Nucleophiles reaction with amide acetal

Many other reactions of ethylene oxide are only of laboratory significance. These iaclude nucleophilic additions of amides, alkaU metal organic compounds, and pyridinyl alcohols (93), and electrophilic reactions with orthoformates, acetals, titanium tetrachloride, sulfenyl chlorides, halo-silanes, and dinitrogen tetroxide (94). 

Synthesis of enamines from carboxylic acid amides via 1-alkoxyazomethi-nium salts and amide acetals—Gyclic enamines via lactam acetals— Easy reaction of amide acetals with nucleophiles, urea acetals s. 16, 785 Enamines from carboxylic acid amides GHg + OG N < G G N <... 

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. 

Dyong and Bendlin52 pointed out the possibility of functionalization of sorbic acid at C-3, -4, and -5 in the desired way. Introduction of two hydroxyl groups, at CA and C-5, may be accomplished stereospecifi-cally by means of cis-hvdroxylation, or by intermediation of an epoxide. Michael-type addition of a nucleophile to C-3 of the conjugated double-bond provides the possibility of obtaining all four diastereo-isomeric products. In this way, N-acetyl-DL-acosamine (137, 3-acet-amido-2,3,6-trideoxy-DL-arabmo-hexopyranose) was synthesized from 133 (obtained from the epoxide 129 in an aluminum chloride-catalyzed reaction with acetone). The amide 134 wasN-acetylated and... 

A broad spectrum of hydrogen-containing nucleophiles react with both aromatic and aliphatic isocyanates compounds containing OH groups (H20, alcohols, phenols, oximes, acids), SH groups (H2S, mercaptans), NH groups (NH3, amines, hydrazines, amides, ureas, urethanes), enolizable compounds such as malonic and aceto acetic esters, etc. Some reactions are given in Table 2.5. 

The amide 2 is paracetamol, the popular analgesic. Amines are much more nucleophilic than phenols (compare the basicities of ammonia and water) so reaction with acetic anhydride gives... 

Additions to l,3-dienes6 (12, 367-368 14, 249-250 15, 245). This reaction can be used to effect intramolecular cyclization of cyclic 1,3-dienes substituted by a suitable nitrogen nucleophile. Thus reaction of the amido diene 1 with lithium acetate catalyzed by Pd(OAc)2 (with benzoquinone as reoxidant) provides the ds-fused heterocycle cis-2, in which the acetoxy group is cis to the ring fusion, formed by an overall trans-1,4-oxyamidation of the diene system. Addition of a trace of LiCl improves the yield and results in an overall cis- 1,4-oxyamidation (equation I). Acetamides and carbamates can also be used in place of amides. 1,4-Chloroamidation can also be effected by use of 2 equiv. of LiCl. 

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>. 

Isatin reacts with ammonium hydroxide or ammonium acetate to furnish a mixture of compounds. Amongst them are isamic acid and its corresponding amide, isamide. Since 1877 there had been a discussion as to their structure, which in 1976 was finally elucidated, by Sir John Comforth on the basis of chemical and spectroscopic data228. Isamic acid can be regarded as a dimer formed by the addition/condensation of one equivalent of ammonia with two equivalents of isatin. This intermediate suffers lactonization and subsequent conversion to isamic acid by an internal nucleophilic attack, where upon the acid is converted to isamide by reaction with a second equivalent of ammonia. 1-Methylisatin reacts similarly, furnishing N-methylisamic acid (Scheme 51). 

A similar approach was described by Kim et al. <01MI1403> to build the Furstner synthon from the vinylogous amide 9, previously described, and the commercially available dimethyl aminomalonate hydrochloride as building block for pyrrole systems. The cyclocondensation reaction between the vinylogous amide 9 and dimethyl aminomalonate hydrochloride was performed in acetic acid at room temperature to yield the presumed Intermediate 12 via an acid-catalyzed nucleophilic substitution reaction. The mixture was then diluted with additional acetic acid and heated under reflux to facilitate the intramolecular ring closure and the loss of the methoxycarbonyl moiety to produce the desired pyrrole. Formation of lamellarin O dimethyl ether was achieved as in the Furstner approach <95JOC6637>. 

Yields are in the range 50-70%. The reaction of (3) with nucleophiles at 80 results in elimination of ethanol and formation of an aminomethylene compound. Thus the amide acetal (4) reacts with nilromelhane to give (5) in 60% yield. 

The reaction sequence, which is as shown in equation 43, is analogous to that suggested for the formation of arsonium ylides from triphenylarsine oxide in acetic anhydride Crystalline bisacetoxytriphenylarsine (37) has been isolated and shown to react with amides to give arsinimines . Tosyl and mesyl amides and benzamide react with 37 at room temperature, but less nucleophilic amides required heating in boiling 1,2-dichloroethane for reaction to take place. ... 

As alternatives to the chloro compounds for substrates in nucleophilic displacement reactions, phenoxy compounds and cyclic amides and cyclic thioamides have been used. It appears that 2-phenoxyquinoxaline is significantly less reactive than the corresponding cinnoline or phthalazine derivatives and only gives a negligible yield of 2-aminoquinoxaline when heated with ammonium acetate. However the phenoxyquinoxaline 1 is converted in high yield into the aminoquinoxaline 2 on treatment with this reagent. ... 

Compared with other synthetic intermediates, enolates show a decreased reactivity. The differences in reactivity are most striking in reactions with alkylating agents [1] and epoxides [6]. The reactivities of the various types of enolates towards alkyl halides decrease in the order C=C(0 )NR2 (amide-enolate) C=C(0 )0R (ester enolate) C=CO (ketone-enolate). Metallated nitriles, imines, and S,S-acetals are, in general, much better nucleophiles than enolates in alkylations and ft-hydroxyalkylations [1], Furthermore, the alkylation of aldehyde and ketone enolates usually does not stop after the mono-functionalization [12]. The decreased reactivity of (especially) aldehyde and ketone enolates also appears in thiolations with disulfides [2]. A solution of lithiated cyclohexanone in THF does not react at 20°C with CH3SSCH3 [1,2]. 

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