Condensation amide derivative

A similar method has been described by Badia and co-workers who used chiral amides derived from pseudoephe-drine.139 Moreover, a zirconium-mediated Claisen-aldol tandem reaction of an a,cr-dialkylated ester with several aldehydes has been reported (Scheme 39).140 After the initial Claisen condensation, zirconium enolate intermediate 92 reacts with various types of aldehydes through aldol-type reaction and subsequent lactonization, providing the corresponding pyran-2,4-diones. 

The amide derived from the carboxylic acid in Ugi adducts is in most cases tertiary, and therefore it cannot serve as nucleophilic partner in post-condensation transformations, unless a post-Ugi rearrangement converts it into a free amine [52, 54]. An exception is represented by Ugi adducts derived from ammonia, which give rise to two secondary amides, each of them potentially involved, as nucleophile, in nucleophilic substitution processes. Four competitive pathways are in principle possible (N- or 0-alkylations of the two amides), and the reaction is mainly driven by the stability of the formed rings. In the example shown in Fig. 12, 0-alkylation of the carboxylic-derived amide is favoured as it generates a 5-membered ring (oxazoline 62), while the alternative cyclization modes would have formed 3- or 4-membered rings [49]. When R C02H is phthalic acid, however, acylaziridines are formed instead via Walkylation [49]. In both cases, the intramolecular 8 2 reactions takes place directly under the Ugi conditions. 

Bahrami K, Khodaei MM, Farrokhi A (2009) Highly efficient solvent-free synthesis of dihydropyrimidinones catalyzed by zinc oxide. Synth Commun 39 1801-1808 74. Gross GA, Wurziger H, Schober A (2006) Solid-phase synthesis of 4,6-diaryl-3,4-dihydro-pyrimidine-2(lH)-one-5-carboxylic acid amide derivatives a Biginelli three-component-condensation protocol based on immobilized beta-ketoamides. J Comb Chem 8 153-155 Desai B, Dallinger D, Kappe CO (2006) Microwave-assisted solution phase synthesis of dihydropyrimidine C5 amides and esters. Tetrahedron 62 4651 664 Kumar A, Maurya RA (2007) An efficient bakers yeast catalyzed synthesis of 3,4-dihydro-pyrimidin-2-(lH)-ones. Tetrahedron Lett 48 4569-4571 77. Zalavadiya P, Tala S, Akbari J, Joshi H (2009) Multi-component synthesis of dihydropyrimidines by iodine catalyst at ambient temperature and in-vitro anti mycobacterial activity. Arch Pharm 342 469-475... 

The pyrrole ring can also be constructed starting from an 7V-vinyl-2-halobenzoic amide. The /V-(2-iodobcnzoyl)-1,4-dihydropyndine derivative shown in 3.19. underwent palladium catalysed ring closure to give a condensed isoindolone derivative. The use of formic acid as co-solvent led to the reduction of the intermediate palladium complex formed in the insertion step, instead of / -hydride elimination. The transfer of the stereochemical information from the starting material to the product was poor.25... 

Waxy ketones Synthetic esters Fatty acid amides Amide derivatives Imide condensation products Fatty alcohols Fatty acidis Metal soaps Palmitone cetyl stearate palmitamide stearanilide N-hexadecyl phthalimide stearyl alcohol stearic acid 12 hydroxstearic acid calcium resinate barium resinate calcium stearate barium stearate ... 

The Ugi four-component condensation (U-4CC) between an aldehyde, an amine, a carboxylic acid and an isocyanide allows the rapid preparation of a-aminoacyl amide derivatives. The Ugi Reaction products can exemplify a wide variety of substitution patterns, and constitute peptidomimetics that have potential pharmaceutical applications. This reaction is thus very important for generating compound libraries for screening purposes. 

A stereocontrolled synthesis of the biologically active neolignan (+)-dehydrodiconiferyl alcohol, which was isolated from several Taxus species, was achieved via Evans asymmetric aldol condensation [58] using ferulic acid amide derived from D-phenylalanine. The reaction steps are shown in Fig. 9. This stereocontrolled reaction is also useful for preparing the enantiomer of (+)-dehydroconiferyl alcohol using chiral auxiliary oxazolidinone prepared from L-phenylalanine. This reaction also enables the syntheses of other natural products that possess the same phenylcoumaran framework. 

Oxazolidinones are the products of the acid-catalyzed condensation of a-hydroxyamides with aldehydes and ketones (equation 178). Tertiary amides derived from pyruvic acid undergo intramolecular cyclization when irradiated (equation 179) (78JOC419). Treatment of the a-bromo amide (308) with sodium hydride yields inter alia the dimeric oxazolidinone (309), presumably by way of an a-lactam, which adds to the carbonyl group of a second molecule of the amide (equation 180) (80JCS(P1)2249). 

If we copy Nature rather more exactly, the Claisen ester condensation can be carried out under neutral conditions. This requires rather different reagents. The enol component is the magnesium salt of a malonate mono-thiol-ester, while the electrophilic component is an imidazolide—an amide derived from the heterocycle imidazole. Imidazole has a pK of about 7, Imidazolides are therefore very reactive amides, of about the same electrophilic reactivity as thiol esters. They are prepared from carboxylic acids with carbonyl diimidazole (CDI). 

The reductive cyclization of 2-nitrobenzyl-A, A -bis(formamide) with zinc in acetic acid to quinazoline was first described by RiedelT ° The reaction is used successfully for the synthesis of larger quantities of quinazoline and its benzene-ring-substituted derivatives 12 from 2-ni-trobenzyl-A, A -bis(formamides) 11. The method is suitable only for the preparation of 4-un-substituted quinazolines, because 2-nitro-substituted phenones do not condense with aliphatic amides to yield bis(amide) derivatives. Zinc in acetic acid is the reducing agent of choice, but iron in hydrochloric acid or Raney nickel can also be used. " Applications of compounds other than bis(formamides) [e.g., bis(acetamides) ] and preparation of 2-substituted quinazolines by Riedel s synthesis are scarce. 

Fluoro-l-phenylpyrazole-4-carboxamides 304 have been formed by condensation of the 5-fluoro-l-phenylpyrazole-4-carboxylic acid 303 with amines (Equation 58) <2000EJ0823>. 4-Benzoyl-l-(4-nitrophenyl)-5-phenyl-l//-pyrazole-3-carboxylic acid 305 was converted via reactions of its acid chloride with alcohols or N-nucleophiles, into the corresponding ester or amide derivatives 306 (Equation 59) <2004CHE1039>. Resin-bound pyrazole-4-carboxylic... 

To form the amide derivatives, the acid and amine are condensed in the presence of such agents as N,N -carbonyldiimidazole (18) or a carbodiimide and 1-hydroxybenzotriazole (17). The amides can also be formed via the add chlorides (200,201). Bjorkman (199) described a novel approach to the formation of diastereomeric amides The NSAID indoprofen was coupled by means of ethyl chloroformate to L-leucinamide in a reaction that is complete in 3 min. The derivatives were separated by RP LC, and the procedure was used to study the disposition of the drug in surgical patients (199). Others have adopted this derivatization scheme (209). The chloroformate activation method has also been used with (R)-[42] for resolution of several acids (210). It was found that when hydroxyacids were derivatized, not only did the reaction produce the desired amide moiety at the carboxyl group, but the hydroxyl group was converted to the carbonate derivative of the chloroformate (210). 

In case of the direct reaction of the natural oil or lower alkyl ester of natural fatty acid and the amine the reaction method for producing the amide derivatives is as follows That is, about 1 mol of the said oils and 1 to 100 equivalent mols of the said amines are mixed in the absence or presence of solvents such alcohols as methanol, ethanol or the like, such aromatic hydrocarbons as benzene, toluene, xylene or the like, such halogenoalkanes as methylene chloride, chloroform, carbon tetrachloride or the like, and such alkenes or alkanes as petroleum ether, benzene, gasoline, ligroin or cyclohexane, such ethers as tetrahyrofuran, dioxane and the like, or a mixture thereof, and the mixture is subjected to the reaction in the absence or presence of catalyst amount or equimolar amount to the amine of an auxiliary agent of condensation, such as alkoholate of alkali metal, i.e. lithium, methylate, lithium ethylate, sodium methylate, sodium ethylate, potassium-t-butylate and the like, or acidic auxiliary agents, i.e. p-toluenesulfonic acid and the like, thereby to yield the amide derivatives. In this reaction, a formal alcohol may be removed from the reaction system. 

The O-benzylated aldehyde 517 was also coiu erted into the a,p-unsaturated ester 522 through Wadsworth-Emmons reactioiT-- with ethyl 2-(diethoxyphosphono)acetate5 ° in excellent yield (Scheme 88). The intermediate alkene 522 was subjected to Sharpless asymmetric dihydroxylalion " to afford the diol ester 523 in excellent yield and with a diastereoselectivity in excess of 95 5. Subsequent to alkali-catalyzed hydrolysis of 523, the carboxylic acid obtained was condensed with the p-lolucncsulfonalc salt of glycine benzyl ester or phenylalanine benzyl ester, by the action of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), to afford the benzyl-protected amide derivatives catalytic... 

Phosphonate groups also provided regiochemical control in the aza-annulation reaction. Condensation of 409 with BnNH2, followed by reaction with acryloyl chloride gave 410 in good yield (eq. 83).57 59 Catalytic hydrogenation of 410 was less efficient than the corresponding ester and amide derivatives and resulted in the formation of a mixture of diastereomeric products 411. 

Another significant Improvement was obtained with amine substituents and their derivatives as shown in Table III. The amines were prepared by reduction of the corresponding nltro pyranenamlne. Amide derivatives. III, were prepared from the corresponding nitro-aniline IV and then condensed following reduction as shown in Scheme I. 

Condensation polymers are classified as polyesters, polyamides, polyurethanes, and ether polymers, based on the internal functional group being ester (-COO-), amide (-CONH-), urethane (-OCONH-), or ether (-0-). Another group of condensation polymers derived by condensation reactions with formaldehyde is described under formaldehyde resins. Polymers with special properties have been classified into three groups heat-resistant polymers, silicones and other inorganic polymer, and functional polymers. Discussions in all cases are centered on important properties and main applications of polymers. 

Alternatively these compounds may be obtained from dialkylamino phosphine halides by reaction with alkyl magnesium halides ((7.168) and (7.169)), aluminium alkyls ((7.170) and (7.171)) or organolithium derivatives ((7.172) and (7.173)). Phenylphosphinous chloride can be condensed with a sodium amide derivative (7.174) or a trimethylsilyl derivative (7.175) to give a phosphinous amide. 

Usual attachment of the first amino acid unit to the chloromethylated poly-styrene-divinylbenzene resin has been improved, for example, with Boc-Asn, by-condensing the amino acid (2.0 mmoles) in DMF with triethylamine (1.8 mmoles) during one day at room temperature. Cleavage of the peptide end product from the polymer as the amide derivative has been accomplished using ammonia in DMF in a sealed reaction vessel at room temperature for 5 days. A careful stud - of several peptide bond-forming reagents and polymer supports in respect to racemization has revealed the DCCI procedure to be far inferior to DCCI-NHS or EEDQ. With the model tripeptide Gly-Ala-Leu (racemization assessment by means of the Izumiya procedure), the product was found to... 

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