Ritter reaction nitriles

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. 

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,... 

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>. 

In addition, Hegedus and co-workers extended this chemistry to the /V-alkylation of 1-lithioindole with alkenes (PdC MeCN /THF/HMPA/EtsN/then H2) to afford A/-alkylindoles in 28-68% yields [411], Moreover, a similar reaction of N-allylindole 343 with nitriles leads either to 344a, 344b, or 344c depending on how the intermediate Pd-alkyl (or acyl) complexes are treated [431]. The formation of these pyrazino[ 1,2-a]indoles is similar to a nitrile-Ritter reaction. 

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 )... 

Ritter reaction of cw-indane-l,2-diol with other nitriles leads to C2-symmetric bis(oxazolines) 178-180 that are ligands in a number of transition metal catalyzed... 

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. 

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. 

Extension of the Ritter reaction to conjugated dienes, however, has been less successful. The reaction is often met with competing Diels-Alder reactions or extensive polymerization. The polymerization that occurs during the reaction of 1,3-dienes and nitriles has been used in the synthesis of linear... 

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

In addition to Ritter-type transformations already discussed in previous sections, there are additional examples of the Ritter reaction—that is, the transformation of alkenes or alcohols with nitriles to give carboxamides carried out under superacidic conditions. 

The Ritter reaction (42,42A) is a general method for converting alcohols to amines by reaction with a nitrile and a strong acid (Reaction XXVI). In this reaction only tertiary,... 

The use of the Ritter reaction and cr-naphthylcarbinols and nitriles results in the formation of a single product, the 3,4-dihydrobenzo[/r] isoquinoline with no regioisomer detected (Scheme 20) <2003CHE184>. 

One of the earliest heterocyclic applications of the Ritter reaction was to the synthesis of dihydro-1,3-oxazines.9 It was found that the reaction of the dialcohol (1) with nitriles leads to the oxazines (2) rather than the expected bis-amides (Table I). The yields are only fair... 

The first synthesis of a heterocyclic system (22) by the Ritter reaction was reported24 in 1952, from the reaction of nitriles with methyleugenol (19). The reactions succeed only when the benzene ring is activated and allylbenzene itself gives the expected amide. 

Although the term nitrilium salt was used for the first time in 1931,26 the actual existence of these interesting compounds was not established until 1955 as a result of the work of Klages27,28 and Meerwein.29-30 Nevertheless, long before this last date it was common knowledge that non-isolable intermediate nitrilium salts are formed in numerous reactions. This is specifically the case in the Ritter reaction (Section II, A), as well as in many cognate reactions between nitriles and alkyl halides,31 isoparaffins,32 or a-trisubstituted acids,33 all of which yield a carbonium ion in the presence of sulfuric acid. 

Abb. 7.16. Ritter reaction part I (cf. Fig. 7.17) SN1 reaction between a tertiary alcohol and a nucleophile containing C=N, with hydrogen cyanide acting as the nucleophile. Under reaction conditions the C=N group is tert-alkylated at the N atom and hydrated at the nitrile nitrogen leading to the formation of an W-tert-alkyl-formamide (B). 

Various modifications of the reaction of an alcohol with ammonia provide the most common commercial routes to alkylamines. Some others routes that are used to make certain individual amines include aldehyde/amine additions, nitrile reduction, the Ritter reaction, amination of isobutylene, and hydrogenation of anilines. Capacities of many plants depend on the product mix of mono/di/tri products as well as the variety of amines (ethyl, propyl and butyl). One must know the product mix that the capacity is based upon and the actual scheduled output of produces) to determine what amounts can actually be manufactured. Capacities are often in excess of anticipated demand to satisfy seasonal demands for pesticide uses116. 

Ritter reaction. The original version for this conversion of a tertiary alcohol to an amide involved a reaction with nitriles in a strongly acidic medium.1 In a new version, the alcohol is converted into a triflate, which need not be isolated, but is treated with a nitrile (2 equiv.) in CH2C12 and then with aqueous NaHC03. Overall yields are 50-98%. The advantage of this version is that it is applicable to primary and secondary alcohols as well as tertiary ones.2... 

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