RITTER Amidation

The formation of the products could be explained by hemiacetal formation followed by Prins cyclization and subsequent Ritter amidation. A tentative reaction mechanism to realize the cis selectivity is given in Fig. 20 and could be explained by assuming the formation of an (L )-oxocarbenium ion via a chair-like transition state, which has an increased stability relative to the open oxocarbenium ion owing to electron delocalization. The optimal geometry for this delocalization places the hydrogen atom at C4 in a pseudoaxial position, which favors equatorial attack of the nucleophiles. 

Another interesting sequence is the amidoselenenation of alkenes for the synthesis of allylic amides. The seleniranium ion is trapped by a nitrile group which is first converted to an iminium chloride and then hydrolyzed to the amide (similar to the Ritter amide synthesis). Several differing nitriles (e.g. methyl to phenyl) have been utilized and all provide good yields of amides. The stereochemistry of addition is always trans but mixtures of regioisomers occur with terminal and unsymmetrically substituted oleflns (equation 24). The -seleno amide is easily converted to the allylic amide by oxidation of the phenyl selenide using the standard conditions. ... 

RITTER Amidation 320 Robinson 300 ROBINSON Annufebon 321 ROBINSON - ALLAN - KOSTANECKI Chromone synthesis 321... 

Example 6, A cascade of the Prins/Ritter amidation reaction ... 

This method was designed to produce an acetyl intermediate just like that in the failed recipe a few paragraphs above using only sulfuric acid and acetonitrile [93]. This reaction works, in theory, in a so-so manner on allylbenzene but not on safrole. This method will not make X for many reasons. So why does underground literature and DEA forensic scientists keep claiming that it does Strike doesn t know either. Let s see what the man who invented this. Dr. Ritter, had to say back in 1952 "several attempts to obtain amides from...safrol (sic) were fruitless. [94]. What makes all these people think that this will work unless no one did their homework. This is another sore spot of Strike s and... 

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. 

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. 

Itiswer The n-propyl group had best come from an amide (13) which could be the Ritter product if EtCM is used. Making (13) by more conventional methods Is fine, too. 

Ionic hydrogenation of the same bicyclic diene 382 by Et3SiH in the presence of CF3COOH at room temperature or at 80 °C via ions 387 and 388 is accompanied by transannular cyclizations (equation 139)192. The behavior of diene 382 under Ritter reaction conditions (MeCN, H2SO4) reveals new possibilities to control the transannular cyclizations (equation 140)193. Depending on the sulfuric acid concentration, the reaction temperature and the presence of a nucleophilic solvent, these transformations can be directed to the formation of either the bicyclic amides 389 and 390 having the precursor structure or the tricyclic products 391193. 

Ritter reaction org chem A procedure for the preparation of amides by reacting alkenes or tertiary alcohols with nitriles in an acidic medium. rid-ar re,ak-sh3n ) Ritz s combination principie spect The empirical rule that sums and differences of the frequencies of spectral lines often equal other observed frequencies. Also known as combination principle. rit-soz, kam-b3 na-sh3n. prin-sa-pal )... 

Risocaine, 91 Ritodrine, 39 Ritter reaction, 19 Robinson annulation, 224 Rodocaine, 450 Rolet amide, 103 Rolici/prine, 50 Rolodine, 468 Ronidazole, 245 Rotoxamine, 32... 

Reactions with secondary or tertiary alcohols in strongly acidic media yield amides (Ritter reaction) ... 

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). 

Ritter reactionThis reaction involves the condensation of nitriles with an alcohol in a strongly acidic medium to form an amide.J Yields are generally low with primary and secondary alcohols, which form relatively unstable carbocations. 

Although fluorine is known to be a rather poor leaving group in substitution reactions, some examples have been reported for the replacement of fluorine by N-nucleophiles. Here, substitution can proceed with amines,1 -3 amides,4 amidines,5-6 hydrazines3-7 or azides.8-9 Nitriles in the presence of nitrosyl hexafluorophosphate replace fluorine in alkyl fluorides, in a Ritter-like reaction, to form tV-alkylnitrilium species, which are hydrolyzed to amides.10... 

Exercise 15-24 It is possible to prepare amides from tertiary alcohols and alkane-nitriles, RCN, in concentrated sulfuric acid as the catalyst (Ritter reaction), as illustrated in the equation for the synthesis of W-fe/f-butylethanamide ... 

There are several methods available for the electrophilic addition of hydrogen and nitrogen to alkenes, dienes and alkynes. While the direct electrophilic addition of amines to these substrates is not feasible, aminomercuration-demercuration affords a very useful indirect approach to such amines. The addition of amides to C—C multiple bonds can be effected directly through the Ritter reaction or by the less direct, but equally useful, amidomercuration-demercuration process using either nitriles or amides. Similarly, H—N3 addition to alkenes can be carried out directly or via mercuration to produce organic azides. 

The preparation of amides by the addition of hydrogen cyanide or alkyl nitriles to alkenes in the presence of acids, known as the Ritter reaction, has been reviewed.229-232 The reaction may be considered simplistically as nucleophilic attack of a nitrile on a carbocation formed by the protonation of an alkene. Subsequent hydrolysis of the nitrilium intermediate gives the amide product (equation 164). The overall result is addition of a molecule of H—NHCOR to a C—C double bond. 

Recently, nonconjugated dienes have been successfully used in the Ritter reaction for the preparation of bridgehead amides238 and azatricycloundecane amides (equations 171 and 172).239... 

Keywords alcohol, nitrile, montmorillonite KSF, Ritter reaction, microwave irradiation, amide... 

Tertiary hydroxyls can undergo several reactions under acidic conditions to form artifacts in degradation experiments. In acidic acetonitrile/ water solutions, primary, secondary and tertiary alcohols can undergo a Ritter reaction to form amides (Fig. 83). 

---