine substituted a-amino acids, as an equimolar mixture of regioisomers 3a/3b and 4a /4b, respectively <00JCS(P1)299>. 

Friedel-Crafts acylation of dibenzothiophene with succinic anhydride is known to occur in the 2-position, yielding y-oxo-2-dibenzothiophene-but3Tic acid (135a). Subsequent Wolff-Kishner reduction and internal cyclization yields 7-keto-7,8,9,10-tetrahydrobenzo[6]naphtho[2,3-d]thio-phene (136a). - This reaction has been extended to 4-methyldibenzo-... 

The mixed hydrazones (667), prepared from diacetyl monobenzoyl hydrazone and arylhydrazines, undergo oxidative cyclization to 2-aryl-jV-benzoyl-4,5-dimethyl-l,2,3-triazol-l-ylimines (668) in 32-76% yield upon treatment with lead tetraacetate in acetonitrile (Scheme 132) <92JOC2252>. The cychzation of bishydrazones to 1,2,3-triazoles can also occur in acidic or basic media. For instance, the tetrahydrobenzo[ /]triazol-4-one (669) is prepared by the base-catalyzed cyclization of the corresponding a-hydrazono oxime (Equation (53)) <85HCA1748>. 3-Methyl-1,2-cyclohexanedione reacts... 

When 3-mercaptocyclohexanone condenses with dichloroacet-aldehyde or chloroacetaldehyde in the presence of a catalytic quantity of acid (e.g., p-toluenesulfonic acid), simultaneous cyclization occurs to give 4,5,6,7-tetrahydrobenzo[6]thiophen-4-one (see Section VI, B, 4) and 2,4,5,6,7,7a-hexahydrobenzo[6]thiophen-4-one (see Section... 

Tetrahydrobenzo[6]thiophen-4-one (103) may be prepared from y-(2-thienyl)butyric acid by cyclization with phosphoric acid854 or by Friedel-Crafts cyclization of the corresponding acid chloride.194, 355.358 j s 5-methyl,357 2-ethyl,194 2-isopropyl,358 2- and 3-tert-butyl,359 2,3-dimethyl,360 2-ethyl-3-methyl,360 and 2-bromo 354 derivatives and diethyl 4,5,6,7-tetrahydrobenzo[6]thiophene-4,5-di-carboxylate861 may be prepared similarly. 4,5,6,7-Tetrahydrobenzo-[6]thiophen-7-one (104)357 362,863 and its 5- and 6-methyl 357 and 2-chloro 362 derivatives are obtained from the appropriately substituted y-(3-thienyl)butyric acid, A recent patent 364 describes the vapor phase cyclization of y-(2-thienyl)butyric acid to 103. Ketones (103 and 104) are useful intermediates for the synthesis of 4- and 7-substituted benzo[6]thiophenes, respectively their reactions are discussed in Section VI, B, 4. 

A number of 4,5,6,7-tetrahydrobenzo[6]thiophenes have been synthesized recently from cyclohexanones (Section IV, A). Hydrolysis of ethyl 2-amino-4,5,6,7-tetrahydrobenzo[i>]thiophene-3-carboxylate, prepared in this way, affords the free amino acid, which readily loses carbon dioxide to yield 2-amino-4,5,6,7-tetrahydrobenzo[6]thiophene in 71% overall yield.254... 

The synthesis of 4,5,6,7-tetrahydrobenzo[6]thiophen-4-one and -7-one has been described in Section IV, G 4-methyl-4,5,6,7-tetra-hydrobenzo[6]thiophen-5-one is obtained on oxidation of 136 (R = Me) with per benzoic acid.438... 

Bromination (Br2) of 4,5,6,7-tetrahydrobenzo[6]thiophen-4-one affords either a 2-bromo or a 5-bromo derivative, depending on whether the reaction is carried out at 0° in ether,445,446 or at—5 to 0°in 50% aqueous acetic acid.354 The 5-bromo derivative condenses with morpholine or potassium phthalimide to give 140a or 140b, respectively.445, 446 Hydrazinolysis of 140b fails to give any of the 5-amino derivative.445,446 On nitration, the 2-bromo derivative affords the 3-nitro compound or 141 (R = N02), depending on the reaction conditions.354 With sodium azide in PPA the 2-bromo and 2-bromo-3-... 

The oximes of 4,5,6,7-tetrahydrobenzo[6]thiophen-4-one and -7-one undergo the Beckmann rearrangement to give 146 354 451 and 147 (R = H),362 respectively. Compound 147 (R=C1) may be prepared similarly and by treating 2-chloro-4,5,6,7-tetrahydrobenzo[ ]thio-phen-7-one with ammonia in the presence of PPA.356 The oxime of 4,5,6,7 -tetrahydrobenzo [6]thiophene- 4-one affords 4-aminobenzo [6]-thiophene in a modified Leuckart reaction.241,355 The same oxime may be converted into 4-amino-4,5,6,7-tetrahydrobenzo[ ]thiophene by reduction with aluminum amalgam in methanol.452 The parent ketone also affords 4-amino-4,5,6,7-tetrahydrobenzo[6]thiophene on reaction with formamide at 165°, followed by acidic hydrolysis of the resulting 4-formylamino compound.355... 

A method for synthesizing 1,3,4,5-tetrahydrobenzo[af)indoles 171 from 2-aminotetralins 168, which were first formylated by formic acid or N-formylimidazole, was described. The 2-formyltetralins thus formed were... 

The remaining solution was diluted with DCM (2 ml), and m-chloroperbenzoic acid (mCPBA) (0.30 g, 2.0 mmol) was added portionwise. After stirring at RT for 40 h, the mixture was extracted with DCM and washed successively with aqueous sodium sulfite solution, aqueous sodium bicarbonate solution and water, dried (MgS04) and evaporated in vacuum. Column chromatography (45-70% ether-petrol, gradient elution) of the residue afforded the title epoxides (3aa,6a,7a,7aa)-6,7-epoxy-3a,6,7,7a-tetrahydrobenzo[d]-l,3-dioxol-2-one (73 mg, 47%) mp 87°-89°C and (3aa,6p,7p,7aa)-6,7-epoxy-3a,6,7,7a-... 

Tetrafluoroboric acid-diethyl ether complex (catalytic amount) was added to a stirred solution of epoxide (+/-)-(3aa,6a,7a,7aa)-6,7-epoxy-3a,6,7,7a-tetrahydrobenzo[d]-l,3-dioxol-2-one (32 mg, 0.2 mmol) and (R)-(+)-sec-phenethyl alcohol (0.048 ml, 0.4 mmol) in DCM at RT under argon. After 30 min, water was added and the mixture extracted with DCM (3 times). The combined organic phase was dried (MgS04) and evaporated in vacuum. Column chromatography (30-75% ether-petrol, gradient elution) of the residue afforded the alcohols [3aR-[3aa,4a,5p(R),7aa]-3a,4,5,7a-tetrahydro-4-hydroxy-5-(l-phenylethoxy)benzo[d]-l,3-dioxol-2-one and [3aS-[3aa,4a,5P(R),7aa]-3a,4,5,7a-tetrahydro-4-hydroxy-5-(l-phenylethoxy)benzo[d]-l,3-dioxol-2-one. (37 mg, 67%) as a thick oil and a 1 1 mixture of diastereomers. Subsequent HIPLC (l -Dynamax 83,123-6 column 6% isopropanol-petrol, 15 ml/min) effected separation of the diastereomers. Less polar [3aR-[3aa,4a,5p(R),7aa]-3a,4,5,7a-tetrahydro-4-hydroxy-5-(l-phenylethoxy)benzo[d]-l,3-dioxol-2-one had retention time 16.3 min [a]D2° +90.1° (c 1.1, CHCI3). 

Successive reduction of l,3-dimethyl-4,5,6,7-tetrahydrobenzo[c]-thiophen-4-one (Section III,C) with sodium borohydride and dehydration of the resulting alcohol with polyphosphoric acid gives the unstable 1,3-dimethyl derivative [(18) R = H] in excellent yield,35 and successive treatment of the same ketone with methylmagnesium iodide and acid gives the 1,3,7-trimethyl derivative [(18) R=Me] (Table IV) and a second compound which is reported to be a dimer. 36 When l,3-dimethyl-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one is treated with a mixture of phosphorus oxychloride and dimethyl-formamide (Vilsmeier-Haack formylation), it gives compound 19, which yields 20 on being treated successively with thioglycolic acid... 

The sulfide (21) condenses with cyclohexane-1,2-dione (22) in the presence of sodium ethoxide to give a mixture of the mono- (23a) and diethyl ester (23b) of 4,5,6,7-tetrahydrobenzo[c]thiophene-l,3-di-carboxylic acid (23c).6 The free acid (23c) is obtained by hydrolysis of these esters and it undergoes decarboxylation on being heated to 360° to give 4,5,6,7-tetrahydrobenzo[c]thiophene.6 This compound is also known as 3,4-tetramethylenethiophene and as 8-thiabicyclo-[4.3.0]nona-6,9-diene. 

Friedel-Crafts acetylation of l-methyl-4,5,6,7-tetrahydrobenzo[c]-thiophene is reported10 to give l-acetyl-3-methyl-4,5,6,7-tetrahydro-benzo[c]thiophene. Successive treatment of methyl 4,5,6,7-tetra-hydrobenzo[c]thiophene- 1-carboxylate with /V-bromosuccinimide and sodium methoxide gives benzo[c]thiophene-l-carboxylic acid.16,38... 

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