Carboxylic acids amide adducts

The 36C1 exchanges between gaseous H 36C1 and adducts of carboxylic acid amides with phosphoryl chloride have also been studied291. 

A still unresolved problem is the structure of the often used adducts from phosphorus trihalides and carboxylic acid amides, which might be described by the formulae (8) or (9). With the aid of in situ generated adducts of acid amides and PX3 amidines, isonitriles, quinazolinones, alkyl chlorides, aminomethylenediphosphonic acids, carbamoyl halides, triformylaminomethane, 1,3,4-oxadia-zoles, sulfides (from sulfoxides), nitriles (from primary nitro compounds)" and bromoqui-nolines (from methoxyquinolines)" have been prepared. 

Phosgene and tertiary carboxylic acid amides form very labile adducts (17 equation 6 not yet isolated or used for preparative purposes as such), which decompose with loss of CO2 very rapidly to give amide chlorides (see Section 2.7.2.2.1.i). Decomposition with evolution of CO2 is a common fate of primary adducts of carbonic acid chloride derivatives. Primary adducts from DMF and chloroformic acid esters (18), for example, decompose immediately to give alkoxymethyleneiminium chlorides, which react to give alkyl chlorides and DMF (equation 7). Adducts (19) from secondary and tertiary carboxamides... 

From formylation reactions of CH-acidic compounds, which take place if mixtures of carboxylic acid amides and anhydrides are used as formylating agents, it was concluded that the latter compounds form similar adducts to those from amides and acid halides. ... 

Aromatic isocyanates react with regular olefins only in the presence of metal catalysts. For example, reaction of ethylene with phenyl isocyanate in the presence of liganded nickel (o) catalysts under argon in THF at -20 °C affords a five-membered ring metalla-cycle, which on hydrolysis gives a Af-substituted carboxylic acid amide. Heating of the metallacycle causes jS-elimination with formation of Af-substituted acrylic acid amides Diolefines and allenes also undergo this reaction with phenyl isocyanate. From 1,1-bis-p-dimethylaminophenylethylene and p-nitrophenyl isocyanate a linear 1 1 adduct is obtained... 

The insertion of isocyanates into C-H bonds is also well known. Olefins, alkanes, aromatic and heteroaromatic compounds are known to react with isocyanates to give N-substituted carboxylic acid amides. Often the formation of the linear adduct is the result of a [2+2] cycloaddition reaction and subsequent rearrangement. Electron donating groups on the aromatic nucleus on the one side and electron withdrawing groups on the isocyanate enhance the reactivity of both components. Lewis acids, such as aluminum chloride, are supplied successfully as catalysts... 

In the case of esters, carboxylate anions, amides, and acid chlorides, the tetrahedral adduct may undergo elimination. The elimination forms a ketone, permitting a second addition step to occur. The rate at which breakdown of the tetrahedral adduct occurs is a function of the reactivity of the heteroatom substituent as a leaving group. The order of stability of the... 

The highly ordered cyclic TS of the D-A reaction permits design of diastereo-or enantioselective reactions. (See Section 2.4 of Part A to review the principles of diastereoselectivity and enantioselectivity.) One way to achieve this is to install a chiral auxiliary.80 The cycloaddition proceeds to give two diastereomeric products that can be separated and purified. Because of the lower temperature required and the greater stereoselectivity observed in Lewis acid-catalyzed reactions, the best diastereoselectivity is observed in catalyzed reactions. Several chiral auxiliaries that are capable of high levels of diastereoselectivity have been developed. Chiral esters and amides of acrylic acid are particularly useful because the auxiliary can be recovered by hydrolysis of the purified adduct to give the enantiomerically pure carboxylic acid. Early examples involved acryloyl esters of chiral alcohols, including lactates and mandelates. Esters of the lactone of 2,4-dihydroxy-3,3-dimethylbutanoic acid (pantolactone) have also proven useful. 

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. 

Fluorinated alkylisocyanates and isothiocyanates add alcohols, mercaptans, and amines to yield stable 1 1 adducts [76]. When the reaction is performed with carboxylic acids, the anhydrides first formed decompose to give A -fluoroalky-lated amides [77]... 

The discovery of this behavior was of great importance because a single product was converted into a variety of products. The conversion into primary amides or other carboxylic acid derivatives depended upon the structure of the Ugi adducts. An electron-rich N-acyl moiety was required for the formation of munch -nones, otherwise the primary amide was obtained [7]. The conversion of cydo-... 

Chiral homoallylamines are valuable synthons for the preparation of biologically active components including P-amino carboxylic acids or esters, obtained by oxidation of the ally lie functionality.1-29 Because removal of the chiral auxiliary by hydrogenation leads to the loss of the allylic functionality, we developed alternative routes for the conversion of the adduct into the unprotected homoallylamines. As a typical example, (f ,f )-PGA-homoallylamine derived from isobutyraldehyde Hi was used to develop the so-called mroStrecker and the decarbonylation method for the conversion of (R)-phenylglycine amide protected homoallylamines into /V-benzylidene protected homoallylamines 15 (Scheme 25.7). 

With BF3 and PF5, SF5NH2 forms 1 1 adducts (183). Reaction occurs at room temperature between SF5NH2 and various acid chlorides and fluorides containing electron-deficient carbonyl groups to produce iV-pentafluorosulfanyl amides, F5SNHC(0)R (R = F, CF3, CH3) (149). The reaction of SF5NCO with certain carboxylic acids at room temperature provides an alternate route for the preparation of amides, SF5-... 

Cyclic anhydrides react well with trimethyl(trifluoromethyl)silane however, a stoichiometric amount of tctrabutylammonium fluoride is required. - For example, succinic anhydride undergoes efficient addition of trimethyl(trifluoromethyl)silane to initially form an adduct, which upon hydrolysis aflbrds the trifluoromethyl-substiluted 0x0 carboxylic acid 27. Simple amides, such as benzamide and acetamide, do not react with trimetliyl(trifluoromethyl)silane even when a molar quantity of tetrabutylainmonium fluoride is used. Furthermore, lactams, such as caprolactam, do not react with trimethyl(trifluoromethyl)silane under similar conditions. An activated amide carbonyl, such as that in A -methylsuccinimide. however, reacts smoothly to afford an interesting adduct, which upon acid hydrolysis affords the hcmiaminal 28. 

A few years later Passerini, developed a new 3CR towards a-acyloxy amides 9 which are formed by reacting an aldehyde or ketone 6, a carboxylic acid 8 and an isocyanide 7 (Scheme 2) ([25] and see for review [26]). Since the first synthesis of isocyanides (formerly known as isonitriles [27]) in 1858, the Passerini 3-component reaction (P-3CR) was the first MCR involving these reactive species. It has become one of the renowned examples of an important subclass of MCRs, the isocyanide-based MCRs (IMCRs). Especially important for the Passerini reaction, but also for a lot of other IMCRs, is the ability of isocyanides to form a-adducts, by reacting with nucleophiles and electrophiles (at the carbon atom). The nucleophilic... 

Amides. Barstow and Hruby have published two methods for synthesis of amides. In one, the two reagents are heated in THF to form the adduct the carboxylic acid and, after 10 minutes, the amine (2 equiv.) are added. The amide is obtained after a reflux period of about 1 hour. Yields are generally 80-90%. The second method involves triphenylphosphine, bromotrichloromethane, the acid, and the amine. The reported yields are somewhat higher than those obtained with the first method. One example of peptide synthesis by this method was reported (85% yield). 

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