Active condensations

The primary results of all of these studies are that condensation occurs far more readily at the para position than at ortho and that methylolation tends to activate condensation much as it does methylolation. An important inference from these results is that steric factors appear to be quite influential in the condensation process,... 

Yet another example of a so-called pharmacophoric group is the biguanide functionality, a grouping associated with oral antidiabetic activity (see the section on sulfonylureas for a fuller discussion of this activity). Condensation of 2-phenethylamine with dicyanamide affords directly the orally active hypoglycemic agent phenformin (88). ... 

Further work in this area showed that only one of the cou-marin rings was needed for biologic activity. Condensation of the hydroxyacetophenone, 4, with diethyl carbonate affords 4-hydroxycoumarin (2). The reaction may involve the 3-ketoester (5) cyclization of this would afford 2. Alternately, the reagent may first give the 0-acyl derivative cyclization as above will give the same product. Michael condensation of the coumarin with benzalacetone (6) affords the anticoagulant warfarin (named after its place of origin Wisconsin Alumni Research Foundation,... 

Methylation of nitrogen at the 2 position also proves to be consistent with diuretic activity. Condensation of 160 with urea affords the heterocycle, 193. Treatment of this compound with methyl iodide and base effects alkylation on the more acidic ring nitrogen (194). Basic hydrolysis then gives the N-methylated aminosulfonamide (195). Condensation of this with chloroacetalde-... 

An acridine with a radically different substitution pattern, interestingly, still exhibits antimalarial activity. Condensation of acetone with diphenylamine in the presence of strong acid affords the partly reduced acridine, 20. Alkylation with 3-chloro-dimethylaminopropane (via the sodium salt of 20) affords dimethacrine (21). ... 

Interposition of a methylene group between the phenyl ring and the heterocycle leads to the benzyldiami nopyrimidines, a class of compounds notable for their antibacterial activity. Condensation of hydrocinnamate 54 with ethyl formate leads to the hydroxymethylene derivative 55. In this case, too, the heterocyclic ring is formed by reaction with guanidine. This sequence probably involves initial addition-elimination to the forniyl carbon to form 56 cyclization in this case involves simple amide formation. Tautomerization then affords the hydroxy derivative 57. This is converted to tetroxoprim (58) by first... 

An imidazoquinazoline constitutes still another compound that does not fall in the classification of a nonsteroid antiinflammatory agent yet shows good platelet anti aggregating activity. Condensation of benzyl chloride 128 with the ethyl ester of glycine gives alkylated product... 

Thiazolo[2,3-c][l,2,4]triazines 658 were prepared (84LA1302) regio-specifically by cyclizing 2-hydrazono-2-thiazoline 659 with glyoxylic acid or ester. They had herbicidal activity. Condensation of 659 with oxamic acid ethyl ester gave hydrazide 660, which was cyclized with sodium... 

Apparently, minor chemical modifications of the benzilcarboxylic acid containing molecules led to a compound which shows surprising analgesic activity. Condensation of N-methylphenethylamine 74 with... 

Incorporation of additional basic centers into the phenylpiperidinol nucleus leads to a molecule that shows local anesthetic rather than CNS activity. Condensation of the protected piperidone 106 with... 

A more highly oxidized derivative of quinazoline forms the heterocyclic moiety of a compound with CNS activity. Condensation of the aminopropylpiperazine 141 with isatoic anhydride gives the anthranilamide 142. Reaction of that amide with phosgene gives directly the heterocyclic ring. (The reaction may proceed by initial formation of the carbamoyl chloride ... 

A satisfactory result was obtained in AgOTf- or NIS/TfOH-activated condensation of S-benzothiazolyl pentofuranosides 93, 94 and 95 with l,2 3,4-di-isopropylidene-a-D-galactopyranose 96 and l,6-anhydro-3,4-isopropylidene-P-D-galactopyranose 97 as the acceptor to afford the corresponding disaccharides in moderate to good yields and stereoselectivity [445],... 

A recent extension of this methodology includes condensation of 44 with a variety of substituted benzaldehydes, furfurals, and thiophene carboxaldehydes afforded analogues of 48 in good to excellent yield as shown in Table 6.2 (Fig. 6.6). These products were completely characterized spectroscopically with an excellent discussion of the effects of substituents on the corresponding UV, IR, MS, and NMR spectra. Neutralization of 48 with sodium bicarbonate in aqueous ethanol produced the corresponding free bases uneventfully. These compounds were evaluated both as cyanine dyes and for biological activity. Condensation of 44 with ( )-3-(5-methylfuran-2-yl)-2-propenal affords the expected E, )-dienes 49a and 49b in 50 and 90% yield, respectively (Fig. 6.7). 

This vapor velocity may lead to flooding of the vapor tube and so requires an active condenser. 

Irradiation of the M-crystals caused solid-state photodecarboxylation, and then enantioselective condensation occurred, to give the optically active condensation product (S)-( —)-151 as the main product with [a] = —30 in 35% ee and in 37% chemical yield (Scheme 35). Conversely, irradiation of the P-crystals resulted in formation of the opposite handed condensation product (/ )-(+ )-151 with [a]r = +30 in 33% ee and in 38% chemical yield. For a comparison, solution phase photolysis of acridine 150 and diphenylacetic acid DPA in acetonitrile did not produce chiral product 151 but rather gave the achiral condensation product 153 in 74% as the major product at complete conversion of DPA. 

A six to eight page bar chart MPS, including 150-200 activities condensed to 60-80 lines. 

A useful extension of sulfoxide-sulfenate rearrangements exploits the greater stability of allylic vs. vinylic sulfoxides.For example, the Knoevenagel product (202) is deconjugated under the conditions of its formation. This sets the stage for a 2,3-rearrangement in the same pot (equation 66). Optically active condensation products give hydroxy esters (201) with 64-72% 50-80% ee were reported for... 

Another important property ol aerosol particles is their role in the atmosphere as condensation nuclei for water vapour. Potentially, all particles may be condensation centres. However, under normal atmospheric conditions only a proportion of the particles take part in the formation of clouds. According to recent studies of Twomey (1971 and 1972) the majority of active condensation nuclei consists of ammonium sulfate and have a radius of the order of 10" 2 jim (see Subsection 5.3.1). 

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