Cyclization of carboxylic acids

Table 8. Cyclization of carboxylic acids onto alkenes acyl radical synthon...

The relationship between regioselectivity and acid-base effects in the cyclization of carboxylic acids with a pendant triple bond has been systematically investigated both experimentally and with the density functional theory calculations. Regiocontrolled cyclizations by acid or base catalyst has been developed [(21) (22) or (23)].39... 

Three new monoterpenoid lactones, (28)—(30), isolated from the urine of koala bears fed on Eucalyptus punctata, appear to have arisen from the cyclization of carboxylic acids formed as hydrolysis products of glucuronide conjugates from the metabolism of a- and /3-pinenes.70 Linalool injected into various plant species has been claimed to be converted into a-terpineol and other monoterpenoids.71 However, direct interconversions cannot be inferred from this type of non-radioactive tracer study. The terpenoids alleged to be produced may well be stress metabolites or be formed b secondary processes that perturb the usual pattern of terpenoid formation. 

When a 2-alkylbenzo[b]thiophene undergoes Friedel-Crafts acylation with A1C13-cinnamoyl chloride, the resulting 3-ketone cyclizes spontaneously into the 4-position with loss of benzene to give the cyclic ketone 124.515 With 2-bromobenzo[b]thiophene, a similar reaction gives a mixture of 124 [R = Cl (sic)] and the 2-Br, 3-COCH2CHPh2 substituted benzo[f>]thiophene derivative with 2-methoxybenzo[h]thiophene, the ether is demethylated to give 124(R = OH).516 The formation of other cyclic ketones by intramolecular cyclization of carboxylic acids will be considered in Section IV,M. 

Periluoroalkyl-1,2,4-triazoles are often formed by rearrangement of other heterocycles or by cyclization of carboxylic acid hydrazides or their analogues. In 1962 Brown and Cheng described for the first time the synthesis of 3,5-bis(perfluoroaIkyl)-l,2,4-triazoles 70 by treatment of bis(perfluoroaIkyl)-1,3,4-oxadiazoles with methylamine [71], The method for the synthesis of NH-unsubstituted 3,4-bis(perfluoropropyl)-l,2,4-triazole by the action of P2O5 on the corresponding hydrazine was also reported in this paper. Thirty years later Threadgill et al. [72] prepared 3,5-bis(trifluoromethyl)-4-(3-benzyloxypropyl)-4H-1,2,4-triazole by the reaction of 2,5-bis(trifluoromethyl)-l,3,4-oxadiazole with 3-benzyloxypropylamine in methanol (reflux, 9 days). 

Dicarboxylic acid imides e.g. (189) were prepared in high yield by cyclization of carboxylic acid amides (190) with trifluoroacetic acid this technique avoided dehydration to the nitrile (191), which was easily achieved with acetic anhydride. This work is part of a total synthesis of maleimycin. ... 

To verify the generality of the cyclization of iodopyrazolecarboxylic acids, copper p-phenylbenzoylacetylide was used in the reaction with 3-iodo-l-methylpyra-zole-4-carboxylic acid. The assumed intermediate, alkynylpyrazolylcarboxylic acid, has a distribution of the electron density which is the most favorable for closure of the five-membered cyclic ether. However, the reaction leads only to the 5-lactone (Scheme 120). 

Whereas cycHzation of the cu-keto-co -hydroxyamide 1466 in boihng toluene or xylene in the presence of camphorsulfonic acid (CSA) results in decomposition of the starting material 1466, heating of 1466 with excess TMSOTf 20 and N-methyl-morphoHne in 1,2-dichloroethane affords 46% of the desired cycHzation product 1467 [30] (Scheme 9.16). The close relationship of product 1467 to d -oxazolines suggests that reaction of carboxylic acids 11 with free (or C-substituted) ethanola-mines 1468 and HMDS 2/TCS 14 might lead analogously, via the silylated intermediates 1469, to d -oxazolines 1470 and HMDSO 7. As demonstrated in the somewhat related cyclization of 1466 to 1467, combination of TMSOTf 20 with N-... 

The reaction of CO2 with 1,3-butadienes in the presence of Ni catalysts usually gave an isomeric mixture of carboxylic acids 89 and 90 after hydrolysis (Scheme 32).47,48 The oxa-7r-allylnickel complexes 87 and 88 might be the reaction intermediates, which could be formed through oxidative cyclization of Ni(0) with C02 and the dienes. When Me2Zn was used as a transmetallation agent to react with the oxa-7r-allylnickel intermediates under a C02 atmosphere, further carboxylation took place at the 7r-allylnickel unit. Thus, the 1,4-diesters 95 were obtained after acidic hydrolysis and treatment with diazomethane as shown in Scheme 32.47... 

The direct cyclization of 5-styrylpyrazole-4-carboxylic acids can be accomplished only if N-1 is substituted by methyl [83H(20)1581]. Otherwise, the three-step route (hydrogenation, cyclization, and dehydrogenation) remains an alternative (Section II,A,l,a). An exception is the cyclization of phenylbenzofuranpropionic acids which forms dibenzofurotropone systems this reaction is accompanied by spontaneous dehydrogenation [78IJC(B)567],... 

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... 

Hu et al. (91MI1) report the Dimroth rearrangement of 2-hydrazino- to 2,3-diamino quinazolin-4-ones under catalysis of carboxylic acid derivatives this reaction is followed by an in situ cyclization in which the same carboxylic acid derivatives serve as C,-synthons. l-Acylamino-2-alkylthiopyrimidines are hydrazinolyzed and cyclized to 3-amino-1,2,4-triazolofl, 5-a]pyrimidinium salts (89EGP270711). 

Aminobenzenesulfonamides are ring closed directly to AH- 1,2,4-benzothiadiazine 1,1-dioxides (500) with a variety of carboxylic acids, employing polyphosphoric acid trimethylsilyl ester as the cyclization agent (83S851, 85JAP(K)6025984, 90JMC172l). 

Another reaction of such azides attached to the benzene part of benzo[7>]thiophene is the formation of benzoxazoles when heated in a mixture of carboxylic acid and PPA. The mechanism has been discussed in detail (79AG(E)900) and involves insertion of the singlet nitrene into the anhydride, followed by migration of the acyloxy group to the ortho position, and cyclization. The 5- and 6-azides thus given angularly fused benzoxazoles (Scheme 147). 

Further support for the intermolecular route is provided by the isolation of the substituted trans-cinnamic acid, the normal Perkin product. This arises through elimination of carboxylic acid from the fully acylated species (393) rather than cyclization. For example, a considerable amount of 2-acetoxy-3-methoxycinnamic acid is formed from 3-methoxysalicylaldehyde, perhaps as a result of steric interference with cyclization so allowing the intermolecular process to predominate (39JPR(152)23). It should be noted that trans- 2-hydroxycinnamic acids do not cyclize under normal Perkin conditions, though the cis isomer does so quite readily. Isomerization of the trans acid has been effected by treatment with a trace of iodine in acetic anhydride or by UV irradiation. 

Mercury salts, such as mercury(II) acetate,521-525 mercury(II) oxide,524,526-528 metcury(II) trifluoroace-tate,529,530 mercury(II) sulfate524,531 and mercury(II) phosphate531 catalyze the addition of carboxylic acids to alkynes. Acetic anhydride in the presence of boron trifluoride etherate can also be effectively used in this reaction (equation 292).521,522 Alkynoic acids undergo mercury-catalyzed cyclization to lactones (equation 293).523,532,533... 

Highly stereoselective aldol reactions of lithium ester enolates (LiCR1 R2CC>2R3) with (/0-2-(/ -tolylsulfiny I (cyclohexanone have been attributed to intermediacy of tricoordinate lithium species which involve the enolate and the sulfinyl and carbonyl oxygens of the substrates.43 The O-metallated /<-hydroxyalkanoatcs formed by aldol-type reaction of carbonyl compounds with enolates derived from esters of alkanoic acids undergo spontaneous intramolecular cyclization to /1-lactones if phenyl rather than alkyl esters are used the reaction has also been found to occur with other activated derivatives of carboxylic acids.44... 

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