Acid-catalyzed cyclization

Borsche-Drechsel cyclization. Acid-catalyzed rearrangement of cyclohexanone phenylhy-drazone to tetrahydrocarbazole. Subsequent oxidation yields carbazole. 

A simple acid-catalyzed cyclization transforms i//-ionone into n-ionone (W. Kimel, 1957, 1958). Further treatment with protic acids transforms the tr-ionone to the thermodynamically more stable -ionone. 

The following acid-catalyzed cyclizations leading to steroid hormone precursors exemplify some important facts an acetylenic bond is less nucleophilic than an olelinic bond acetylenic bonds tend to form cyclopentane rather than cyclohexane derivatives, if there is a choice in proton-catalyzed olefin cyclizations the thermodynamically most stable Irons connection of cyclohexane rings is obtained selectively electroneutral nucleophilic agents such as ethylene carbonate can be used to terminate the cationic cyclization process forming stable enol derivatives which can be hydrolyzed to carbonyl compounds without this nucleophile and with trifluoroacetic acid the corresponding enol ester may be obtained (M.B. Gravestock, 1978, A,B P.E. Peterson, 1969). 

The Lewis acid-catalyzed cyclization of 3-anaino-2-alkerLirnines (21) leads to a wide variety of alkyl- and aryl-substituted quinolines (59). The high regiospecificity and the excellent yields obtained make this process promising. 

In perfumery bisabolol functions as a fixative. The racemic form is manufactured by the acid-catalyzed cyclization of nerohdol (193). 

Enantioselective addition of hydrogen cyanide to hydroxypivaldehyde (25), catalyzed by (lf)-oxynittilase, afforded (R)-cyanohydrin (26) in good optical yield. Acid-catalyzed hydrolysis followed by cyclization resulted in (R)-pantolactone in 98% ee and 95% yield after one recrystallization (56). 

Diaryl derivatives of the 1,3-oxathiolylium system (29) are prepared by acid-catalyzed cyclization of the /3-keto thioesters (28) which are readily prepared from thioacid salts (27)... 

Application of the above principles to the synthesis of 1,3-diselenolylium ions has been successful. iVjA -Dialkyldiselenocarbamates as their oxo esters (30) undergo acid-catalyzed cyclization and dehydration to give the cation (31) in nearly 90% yield (75JOC746, 77CC505, 80CC866, 80CC866). 

An example of preferred conrotatory cyclization of four-7c-electron pentadienyl cation systems can be found in the acid-catalyzed cyclization of the dienone 12, which proceeds through the 3-hydroxypentadienyl cation 13. The stereochemistry is that expected for a conrotatory process. 

A-Nor-B-homo steroids with different substitution patterns than those described above may be prepared by acid catalyzed cyclization of 3)3-hydroxy-5(10)-seco-cholest-tra/w-l(l0)-en-5-one acetate (134a) formed in 30-40% yield by mercuric oxide-iodine sensitized irradiation of cholestane-3j3,5a-diol... 

In general, fluorinated sulfonic acids can be used as eatalysts for various cationic cyclizations Typical examples are the triflic acid catalysis in the double cyclization of A,VV-dibenzylpropynylamine [82] (equation 30) and the fluorosulfonic acid catalyzed condensation of phenylacetaldehyde [<5J] (equation 31)... 

Ryder reported the preparation of an interesting alkyl diaryl furan that was subsequently polymerized and studied as a conducting polymer. The monomer furan 49 was available fron the acid catalyzed cyclization of dione 48. ... 

The Pictet-Spengler reaction is an acid-catalyzed intramolecular cyclization of an intermediate imine of 2-arylethylamine, formed by condensation with a carbonyl compound, to give 1,2,3,4-tetrahydroisoquinoline derivatives. This condensation reaction has been studied under acid-catalyzed and superacid-catalyzed conditions, and a linear correlation had been found between the rate of the reaction and the acidity of the reaction medium. Substrates with electron-donating substituents on the aromatic ring cyclize faster than the corresponding unsubstituted compounds, supporting the idea that the cyclization process is involved in the rate-determining step of the reaction. 

The mercaptals obtained by the acid catalyzed reaction of J3-ketoesters, e.g., ethyl acetoacetate, with methyl thioglycolate (73) undergo the Dieckmann cyclization with alcoholic potassium hydroxide at lower temperatures to give ethyl 3-hydroxy-5-methyl-2-thiophenecarboxylate (74) in 75% yield. ° Besides ethyl acetoacetate, ethyl a-ethylacetoacetate, ethyl benzoyl acetate, and ethyl cyclopentanonecarboxylate were also used in this reaction/ It is claimed that /8-diketones, hydroxy- or alkoxy-methyleneketones, or /8-ketoaldehyde acetals also can be used in this reaction. From acetylacetone and thioglycolic acid, 3,5-dimethyl-2-thiophenecarboxyl-ic acid is obtained. ... 

There can be little doubt that the crucial, acid-catalyzed step in these cyclization reactions, analogous to that in the Pictet-Spengler type ring closure, involves the charged species 64 (cf. 11). 

Further elaboration of 152 resulted in the synthesis of (derived from the reduction of pyridinium salt 150b with excess of LiAlFt4 in THE Acid-catalyzed cyclization of 154 led to indoloquino-lizidine 155 (25% yield from 150b), a precursor of deplancheine (80TL2341) (Scheme 5). 

Compound 68 can also be obtained by an acid-catalyzed cyclization of 42, which was prepared by the Michael addition reaction of 39 to mesityl oxide as shown in Section IV.A. As for the product 69, the presence of the tosyloxy group at the 5 position instead of the 6 position is determined, utilizing the anisotropy effect of the 1-acetyl group to the C-7 proton, by comparing its H NMR spectrum with that of 70, obtained in 69% yield by the treatment of 69 with NaH and AcCl. 

Cyclization takes place under acid-catalyzed conditions (sulfuric acid in dry dioxane), the yield being 76%. 

The finding that the anthelmintic thiazoloimidazole levamisole showed immunoregulatory activity spurred further investigation of this heterocyclic system. Synthesis of a highly modified analogue starts by displacement of bromine in keto ester 149 by sulfur in substituted benzimidazole 148. Cyclization of the product (150), leads initially to the carbinol 151. Removal of the ester group by saponification in base followed by acid-catalyzed dehydration of the carbinol affords the immune regulator tilomisole (152) [28]. 

Raston has reported an acid-catalyzed Friedel-Crafts reaction [89] in which compounds such as 3,4-dimethoxyphenylmethanol were cyclized to cyclotriveratrylene (Scheme 5.1-57). The reactions were carried out in tributylhexylammonium bis(tri-fluoromethanesulfonyl)amide [NBu3(QHi3)][(CF3S02)2N] with phosphoric or p-toluenesulfonic acid catalysts. The product was isolated by dissolving the ionic liq-uid/catalyst in methanol and filtering off the cyclotriveratrylene product as white crystals. Evaporation of the methanol allowed the ionic liquid and catalyst to be regenerated. 

Recently reported289 is an analogous reaction involving the acid-catalyzed cyclization of (lZ,3 ,5Z)-l,6-diphenylhexa-l,3.5-triene-l,6-diamine (14) in refluxing toluene to 2,7-diphenyl-3//-azepine (15). The l,6-bis(4-tolyl) and 1,6-dibenzyl derivatives behave similarly, but give substantially lower yields (14-18%). 

Alkyl A-(3-oxobuten-l-yl)-2-aminobenzyl ketones 9 (as their cyclic acetals), formed by condensation of alkyl 2-aminobenzyl ketones with 3-methoxybut-3-ene-2-one, undergo acid-catalyzed cyclization to give rare examples of A -unsubstituted 1H-1 -benzazepines 10 in high yields.81... 

Compound 15 is prepared in two steps acid-catalyzed condensation of the pyrimidinediamine with ethyl aceloacelale provides ester 14, which cyclizes under strongly basic conditions. The pyrimidodiazepinone 15 undergoes ring contraction to 7-isopropenyl-7//-purin-8(9//)-one (16) on prolonged heating under basic conditions.297... 

Acid-catalyzed cyclization of thiosemicarbazide 1 leads to the 1,2,4,6-tetrazocine 2.5... 

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