Imines, with carboxylic acids

A mild phosphorylation reaction is the reaction of imines with carboxylic acids, tri-phenylphosphine, carbontettabromide and triethylamine at —78 °C to form the cycloadducts... 

P-Lactams may be prepared either by condensation of imines with carboxylic acids (eq 9) or by cyclization of p-amino acids (eq 10).i ... 

Another occasionally used method for the preparation of acyclic A-(l-alkoxyalkyl)amides (or carbamates) proceeds via addition of reactive carboxylic acid derivatives to aldimines. In a one-pot procedure, treatment of the imine with the acid chloride (or ethyl chloroformate) and subsequent (m)ethanolysisofthe intermediary a-chloroamide leads to the oc-alkoxyamide56-58. 

Meijer and co-workers have also explored hybrids based on polystyrene and polypropylene imine) dendrons with carboxylic acid functionalities on the surface of the dendrons [48], In these materials the polarity of the head group can easily be modified in a controlled manner leading to both pH and gener-... 

The synthesis of 6-substituted pipecolic acid derivatives has been carried out, in most cases with excellent stereoselectivities (> 95 5 transicis) and yields, by U-3CR between six-membered cyclic imines 53, carboxylic acids and the convertible isonitriles 52. Representative examples are reported in Scheme 1.20. On the other hand, when the chirality was present only on the isocyanide no stereoselectivity was observed, as expected [57]. In situ treatment of enamides 54 with an appropriate nucleophile allowed the conversion into the final products. The same trend in stereoselectivity was observed when similar imines were condensed with isocyanoace-tic acid methyl ester and Boc-glycine to give a series of tripeptides [58]. 

Banfi and co-workers applied the tandem Ugi reaction/ring-dosing metathesis to the synthesis of unsaturated nine-membered lactams as potential reverse-turn inducers. Reaction of allyl-substituted racemic isocyanoacetates with preformed imines and carboxylic acids gave adducts 195 that were treated with Grubbs first-generation catalyst to give nine-membered lactams 196 (Scheme 2.70) [102],... 

Polypropylene imine) dendrimers (see Scheme 1 for structure) have been constructed step by step onto an amine functionalized polystyrene [38, 130, 131]. The challenge in this synthesis is finding conditions for the polypropylene imine) synthesis under which the low MW polystyrene (MW=3200) is soluble [38]. Similar poly(imine) dendrimers with carboxylic acid end groups have also been prepared [130]. The polypropylene imine) dendrimer has also been synthesized on an amino-terminated poly(2-methyl-2-oxazoline) [132]. 

Three different ways have been developed to produce nanoparticle of PE-surfs. The most simple one is the mixing of polyelectrolytes and surfactants in non-stoichiometric quantities. An example for this is the complexation of poly(ethylene imine) with dodecanoic acid (PEI-C12). It forms a solid-state complex that is water-insoluble when the number of complexable amino functions is equal to the number of carboxylic acid groups [128]. Its structure is smectic A-like. The same complex forms nanoparticles when the polymer is used in an excess of 50% [129]. The particles exhibit hydrodynamic diameters in the range of 80-150 nm, which depend on the preparation conditions, i.e., the particle formation is kinetically controlled. Each particle consists of a relatively compact core surrounded by a diffuse corona. PEI-C12 forms the core, while non-complexed PEI acts as a cationic-active dispersing agent. It was found that the nanoparticles show high zeta potentials (approximate to +40 mV) and are stable in NaCl solutions at concentrations of up to 0.3 mol l-1. The stabilization of the nanoparticles results from a combination of ionic and steric contributions. A variation of the pH value was used to activate the dissolution of the particles. 

Adducts (6) and (7) from amides and chlorophosphoric acid aiyl esters or dichlorophosphoric acid aryl esters respectively are well known. - The adducts are formed in a 1 1 ratio. They have been applied to the synthesis of mixed anhydrides from diarylphosphoric acids and carboxylic acids, as well as mixed substituted esters of pyrophosphoric acid. The adduct formation between primary or secondary carboxamides and dichlorophosphates has been used to prepare nitriles and isonitriles respectively. The adduct from DMF and phenyldichlorophosphate is a useful reagent for the preparation of carboxylic acid esters from the corresponding acids and alcohols, 3-lactams from imines and carboxylic acids," carboxylic acid anhydrides, carboxylic acid esters and thiol esters. Adducts of amides with ester amides or diamides of chlorophosphoric acid have been studied. ... 

Thionyl chloride forms a fairly stable primary adduct (15) with DMF, which has been isolated. On heating it decomposes to SO2 and NA -dimethylformamide chloride (equation 4). Treatment of the adduct (15) with carboxylic acids affords iminium salts (16 equation S) in which the carboxylic acid function is strongly activated, e.g. for amide formation. With imines -lactams are formed, sodium azide is converted to acyl azides. ... 

The ketones are mainly used for the formation of imines (see Section 3.4.2.1.), while the alcohols form esters with carboxylic acids (vide infra) or sulfonic acids which can be derivatized further (Sections B.I., D. 1.6.1.1., D.9.), or ethers with phenols, which have been used as chiral leaving groups in asymmetric binaphthol syntheses (Section D.1.1.2.2.2.2.). 

Since that review, Chen et al. have reported on the supramolecular interaction of polyethyleneimines with carboxylic acids, which form through proton transfer from the acid to the imine groups. Thermotropic liquids crystal nematic phases were observed for those PILs at temperatures between 58 and 138 °C. 

A one-pot synthesis of indol-2-ones has been reported by Umkehrer and co-workers via a tandem U-4CR/Heck coupling process. In this case, optimized conditions involved the precondensation of bromoaniline 29 and aldehyde 30. The resulting imine was then reacted with carboxylic acid 31 and isocyanide 32 to give the intermediate Ugi product 33. The exchange of solvents from polar protic to a polar aprotic medium followed by the introduction of a palladium catalyst afforded the indol-2-one 34 in 63% yield. 

Intramolecular Reactions of Alkynes with Carboxylic Acids, Alcohols, and Amines. Addition of carboxylic acids, alcohols, and amines to alkynes via oxypaUadation and aminopallada-tion proceeds with catalysis by Pd salts. Intramolecular additions are particularly facile. Unsaturated y-lactones are obtained by the treatment of 3-alkynoic acid and 4-alkynoic acid with Pd(PhCN)2Cl2 in THF in the presence of Et3N (eq 54), and -lactones are obtained from5-alkynoic acids. 5-Hydroxyalkynes are converted to the cyclic enol ethers (eq 55). The oxypalla-dation is a irons addition. Thus stereoselective enol ether formation by reaction of the alkynoic alcohol with Pd(PhCN)2Cl2, followed by reduction with ammonium formate, has been applied to the synthesis of prostacyclin (eq 56). Intramolecular addition of amines affords cyclic imines. 3-Alkynylamines are cyclized to 1-pyrrolines while 5-alkynylamines are converted to 2,3,4,5-tetrahydropyridines (eq 57). ... 

Hexafluoroacetone and certain perfluorinated or partially fluorinated ketones, aldehydes, and imines react with a-functionalized carboxylic acids (e.g., a-amino, a-At-methylamino [S3, 84], a-hydroxy [S5], and a-mercapto [Sd] acids) to give five-membered heterocyclic systems (equation 13). 

An example of 1,3-dipolar cycloaddition involving a thiazole dioxide derivative was described (99T(55)201). A-Benzoyl-(R)-thiazolidin-4-carboxylic acid 5,5-dioxide 120 was cyclized to the bicylic mesoionic thiazolo-oxazolium 5,5-dioxide with Ac O and reacted with the imine 121 in DMF... 

With most reducing agents, reduction of carboxylic acids generally gives the primary alcohol (19-34) and the isolation of aldehydes is not feasible. However, simple straight-chain carboxylic acids have been reduced to aldehydesby treatment with Li in MeNH2 or NH3 followed by hydrolysis of the resulting imine, ... 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

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