Acetic acid, derivatives series

The acid chlorides have served as useful synthetic intermediates leading to ketones via the malonic acid synthesis and Friedel rafts reaction, thiadiazole acetic acid derivatives, and halo ketones via the Arndt Eistert synthesis and carbinols by hydride reduction <68AHC(9)107>. The dialkylcadmium conversion of acid chlorides into ketones fails in the 1,2,5-thiadiazole series. The major product is either a tertiary carbinol or the corresponding dehydration product, by virtue of the high reactivity of the intermediate ketone. 

Losartan potassium (1), the prototype highly selective ATi receptor antagonist (Goa and Wagstaff, 1996), was derived from the Takeda series of l-benzylimidazole-5-acetic acid derivatives, which were themselves weak angiotensin II antagonists. Losartan potassium... 

Early members of the carboxylate series (< four carbon atoms) form many stable coordination complexes. Formic acid offers the advantage of minimal steric requirements, while thermodynamic and kinetic data reveal that frequently propionic acid forms stable complexes at a faster rate than acetic acid. Derivatives of higher acids (> four carbon atoms) show the same chemical characteristics except that, as the carbon chain of the acid grows, the tendency to coordinate decreases. 

Another way to potential antiinflammatory activity is to mimic a carboxylic acid by a tetrazole moiety (compare thepKa 4 8 for tetrazole itself). A good example is IntrazolR which is closely related to Indomethacin (an indolyl-3-acetic acid derivative). Therefore we have also reduced the carbonyl group in 39 yielding compounds of type 44 [84JHC1881], Unfortunately no compound of this series showed antiinflammatory activity. 

Three arm star polymers of IBVE were synthesized by living cationic polymerization using trifunctional initiators 8 and 9 with the same trifluoroacetate initiating functions but different cores [19, 20]. The experimental conditions were selected to obtain living polymerization. A series of acetic acid derivatives including trifluoroacetic acid and the IBVE-acid adduct were found to be efficient... 

Starting from the known inhibitory activity of (2- and 3-benzoylpyrrol-l-yl)acetic acids, a series of 3-aroyl and 2,4-bisaroyl A -acetate derivatives 88 were synthesized using phase-transfer catalysis conditions (Equation 13) <1995JPS79, 2003JME417>. 

Several new routes involve formation of one carbon-carbon bond in pre-formed substrates. Palladium-catalyzed cyclization of /3-hydroxyenamine derivatives has been employed in a route to substituted pyrroles and 4,5,6,7-tetrahy-droindoles with multiple substituents by formation of the C-3-C-4 bond as the key feature, as illustrated by construction of the molecule 534 (Equation 146) <2006T8533>. Zinc perchlorate-catalyzed addition of alcohols to the nitrile functionality of a-cyanomethyl-/3-ketoesters, followed by annulation gave access to a series of substituted ethyl 5-alkoxypyrrole-3-carboxylates <2007T461>. Similar chemistry has also been used for synthesis of a related set of pyrrole-3-phosphonates <2007T4156>. A study on preparation of 3,5,7-functionalized indoles by Heck cyclization of suitable A-allyl substituted 2-haloanilines has also appeared <2006S3467>. In addition, indole-3-acetic acid derivatives have been prepared by base induced annulation of 2-aminocinnamic acid esters (available for instance from 2-iodoani-lines) <2006OL4473>. 

TABLE 2. Metal selectivity series for some basis polymers. PEI, poly(ethylenimine) (PEI) PTU, thiourea derivative of PEI PDA, diamino acetic acid derivative of PEI POX, oxine derivative of PEI. 

Acetic acid derivatives are often used as a test of electronic effects of a series of substituents they are fairly easily synthesized (or are commercially available), and pK values are easily measured by titration. 

Other agents which have shown activity in experimental animals include phenyramidol which appears to inhibit hepatic microsomal enzymes, o-benzoylthlamine disulfide," a series of pyrimidine-5-acetic acid derivatives, " the antifertility agent and chondroitin sulfate A," which... 

Amine containing ketone based photoinitiators bearing an amine moiety in the benzophenone or thioxanthone series [162] as well as a new thioxanthone derivative (where the coinitiator such as a thiol [163], an acetic acid derivative [164,165] is grafted) have been developed (10.51) Covalently bonded camphorquinone/ amine [166] or amino alkyl ketone/thiol [167] were also recently reported. 

Carboxylic acids having 6—24 carbon atoms are commonly known as fatty acids. Shorter-chain acids, such as formic, acetic, and propionic acid, are not classified as fatty acids and are produced synthetically from petroleum sources (see Acetic acid Formic acid and derivatives Oxo process). Fatty acids are produced primarily from natural fats and oils through a series of unit operations. Clay bleaching and acid washing are sometimes also included with the above operations in the manufacture of fatty acids for the removal of impurities prior to subsequent processing. 

Nitration of a series of methyl-1,2-benzisoxazoles was studied by Tahkar and Bhawal using fuming nitric acid and sulfuric acid in acetic acid at 100 °C. 3-Methyl-1,2-benzisoxazole gave a mixture of 5-nitro- and 5,7-dinitro-3-methyl-l,2-benzisoxazole, with the 5-nitro isomer predominant. The product obtained from 3,5-dimethyl-1,2-benzisoxazole was the 4-nitro derivative and not the 7-nitro compound as proposed by Lindemann (26LA(449)63). The synthesis of the 7-nitro compound by an alternative method was used as structural proof. Two products were obtained from 3,6-dimethyl-l,2-benzisoxazole and these were the 5-nitro and 5,7-dinitro derivatives. 3,7-Dimethyl-l,2-benzisoxazole was converted into the 5-nitro derivative (Scheme 25) (77lJC(B)l06l). 

Esters of diphenylacetic acids with derivatives of ethanol-amine show mainly the antispasmodic component of the atropine complex of biologic activities. As such they find use in treatment of the resolution of various spastic conditions such as, for example, gastrointestinal spasms. The prototype in this series, adiphenine (47), is obtained by treatment of diphenyl acetyl chloride with diethylaminoethanol. A somewhat more complex basic side chain is accessible by an interesting rearrangement. Reductive amination of furfural (42) results in reduction of the heterocyclic ring as well and formation of the aminomethyltetrahydro-furan (43). Treatment of this ether with hydrogen bromide in acetic acid leads to the hydroxypiperidine (45), possibly by the intermediacy of a carbonium ion such as 44. Acylation of the alcohol with diphenylacetyl chloride gives piperidolate (46). ... 

The wide latitude of structural variation consistent with bioactivity in this series is illustrated by the observation that antiinflammatory activity is maintained even when the second aromatic group is attached directly to the pyrrole nitrogen rather than to the heterocyclic ring via a carbonyl group as in the previous case. Condensation of p-chloroaniline with hexane-2,5-dione (or its dimethoxy-tetrahydrofuran equivalent) affords pyrrole 7. The acetic acid side chain is then elaborated as above. Thus, Mannich reaction leads to the dimethylaminomethyl derivative 8, which is in turn methylated (9) the quaternary nitrogen replaced by cyanide to afford 10. Hydrolysis of the nitrile then gives clopirac (11). 

A series of publications appeared regarding the transformation of corynanthe-type alkaloids to yohimbane derivatives (285-287). The saponification of cory-nantheine (52) in methanol yielded a complex mixture of corynantheic acid (588), two C-16-epimer acetal acids (589), and demethoxycarbonylcory-nantheine (590). All four compounds upon hydrolysis in acid resulted in cory-... 

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