Amides acetalization

Insight into the factors that govern breakdown of tetrahedral intermediates has also been gained by studying the hydrolysis of amide acetals. If the amine is expelled, an ester is formed, whereas elimination of an alcohol gives an amide ... 

Conversion of Acid Anhydrides into Amides Acetic anhydride is also commonly used to prepare iV-substituted acetamides from amines. For example, acetaminophen, a drug used in over-the-counter analgesics such as Tylenol, is prepared by reaction of p-hydroxyaniline with acetic anhydride. Note that the more nucleophilic -NH2 group reacts rather than the less nucleophilic -OH group. 

A. Claisen Rerrangements of Ketene Aminats and Imidates. A reaction that is related to the orthoester Claisen rearrangement utilizes an amide acetal, such as dimethylacetamide dimethyl acetal, in the exchange reaction with allylic alcohols.257 The products are y, 8-unsaturated amides. The stereochemistry of the reaction is analogous to the other variants of the Claisen rearrangement.258... 

Honomer Properties (Table I). The amide/acetal 1 (R=He or Et) and Its amine precursor are Ames negative. Compound 1 shows a very high LD50 and low skin or eye Irritation. A low vapor pressure, Its liquid form and Infinite miscibility with water and common solvents are additional pluses. 

Bonds typically hydrolyzed include carboxylic and phosphoric esters, amides, acetals, amidines, as well as metal ion complexes. (When a nucleophilic substitution reaction uses the solvent as the nucleophile, the reaction is often referred to as solvolysis.)... 

Alkylations by oxonium salts have added several new weapons to the synthetic chemist s armamentarium. For example, the O-alkylated products from amides [R1C(OR)=NR2R3]+ (R == CH3 or C2H5) may be hydrolyzed under mild conditions to amines and esters,14-34 reduced to the amines RjCH-jNRaRa by sodium borohydride,13 converted to amide acetals RiC(OR)2NR2R3 by alkoxides,4-16 and (for R3 = H) deproton-ated to the imino esters R1C(OR)=NR2.16-18 Amide acetals and imino esters are themselves in turn useful synthetic intermediates. Indeed, oxonium salts transform the rather intractable amide group into a highly reactive and versatile functionality, a fact elegantly exploited in recent work on the synthesis of corrins.34... 

Management of endometriosis, uterine leiomyomata (Fibroids) CAS Registry 53714-56-0 (leuprorelin) 74381-53-6 (leuprorelin acetate) 5-oxo-L-prolyl-L-his tidyl-L-tryptophyl-L- seryl-L-tyrosyl-D-le ucyl-L-leucyl-L-argi nyl-A-ethyl-L-prolin amide acetate NA... 

Orthoesters and related species as precursors 49 Amide acetals as precursors 55 Ketene acetals as precursors 57 Oxocarbocations as precursors 59... 

Other ortho-acid derivatives which will not be considered in detail in this chapter are the thio ortho esters, amide acetals, ester aminals, and the ortho amides which have the following structures, respectively, RC(SR)3, RC(OR)2-NR2, RC(OR)(NR2)2, and RC—(NR2)3. 

The reactivity of functional groups presenting some similarities to cyclic acetals, such as cyclic orthoesters, and stannylidene and amide acetals, falls outside the scope of the present article, but attention has to be drawn to the fact that they may be considered to be special types of acetals having distinct properties, and a growing interest is focused... 

Methiniminium salts have been used for the direct introduction of an alkylidene chain at the a-position of a carbonyl group [179]. 3-Chloro-3-phenylprop-2-enylidenedimethyl-iminium perchlorate reacts with 2- or 3-ketosugars 7 and 18 in the presence of DBU to form an E-Z mixture of compounds 141 and 142 (Scheme 48). Amide acetals also react with... 

Although complexes with these ligands are common in palladium(II) chemistry, their occurrence is more scarce in platinum(II) compounds. Nevertheless these complexes can be prepared, examples being platinum(II) complexes of the optically active quadridentate Schiff base of salicylaldehyde and (R)-l, 2-diamines.1212 An alternative synthesis involves formation of the Schiff base by reaction of a complexed amino ligand on platinum(II) with amide acetates (equation 372).1213... 

Reagent 1 is preferred because of commercial availability, but it is less reactive than the amide acetal f-butoxybis(dimethylamino)methane 4 (Brederick s reagent). Thus 4 reacts with a-methylcyclohexanone to give the enaminone 2 in 99% yield. Trisdimethylaminomethane (5) is even more reactive than 4, but is not as readily available. 

Hydrolysis of the amide acetal (123 R1 = R2 = OMe) to the related codeinone (123 RXR2 = O) is effected by 0.1 M hydrochloric acid at room temperature. Use of more concentrated acid or elevated temperatures leads to... 

In the synthesis of specially substituted methylene diphosphines, made from secondary phosphines and carbonyl derivatives (7), a carbenium ion adjacent to trivalent phosphorus as the transition state has been discussed. The transfer of this reaction principle to primary phosphines and suitable carbonyl compound revealed a further pathway to derivatives of dicoordinated phosphorus (8). Aromatic phosphines react with carboxylic acid amide acetals under elimination of alcohol giving dialkylamino-alkylidene phosphines (Scheme 5). A modification of the synthesis... 

The synthesis of 1,3-dithiolanes (284) which contain a 2-dimethylamino group results from the reaction of ethanedithiol with amide acetals of type (283) (69BSF332). 

Bicyclic amide acetals have synthetic utility, as illustrated by the catalytic reduction of (84 R1 = H, R2 = Pr") leading to amino alcohols (85) reaction of (84 R1 = OH, R2 = H) with formic acid involves double ring fission to give (86) (71S16,78MI43600). 

Reactions of nitriles with nucleophilic reagents normally require catalysis by acids or bases. Heating iminodiethanols with aliphatic nitriles in the presence of catalytic amounts of sodium alkoxide leads to oxazolo[2,3-6Joxazoles ( bicyclic amide acetals ), in a single process via oxazolidine intermediates (equation 18) (73AG(E)1055>. 

Finally, the [3,3]-sigma tropic rearrangement can be carried out by heat as part of the same step or as a separate step depending on the compounds. This is a very flexible reaction sequence and can be used for aldehydes (as shown above), ketones, esters, or amides. In each case acetal-like compounds are used—acetals themselves for aldehydes and ketones orthoesters and orthoamides for the other two (though the orthoamides are often called amide acetals ). 

The reaction of propargyl alcohols with an amide acetal affords enamine products512. 

In contrast, morpholine enamines from higher alkyl ketones do not dimerise but undergo disproportionation to the reduced enamine and various oxidation products. Aldehyde enamines dimerise, but with more difficulty at higher temperatures544. Cross-conjugated545 and linear dienamines (e.g. 132)546 have been prepared by condensation of amide acetals with alkynyl alcohols (equation 37). 

The addition of a base to an acetylenic ester or ketone provides another method of preparation of enaminones594,595. A convenient one-pot synthesis of enaminones from trimethylsilylethynyl ketones and amines was described596. The reaction of activated methylene compounds, such as cycloalkanones, MeCOPh and PhCH2COOMe, with amide acetals gave high yields of enaminones597 (equation 39). 

By the exposure of an allylic alcohol to an amide acetal, a y,<5-unsaturated amide is obtained. For example, 9787 and 9988 are produced from 95 and corresponding alcohols (equations 19 and 20). 

---