Amides addition reactions

Poly(phenylene oxide)s undergo many substitution reactions (25). Reactions involving the aromatic rings and the methyl groups of DMPPO include bromination (26), displacement of the resultant bromine with phosphoms or amines (27), lithiation (28), and maleic anhydride grafting (29). Additional reactions at the open 3-position on the ring include nitration, alkylation (30), and amidation with isocyanates (31). 

The reactions of amides fall into hydrolysis, dehydration and degradation (to amines) acid hydrazides and acid azides undergo additional reactions. 

The chain addition of formamide to alkenes is a closely related reaction. It results in the formation of primary amides. The reaction is carried out with irradiation in acetone. The photoexcited acetone initiates the chain reaction by abstracting hydrogen from formamide ... 

Arynes are intermediates in certain reactions of aromatic compounds, especially in some nucleophilic substitution reactions. They are generated by abstraction of atoms or atomic groups from adjacent positions in the nucleus and react as strong electrophiles and as dienophiles in fast addition reactions. An example of a reaction occurring via an aryne is the amination of o-chlorotoluene (1) with potassium amide in liquid ammonia. According to the mechanism given, the intermediate 3-methylbenzyne (2) is first formed and subsequent addition of ammonia to the triple bond yields o-amino-toluene (3) and m-aminotoluene (4). It was found that partial rearrangement of the ortho to the meta isomer actually occurs. 

Fusion of an additional heterocyclic ring onto a benzodiazepine is well known to considerably increase potency. This increase in potency is apparently maintained when the benzene ring is replaced by thiophene. Thiophene aminoketone 161 is converted to the benzodiazepine analogue 164 via chloroacetamide 162 and then glycine derivative 163 by the same sequence as that used in the benzene series. Treatment of the product 164 with phosphorus pentasulfide gives the thio-amide 165 reaction of that intermediate with hydrazine leads to the amino amidine 166. Conden-... 

A sequence of straightforward functional group interconversions leads from 17 back to compound 20 via 18 and 19. In the synthetic direction, a base-induced intramolecular Michael addition reaction could create a new six-membered ring and two stereogenic centers. The transformation of intermediate 20 to 19 would likely be stereoselective substrate structural features inherent in 20 should control the stereochemical course of the intramolecular Michael addition reaction. Retrosynthetic disassembly of 20 by cleavage of the indicated bond provides precursors 21 and 22. In the forward sense, acylation of the nitrogen atom in 22 with the acid chloride 21 could afford amide 20. 

Addition Reactions of Metal Enolates of Non-stabilized Esters, Amides, and Ketones to Epoxides... 

In spite of their intrinsic synthetic potential, addition reactions of metal enolates of non-stabilized esters, amides, and ketones to epoxides are not widely used in the synthesis of complex molecules. Following the seminal work of Danishefsky [64], who introduced the use of Et2AlCl as an efficient catalyst for the reaction, Taylor obtained valuable spiro lactones through the addition reaction of the lithium eno-late of tert-butyl acetate to spiro-epoxides, upon treatment of the corresponding y-... 

Process economics dictate the recycling of the unwanted isomer. Path A in Figure A8.2 illustrates that racemisation of the D-N-benzylidene amino add amide is fadle and can be carried out under very mild reaction conditions. After removal of die benzaldehyde die D,L-amino add amide can be recyded 100% conversion to the L-amino add is theoretically possible. Another method for racemisation and recycling of the L-amino add (path B, Figure A8.2) comprises the conversion of the L-amino add into die ester in the presence of concentrated add, followed by addition of ammonia, resulting in the formation of the amide. Addition of benzaldehyde and racemisation by OH- (pH =13) gives the D,L-amino add amide. In this way 100% conversion to die D-amino add is possible. 

Most successful approaches involving addition reactions in the presence of chiral additives utilize organolithium, organomagnesium and the recently introduced organotitanium reagents, which are known to coordinate with amines, ethers, metal amides and alkoxides. 

ZnEt2 addition reactions to acetophenone withbis(snlfon-amides) diol ligand 157-8 to acetophenone with camphor-derived mesylamide hgand 174, 176... 

The addition reaction of enolates and enols with carbonyl compounds is of broad scope and of great synthetic importance. Essentially all of the stabilized carbanions mentioned in Section 1.1 are capable of adding to carbonyl groups, in what is known as the generalized aldol reaction. Enolates of aldehydes, ketones, esters, and amides, the carbanions of nitriles and nitro compounds, as well as phosphoms- and sulfur-stabilized carbanions and ylides undergo this reaction. In the next section we emphasize the fundamental regiochemical and stereochemical aspects of the reactions of ketones and aldehydes. 

Note also the stereochemistry. In some cases, two new stereogenic centers are formed. The hydroxyl group and any C(2) substituent on the enolate can be in a syn or anti relationship. For many aldol addition reactions, the stereochemical outcome of the reaction can be predicted and analyzed on the basis of the detailed mechanism of the reaction. Entry 1 is a mixed ketone-aldehyde aldol addition carried out by kinetic formation of the less-substituted ketone enolate. Entries 2 to 4 are similar reactions but with more highly substituted reactants. Entries 5 and 6 involve boron enolates, which are discussed in Section 2.1.2.2. Entry 7 shows the formation of a boron enolate of an amide reactions of this type are considered in Section 2.1.3. Entries 8 to 10 show titanium, tin, and zirconium enolates and are discussed in Section 2.1.2.3. 

The synthesis in Scheme 13.37 also used a me,ro-3,4-dimethylglutaric acid as the starting material. Both the resolved aldehyde employed in Scheme 13.36 and a resolved half-amide were successfully used as intermediates. The configuration at C(2) and C(3) was controlled by addition of a butenylborane to an aldehyde (see Section 9.1.5). The boronate was used in enantiomerically pure form so that stereoselectivity was enhanced by double stereodifferentiation. The allylic additions carried out by the butenylboronates do not appear to have been quite as highly stereoselective as the aldol condensations used in Scheme 13.37, since a minor diastereoisomer was formed in the boronate addition reactions. 

P(0)(0Me)H and [TpAr Me]Zn0P(0)(0R)2, respectively (Scheme 26) (35). In addition, [TpAr Me]ZnOH also cleaves activated esters and amides in a stoichiometric fashion, as illustrated in Scheme 27. Kitajima has described a similar amide cleavage reaction between the copper and nickel hydroxide complexes [Tp JMtOH) (M = Ni, Cu) and p-nitroacetanilide to give [TpPr 2]M p2-MeC(0)NC6H4N02 [Eq. (34)] (198). 

Since mild activation conditions appear to be important, a number of solution activation conditions were tested. PAMAM dendrimers are comprised of amide bonds, so the favorable conditions for refro-Michael addition reactions, (low pH, high temperature and the presence of water) may be able to cleave these bonds. Table 1 shows a series of reaction tests using various acid/solvent combinations to activate the dendrimer amide bonds. Characterization of the solution-activated catalysts with Atomic Absorption spectroscopy, FTIR spectroscopy and FTIR spectroscopy of adsorbed CO indicated that the solution activation generally resulted in Pt loss. Appropriate choice of solvent and acid, particularly EtOH/HOAc, minimized the leaching. FTIR spectra of these samples indicate that a substantial portion of the dendrimer amide bonds was removed by solution activation (note the small y-axis value in Figure 4 relative... 

Bunting and Kanter have developed a modified form of the Marcus equation to treat the changes in intrinsic barrier A observed for deprotonation of /J-keto esters and amides.81 It would be useful to consider similar modifications of the Marcus equation to model the variable intrinsic barriers observed for carboca-tion-nucleophile addition reactions. 

The propensity of S-S dications to undergo dealkylation was found to decrease in the order of methyl > ethyl > benzyl. This order of reactivity parallels the increase in the stability of the corresponding carbocations.94 Dealkylation of dication 77 affords thiosulfonium salt 78 in quantitative yield.95 Kinetic studies suggest SN1 mechanism of dealkylation. In addition, reaction of sulfoxide 79 with a substituent chiral at the a-carbon results in racemic amide 80 after hydrolysis. 

Silyl esters of trivalent phosphorus acids have been used successfully in conjugate addition reactions using acrylates,393 395 nitriles,394 amides,396 397 ketones and aldehydes,398-404 and nitro compounds.387... 

The first example of asymmetric rhodium-catalyzed 1,4-addition of organoboron reagents to enones was described in 1998 by Hayashi and Miyaura. Significant progress has been made in the past few years. This asymmetric addition reaction can be carried out in aqueous solvent for a broad range of substrates, such as a,/ -unsaturated ketones, esters, amides, phosphonates, nitroalkenes. The enantioselectivity is always very high (in most cases over 90% ee). This asymmetric transformation provides the best method for the enantioselective introduction of aryl and alkenyl groups to the / -position of these electron-deficient olefins. 

Isocyanates are quite reactive and they react with compounds which contain active hydrogen such as hydroxy, amine, carboxylic acids, amide, urea, etc. They can also undergo addition reaction ... 

Dienamides such as 167 react by a different reaction pathway168, namely by addition of the amide oxygen to the alkene by a radical addition reaction (equation 111). 

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