The Ritter Reaction

This reaction can be carried out on natural rubber and on synthetic polyisoprenes  

The carbon cation apparently reacts with any nucleophile present. When the reaction is carried out in dichloroacetic acid, chlorine atoms can be detected in the product.  

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The last recipe deserves to be last The Ritter Reaction [not affiliated with the above Ritter]. 

Ritter Reaction (Method 4). A small but important class of amines are manufactured by the Ritter reaction. These are the amines in which the nitrogen atom is adjacent to a tertiary alkyl group. In the Ritter reaction a substituted olefin such as isobutylene reacts with hydrogen cyanide under acidic conditions (12). The resulting formamide is then hydroly2ed to the parent primary amine. Typically sulfuric acid is used in this transformation of an olefin to an amine. Stoichiometric quantities of sulfate salts are produced along with the desired amine. 

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 ... 

The Ritter reaction with unsaturated carbenium ions under either silver-assisted solvolysis or photolytic conditions leads to excellent yields of isoquiaolines (173). The ease of preparation of the requited vinyl bromides makes an attractive route to highly substituted isoquiaolines. 

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. 

The Ritter reaction can be applied to cyanamides RNHCN to give ureas (RNHCONHR ). ... 

PhentEimine (11),used in the treatment of obesity, is a t-alkyl amine. The Ritter reaction, using HCN as the nitrile (p T63), is ideal for this,... 

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. 

Application of the Ritter reaction conditions on y-hydroxy-a,P-alkynoic esters, 102, produced ethyl 5-oxazoleacetates 103 or y-A-acylamino-P-keto ester 104 by reaction with aryl or alkyl nitriles respectively. The y-A-acylamino-P-keto ester 104 can also be transformed into oxazole derivatives using an additional step involving POCI3 <06TL4385>. 

This procedure constitutes the first example of one-step conversion of a /-alkane to the corresponding /-alkyfamine. Other hydrocarbons in this class, such as isobutane, have also been aminated with good results.7 Only a very limited number of convenient routes, e.g., the Ritter reaction, are available for the preparation of /-carbinamines. The present preparation illustrates a simple method that utilizes a novel substrate. 

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... 

The Ritter reaction [6] proceeds by the electrooxidation of alkyl iodides (56) in an MeCN-(Pt) system to form Ai-alkyl acetamides (58) (Scheme 21). Attack of carbenium ion intermediate - from dissociation of the initially formed alkyl cation radical - to acetonitrile would give the iminium cation (57). However, a different mechanism is proposed, whereby the alkyl iodide reacts with the electrogenerated iodo cation [I]" " [73]. 

Several procedures have been reported using acetonitrile as solvent for Bi(III) salt-catalyzed transformations involving epoxides as substrates [54, 93-95]. However, no reference has been made about the occurrence of the Ritter reaction, even... 

Under the Ritter reaction conditions above described, the sesquiterpene (—)-cariophyllene oxide undergoes an interesting rearrangement, originating an A-acyl amino clovane-type compound, in 33% yield, after purification by flash chromatography (Scheme 21) [92]. 

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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