Alcohols cyclocondensation

In the reverse reaction, thioheteroaryl amides reacted under reflux in alcohol with haloketones or aldehydes to give the corresponding 2-heteroarylthiazole derivatives (238, 271, 482, 550, 751, 765, 776, 781). 2,2 -Bithiazoles (4,4 -disubstituted) have been obtained in 80 to 90% yield by cyclocondensation of 1 mole rubeanic acid with 2 moles of a-bromoketones in polyphosphoric acid at 95 to 135 C (780). Some multiheteroaryl substituted thiazoles have been also reported (704). 

Cyclocondensation of l,6-dimethyl 4-phenyl-5-carbethoxy-3,4-dihydropyrimidine-2-thione with ClCO-Ph-Cl I—(—() in alcohol-free chloroform or with 2-methylmalonyl dichloride in DCM resulted in the thiazinium... 

Palladium-catalyzed cyclization reactions with aryl halides have been used to synthesize pyrazole derivatives. V-Aryl-lV-(c>-bromobenzyl)hydrazines 26 participated in a palladium-catalyzed intramolecular amination reaction to give 2-aryl-2W-indazoles 27 . Palladium-catalyzed cascade intermolecular queuing-cyclocondensation reaction of o-iodophenol (28) with dimethylallene and aryl hydrazines provided pyrazolyl chromanones 29 <00TL7129>. A novel one-pot synthesis of 3,5-disubstituted-2-pyrazolines 32 has been achieved with an unexpected coupling-isomerization sequence of haloarene 30, propargyl alcohol 31, and methylhydrazine <00ACIE1253>. 

Cyclocondensation between substituted /3-amino alcohols and carbonyl derivatives 184... 

The cyclocondensation of l,3-amino alcohols with carboxylic acid derivatives is a method often applied for the synthesis of 5,6-dihydro-4/7-l,3-oxazines <1996CHEC-II(6)301 >. Ebsorb-4, a weakly acidic zeolite-type adsorbent with 4 A pore size, proved an efficient catalyst of the cyclization of benzoic acid and 3-aminopropanol <2002TL3985>. In the presence of zinc chloride as a catalyst, the expulsion of ammonia drove the reactions of 3-aminopropanol with nitriles to completion, affording 2-substituted 5,6-dihydro-47f-l,3-oxazines in good yields... 

The reaction of 2-aminobenzyl alcohol 376 with 2-chloro-4,5-dihydroimidazole afforded [2-(4,5-dihydro-177-imidazol-2-ylideneamino)phenyl]methanol hydrochloride 377, which upon treatment with carbon disulfide gave l-(477-3,l-benzoxazin-2-yl)imidazolidine-2-thione 378 (Scheme 71). The assumed reaction mechanism involved the initial formation of the dithiocarbamate 379, which underwent intramolecular nucleophilic addition to furnish the unstable thiazetidine 380. By nucleophilic attack of the hydroxy group on the carbon atom of the thiazetidine ring, thiocarbamate derivative 381 was formed, which gave the final 3,1-benzoxazine 378 by an intramolecular cyclocondensation with the evolution of H2S <2006H(68)687>. 

Cyclocondensation of ethyl 2-aminonicotinate in presence of HC(OEt)3 and various primary amines gave 22 3-substituted pyrido[2,3-,7]pyrimidin-4(377)-ones 371 <1995PHA719>. Fourteen 3,5,7-triarylpyrido[2,3-r7]pyrimi-dine-2,4(l/7,37/)-diones 372 have been prepared from the reaction of either 2-amino-3-cyano-4,6-diarylpyridines or the 3-carboxamido products of alcoholic KOH hydrolysis, with aryl isocyanates better yields were obtained from the amides <1995IJB740>. 4-Aminopyrido[2,3- pyrimidin-5(8//)-one 158 was synthesized by treatment of 2-amino-3-cyano-4-methoxypyridine with trimethylsilyl iodide to give the corresponding pyridin-4(177)-one, which was refluxed with formamidine acetate in ethoxyethanol to effect the cyclization <2000JME3704>. 

C12H18O, Mr 178.28, does not occur in nature. It is a colorless liquid, >/ o.oi3kPa 86-91 °C, 20 0.960-0.964, Up 1.511-1.514, with a long lasting diffusive, fresh, floral, rose odor. The alcohol is prepared by hydrogenation of tetrahydro-4-methylene-5-phenylpyran which is obtained by cyclocondensation of benzaldehyde with 3-methyl-3-buten-l-ol in the presence of -toluenesulfonic acid [144]. 

Cyclocondensation of 5-halovaleraldehydes (186) and 1,3-amino alcohols (187) gave equilibrium mixtures of tram- and c s-pyrido[2,l-h][l,3]oxazines (188 and 189), with a predominance of the frans-fused bicycle both diastere-omers contained the substituent in the equatorial position (90TL4281 94JA2617,94JOC6904). However, kinetic selectivity for the formation of cis-pyrido[2,l-h][l,3]oxazine (189) was exhibited versus the tram compound 188 in the case of the dimethyl derivative (R = R1 = Me) (90TL4281). 

The side chains R in Table 7.8 and S02R in Table 7.9 can be added before or after cyclocondensation, for example, by the attachment of NaHS03, amines, or alcohols to vinyl or allylsulfonyl groups. 

Interaction of 8a with ethylchloroacetate in methanolic sodium methoxide leads to cyclocondensation with elimination of EtOH and HC1, affording the triazine-3,14-dione derivative (14), while 8a was reacted with alcoholic CS2-KOH to give 14-methyl-2,3-dihydro-13-oxo-2H,13H,14H-[l]Benzopyrano [3/,4/ 5/,6/]pyrano[3,2-e]-[l,2,4]triazolopyrimidine-2-thione (15) (Scheme 5). 

MUller reports a four component, one-pot synthesis of pyridines <02TL6907>. For example, aryl halide 15 and propargylic alcohol 16 were combined in the presence of copper and palladium to afford enone 17. The addition of cyclic enamine 18 led to Michael addition and the subsequent cyclocondensation was achieved by adding ammonium chloride and acetic acid (19—>20). Other multicomponent approaches to substituted pyridines have been reports by Litvinov <02RCBIE362>, Elkholy <02SC3493> and Veronese <02T9709>. 

As a consequence of the mild reaction conditions in the sequence to 3-halo furans 55 the palladium catalyst should be still intact to trigger another Pd-catalyzed coupling in the sense of a sequentially Pd-catalyzed process [31]. As a consequence, a sequential Sonogashira-deprotection-addition-cyclocondensation-Suzuki reaction, where the same catalyst system is applied in two consecutive significantly different cross-coupling reactions in the same reaction vessel should be feasible. Therefore, upon consecutive reactions of (hetero)aroyl chlorides 7 and THP-protected propargyl alcohols 54, Nal and PTSA, and finally, addition of 1.05 equiv of boronic acids 60 and sodium carbonate, the substituted 3-aryl furans 61 can be obtained in decent yields (Scheme 35). 

Likewise, pyrroles are accessible if in the last cyclocondensation step a primary amine is applied. Therefore, upon CIR of electron-deficient (hetero)aryl halides 11 and (hetero)aryl propargyl alcohols 12, after subsequent Stetter reaction with aldehydes 92 in presence of catalytic amounts of thiazolium salt 93, and after addition of primary amines 96 or ammonium chloride and glacial acetic acid, the 1,2,3,5-tetrasubstituted or 2,3,5-trisubstituted pyrroles 97 are obtained in good yields in a one-pot procedure (Scheme 52) [259, 260]. 

Cyclocondensation of 2-halobenzimidazole 322 (or 2-haloimidazoles) with 2-hydroxybenzyl alcohol 321 in the melt gave 85-91% of 2//-benzimidazo[2,l-/ ][l,3]benzoxazine 323 (Scheme 76) <2005CHE1201>. 

One of the most widely used synthetic methods for preparation of the linearly annelated tricycles 205, containing a six-membered aromatic ring A, is the cyclocondensation of anthranilic acids and lactim ethers. - " Cyclocondensations have been carried out without solvent or in solutions in acetone, " alcohol, chloroform, benzene, - - or ethylene glycol monomethyl ether acetate. - Besides lactim ethers, lactim thioethers have been used as reaction partners of anthranilic acids. - ... 

The reaction between secondary enediamines and propiolic acid esters has been studied in detaiP. In aprotic solvents such as benzene and dioxane, 8 adds to methyl propiolate at ambient temperature to give almost quantitatively product 118 with a tron -configuration of the new double bond, as indicated by a Jhh coupling constant of around 16 Hz in the NMR spectrum. It appears that the reaction proceeds via an ene-addition mechanism. In refluxing ethanol, the C-adducts 118 are converted to the heterocyclic compounds 119. The direct transformation of 8 to 119 is easily achieved in alcoholic solvents. 1,1-Enediamines with jS-nitro, ester and acetyl substituents undergo analogous addition and cyclocondensation reactions to give heterocyclic compounds jj5(39,i2o A -Ethynylcarbonyl imidazole behaves similarly to propiolic acid esters ° (equation 41). 

Furthermore, it has been shown that compounds of type 235 are versatile starting materials for addition and cyclization reactions employing reactive triple and double bonds. With methyl propiolate, syn addition takes place to aiford the adducts 240. In the presence of alcohols, compounds 240 are cyclized to give the imidazo[l,2-a]pyridines and pyrido[l,2-a]pyrimidines 241136 (Scheme 63). By treatment with methyl acrylate, the lactone derivatives 235 give the spiro compounds 242 in an addition and cyclocondensation sequence.137 With dimethyl acetylenedicarboxylate, 235 forms several condensed and unsaturated spiro compounds 243, similar to 242,137 as well as the tricyclic 5-lactone 244 (Scheme 64). 

---