And the Ritter reaction

CH3)2CH0H + CH2=C=0 CH3C00CH(CH3)2 and the Ritter reaction to prepare A/-isopropylacrylamide [2210-25-5] from acrylonitrile [107-13-1] and isopropyl alcohol ... 

A combination of the Pummerer rearrangement and the Ritter reaction occurs in the reaction of acetonitrile with methyl phenyl sulfoxide (equation 25) in a mixture of irifluoroacetic acid and its anhydride, although a substantial amount of the nonnal a-acetoxylation also occurs. Participation by amido groups is also possible, the interest here being largely in the construction of lactams via the intramolecular cycli-zation mode. Whereas Wolfe and his coworkers were unable to find conditions for the cyclization of S-phenylcysteinamide sulfoxides under Pummerer conditions, Kaneko found that variously substituted... 

Not all psychedelic amphetamines can be produced in this manner. For instance, B-asarone, the precursor of TMA-2, is a 2propenyl-benzene, rather than an allylbenzene. The breakthrough method will fail in this case, and the Ritter reaction will yield an isoquinoline. To convert... 

For most laboratory purposes, the important reactions under this heading are the Bucherer Reaction, chiefly useful in the naphthalene series, and the Ritter Reaction, which will be considered in sections IV.B and VI.B. 

Conversion of the C-2 amide to a biologically inactive nitrile, which can be further taken via a Ritter reaction (29) to the corresponding alkylated amide, has been accomphshed. When the 6-hydroxyl derivatives are used, dehydration occurs at this step to give the anhydro amide. Substituting an A/-hydroxymethylimide for isobutylene in the Ritter reaction yields the acylaminomethyl derivative (30). Hydrolysis affords an aminomethyl compound. Numerous examples (31—35) have been reported of the conversion of a C-2 amide to active Mannich adducts which are extremely labile and easily undergo hydrolysis to the parent tetracycline. This reverse reaction probably accounts for the antibacterial activity of these tetracyclines. 

Other sequences that transform primary alcohols to primary amines include (a) conversion of the alcohol to a cyanate, rearrangement to an isocyanate, and hydrolysis,3 and (b) conversion of the alcohol to an -V alkylformamide via the Ritter reaction, followed by hydrolysis.4... 

Alkenes of the form RCH=CHR and RR C=CH2 add to nitriles in the presence of mercuric nitrate to give, after treatment with NaBHj, the same amides that would be obtained by the Ritter reaction. This method has the advantage of avoiding strong acids. 

Davies and Reider (1996) have given some details of the HIV protease inhibitor CRDCIVAN (INDINAVIR) for which (lS,2R)-c -amino indanol is required. Indene is epoxidized enantioselectively, using the lacobsen strategy (SS-salen Mn catalyst, aqueous NaOH and PiNO), to (lS,2/ )-indene oxide in a two-phase system, in which the OH concentration is controlled. Indene oxide was subjected to the Ritter reaction with MeCN, in the presence of oleum, and subsequent hydrolysis and crystallization in the presence of tartaric acid gives the desired amino indanol. 

The formation of the tetrazoles 66 and 67 from 62 and 63, respectively, has been rationalized on the basis of the solvent-assisted opening of the initially formed iodonium ion to give the Ritter reaction intermediate 68, which undergoes cycloaddition with azide... 

Dorzolamide contains two chiral centers, and is therefore capable of existing in four diastereomers. The stereochemistry at the C-6 position of the starting material is preserved during the various chemical reactions which take place during the synthesis. The stereochemistry at the C-4 position (absolute configuration being 5) results from the Ritter substitution reaction (Scheme 1, Steps I-II) used to transform the alcohol to an acetamide. The Ritter reaction yields mostly the rra j-diastereomer, and the c/s-diastereomers are easily separated as their maleate salts. The potential sulfonamide positional isomer (3-sulfonamide) has not been observed at levels greater than 0.1% in HPLC analyses. 

Enantiomerically pure epoxides and diols, readily available through the asymmetric epoxidation and asymmetric dihydroxylation reactions, are ideal precursors to prepare cis-amino alcohols via the Ritter reaction. " " A Merck group has shown that indene oxide 175a can be converted effectively to c/i-l-amino-2-indanol, a key fragment of the HlV-protease inhibitor Indinavir via the cis-... 

Epoxides also participate in the Ritter reaction with nitriles. An investigation of the ring opening of several alkyl-substituted glycidic esters and amides 181 showed that this transformation occurs with inversion and is completely regiospecific. ° Esters appeared to be somewhat more reactive than amides. However, phenyl-substituted glycidic esters and amides 184 are almost totally nonstereoselective. In addition, the oxazolines 186 are isolated in low yield due to the propensity of intermediate 185 to generate an aldehyde byproduct 187 (Scheme 8.53). 

Epoxides also undergo the Ritter reaction in good yields with retention of configuration via a episulfonium intermediate 190a (double-inversion process). For monosubstituted epoxides, the yields of oxazolines are lower due to nondis-criminatory attack of the nitrile on both the primary and the secondary carbon atom of the episulfonium intermediate. Complete retention of configuration is still observed despite the lower yield (Scheme 8.54). 

Olefins also undergo the Ritter reaction with nitriles in the presence of diphenyl diselenide, ammonium persulfate, and trifluoromethanesulfonic acid to produce oxazolines.When cyanamide is used, 2-aminooxazolines are obtained. The active electrophilic agent is phenylselenyl sulfate formed by oxidation of diphenylselenide with ammonium persulfate. The reaction is trans-stereospecific. 

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