Dehydrative cyclization

As shown in Scheme 14, a sulfuric acid-catalyzed dehydration-cyclization-elimination domino sequence starting from protonation of the secondary hydroxy group of the indolo[2,3- ]quinolizidine 112 led to the isolation of the pentacyclic compound 113 in good yield <1999EJ03429>. 

One of the most common approaches to pyrrole synthesis is the Paal-Knorr reaction, in which 1,4-dicarbonyl compounds are converted to pyrroles by acid-mediated dehydrative cyclization in the presence of a primary amine. The group of Taddei has reported a microwave-assisted variation of the Paal-Knorr procedure, whereby a small array of tetrasubstituted pyrroles was obtained (Scheme 6.181) [342], The pyrroles were effectively synthesized by heating a solution of the appropriate 1,4-dicarbonyl compound in the presence of 5 equivalents of the primary amine in acetic acid at 180 °C for 3 min. The same result was obtained by heating an identical mixture under open-vessel microwave conditions (reflux) for 5 min. Interestingly, the authors were unable to achieve meaningful product yields when attempting to carry out the same transformation by oil-bath heating. 

A set of heterocyclic ketones including 1,3,4-oxadi azole-linked compounds were synthesized via a dehydrative cyclization using the Burgess reagent in a single-mode microwave <2003BML3909>. 

Arylbenzoxazoles were prepared by Pd-catalyzed three-component condensation of aryl halides with o-aminophenols and carbon monoxide followed by dehydrative cyclization [24], A variant of such methodology using o-fluorophenylamines in place of o-aminophenols was used to synthesize arylbenzoxazoles [25]. 

The photolysis of 2-methyl-5-nitro-l//-imidazoles 132 in a water-containing solvent80 gives oxime 133, which is in turn hydrolysed to 134 followed by a dehydrative cyclization to the 1,2,4-oxadiazole 135. Light-induced hydrolysis of 135 gives 136 (equation 68). 

Sakakura A, Umemura S, Ishihara K (2008) Convergent Total Syntheses of Fluvibactin and Vibriobactin Using Molybdenum(vi) Oxide-catalyzed Dehydrative Cyclization as a Key Step. Chem Commun 3561... 

The C-nucleoside analog 907 was prepared from 903 by hydrolysis to the amide 904 followed by condensation with the diamine 905 to give 906, which underwent dehydrative cyclization to 907 (83JHC1169). 

Although furazan ring formation by various routes has been reported the three most synthetically useful approaches involve the dehydrative cyclization of 1,2-dioximes, the deoxygenation of furoxans, and the Boulton-Katritzky rearrangement of other five-membered heterocyclic systems. 

Dehydrative cyclization of iV-acylanthranilamide derivative 418 with a large excess of a PPh3/l2/tertiary amine combination gave the 4-imino-4//-3,l-benzoxazine 108 in good yield (Scheme 80) <1999JOC1397, 2000JOC1022>. 

PCls-induced dehydrative cyclization of the amino and amide functionalities of the thiadiazole moiety of the pyrazolopyrimidine 172 led to the formation of the imidazo[4,5-f][l,2,5]thiadiazole suhstmcture (Equation 13) <2001W0040231>. 

Monocyclic diazepines have also been prepared by the Raney nickel-catalyzed ring closure of compounds of type H2NCH2N(R)(CH2)3NH2 or dehydrative cyclization of HOCH2N(R)(CH2)3NH2 <67AHC(8)21, p. 62). 

Sillcon(IV) chloride, SiCl4. Mol. wt. 169.90, b.p. 57.6°. Supplier Alfa. Silicon(IV) chloride is the most effective Lewis acid eatalyst for dehydrative cyclization of the enamino ketone 1 to julandinc (2). TiCI4 is almost as effective. Other Lewis acids are markedly less effective.1... 

Members of this ring system (194) were synthesized by reduction of the 2-acyloxyquinazolines 192 with alkali metal borohydrides followed by dehydrative cyclization of the resultant hydroxyalkyl derivatives (193) [74JIC453 85IJC(B) 1035]. 

The oxazolo[3,2-tf]quinazoline (200) was obtained by cyclization of 3-(2-chloroethyl)quinazoline-2,4-dioine (199) with potassium carbonate (60JCS3551). The same compound was also obtained when ethylene oxide reacted with 2-chloroquinazolin-4-one (201) in the presence of sodium hydroxide (60JCS3551). 3-Acylalkylquinazoline-2,4-diones (201) underwent intramolecular dehydrative cyclization upon heating with polypho-phoric acid to 203 [89IJC(B)274]. 

Singh and Lai [73IJC959 76IJC(B)685] prepared 8,9,10,11-tetrahydro-benzothiazolo[3,2-c]quinazolin-7-ium perchlorate (287) by dehydrative cyclization of 4-[(2-oxocyclohexyl)thio]quinazoline (286) with sulfuric acid and then perchloric acid. 2-(2-Azidophenyl)benzothiazole (288) reacted with triphenylphosphine to give the iminophosphorane, which cyclized to 289 on treatment with ethoxycarbonyl isocyanate (89T4263). 

The title compounds were synthesized from quinazoline precursors as exemplified by the dehydrative cyclization of the diformyl derivatives (456), obtained from 2-methyl-3-phenylquinazoline (455), with phosphoric acid to give the 6-formylquino[2,1 -b]quinazolin-12-one 457 (73IJC532). 

The title compounds were also synthesized from quinazoline precursors through the formation of their 1,4-oxazine rings. N-Methylisatoic anhydride was first condensed with ethanolamine to give N-(2-hydroxyethyl)-2-methylaminobenzamide (580). Cyclization of the latter with ethyl pyruvate gave quinazoline derivatives 581 which, upon hydrolysis and dehydrative cyclization with l-methyl-2-chloropyridinium iodide, afforded the l,4-oxazines[3,4- ]quinazoline (582) (8QJHC1163). 

Dehydrative cyclization of 3-(2-hydroxyethyl)-l-methyl-4-oxo-2-quin-azolinacetic acid (692) yielded the l,4-oxazepino[5,4-[Pg.122]

Acidic cyclodehydration of 3-amino-2-formamidothiazolium mesylate to give 138143 and preparation of imidazo[l,2-a]imidazoles (140 X = NH)144 and imidazo[2,l-6]thiazoles (140 X = S)145 by dehydrative cyclization of the corresponding imidazoles (139 X = NH, S) are examples of syntheses by cyclization of exocyclic amines to carbonyl groups. 

The monocyclic systems (351) and (353) have been obtained by the dehydrative cyclization of (350) and (352), respectively. 

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