Cyclo dehydration

A viscous solution of poly(amic acid) can be processed into films, fibers, and coatings, and the final product undergoes thermal cyclo dehydration. 

Properties of ferrocene-containing polymers have been improved by inclusion of pyrazole systems in the backbone. The synthesis of (748) was achieved by condensation of bis()3-diketoferrocenes) with aromatic dihydrazines to give polyhydrazones that were later cyclo-dehydrated (B-80MI40408). 

Davies et al. describe the preparation of both oxazole- and thiazole-containing derivatives of combretastatin. By formation of the ketoamide intermediate 60, in a 54% yield (Scheme 14), both classes of compounds may be obtained by altering the last step of the reaction [58]. To produce the oxazole 61 a cyclo-dehydration reaction was performed using triphenylphosphine-iodine-triethylamine, and the thiazole compound 62 was formed by thiona-tion using Lawesson s reagent, with an excellent yield (94%). 

In the same publication, it was reported that this cyclo-dehydration could also be affected by using tosyl chloride and the polymer-supported phosphazene base PS-BEMP, and again, microwave heating was found to be advantageous (Scheme 6.25). In utilising this protocol, no scavenger purification strategy was deemed necessary and the authors note that this is the most efficient 1,3,4-oxadiazole synthesis of the three polymer-supported methods described. 

A related series of 5-substituted-2-amino-oxadiazole compounds have also been prepared in a one-pot procedure using a microwave-assisted cyclisation procedure (Scheme 6.26)164. Rapid preparation of the pre-requisite ureas from the mono acyl hydrazines and various isocyanates (or the isothiocyanate) was easily achieved by simple mixing. The resulting products were then cyclo dehydrated by one of the two procedures either by the addition of polymer-supported DMAP and tosyl chloride or alternatively with an immobilised carbodiimide and catalytic sulphonic acid. Purity in most cases was excellent after only filtration through a small plug of silica but an SCX-2 cartridge (sulphonic acid functionalised - catch and release) could be used in the cases where reactions required additional purification. 

Quinolizinium ions fused with thiophene were prepared by cyclo dehydration. A quaternary salt formed by reaction between 2-pyridinecarbalde-hyde and 3-bromomethylthiophene was cyclized with HBr to thieno[3,2-hjquinolizinium salt (270) (72%) (57JA4380). 

Cychdehydration. The sulfonic acid resin Ambcrlite-15 was found to be more satisfactory than Bradsher s reagent (2, 214), sulfuric acid, or formic acid for cyclo-dehydration of 2-methyl-4-phenyl-2-butanol (1) to 1,1-dimethylindane (2). ... 

The maleimide, nadimide, and methyl nadimide endcaps were prepared by reacting the appropriate anhydride and p-aminobenzoic acid in acetone at room temperature to yield the corresponding amic acids. The amic acids were cyclo-dehydrated using acetic anhydride in the presence of sodium acetate according to the method of Rao (II). The endcaps were then treated with oxalyl chloride according to the method of Adams and Ulich (12) to yield the acid chlorides. 

As described previously, thiazolines are versatile intermediates to thiazoles. In addition, thiazoline rings are structural motifs found in numerous natural products. Among a variety of methods for the construction of thiazolines, the cyclodehydration protocol is perhaps most popular. Bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) is used as the cyclo-dehydrating agent for the conversion of 3-hydroxy thioamide 60 to the bis(thiazoline) 15 <04H(63)773>. A more recent protocol for the cyclodehydration of P-hydroxy thioamides to thiazolines involves pyridine-buffered phosphorus oxychloride as exemplified by the formation of 62 from 61 <04JA12897>. 

Involvement of 4-chloroformyl(naphthalic anhydride) in preparing monomers with phenyl-substituted heterocyclic fragments proves to be correct. Thus, bis[l-phenyI-2(4,5-dicarboxynaphthyl) benzimidazoIe-5-yl]-sulfone dianhydride was obtained by treating bis [(3-amino-4-phenylamino)-phenyl]sulfone -a product based on commercial 4,4 -dichlorodiphenyl-sulfone with a two-fold molar amount of 4-chloroformyl(naphthalic anhydride) and subsequent cyclo-dehydration of the compound prepared [124, 125]. 

Dioxopentyl)-2-hydroxychromanones, such as (284), have been cyclo-dehydrated in high yield, under alkaline conditions, to the xanthone (285) this route resembles biosynthetic pathways.In a synthesis of benzoxanthones, a photo-induced Fries rearrangement of a 2-benzoyloxy-4-methoxy-6-methylben-zoyl ester was employed, but in several experiments a mixture of ketones was obtained. However, when the diester (286) was similarly treated, it gave the ketone (287), which cyclized to the xanthone (288). ... 

I. Defaye, A. Gadelle, and C. Pedersen, Process for cyclo-dehydrating ketoses, obtained anhydrides and their use as food additive. American Patent 4,861,871, 29.8.1989. 

Acrolein cyanhydrin 211 was converted into its methoxymethyl ether 212, in turn alkylated with 1,3-dibromopropane to give the key 6-carbon synthon 213. m-Methoxybenzoic acid was utilized as the ring A component. Reductive alkylation via dianion 215 led to dihydroaromatic intermediate 216 which was decarboxylated with ensuing aromatization using lead tetraacetate (or, alternatively, anodic oxidation) to afford 217 in excellent yield. Unmasking of the carbonyl function generated known enone 218 ° (see Volume 2, pp. 693,697), which was condensed with 2-methyl-1,3-cyclopentanedione 12 to produce prochiral trione 219 in high yield. The latter had been cyclized previously to (+) 15c and thence converted into estrone. Alternatively, trione 219 was cyclo-dehydrated to the well-known estrone precursor estrapentaene 193 (see Volume 2, pp. 697, 701, 705). 

In contrast to the synthesis of 128, the preparation of tribenzotriquinacenes is relatively efficient when 2,2-disubstituted 1,3-indanediols are subjected to two-fold cyclo dehydration [65] (Scheme 29). Somewhat varied conditions have been used, depending on the starting material. Best yields (>30%) were obtained for the ce tro-methyl derivative 7, whereas the yield of the benzyl-substituted analogue 135 is relatively low. The moderate yields of the tribenzotriquinacenes shown in Scheme 29 have to be attributed to several unfavorable... 

The structure of the proposed intermediate has not been confirmed but the fact that the reaction does not occur without an acid catalyst supports this belief. Upon protonation the strained ring can easily rearrange to give a very stable triphenyl carbocation which combines with the nucleophilic amine to give the unstable intermediate. This compound then easily undergoes cyclo-dehydration to give 2,3,3-tri-phenylphthalimidine. 

The formation of the keto-amide intermediate can occur in one day at room temperature which indicates that the cyclo-dehydration of the intermediate is the slow step in the synthesis of 2-pheny1-3-benzyl-id inephthalimidine. ... 

In a recent investigation (described below), we expanded the utility of the carbazate resin by applying it to the efficient solid-phase syntheses of 1,3,4-oxadiazole derivatives 11 and 1,3,4-thiadiazole derivatives 12 via selective, reagent-based cydization of an acyl-dithiocarbazate." The process employs an acyidithiocarbazate resin, from which the respective targets are generated by cyclodesulfurization (Figure 10.2, route a) or cyclo-dehydration (Figure 10.2, route b). 

Wipf et al. (2005) reported microwave irradiated rapid 0,N-acylation-cyclo-dehydration cascade reaction of oximes and acid chlorides to give oxazoles. The microwave irradiation allowed considerable acceleration of the rate of oxazole formation and increased the yield of this synthetically attractive heterocycle formation process. The starting oximes were readily obtained from commercially available ketones in yields exceeding 90%, while the yields of isolated oxazoles ranged from 23% to 62%. 

Kanaoka, Y., E. Sato, and O. Yonemitsu Amino Acids and Peptides. II. Cyclo-dehydration of Some Tryptophan-Dipeptides and their Derivatives with Polyphosphate Ester. Tetrahedron 24, 2591-2594 (1968). 

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