Amides conversion

Tin reagents such as Sn[N(TMS)2]2 in the presence of an amine can also be use to convert an ester to an amide. This reagent can also be used to convert p-amino esters to P-lactams. The ester-to-amide conversion has also been accomplished electrochemically, by passing electric current in the cathodic compartment. 

These have been prepared by various combinations of straightforward steps including ester to amide conversion, alcohol protection, direct reduction of the ester or amide to the aldehyde group, and reduction of the ester to the alcohol followed by reoxidation to the aldehyde. The sensitivity of the (5)-propanals to epimeriza-tion has been of paramount concern. One of the best procedures which avoids racemization and has been run on a preparative scale is noted (eq 2). ... 

Figure 3 375 MHz 19F gel phase NMR spectrum for resin linked butyl amide. Conversion to product is monitored (a) on TentaGel resin and (b) in solution.

Amides. Conversion of esters to heating with solid t-BuOK. - Oxidai aldehydes with f-BuOK in DMSO also Hydrolysis. Amino esters la- a (r-BuOK-THF) at 0° or below. This aziridine esters. " ... 

Hofmann rearrangement of amides Conversion of a primary amide to an amine (with one less carbon) by treatment with a basic bromine solution. The C=0 group is lost as CO2. (pp. 919, 1023)... 

In 1992 Murahashi, Hosokawa, and co-workers described the anti-Markovnikov oxidative addition of amides and carbamates to electron-deficient olefins by applying a palladium and copper cooperative catalysis under oxygen atmosphere [41]. The proposed mechanism involved a ff-bonded palladium(II) intermediate resulting from the addition of the nucleophile to the olefin, and subsequent ) -palladium hydride elimination to yield the functionalized alkene. Interestingly, both lactams and cyclic carbamates gave predominantly the corresponding E-enamide derivatives. Acyclic amides, conversely, afforded ElZ mixtures of products. The addition of a catalytic amount (5 mol%) of hexamethylphosphoric triamide (HMPA) was found notably beneficial for the reaction of 5-membered lactams and reduced the reaction time of such particular oxidative amidations (Scheme 2). 

The overall result is that the Li substituent is more shielded in the (5)-MTPA than in the (i -MTPA amide. Conversely, substituent L2 is more shielded in the (/ -MTPA than in the (5)-MTPA amide. When the differences in the chemical shifts are calculated for an amine with the configuration shown in Figure... 

In organic chemistry the term is used to describe the conversion of an ester to an acid and an alcohol (saponification), the addition of the elements of water to a molecule, e.g. the conversion of a nitrile to an amide... 

Place 125 ml. of concentrated ammonia solution (sp. gr. 0-88) in a 600 ml. beaker and surround the latter with crushed ice. Stir the ammonia solution mechanically, and introduce the n-caproyl chloride slowly by means of a suitably supported separatory funnel with bent stem. The rate of addition must be adjusted so that no white fumes are lost. The amide separates immediately. Allow to stand in the ice water for 15 minutes after all the acid chloride has been introduced. Filter oflF the amide at the pump use the flltrate to assist the transfer of any amide remaining in the beaker to the Alter (2). Spread the amide on sheets of Alter or drying paper to dry in the air. The crude n-capro-amide (30 g.) has m.p. 98-99° and is sufficiently pure for conversion into the nitrile (Section 111,112) (3). Recrystallise a small quantity of the amide by dissolving it in the minimum volume of hot water and allowing the solution to cool dry on filter paper in the air. Pure n-caproamide has m.p. 100°. 

The conversion of an amide into an amine in this way is termed the Hofmann reaction or the Hofmann rearrangement. 

By treatment of this oxime with phosphorus pentachloride or thionyl fhloride in ether solution, smooth conversion into benzanilide, m.p. 163°, results. The change of any oxime into a substituted amide under the conditions mentioned is usually termed the Beckmann rearrangement. The above example may be represented ... 

Acyl hahdes may be identified by —hydrolysis to the corresponding acids (the latter may be further characterised as in Section IV,175) conversion into amides (Section IV,191), anihdes or p-toluidides (Section IV,100) and conversion into sohd esters (Section IV,183). 

The conversion of a diazo ketone to an acid amide may be accomplished by treating a warm solution in dioxan with 10-28 per cent, aqueous ammonia solution containing a small amount of silver nitrate solution, after which the mixture is heated at 60°-70° for some time. Precautions should be taken (by use of a. safety glass shield) when heating mixtures containing ammoniacal silver nitrate. 

The conversion of a carbonyl compound by ammonium polysulphide solution into an amide with the same number of carbon atoms is known as the Willgerodt reaction. The procedure has been improved by the addition of about 40 per cent, of dioxan or of pyridine to increase the mutual solubility of the ketone and aqueous ammonium polysulphide the requisite temperature is lowered to about and the yield is generally better. 

Acid derivatives are made directly from acids or by conversion from other acid derivatives depending on their stabihty. The most important are esters (RCOiEt), amides (RCO2NR2), anhydrides (RCOO COR) and add clilorides (RCOCI). Arrange these in an order of stabilily, the most reactive at the top of the list, the most stable at the bottom. 

The conversion of acetylenes into acetyl ides, M-C=C-R (M = Li, Na, K, MgBr), by means of alkyllithium or Grignard reagents in organic solvents or by alkali metal amides in liquid ammonia is well documented (for practical examples see ref. 1, for review articles consult inter alia refs. 2-5). 

Anhydrous liquid ammonia (note 2) (900 ml) was drawn from a cylinder and introduced into the flask. Iron(III) nitrate (lOO mg) was added and, as soon as a uniformly brown solution had formed (after stirring for a few seconds), about 0.7 g of lithium (from the starting amount of 7 g) was cut into two or three pieces and immediately introduced into the flask. After 10-15 min the blue colour had disappeared completely and a white suspension of lithium amide had formed. The remainder of the 7 g (1 mol) of lithium was then cut up and introduced. In most cases the conversion was finished v/ithin about 30 min (note 3). 

The conversion into sodium amide (1 mol) was carried out in a similar way. 

The amount of metal required gives an indication of the water content. note 3. If the conversion takes longer, add some liquid ammonia to keep the volume of the suspension between 500 and 800 ml. iinte 4. The conversion of lithium and potassium into the alkali amides has never given problems. 

This isomerization, which must proceed through a 1,2,3-trienylanine, is not "contra-thermodynamic", since with a catalytic amount of potassium tert.-butoxide the same result is obtained. Enyne ethers, H2C=CH-CsC-0R, undergo a similar conversion into HCeC-CH=CH-OR upon interaction with alkali metal amides in liquid NH3, followed by hydrolysis . Enyne sulphides, H2C=CH-CsC-SR, and the hydrocarbons H2C=CH-CsC-R (R = or phenyl) give only tars or polymeric products under... 

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

As a further application of the reaction, the conversion of an endocyclic double bond to an c.xo-methylene is possible[382]. The epoxidation of an cWo-alkene followed by diethylaluminum amide-mediated isomerization affords the allylic alcohol 583 with an exo double bond[383]. The hydroxy group is eliminated selectively by Pd-catalyzed hydrogenolysis after converting it into allylic formate, yielding the c.ro-methylene compound 584. The conversion of carvone (585) into l,3-disiloxy-4-methylenecyclohexane (586) is an example[382]. 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

In base the tetrahedral intermediate is formed m a manner analogous to that pro posed for ester saponification Steps 1 and 2 m Figure 20 8 show the formation of the tetrahedral intermediate m the basic hydrolysis of amides In step 3 the basic ammo group of the tetrahedral intermediate abstracts a proton from water and m step 4 the derived ammonium ion dissociates Conversion of the carboxylic acid to its corresponding carboxylate anion m step 5 completes the process and renders the overall reaction irreversible... 

We already discussed bolh Ihe acidic and basic hydrolysis of amides (see Seclion 20 17) All lhal remains to complete Ihe mechamslic piclure of nilrile hydrolysis is to examine Ihe conversion of Ihe nilnle to Ihe conespondmg amide... 

A key biochemical reaction of ammo acids is their conversion to peptides polypeptides and proteins In all these substances ammo acids are linked together by amide bonds The amide bond between the ammo group of one ammo acid and the carboxyl of another IS called a peptide bond Alanylglycme is a representative dipeptide... 

Acylation (Section 12 7 and Chapter 20) Reaction in which an acyl group becomes attached to some structural unit in a molecule Examples include the Fnedel-Crafts acylation and the conversion of amines to amides Acyl chloride (Sections 4 1 and 20 1) Compound of the type... 

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