Cyclic carboxylic acid derivative

For cyclic carboxylic acid derivatives, decreasing ring size shifts a carbonyl absorption to higher frequencies. 

Several related reactions involve reduction of cyclic carboxylic acid derivatives to masked aldehydes which resist further reduction but can be converted into the required aldehydes by acid hydrolysis. In a series of papers, it was established that carboxylic acids could be converted into dihydro-1,3-thiazines or dihydro-1,3-oxazines which could be reduced by NaBH4 in weakly acidic ethanol. Thus, as shown in Scheme 20, dihydro-1,3-thiazines (41) were reduced to tetrahydro-1,3-thiazines (42) in yields of 66-84%. The resulting tetrahydro compounds could be hydrolyzed to aldehydes by aqueous acid. - In a later publication, these workers showed that there was little evidence for ring opening during reduction and that other methods of reduction e.g. hydrogenation over Pt, Pd or Rh or use of dissolving metals such as Zn, Sn or Na) were totally unsuccessful. In closely similar work, reduction of 5,6-dihydro-4W-... 

Scheme 55. Formation of cyclic carboxylic acid derivatives by enyne cycloisomerization and CO2 insertion at Ni(0).

After acyl halides acid anhydrides are the most reactive carboxylic acid derivatives Three of them acetic anhydride phthahc anhydride and maleic anhydride are mdus trial chemicals and are encountered far more often than others Phthahc anhydride and maleic anhydride have their anhydride function incorporated into a nng and are referred to as cyclic anhydrides... 

Electrochemical fluonnation ot N,N dialkylammo-substituted carboxylic acids as their methyl esters produces the analogous perfluonnated tertiary amine carboxylic acid derivatives in 18-30% yields as well as cyclic amine ethers [JOO]... 

Reaction of 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l, 2,3- e]-1,4-ben-zothiazine-6-carboxylic acid and its ethyl ester with B(OH)3 in AC2O in the presence of ZnCl2 afforded 6-[(diacetoxyboryl)oxycarbonyl] derivative 323 (R = OAc)], which was reacted with primary and cyclic amines to give 10-amino-9-fluoro-7-carboxylic acid derivatives 324 (97MI41, 98MI30). 6-[(Difluoroboryl)oxycarbonyl derivative 323 (R = F) was obtained from ethyl 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate with BF3-THF complex. Reaction of 323 (R = F) and 1-methylpiperazine in DMF at 50-60 °C and subsequent acidic hydrolysis afforded 7 (97MI1). 

Esters undergo the same kinds of reactions that we ve seen for other carboxylic acid derivatives, but they are less reactive toward nucleophiles than either acid chlorides or anhydrides. All their reactions are equally applicable to both acyclic and cyclic esters, called lactones. 

The photolysis of cyclic diazo ketones in hydroxylic solvents leads to ring contracted carboxylic acid derivatives via this ketocarbene -> ketene rearrangement. Examples of such reactions are given in (2.24)239) and (2.25) 240). In this last example a photoequilibrium between the diazo ketone and its valence isomer, a diazirine, has been observed, both products then eliminating nitrogen to afford the cyclobutane carboxylic acid. 

Five- or six-membered saturated cyclic ketones can also react by another pathway that does not involve decarbonylation. In these reactions, the biradical initially formed by a-cleavage undergoes internal disproportionation without loss of carbon monoxide, resulting in the formation of either an unsaturated aldehyde or a ketene. Methanol is usually added to convert the reactive ketene to a stable carboxylic-acid derivative (Scheme 9.2). 

In the early days, greatest interest was focused on the acid-catalyzed hydrolysis (by hydrochloric acid in the presence of 2,4-dinitrophenylhydrazine) of Reissert compounds to aldehydes and the corresponding heterocyclic carboxylic acid derivatives. This reaction is fairly general for compounds of quinoline (178) and isoquinoline (179) (Table 18), but it is not applicable to pyridines as they rarely form Reissert compounds. The 3-hydroxyquino-line Reissert compound does not yield benzaldehyde, probably because acylation of the 3-hydroxy group prevents formation of the required cyclic intermediate (180). Some nitroquinolines and isoquinolines give low yields of benzaldehyde. Rather curiously, disub-stituted quinoline Reissert compounds yield less of the aldehyde than of the corresponding... 

The condensation of 1,4-diamines with a variety of carboxylic acid derivatives, e.g. imidate esters, orthoformic esters, /V-ethoxycarbonylthioamides (77JOC2530), nitriles and ethoxyacetylene, produces the cyclic amidine linkage —N = C(R)NH— (67AHC(8)2l, p. 40). Cyclic ureas, —NHC(0)NH—, have been similarly produced using carbonyl chloride, A, A -carbonyldi imidazole, carbon monoxide, thiocarbonyl chloride or carbon disulfide (67AHC(8)21, p. 38). 

Two widely used general methods of synthesizing 1,2,4-oxadiazoles embrace 95% of the practical preparations of these compounds the conversion of amidoximes5 by means of carboxylic acid derivatives to the cyclic structure [shown schematically as the combination of two skeletons (I)] and the cycloaddition of nitrile oxides6 to nitriles (II). The... 

The cyclic ketenes were generated from /V-acy 1-1,3-thiazolidine-2-carboxylic acids by means of Mukaiyama s reagent. The same reaction generated enantio-merically pure 1,3-thiazolidine-derived spiro-p-lactams, using optically active /V-A rt-butoxycarbonyl-1,3-thiazolidine-2-carboxylic acid derivatives as precursors of the asymmetrical chiral cyclic ketenes (7< r/-butoxy carbonyl Boc) [101]. 

The asymmetric aziridination of a, P-unsaturated carboxylic acid derivatives is a direct route to optically active aza-cyclic a-amino acids, and this class of chiral aziridines can also be used as chiral building blocks for the preparation of other amino acids, P-lactams, and alkaloids. Prabhakar and coworkers carried out an asymmetric aziridination reaction of tert-butyl acrylate with O-pivaloyl-N-arylhydroxylamine 25 in the presence of cinchonine-derived chiral ammonium salt 2e under phase-transfer conditions, which furnished the corresponding chiral N-arylaziridine 26 with moderate enantioselectivity (Scheme 2.24) [46],... 

Ozonolysis of tosyl derivative 295a led to the corresponding protected azonane-3,8-dione in 50% yield (Equation 41). Ruthenium-catalyzed oxidation was found to be more efficient, resulting in an increased 70% yield of the product, which is consistent with the result obtained for dialkyl-substituted systems (Scheme 32, Section 14.10.6.3) <1995J(P1)1137>. Similar ozonolysis of pyrrolo ethyl carboxylate 295c led to 75% of cyclic amino acid derivative <20010L861>. 

In addition, other carboxylic acid derivatives, such as tertiary carboxamides and cyclic carbonates, readily undergo cyclopropanation reactions under similar conditions to provide cyclopropylamines ° and cyclopropanone hemiacetals," respectively. The cognate titanium-mediated coupling of imides has been shown to afford synthetically useful N-acylhemiaminals. ... 

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