A new procedure for the cyclization of 2-indole- and 3-indolecarbohydrazones to 5H-pyridazino[4,5-b]indole derivatives

A new procedure for the cyclization of 2-indolecarbohydrazones (5) to 1,2,3,4-tetrahydro-4-oxo-5H-pyridazino[4,5-b]indoles (6) and for the cyclization of 3-indolecarbohydrazones (7) to 1-oxo-1,2,3,4-tetrahydro-5H-pyridazino[4,5-b]indoles (8 and 9) is described. The hydrazones (5 or 7) were treated with an acyl halide (acetyl or benzoyl chlorides) and triethylamine in ethyl acetate of chloroform as solvents to give the compounds 6 (20–70%) from the compounds 5 , and the compounds 8 (20–60%) from the compounds 7 . Through refluxing with ethanol-hydrochloric acid the compounds 8a-8f selectively separate the acetyl group on N⁵ to give the respective compounds, 9a-9f. The ir and ¹H-nmr spectra of all the compounds 5, 6, 7, 8 and 9 and the uv, mass and ¹³C-nmr spectra of the compounds 7h, 7i, 8h and 8i are discussed.     

The formation of 3‐ferrocenylpyrazole‐4‐carboxylates and alkylhydrazine insertion products from α‐ferrocenylmethylidene‐β‐oxocarboxylates

The reactions of α‐ferrocenylmethylidene‐β‐oxocarboxylates ( 1 , 2 , 3a , and 3b ) with N‐methyl‐ and N‐(2‐hydroxyethyl)hydrazines ( 5a , 5b ) afford ethyl 1‐alkyl‐5‐aryl(methyl)‐3‐ferrocenylpyrazole‐4‐carboxylates ( 6a , 6b , 6c , 6d , 6e ) (～50%) and N‐alkylhydrazine insertion products, viz., ethyl (N′‐acyl‐N′‐alkylhydrazino)‐3‐ferrocenylpropanoates ( 7a , 7b , 7c , 7d , 7e ) (～20%) and 1‐acyl‐2‐(N′‐alkyl‐N′‐ethoxycarbonylhydrazino)‐2‐ferrocenylethanes ( 8a , 8b , 8c , 8d , 8e ) (～10%). The structures of the compounds obtained were established based on the spectroscopic data and X‐ray diffraction analysis (for pyrazoles 6a and 6b ). J. Heterocyclic Chem., (2011).     

Thermische Lactonisierung von Estern γ-Brom-α, β-ungesättigter Carbonsäuren zu Δα-Butenoliden. Direkte γ-Bromierung von α, β-ungesättigten Säuren

By heating with iron powder at 120–150° some γ-bromo-α, β-unsaturated carboxylic methyl esters, and, less smothly, the corresponding acids, were lactonized to Δ^7alpha;-butenolides with elimination of methyl bromide. The following conversions have thus been made: methyl γ-bromocrotonate ( 1c ) and the corresponding acid ( 1d ) to Δ^α-butenolide ( 8a ), methyl γ-bromotiglate ( 3c ) and the corresponding acid ( 3d ) to α-methyl-Δ^α-butenolide ( 8b ), a mixture of methyl trans- and cis-γ-bromosenecioate ( 7c and 7e ) and a mixture of the corresponding acids ( 7d and 7f ) to β-methyl-Δ^α-butenolide ( 8c ). The procedure did not work with methyl trans-γ-bromo-Δ^α-pentenoate ( 5c ) nor with its acid ( 5d ). Most of the γ-bromo-α, β-unsaturated carboxylic esters ( 1c, 7c, 7e and 5c ) are available by direct N-bromosuccinimide bromination of the α, β-unsaturated esters 1a, 7a and 5a ; methyl γ-bromotiglate ( 3c ) is obtained from both methyl tiglate ( 3a ) and methyl angelate ( 4a ), but has to be separated from a structural isomer. The γ-bromo-α, β-unsaturated esters are shown by NMR. to have the indicated configurations which are independent of the configuration of the α, β-unsaturated esters used; the bromination always leads to the more stable configuration, usually the one with the bromine-carrying carbon anti to the carboxylic ester group; an exception is methyl γ-bromo-senecioate, for which the two isomers (cis, 7e , and trans, 7d ) have about the same stability. The N-bromosuccinimide bromination of the α,β-unsaturated carboxylic acids 1b , 3b , 4b , 5b and 7b is shown to give results entirely analogous to those with the corresponding esters. In this way γ-bromocrotonic acid ( 1 d ), γ-bromotiglic acid ( 3 d ), trans- and cis-γ-bromosenecioic acid ( 7d and 7f ) as well as trans-γ-bromo-Δ^α-pentenoic acid ( 5d ) have been prepared. Iron powder seems to catalyze the lactonization by facilitating both the elimination of methyl bromide (or, less smoothly, hydrogen bromide) and the rotation about the double bond. α-Methyl-Δ^α-butenolide ( 8b ) was converted to 1-benzyl-( 9a ), 1-cyclohexyl-( 9b ), and 1-(4′-picoly1)-3-methyl-Δ^α-pyrrolin-2-one ( 9 c ) by heating at 180° with benzylamine, cyclohexylamine, and 4-picolylamine. The butenolide 8b showed cytostatic and even cytocidal activity; in preliminary tests, no carcinogenicity was observed. Both 8b and 9c exhibited little toxicity.     

Reactivity of 5,10:8,14-Disecosteroids: An unusual rearrangement of cyclodecene-1,4-dione systems to five-membered-ring spiro-γ-lactones

Upon heating in AcOH, the stereoisomeric (Z)- and (R)-6,9-dioxocyclodex-3-enyl derivatives, 5 and 6 , respectively, obtained by HgO/I₂ oxidation of 5-hydroxy-8-oxo-8,14-seco-5α-androstane-3β,17β-diyl diacetate ( 3 ), undergo an unusual intramolecular rearrangement to give the corresponding unsaturated (5R,9R)- and (5R,9S)-spiro-lactones 7 and 8 , respectively. Hydroxylation of the C?C bond in 7 and 8 , and subsequent glycol cleavage of the resulting diols 9 and 10 afforded the epimeric spiro-lactones (5R,9S)- 11 and (5R,9R)- 14 , respectively, and in both cases, the ring-D-containing fragments 12 and 13 .     

Synthesis and reactions of halo-, nitro-, and arylazo-substituted 3-cinnamoyltropolones. Formation of styryl-substituted heterocycle-fused troponoid compounds

3-Cinnamoyltropolone ( 1 ) reacted with bromine to afford 7-bromo- ( 2 ), 5,7-dibromo-3-cinnamoyltropolone ( 3 ), and 6,8-dibromo-4,9-dihydrocyclohepta[b]pyrane-4,9-dione ( 4 ) according to amount of the reagent. Iodination and nitration of 1 gave respectively 7-iodo- ( 5 ) and 5-nitro-3-cinnamoyltropolone ( 6 ). Azo-coupling reactions gave 5-arylazo-3-cinnamoyltropolones 7a-f . Compounds 1, 2, 3 and 5 reacted with hydroxylamine to give 3-styryl-8H-cyclohept[d]isoxazol-8-ones 10-13 , while 6 and 7a gave 5-nitro-3-styryl-8H-cyclohept[d]-isoxazol-8-one oxime ( 14 ) and 2-cinnamoyl-7-methoxy-4-phenylazotropone ( 15 ), respectively. The reactions of 1,3 , and 5 with phenylhydrazine gave 3-styryl-1,8-dihydrocycloheptapyrazol-8-ones 16-19 .     

Synthesis and Evaluation of 2-{[(2-Oxo-1H-quinolin-8-yl)oxy]methyl}-Substituted α-Methylidene-γ-butyrolactones

O-Alkylation of 8-hydroxy-1H-quinolin-2-one ( 1 ) afforded 8-(2-oxopropoxy)-1H-quinolin-2-one ( 2 ) which was immediately cyclized to form the tricyclic 2,3-dihydro-3-hydroxy-3-methyl-5H-pyrido[1,2,3-de][1,4]benzoxazine,-5-one ( 3). The Reformatsky-type condensation of 3 furnished antiplatelet 8-[(2,3,4,5-tetrahydro-2-methyl-4-methylidene-5-oxofuran-2-yl)melhoxy]-1H-quinolin-2-one ( 4 ). Its counterparts 7a – f , Ph-substituted at C(2) of the furan ring, were obtained from 1 via alkylation and the Reformatsky-type condensation. Although compound 4 was less active against platelet aggregation than 7a – f , it was the only compound which exhibited significant inhibitory activity on high-K⁺ medium, Ca²⁺-induced vasoconstriction and was more active than most of its Ph-substituted counterparts against norepinephrine-induced vasoconstrictions.     

Conformations of the Ten-membered Ring in 5, 10-Secosteroids. III: (Z)-3β- and (Z)-3α-Hydroxy-5, 10-seco-1 (10)-cholesten-5-one Esters and (Z)-5, 10-seco-1 (10)-Cholestene-3, 5-dione

(Z)-3β-Acetoxy- and (Z)-3 α-acetoxy-5, 10-seco-1 (10)-cholesten-5-one ( 6a ) and ( 7a ) were synthesized by fragmentation of 3β-acetoxy-5α-cholestan-5-ol ( 1 ) and 3α-acetoxy-5β-cholestan-5-ol ( 2 ), respectively, using in both cases the hypoiodite reaction (the lead tetraacetate/iodine version). The 3β-acetate 6a was further transformed, via the 3β-alcohol 6d to the corresponding (Z)-3β-p-bromobenzoate ester 6b and to (Z)-5, 10-seco-1 (10)-cholestene-3, 5-dione ( 8 ) (also obtainable from the 3α-acetate 7a ). The ¹H-and ¹³C-NMR. spectra showed that the (Z)-unsaturated 10-membered ring in all three compounds ( 6a , 7a and 8 ) exists in toluene, in only one conformation of type C ₁, the same as that of the (Z)-3β-p-bromobenzoate 6b in the solid state found by X-ray analysis. The unfavourable relative spatial factors (interdistance and mutual orientation) of the active centres in conformations of type C ₁ are responsible for the absence of intramolecular cyclizations in the (Z)-ketoesters 6 and 7 ( a and c ).     

Reaktion von 3-(Dimethylamino)-2H-azirinen mit 1,3-Thiazolidin-2-thion

Reaction of 3-(Dimethylamino)-2H-azirines with 1,3-Thiazolidine-2-thione Reaction of 3-(dimethylamino)-2H-azirines 1 and 1,3-thiazolidine-2-thione ( 6 ) in MeCN at room temperature leads to a mixture of perhydroimidazo[4,3-b]thiazole-5-thiones 7 and N-[1-(4,5-dihydro-1,3-thiazol-2-yl)alkyl]-N′,N′-dimethylthioureas 8 (Scheme 2), whereas, in i-PrOH at ca. 60°, 8 is the only product (Scheme 4). It has been shown that, in polar solvents or under Me₂NH catalysis, the primarily formed 7 isomerizes to 8 (Scheme 4). The hydrolysis of 7 and 8 leads to the same 2-thiohydantoine 9 (Scheme 3 and 5). The structure of 7a, 8c , and 9b has been established by X-ray crystallography (Chapt. 4). Reaction mechanisms for the formation and the hydrolysis of 7 and 8 are suggested.     

Stereoselective synthesis of pyrrolo[2,3-d]pyrimidine α- and β-D-ribonucleosides from anomerically pure D-ribofuranosyl chlorides: Solid-Liquid Phase-Transfer Glycosylation and 15N-NMR Spectra

Solid-liquid phase-transfer glycosylation (KOH, tris[2-(2-methoxyethoxy)ethye]amine ( = TDA-1), MeCN) of pyrrolo[2,3-d]pyrimidines such as 3a and 3b with an equimolar amount of 5-O-[(1,1 -dimethylethyl)dimethylsilyl]-2,3-O-(1-methylethylidene)-α-D -ribofuranosyl chloride (1) [6] gave the protected β-D -nucleosides 4a and 4b , respectively, stereoselectively (Scheme). The β-D -anomer 2 [6] yielded the corresponding α-D -nucleosides 5a and 5b with traces of the β-D -compounds. The 6-substituted 7-deazapurine nucleosides 6a , 7a , and 8 were converted into tubercidin (10) or its α-D -anomer (11) . Spin-lattice relaxation measurements of anomeric ribonucleosides revealed that T₁ values of H? C(8) in the α-D -series are significantly increased compared to H? C(8) in the β-D -series while the opposite is true for T₁ of H? C(1′). ¹⁵N-NMR data of 6-substituted 7-deazapurine D -ribofuranosides were assigned and compared with those of 2′-deoxy compounds. Furthermore, it was shown that 7-deaza-2′deoxyadenosine ( = 2′-deoxytubercidin; 12 ) is protonated at N(1), whereas the protonation site of 7-deaza-2′-deoxyguanosine ( 20 ) is N(3).     

Geiparvarin Analogues: Synthesis and Anticancer Evaluation of α-Methylidene-γ-butyrolactone-Bearing Coumarins

To determine some of the structural features of geiparvarin that account for its cytostatic activity in vitro, certain geiparvarin analogues modified in the furan-3(2H)-one moiety and the alkenyloxy substituent were synthesized and tested against the growth of 60 human cancer cell lines derived from nine cancer-cell types. These compounds demonstrated a strong growth-inhibitory activity against leukemia cell lines but were relatively inactive against non-small-cell lung cancers and CNS cancers. Comparison of the mean log GI₅₀ values of γ-[(E)-1-methylprop-1-enyl]-α-methylidene-γ-butyrolactones 7 – 9 revealed that 7-[(E)-3-(2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl)but-2-enyloxy]-2H- 1-benzopyran-2-one ( 8 ; −5.47) was more active than its 6-substituted counterpart 7 (−5.21) and its 3-chloro-4-methyl derivative 9 (−5.31) and had a potency similar to that of geiparvarin (log GI₅₀=−5.41). These results indicated that the furan-3(2H)-one moiety of geiparvarin could be replaced by an α-methylidene-γ-butyrolactone unit without losing the anticancer potency, and that the best substitution site at the coumarin moiety was C(7). The alkenyloxy substituent of 8 was also replaced by a methoxy substituent. Among these α-methylidene-γ-butyrolactones, 7-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-phenylfuran-2-yl)methoxy]-2H-1-benzopyran-2-one ( 11 ) was the most potent with a mean log GI₅₀ value of −5.83 and a range value of 132 (10^2.12).     

Synthesis of potential metabolites of the brain imaging agents methyl (1R,2S,3S,5S)-3-(4-Iodophenyl)-8-alkyl-8-azabicyclo[3.2.1]octane-2-carboxylate

The synthesis of potential hydroxy metabolites of the brain imaging agents methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate and methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-(3-fluoropropyl)-8-azabicyclo[3.2.1]octane-2-carboxylate are reported. The nitration of iodophenyltropanes 1 or 2 with nitronium tetrafluoroborate afforded the nitro compounds 3 or 4 which were reduced with iron powder to the corresponding amino compounds 5 and 6 . The final hydroxylated products 7 and 8 were obtained via a modified Sandmeyer reaction.     

Behavior of 3‐benzylamino‐5‐aryl‐2(3H)‐furanones towards some nitrogen nucleophiles

Ring closure of 2‐N‐benzylamino‐3‐aroylpropionic acids ( 3 ) with acetic anhydride afforded 3‐N‐benzylamino‐5‐aryl‐2(3H)‐furanones ( 4 ). The reaction of the furanones ( 4 ) with benzylamine in benzene was found to be time dependent. Thus refluxing the reaction mixture for 1 h only afforded the open‐chain amides ( 5a‐c ). When the reaction was conducted for 3 h the 2(3H)‐pyrrolones ( 6 ) were obtained. Hydrazine hydrate affected ring opening of the furanones to give the hydrazides ( 5d‐f ). Also, semicarbazide converted ( 4 ) into the corresponding semicarbazide derivatives ( 5g‐i ). The hydrazides ( 5d‐f ) were reacted with benzoyl chloride to give the corresponding diaroylhydrazines ( 5j‐l ). The open‐chain derivatives ( 5 ) were converted into a variety of heterocycles: isothiazolones ( 7 ), dihydropyridazinones ( 8 ), 1,3,4‐oxadiazoles ( 9 ) and 1,2,4‐triazole derivatives ( 10 ) via cyclization reactions.     

Cytotoxic Naphtho‐γ‐pyrones from the Mangrove Endophytic Fungus Aspergillus tubingensis (GX1‐5E)

Four new dimeric naphtho‐γ‐pyrones, named rubasperone D ( 1 ), rubasperone E ( 2 ), rubasperone F ( 3 ), and its atropisomer rubasperone G ( 4 ), together with four known monomeric naphtho‐γ‐pyrones, TMC 256 A1 ( 5 ), rubrofusarin B ( 6 ), fonsecin ( 7 ), and flavasperone ( 8 ), were isolated from the mangrove endophytic fungus Aspergillus tubingensis (GX1‐5E) cultivated in solid rice medium. Their structures were elucidated by spectroscopic methods, including IR, 1D‐ and 2D‐NMR, and MS. In the in vitro cytotoxicity assays, 5 displayed inhibitory activities against tumor cell lines of MCF‐7, MDA‐MB‐435, Hep3B, Huh7, SNB19, and U87 MG with IC₅₀ values between 19.92 and 47.98 μM . Compounds 1, 6 , and 8 also showed mild cytotoxic activity.     

Syntheses of 1,3,8,10,12-pentazanaphthacene-2,4,7,9-(12H,3H,8H,10H)-tetraones (linear pyrimidine-fused 5-deazaflavins), 1,3,6,8,12-pentazabenz[a]anthracene-2,4,7,9(12H,3H,6H,8H)-tetraones(bent pyrimidine-fused 5-deazaflavins), and their flavin analogs

1,3,8,10,12-Pentazanaphthacene-2,4,7,9(12H,3H,8H,10H)-tetraones (linear pyrimidine-fused 5-deazaflavins) and 1,3,6,8,12-pentazabenz[a]anthracene-2,4,7,9(12H,3H,6H,8H)-tetraones (bent pyrimidine-fused 5-deazaflavins) were synthesized by condensation of 7-alkylaminoquinazoline with 6-chloro-5-formyl-3-methyluracil. Also, their flavin analogs, 1,3,5,8,10,12-hexazanaphthacene-2,4,7,9(12H,3H,8H,10H)-tetraones (linear pyrimidine-fused flavins) and l,3,5,6,8,12-hexazabenz[a]anthracene-2,4,7,9(12H,3H,6H,8H)-tetraones (bent pyrimidine-fused flavins) were synthesized by cyclization of 7-[N-alkyl-N-(5-nitrouracil-6-yl)]aminoquin-azolines with the Vilsmeier reagent.     

Synthesis and Structure Investigations of Potential Sedative and Anticonvulsant Hydroxy- and Acetoxy-N-(3-oxobutyl)-pyrido[2,3-d]pyridazinonesa

Summary.  Novel N-(3-oxobutyl)-hydroxy- and acetoxypyrido[2,3-d]pyridazinones were synthesized and tested in vivo for their sedative and anticonvulsant activity. The Michael-type reaction of quinolinic acid hydrazide and methyl vinyl ketone afforded a mixture of two isomers, 5-hydroxy-N ⁷-(3-oxobutyl)-pyrido[2,3-d]pyridazin-8(7H)-one and 8-hydroxy-N ⁶-(3-oxobutyl)-pyrido[2,3,-d]pyridazin-5-(6H)-one, in a ratio of 2:1 which were separated by crystallization. Subsequent acetylation of both isomers yielded the corresponding 5- and 8-acetoxy compounds. The structures of the compounds were proven and completely assigned on the basis of ¹H, ¹³C, ¹⁵N NMR, and 1D NOE difference spectra as well as 2D C,H-correlation experiments. Preliminary pharmacological tests showed low acute toxicity with a LD ₅₀ > 1000 mg/kg in the mouse and sedative activity for the title compounds. 5-Acetoxy-N ⁷- (3-oxobutyl)-pyrido[2,3-d]pyridazin-8(7H)-one displayed a borderline anticonvulsant activity in the metrazole test model. Corresponding author. E-mail: edith.goessnitzer@uni-graz.at Received March 20, 2002; accepted April 3, 2002     

Synthesis and reactions of halo-, nitro-, and arylazo-substituted 3-acetyltropolones. Formation of heterocycle-fused troponoid compounds

3-Acetyltropolone ( 1 ) reacted with bromine, iodine, and nitric acid to afford respectively 3-acetyl-5,7-di-bromotropolone ( 2 ), 3-acetyl-7-iodotropolone ( 3 ), and 3-acetyl-5-nitro- ( 4 ) and 3-acetyl-5,7-dinitrotropolone ( 5 ). Azo-coupling reactions of 1 gave 3-acetyl-5-arylazotropolones 7a-f. The Schmidt reactions of 2 and 3 gave respectively 5,7-dibromo- ( 9 ) and 7-iodo-2-methyl-8H-cyclohept[d]oxazol-8-one ( 10 ), while 4 gave 3-acetamido-5-nitrotropolone ( 11 ). Compounds 2 and 4 reacted with hydroxylamine to give 3-methyl-8H-cyclohept[d]isoxazol-8-ones 12 and 13. The reactions of 2 , 3 , and 4 with hydrazine gave 3-methyl-1,8-dihydrocycloheptapyrazol-8-ones 15 , 16 , and 17.     

Heterocyclische und carbocyclische 12-π- and 14-π-Molekülsysteme, 47. Mitteilung. Herstellung von 7, 9-Dimethyl-4, 5-dihydro-3 H-benz [cd]- azulen-3-on and 7,9-Dimethyl-3H-benz [cd]azulen-3-on. Eine einfache Synthese eines Azulenopseudophenalenons

Heterocyclic and Carbocyclic 12-π-and 14-π-Systems, 47th Commnunication¹. Synthesis of 7,9-Dimethyl-4,5-dihydro-3H-benz[cd]azualene-3-one and 7,9-Dimethyl-3H-benz[cd]azulene-3-one. A Simple Synthesis of Azulenopseudophenalenons 4, 6, 8-Trimethylazulene ( 3 ) reacts after metalation with lithiumdiisopropyl-amide in ether with bromoacetic acid to the 6, 8-dimethylaltulene-4-propionic acid ( 4 ), which undergoes cyclization to the 7, 9-dimethyl-4, 5-dihydro-3H-benz [cd]-azulene-3-one ( 5 ) in the presence of p-toluenesulfonic acid; oxidation of 5 with 2, 3-dichloro-5, 6-dicyanobenzoquinone yields 7, 9-dimethyl-3H-benz [cd]azulene-3--one ( 1b ). Alkylation of 1b with triethyloxonium tetrafluoroborate in CH₂C1₂ gives the 3-ethoxy [cd]benzazulenium tetrafluoroborate ( 6 ).     

Substituted γ-lactones. XXX. Reactions of α-Keto-β-Subtituted-γ-butyrolactones with diamines

The condensation reaction between α-keto-β-aroyl (or acyl) -γ-butyrolactones, 4a-4e and o-phenylenediamine or 2, 3-diaminonaphthalene leads under retrograde aldol condensation involving loss of formaldehyde to formation of 3-substituted-3, 4-dihydro-2 (1H) quinoxalinones or benzo [g] quinoxalinones, 7a-7g , respectively as a new convenient synthesis of this type of heterocyclic systems. The reaction of type 4 compound with 4, 5-diaminopyromidine, 8 , was found to proceed differently. 2-[(4-Amino-5-pyrimidinyl)amine]-4-oxo-3-(hydroxymethyl)-4-phenyl-2-butenoic acid 9 was the only product formed when the reaction between 4a and 8 was run in ethanol. The same reaction in glacial acetic acid proceeds with loss of formaldehyde, to afford 7-phenacylidene-7,8-dihydro-6 (1H)-pteridione 10 . The reaction between type 4 compounds and ethylenediamine or 1, 4-phenylenediamine leads to the formation of the bis-condensation products 13–15 , respectively.     

Reactions of 3-isopropenyltropolones with bromine and N-bromosuccinimide: Formation of 8H-cyclohepta[b]furan-8-one derivatives

3-Isopropenyltropolones 1a-c were treated with bromine in carbon tetrachloride to give 3-methyl-8H-cyclohepta[b]furan-8-ones 2a-c and their corresponding 7-bromo-substituted compounds 3a-c , while reactions in acetic acid gave the bromo-substituted compounds 3a-c . On the other hand, bromination of 1a-c with N-bromosuccinimide afforded 7-bromo-3-(2-bromo-1-methylethenyl)tropolones 5a-c . The compound 2a was treated with bromine to give 2-bromo-3-methyl-8H-cyclohepta[b]furan-8-one ( 4 ). The tropolones 5a-c were heated in the presence of potassium carbonate to give the cyclized compounds 3a-c .