Intramolecular condensations

An important general method of preparing indoles, known as the Fischer Indole synthesis, consists in heating the phenylhydrazone of an aldehyde, ketone or keto-acld in the presence of a catalyst such as zinc chloride, hydrochloric acid or glacial acetic acid. Thus acrtophenone phenylhydrazone (I) gives 2-phenyllndole (I V). The synthesis involves an intramolecular condensation with the elimination of ammonia. The following is a plausible mechanism of the reaction ... 

Intramolecular condensation reactions to generate six-membered carbocycles are mentioned in section 1.12, the polyene cyclization in section 1.15. 

The synthesis of five-, six-, and seven-membered cyclic esters or timides uses intramolecular condensations under the same reaction condifions as described for intermolecular reactions. Yields are generally excellent. An example from the colchicine synthesis of E.E. van Ta-melen (1961) is given below. The synthesis of macrocyclic lactones (macrolides) and lactams (n > 8), however, which are of considerable biochemical and pharmacological interest, poses additional problems because of competing intermolecular polymerization reactions (see p. 246ff.). Inconveniently high dilution, which would be necessary to circumvent this side-... 

For monomers of the AB type, reactions (5.CC) and (5.DD) become AB -> and 2AB AbaB, respectively. If kj. and k are the respective rate constants for these reactions, derive an expression which gives the ring to linear ratio in the product as a function of AB concentration and the two rate constants. Criticize or defend the following proposition To obtain a test of Eq. (5.47) without the complications of intramolecular condensations, a series of otherwise identical polymeriztion reactions could be carried out on monomer mixtures at different concentrations. By... 

The Madelung Synthesis and Related Base-Catalyzed Condensations. The Madelung cyclization involves an intramolecular condensation of an o-aLkylanilide. A classic example of the Madelung synthesis is the high temperature condensation of o-methylacetanihde [120-66-1] to 2-methylindole [95-20-5] by sodium amide. 

Decomposition of the diazoimide (551) by heating in the presence of copper acetylaceton-ate also generated a ketocarbene (552). This undergoes an intramolecular condensation to give the anhydro-4-hydroxy-3-methyl-4-p-nitrophenyl-2-phenyloxazolium hydroxide (553), which cannot be prepared by more classical means (75CL499). 

This polymer may be prepared by stirring the molten w-aminoundecanoic acid at about 220°C. The reaction may be followed by measurements of the electrical conductivity of the melt and the intrinsic viscosity of solutions in w-cresol. During condensation 0.4-0.6% of a 12-membered ring lactam may be formed by intramolecular condensation but this is not normally removed since its presence has little effect on the properties of the polymer. 

This s3mthesis depends on intramolecular condensation of an acylamino-alcohol of the type R—CH(OH)—CH — HN—CO—R, ... 

Conversion to dialkyl ethers (Section 15.7) On being heated in the presence of an acid catalyst, two molecules of a primary alcohol combine to form an ether and water. Diols can undergo an intramolecular condensation if a five-membered or six-membered cyclic ether results. 

Formally analogous to the foregoing Grignard additions are the intramolecular condensations of amides with aromatic systems, found in the Bischler-Napieralski reaction 101), which is of particular interest in isoquinoline and indole alkaloid syntheses (102). Condensations of amidines with reactive methylene compounds also led to enamines (103-106). 

For unsymmetrieal ketones, two eondensation produets are possible. For example, intramolecular condensation of 2,7-octadione may lead to products which follow from the two possible enolates. 

Formation of 5-oxazolones (or azlactones ) (2) by intramolecular condensation of acylglycines (1) in the presence of acetic anhydride is known as the Erlenmeyer-Plochl azlactone synthesis. ... 

The Camps quinoline synthesis entails the base catalyzed intramolecular condensation of a 2-acetamido acetophenone (1) to a 2-(and possibly 3)-substituted-quinolin-4-ol (2), a 4-(and possibly 3)-substituted-quinolin-2-ol (3), or a mixture. 

A possible mechanism is shown. Condensation of 6 and 3 provides 11, which can be attacked by the enol of 2 (12) to provide 13. Intramolecular condensation yields 16, which is then oxidized to 17. A common variant of the Doebner reaction involves first... 

An ingenious synthesis of 1-arylisoindolcs has been developed by Vebor and Lwowski, based upon the reaction of an o-phthalimido-methylbenzophenone (41, R = aryl) with hydrazine (Table IV). The benzophenone is prepared by a Friedel-Crafts reaction with o-phthalimidomethylbenzoyl chloride (40). The mechanism of isoindole formation can be represented sehematically by a sequence involving attack by hydrazine at the imide to give the ring-opened hj drazide (42), followed by cyclization to phthalazine-l,4-dione (44) with displacement of the o-aminomethylbenzophenone (43). Intramolecular condensation of the latter can lead, via the isoindolenine... 

It is believed (54IZV47 72JPR353) that in the first stage the intermediate 282 is formed due to the addition of the CH acid to the enamine moiety with subsequent elimination of amine. The enol form of the intermediate 282 undergoes cyclization in two fashions, depending on the nature of substituent X. In the case of the ester (X = OMe) the attack is directed to the cyano group to form substituted 3-methoxycarbonyl-I//-pyridin-2-one (283) or its tautomer (2-hydroxy-3-methoxycarbonylpyridine). With the amide (X = NH2) intramolecular condensation leads to 3-cyano-l//-pyridin-2-one and its hydroxy tautomer (284). 

The intramolecular condensation reaction of diesters, the Dieckmann condensation, works best for the formation of 5- to 7-membered rings larger rings are formed with low yields, and the acyloin condensation may then be a faster competitive reaction. With non-symmetric diesters two different products can be formed. The desired product may be obtained regioselectively by a modified procedure using a solid support—e.g with a polystyrene 10 ... 

Intramolecular condensation of two amide functions is the key step in the synthesis of 1,3,5-triazocine derivative 5.15... 

Polymeranalogous reactions considered above may be referred to as intramolecular condensation transformations since they are accompanied by elimination of low-molecular products. On the other hand, PCSs can be obtained via polymeranalogous transformations, principally intramolecular polymerization reactions . Thermal and chemical cyclization of poly(acrilonitrile) (PAN) is an example of processes of this type. It was demonstrated by a number of researchers216-225 that thermal transformations of PAN follow the scheme ... 

A cyclic trimer, resulting from the facile intramolecular condensation of the linear trimer coupled with elimination of lithium alkoxide, is produced in the early stages of polymerization carried out at ambient temperature U). Similar condensations might... 

The results of the experiment depicted in Fig. 62 and others similarly obtained are summarized in Table XXXI. In every case the observed gel point is reached at higher than the theoretical extent of reaction. The discrepancies between the observed and calculated ojc s appear to be due to the failure of the theory to take into account a minor degree of intramolecular condensation. Since some of the interunit linkages... 

The preceding equations will, of course, be somewhat in error owing to the neglect of intramolecular condensations. Very large species will be suppressed relatively more on this account. All conceivable errors can do no more, however, than to effect a distortion of the quantitative features of the predictions, which will be small in comparison with the vast difference between the branched polymer distribution and that usually prevailing in linear polymers. From this point of view, the statistical theory given offers a useful description of the state of affairs. 

At extents of reaction which are not too large (i.e., up to the gel point see text), the total number N of molecules may be taken as the number of units less the number of linkages formed, intramolecular condensation being neglected as previously. Thus... 

Intramolecular condensation of phosphonate carbanions with carbonyl groups carried out under conditions of high dilution have been utilized in macrocycle syntheses. Entries 7 and 8 show macrocyclizations involving the Wadsworth-Emmons reaction. Entries 9 to 11 illustrate the construction of new double bonds in the course of a multistage synthesis. The LiCl/amine conditions are used in Entries 9 and 10. 

The original route for the synthesis of potassium 5-methyl-l,3,4-oxadiazole-2-carboxylate (39) via an intramolecular condensation of ethyl (2-acetylhydrazinyl)-(oxo)acetate (37) suffered from moderate yields (Scheme 6.10). 

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