Cyclodehydration alcohol

Nicolaou and co-workers established the severely strained A-ring oxazole (21) in their total synthesis of antitumor agent diazonamide A through initial oxidation of the hindered alcohol of intermediate 20 with TPAP and subsequent Robinson-Gabriel cyclodehydration of the resultant ketoamide with a mixture of POCI3 and pyridine (1 2) at 70°C. ... 

A direct catalytic conversion of esters, lactones, and carboxylic acids to oxazolines was efficiently achieved by treatment with amino alcohols in the presence of the tetranuclear zinc cluster Zn4(0C0CF3)60 as catalyst, essential for condensation and cyclodehydration reactions. For example, the use of (5)-valinol allowed the easy synthesis of oxazolines 125 and 126 in satisfactory yields <06CC2711>. A one-pot direct preparation of various 2-substituted oxazolines (as well as benzoxazoles and oxadiazoles) was also performed from carboxylic acids and amino alcohols (or aminophenols or benzhydrazide) using Deoxo-Fluor reagent <06TL6497>. 

Recently, Settambolo et al. [194] reported a formal synthesis of (S)-myrmi-carin 217 (206) using a sequence of reactions slightly modified from the one described in Scheme 4. Indeed, rather than to cyclize directly the diester (S)-207, the latter was first transformed into the aldehyde 219 (Scheme 7) that was further intramolecularly cyclodehydrated into ester 220. The latter can be converted into (S)-myrmicarin 217 (206) via the alcohol (S)-209 as described previously by Sayah et al. [192] (see Scheme 5). 

The second type of cyclodehydration to be presented is the formation of cyclic enol ethers and cyclic enamines. Here, an alcohol or amino group reacts with an enol, resulting in ring closure with loss of H20. Such reactions... 

The conceptually simple cyclodehydration of a carboxylic acid and a (3-amino alcohol to an oxazoline requires harsh conditions of high temperature with azeotropic water removal (e.g., boric acid in refluxing xylene). Nonetheless, good yields of the oxazoline can be obtained if sensitive functionalities are absent. " A much milder approach has been developed by Vorbriiggen where the reaction of carboxylic acids with (3-amino alcohols is carried out in the... 

Wuts and co-workers recently reported that the Vilsmeier reagent is superior to thionyl chloride for the cyclodehydration of primary and secondary p-hydroxy amides to prepare oxazolines, in particular, for oxazoline 18b, which is used in Taxol synthesis (Scheme 8.10). Some other examples are shown in Table 8.5 (Fig. 8.3). As expected, inversion of configuration at the alcohol bearing carbon atom is observed. Of the examples examined, serine afforded low yields due to the formation of dehydroalanine. The reaction is conveniently carried out in pyridine at room temperature. p-Chloro amides are also formed, which can be converted to the oxazoline with DBU, generally using the same mixture without isolation. The... 

Tetralins indanes. P205 can be used for cyclodehydration for substrates such as 1-aryl-l-pentanols or 2-aryl-2-hexanols. In the case of secondary alcohols, yields are sometimes improved by dehydration with TsOH to a styrene followed by cyclization with P2O5.1 The product of the second example is a known sesquiterpene, calamenene. 

Reaction of N-(2-aminobenzoyl)-2-aminobenzyl alcohol (711JC647) or anthraniloyl anthranilic acids (597) (76JIC382) with carbon disulfide gave the 3-(2-carboxyphenyl)-2-mercaptoquinazolin-4-ones (598), which underwent cyclodehydration to the title compounds 599 (76JIC382). 

Aziridines.4 This reagent (1) effects cyclodehydration of p-amino alcohols to aziridines in 85-95% yield. 

This cyclodehydration is well known, especially for the synthesis of isosorbide (2-5) and is usually carried out in strongly acidic medium. Its mechanism was proved (4) to be a SN2 intramolecular reaction catalyzed by protonation of the alcoholic functions. The products distributions we obtained are close to those obtained by acidic catalysis. 

Another example is the cyclization of the racemic allylic alcohol 232 at -80°C which furnished the racemic tetracyclic bis-olefin 233 in 70% yield (89, 90). Ozonolysis of 233 gave the bicyclic triketone aldehyde 234 which underwent under acidic conditions a double intramolecular aldol cyclodehydration to produce racemic 16,17-dehydroprogesterone 235. This represents the first synthesis of a steroid via the now so-called "biomimetic" polyene cyclization method. 

Cyclization of the alcohols (142) with phosphorus oxychloride gives the derivatives (143) (Equation (10)) <72AHC(l4)i>. The meso-ionic derivatives (145) are produced by cyclodehydration of the acids (144) using acetic anhydride (Equation (11)) <83IJC243>. Reacting amine (146) with ethyl... 

Cyano halides, see Halo cyanides Cyanohydrins, see Hydroxy cyanides Cyanohydrin synthesis, 414, 604 Cyano iniides, preparation, 434 Cyano ketones, see Keto cyanides a-Cyano lactones, preparation, 534 Cyclodehydration of ketones and alcohols, 15, 843... 

Xylose-based chemicals analogous to some of the glucose derivatives discussed in the next section are commercially available. An example is xylitol, the pentahydric alcohol that is manufactured by hydrogenation of the aldehyde group in xylose. One of the unique reactions of the pentoses known since the nineteenth century is cyclodehydration to yield furfural. Xylose, for example, is dehydrated by acid treatment through one or two intermediates to form the furan-substituted aldehyde in quantitative yield, or 64.0 wt % of the xylose... 

Bogert-Cook synthesis. Condensation of (1-phenylethylmagnesium bromide with cyclohexanones, followed by cyclodehydration of the tertiary alcohol with concentrated sulfuric acid, with formation of octahydrophenanthrene derivatives and a small amount of spiran. 

Anhydrous piperazine is a white solid which is obtained as leaflets when crystallised from alcohol, m.p. 106°C (b.p. 145-146 C). Piperazine may be prepared by several methods [40], However, industrially it is best prepared by cyclodehydration of 2-hydroxyethylamine (34) or N-(2-aminoethyl)-2-hydroxyethylamine (35) at high temperatures in the presence of a catalyst like Ra-Ni and habdes of Zn, Fe, A1 or Mg [41-43]. Catalytic deamination of diethylenetriamine (36) in the presence of Ra-Ni catalyst in an autoclave at 150°C also gives piperazine. Another useful method to prepare piperazine involves reduction of pyrazine (37) by sodium and ethanol [40] (Scheme 1). 

---