4- -one, cyclization

Uretdoquinazolin-4-one cyclizes on heating with either urea or thiourea to form a fused tetrazepinone ring. 

The carbanion derived from 3-(o-chlorophenyl)-2-methyl-3H-quinazolin-4-one cyclizes in liquid ammonia under irradiation to yield 6H-indolo[2,l-h]quinazolin-12-one 20 (60%) " ... 

If the condensation is done with /S-aminocrotonic ester or (2-aminopent-2-en-4-one)enamine, intermediates 245b are also obtained then they are cyclized either to 2--aininothiazoles (243b) under the influence of alkalis or to A-4-thiazol-2-ones by acids (Scheme 125b) (728). 

There is also the possibility of removing the 2-oxo group by ring cleavage and subsequent recyclization. Lumazine can be hydrolyzed by strong alkali to 2-aminopyrazine-3-carboxylic acid (153) which is converted first into the amide (154) and then cyclized by ethyl orthoformate into pteridine-4-one (155 equation 47) (51JCS474). 

The formation of transient benzazetidinones (251) in the photolysis and thermolysis of benzotriazin-4-ones (250) is well established (76AHC215) and the highly hindered adamantyl derivative has actually been isolated from flash pyrolysis of 4-adamantylbenzotriazinone (73JCS(Pl)868). A second route to such hindered benzazetidinones involves cyclization of the iminoketene valence tautomer (252 R = Bu ), the latter being generated by deprotonation of the anthranilium salts (253) (71JA1543). 

The alkylation of enamines with nitroolefins, which gives intermediates for reductive cyclization (6S2), also provided an example of a stable cycliza-tion product derived from attack of the intermediate imonium function by the nitro anion (683). A previously claimed tetrasubstituted enamine, which was obtained from addition of a vinylsulfone to morpholinocyclohexene (314), was shown to be the corresponding cyclobutane (684). Perfluoro-olefins also gave alkylation products with enamines (685). Reactions of enamines with diazodicarboxylate (683,686) have been used diagnostically for 6-substituted cyclohexenamines. In a reaction of 2-penten-4-one with a substituted vinylogous amide, stereochemical direction was seen to depend on solvent polarity (687). 

The rationale for the predominance of linear cyclization products versus angular cyclization products has been accepted as qualitative." The mechanism of the Combes reaction has been argued. It was initially proposed that cyclization to linear products was due to initial protonation of a more reactive site on the aromatic ring (1-position of 13 corrresponding to the 10-position of 15) thus, blocking cyclization to angular products. Bom showed this not to be the case for the cyclization of 2-naphthyl amino-2-penten-4-one. No 10-deutero material was observed. 

A treatment of 2-butyltelluroaniline with an equimolar amount of bromoacetic acid results in spontaneous cyclization of the formed telluronium salt 31 to give 1-butylbenzotellurazinonium bromide 30. That the alkylation occurs at the tellurium and not at the nitrogen atom of 2-butyltelluroaniline has been proved by the isolation of the methyl ester of 31 in 60% yield when the amine was coupled with methyl bromoacetate under the same reaction conditions. Elimination of butyl bromide from 30 readily occurs on heating of its DMF solution leading to 2//-l,4-benzotellurazin-3(4//)-one 32 in 90% yield. 

When bromoacetyl chloride is used instead of bromoacetic acid, the anilide 33 is formed at the first stage. Its subsequent cyclization also leads to 32. This approach to benzotellurazinone is similar to that developed for the synthesis of 2//-l,4-benzothiazin-3(4//)-ones (66CJC1247). Significantly, attempts to isolate the intermediate sulfonium salts analogous to 30 were unsuccessful. 

The interaction between l,5-diphenylpentadiyn-2,4-one-l and its aliphatic analog, 1,5-dimethylpentadiyn-2,4-one, with substituted hydrazines gives rise to a linear adduct, vinylacetylenylketone, which then cyclizes into 5-phenylethynylpyra-zoles and 5-methyl-3-propynylpyrazoles in 70-90% yields, respectively (73S47) (Scheme 21). 

Cyclization of methyl 2-[2-benzoyl-2-ethoxycarbonyl-l-vinyl)amino]-3-[(4-methyl-2-pyridyl)amino]acrylate (311) afforded the 3-amino-8-methyl-4//-pyrido[l,2-n]pyrimidin-4-one derivative 312 (97JHC1511). 

Cyclization of 4-[(2-pyridylamino)methylene]-2-methoxythiazolin-5(4//)-one 313 (R = Me) in the presence of NaOMe gave 3-(methoxythiocarbo-nylamino)-4//-pyrido[l,2-n]-pyrimidin-4-one 314. When the reaction mixtures were subsequently treated with Mel, and the evaporated reaction mixtures with cone. HCl in EtOH, 3-amino-4//-pyrido[l,2-n]pyrimidin-4-ones 315 were obtained (94JHC125). 

Dodecyloxy-3-(2-chloroethyl)-2-methyl-4//-pyrido[l,2-n]pyrimidin-4-one 317 was obtained by cyclization of 3- l-[(3-dodecyloxy-2-pyridyl)ami-no]ethylidene -4,5-dihydro-2(3//)-furanone (316) in boiling POCI3 (95MIP4). 

Cyclization of ethyl A -(2-pyridyl)-2-methyl)- and A -(5-ehloro-2-pyridyl)-malonamates in a mixture of POCI3 and PPA at 130°C gave 2-ehloro-3-methyl- and 2,7-diehloro-4/7-pyrido[l,2-n]pyrimidin-4-ones in 26 and 61% yields, respeetively (00BMC751). 

Chloro-9,10-dimethoxy-6,7-dihydro-4//-pyrimido[6,1 -a]isoquinolin-4-one was obtained by the cyclization of 7V-[2-(3,4-dimethoxyphenyl)ethyl]barbi-turic acid on the action of boiling POCI3 in 62% yield (98MIP15, 00MIP19,P20). 

The Parham cyclization of the iodinated imide 270 by BuLi in dry THF at —78°C afforded 1 lZ -hydroxy-l,3,4,6,7,l lZ -hexahydro[l,4]oxazine[3,4-a]iso-quinolin-4-one 258 (97JOC2080). Iodide-lithium exchange was faster then addition to the carbonyl group of imide 270 and intramolecular cyclization of the initially formed anion gave compound 258. 

Cyclization of amide 312 by treatment with TFA gave 1 li-butyl-1,3, 4,6,7,1 l -hexahydro[l,4]oxazino[3,4-a]isoquinolin-4-one 313 (97JOC2080). 

Cyclization of (25)-2-(rerc-butoxycarbonylaminomethyl)-l-(2-chloro-acetyl)piperidine on the action of NaH in THF gave (9aS)-2-(rerc-butoxycarbonyl)perhydropyrido[l,2-a]pyrazin-4-one (99H(51)2065). 3-Benzyl-2,3,4,4 ,5,6-hexahydro-l//-pyrazino[l,2-a]quinolin-l-ones 413... 

The acetal 1, obtained from salicylamide and bromoacetaldehyde diethyl acetal, cyclizes on heating to provide l,4-benzoxazepin-5(4//)-one (2).32... 

Alkylamino)- or 2-(arylamino)-3//-l, 3,4-benzotriazepin-5(4//)-ones 15 are obtained from 2-aminobenzoic acid hydrazide. Treatment with isothiocyanates yields the thiosemicarbazides 14, which readily cyclize under the influence of dieyclohexylcarbodiimide. Selected examples are given.357... 

Novel isosteres 545 of the antiviral agent acyclovir were synthesized in three stages (84JHC697) by dehydrative coupling of 3-amino-6-aminomethyl[ 1,2,4]triazin-5-(4//)-one with 2-(benzoyloxy)ethoxyacetic acid to give the respective amide that cyclized and deprotected to give 545. It showed no activity against herpes simplex virus types I and II in cell culture (Scheme 112). 

A 6-endo cyclization by a y-epoxy alcohol can be accomplished through the presence of an appropriately disposed electron-withdrawing group, as found in the total synthesis of (+)-phonomactin. Treatment of the hydroxy-epoxy ketone 30 (R = H) with HC1 afforded the bicyclic compound 31, containing a pyran-4-one ring, in which nucleophilic attack of the y-OH group occurred at the oxirane carbon distal from the unfavorable electronic effect of the carbonyl group (Scheme 8.7) [20a]. 

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