Ritter reaction alkenes

KEY Reaction name functional group conversion steps involved typical reagents Ritter reaction alkene (ere.) into amide, sequence (130) — carbenium ion —> (129) —> (133)... 

Retro-Ritter reaction amide into alkene reverse sequence to above SOCI2 or P4O10. Intramolecular Ritter reaction alkene (etc.) into heterocycle sequence (130) -> carbenium ion - (129) - (131) (where Y is a nucleophilic substituent) H2SO4 then H2O. 

Side reactions consistent with decomposition of intermediate nitrilium salt 7 have also been observed, including retro-Ritter reactions that afford alkenes (8), and VonBraun reactions that provide alkyl chlorides (9). ... 

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. 

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 )... 

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. 

Although terminal alkenes provide the best yields, the Ritter reaction is also successful when using tri-substituted alkenes and haloalkenes. Markovnikov addition is generally observed. Rearranged products arise occasionally, especially with alkenes that are prone to cationic rearrangements (equation 165).233... 

The Ritter reaction of internal alkenes may yield mixtures of regioisomers, and on occasion, small amounts of rearranged products (equation 166).234... 

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. 

This review is written to cover the needs of synthetic chemists with interests in oxidizing alkenes by addition of nitrogenous substituents. Whilst some aspects have been covered in previous reviews (noted in the text), most notably in the Tetrahedron Report No. 144, Amination of Alkenes and prior reviews on aziridines and nitrenes, the present review is the fust conq>ilation of references to the whole range of these particular bond-forming processes. A review by Whitham provides a useful general introduction to reaction mechanisms of additions to alkenes in greater detail than can be covered here. The oxidation requirement excludes from the scope the additions of N H and most additions of N + Metal or N + C. Hence, unmodified Michael and Ritter reactions are excluded. These topics are mostly covered in Volume 4 of the present series. 

The reaction is akin to the Ritter reaction, with activation achieved by nitration, rather than proton-ation, and the products accordingly retain the nitro group. Additions to 1-phenylcyclohexene (59%) and to franr-stilbene (72%) are stereospecific (trans) cfr-stilbene gives the expected tfireo product (39%) plus some erythro (6%). Reactions of nitrogen dioxide with alkenes are very complex and rarely use-ful. A recent mechanistic paper gives many key references. " Addition of NjOs is occasionally usefiil, as with dicyclopentadiene (Scheme 49). ... 

In its utilization of acetonitrile, the oxazoline synthesis shown in Scheme 56 resembles a Ritter reaction.The procedure is convenient, but yields are variable the pyrolysis gives starting alkene plus acetamide as by-products. Another oxazoline synthesis and subsequent conversion to a cif-amino alcohol is discussed later (Scheme 85). A recent y-hydroxy-a-amino acid synthesis incorporates the following type of transformation (Scheme 57).If a three-day equilibration with anhydrous HBr was introduced iMtween stages i and ii, almost pure trans product was obtained. The paper has many usefol references. Yet another modified Ritter reaction is shown in Scheme 58. ... 

If the reactions are carried out in a nitrile as solvent, rather than dichloromethane, using triflic acid as catalyst, a modified Ritter reaction takes place, and the intermediate nitrilium ion traps the liberated amine, forming an amidine (Scheme 67). In an earlier reaction cf. Scheme 67) the lithium perchlorate catalyzed reaction of sulfenyl chlorides with alkenes in the presence of nitriles had also given l-amido-2-sulfenyl adducts. Ritter products are also obtained in good yields by anodic oxidation (Pt or C, 1.2-1.4 V) of disulfides in acetonitrile, in the presence of excess alkene, using B114NBF4 as supporting electrolyte (Scheme 68). ... 

The nitrogen atom of the nitrile possesses some nucleophilic characteristics. When a carbocation is generated by protonation of an alkene, it may be discharged by a nitrile. This reaction, known as the Ritter reaction, leads to the formation of amides (Scheme 3.92). 

Since the amides (especially the formamides) are easily cleaved under hydrolysis conditions to amines, the Ritter reaction provides a method for achieving the conversions R OH R NH2 (see 10-32) and alkene R NH2 (see 15-8) in those cases where R can form a relatively stable carbocation. The reaction is especially useful for the preparation of tertiary alkyl amines because there are few alternate ways of preparing these compounds. The reaction can be extended to primary alcohols by treatment with triflic anhydride ° or Ph2CCl" SbClg or a similar salt in the presence of the nitrile. 

Despite the range of sources available, the majority of reactions described have used alcohol or alkene precursors. This reflects both the availability of such materials and their ease of reaction. Typical examples of alkene reagents are shown in equations (9), (10), (11) and (12). When two reactive groups are in close proximity in the substrate it is possible to combine transannular cyclization with Ritter reaction (equation 13). - ... 

Magat first reported the use of r-alkyl halides as Ritter reaction substrates but, in general, these were less satisfactory than the use of the corresponding alcohol or alkene analogs. This process has since come into its own for polycyclic systems, where simple methods of generating bridgehead halides are often available. An early example is Stetter s conversion of 1-bromoadamantane to the acetamide (30), there-... 

If the internal nucleophile is an alkenic group, then 5,6-dihydropyridine (Scheme 18) " or 1-pyrroline (Scheme 19) rings are produced. In a recent development of the latter process, the diol (44) follows the same sequence to yield the carbenium ion (45 R = Bn). However, this now cyclizes onto the aromatic group originating from the nitrile component and produces the tetrahydrobenz indole (46) in good yield, with the conventional pyrroline structure (47) now being only a minor product. Compound (46), present as a tautomeric mixture, was rapidly autoxidized to (48 Scheme 20). A further unusual variant of this process is the production of small quantities of the 3-azabicyclo[3.3.0]octanes (49) and (50) from Ritter reaction of l-vinylbicyclo(2.1.1]hexane (equation 32). ... 

Until recently, the intramolecular cyclization procedure had been used only to synthesize fused heterocyclic structures. The first report of a bridged product, in 1978, involved only a minor amount (9%) of an azabicyclo[3.3.1]nonane derivative obtained from the reaction of ds-carveol with acetonitrile and BFj-EtiO. However, several effective examples are now known. These all involve reaction of the nitri-lium intermediate with an internal alkenic nucleophile to yield a 1-azacyclohexene ring and a new carbe-nium ion which undergoes conventional, but stereospecific, Ritter reaction fiom the least hindered face. Such reactions are typified by formation of the multicyclic structures (64 equation 38) 5<) and (65 equation 39), 5i considerable potential in the synthesis of complex nitrogen heterocyclic systems... 

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