Cyclodehydration reaction

Ueda and coworkers reported, in 1975, the preparation of polyamides 11 from unsaturated bisazlactones 10 and a variety of diamines (Scheme 3) (JL1). In a DTA study of one of these polyamides (11, R = CHj.Tr = (CHo)g), an endotherm was noted near 200dC. It was suggested, without supporting evidence, that this endotherm might be due to a cyclodehydration reaction leading to polyimidazolinone 12. 

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>. 

The synthesis of benzo[Z>]furan derivatives has become a very active field because these molecules have been recently identified as having a variety of biological activities. For example, they can function as inhibitors of protein tyrosine phosphatase IB with antihyperglycemic properties <00JMC1293>, as well as potent and short-acting p-blockers in the treatment of various cardiovascular diseases . An inexpensive, reusable clay has been utilized to catalyze a facile cyclodehydration under microwave without solvent to form 3-substituted benzo[2>]furans from substituted a-phenoxy acetophenones 104. One of the important features of this procedure is that all the selected cyclodehydration reactions are complete in less than 10 minutes <00SL1273>. 

Treatment of the product with phosphorus oxychloride leads to a cyclodehydration reaction possibly via the imino chloride. There is thus obtained the antipsychotic compound loxapine (38-7) [39]. 

Initial conversion rates are not easy to compare because of the very different coverages obtained according to the second metal used. We can only notice that for M/Cus = 0,10 and 0,17 (Cu-Ir and Cu-Rh), these rates are very low. The main important feature i. that the same cyclodehydration reactions are observed, like that for Cu-Ru catalyst, whatever the nature of the second metal is. 

Above M/Cus = 0,10 to 0,15 (C) the activity increases and the cyclodehydration reaction leading to furanic products is the main one. 

In C, further exchange between metallic copper and Mn+ would create new sites able to catalyze the cyclodehydration reaction (CDOH). These sites must be, as protons, electrophilic centers able to weaken C-O bonds enough to allow intramolecular SN2 reactions mainly on primary carbon atoms. 

In the case of 2,5-dimethylfuran (51) the dicarbonyl compound is revealed by the disconnection of one carbon-oxygen bond ring construction is of type (44). The forward synthetic reaction is a cyclodehydration reaction effected by the action of acetic anhydride in the presence of zinc chloride (Expt 8.12). 

Azine approach. Oxazolo[3,2-a]pyridinium salts (210) were first obtained from the cyclodehydration reaction of l-phenacyl-2(lii)-pyridinone in sulfuric acid (67JHC66). These salts can also be prepared from 2-halo-l-phenacylpyridinium derivatives (211) by treatment with a base which causes ylide formation and hence cyclization by intramolecular substitution (69JOC2129, 76CB3646). It is recommended that a bulky tertiary amine is used as base in order to avoid opening of the ring or substitution of the 2-halo substituent in the starting material (211). Isoquinoline and quinoline analogues have also been prepared by these methods. 

Cyanogen bromide reacts with threo- 2-piperidyl carbinol (278) to form the trans imine (279). The latter is also formed from the erythro 1-carbamate (280) using thionyl chloride for the cyclodehydration reaction. The latter reaction therefore proceeds by inversion of the configuration at the carbinol carbon atom (73AP284). 

Oxadiazoles by cyclodehydration. Reaction of the A-nitrosoglycine derivatives (e.g., 562) with acetic anhydride gives l,2,3-oxadiazolium-5-olates (sydnones) (e.g., 563) (Scheme 254). Additional synthetic approaches to 1,2,3-oxadiazoles are discussed in CHEC-III . 

Probably the best method for synthesizing 2-substituted benzimidazoles makes use of the cyclodehydration reaction between a carboxylic acid or derivative and 1,2-arylenediamines under acidic conditions (81HC6). Both 2-(pyridyl)-l//-benzimidazoles 72, 73 and l-alkyl-(l//-benzimidazol-2-yOpyridinium salts 74 shown in Eq.(l 1) have been efficiently synthesized by Hein s benzimidazole synthesis (92S395, 92UP1 93CPB614) [Eq.(16) and (17)]. 

The carbonyl unit involved in the cyclization process is not restricted to aldehydes and ketones. The carbonyl of acid derivatives, such as amides can also be utilized. One of the more important cyclodehydration reactions is applied to the formation of heterocychc systems via cyclization of p-aryl amides, in what is called the Bischler-Napieralski reaction In this reaction amides of the type 47 are... 

Kim, G., Keum, G. A new route to quinolone and indole skeletons via ketone and ester-imide cyclodehydration reactions. Heterocycles 1997,45, 1979-1988. 

The synthesis of isoquino[3,4-h]acridine 40 from the interaction of p-phenylenediamine with 2-formylcyclohexanone, followed by ring closure (after in situ rearrangement) and then dehydrogenation of 39, has been reported by Berde et al. (72IJC332). Further examination of the cyclodehydration reaction also gave octahydroquino[3,2-fl]acridine 41 as the minor product, which was then dehydrogenated to provide quino[3,2-a]acridine 15 (Scheme 8) (74IJC1324). 

Triazoles are available via cyclodehydration reactions of iV,iV -diacyl-hydrazines with amines, although the conditions are often quite vigorous. An interesting variant utilises i ym-triazine (1,3,5-triazine) as an equivalent of HN(CHO)2. Condensations of aminoguanidine with esters, or an orthoformate, give 3-amino-l,2,4-triazoles. ... 

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