Dinitriles, alkylation

The solvent for ammonia may have an important influence. In reduction of C,o unsaturated dinitriles to primary amines over ruthenium-on-alumina, ammonia-/-butanol proved the preferred system normal alcohols gave poor rates and secondary alcohols produced N-alkylated products 18). 

Previously acrylonitrile had proved to be inert towards transition metal catalysed cross- and self-metathesis using ill-defined multicomponent catalysts [lib]. Using the molybdenum catalyst, however, acrylonitrile was successfully cross-metathesised with a range of alkyl-substituted alkenes in yields of40-90% (with the exception of 4-bromobut-l-ene, which gave a yield of 17.5%). A dinitrile product formed from self-metathesis of the acrylonitrile was not observed in any of the reactions and significant formation (>10%) of self-metathesis products of the second alkene was only observed in a couple of reactions. 

Following the reports of sulfur appended porphyrazines, Fitzgerald et al. (28) reported a facile synthesis of alkyl appended porphyrazines in 1991, preparing the dialkyl dinitrile precursors from alkynes via a Rosenmund von Braun reaction. Later, these types of dinitriles were used in mixed cyclizations to prepare porphyrazines with three dipropyl substituents (6,29). An intriguing extension was the... 

In particular, Fitzgerald s new route for the preparation of alkyl substituted dinitriles was used to prepare ethyl appended porphyrazines that were centrally metalated with iron and rhodium (Schemes 4 and 5). The main focus of Fitzgerald s work was on the magnetic and electronic properties of the metalated octaethylpor-... 

Synthesis. These macrocycles are prepared from seven-membered ring dinitrile complexes, 84a-84c (Scheme 17), which contain either methylene, sulfur or oxygen in the five position (129). These cyclic dinitriles are synthesized by alkylating maleonitrile dithiolate or derivatives thereof with the corresponding dihalide. The dinitriles 84a-84c can be cyclized in magnesium propoxide to form porphyrazines 85a (33%), 85b (19%), and 85c (27%) (Scheme 17), which can be demetalated with trifluoroacetic to form 86a-86c. Additionally, 86a has been remetalated with nickel (87a, 92%), copper (88a, 95%), and zinc (89a, 94%). The sulfur and oxygen derivatives 85b, 85c, 86b, and 86c are of low solubility and are not suitable for further manipulation. 

The products from the N-alkylation of (anilinomethylene)malonodinitriles with a-haloacetic esters and a-haloketones spontaneously cyclize to produce pyrroles (Scheme 5.3) [21]. When the A -acylated product of the reaction of the dinitrile with ethyl chloroformate is treated with an arylamine, 5-cyanopyrimidones are obtained [21]. 

The acid-catalyzed condensation between alkyl methyl ketones and the diiminodinitrile 8 (Scheme 3), with removal of water, yields the dinitriles the reaction fails with other ketones. 2,2-Dimethoxyproprane in tetrahydrofuran (THF) gives a high yield of 9 (R = Me). ... 

This preparation illustrates the alkylation of malononitrile under acid-catalyzed conditions, and the use of diborane for the reduction of a dinitrile to a diamine. The procedure for the preparation of tert-butylmalononitrile has been outlined briefly by Boldt and co-workers.2 The generation of diborane in situ and the general method for nitrile reduction is that described by Brown and co-workers.3 Attempts to reduce the dinitrile to the diamine by other methods including catalytic hydrogenation (5% rhodium on alumina, 5 atm.), lithium aluminum hydride, and lithium aluminum hydride-aluminum chloride were singularly unsuccessful. 

In another development, the statin side chain en route to Atorvastatin (Lipitor , Pfizer) is synthesized via the key intermediate alkyl 3-hydroxy-4-cyanobutyrate (Figure 13.17). Instead of the currently practiced six-step route, a much more concise three-step route starts from epichlorohydrin via Cl chain length enhancement by both nucleophilic substitution of chloride and nucleophilic ring opening of the epoxide with cyanide to yield symmetric dicyanoisopropanol. Nitrilase action desymmetrizes the dinitrile intermediate with the creation of a chiral center in C3 to yield (R)-3-hydroxy-4-cyanobutyrate, which is esterified to the key intermediate ethyl (R)-3-hydroxy-4-cyanobutyrate. 

Since an important feature of Biicherer-Bergs hydantoin formation is that the process can only work for a-aminonitriles without substituent on the amino group, it follows that one compound of the equilibrium mixture formed from an aldehyde, ammonia, and cyanide is selectively reacted through an irreversible process leaving N-alkylated aminonitriles or imino-dinitriles unreacted. However, the difficulty with this process is that CAAs and hydantoins are poorly reactive towards hydrolysis and need long periods of time to be converted into free AAs. But, CAAs may also have per se a prebi-otic importance in activation pathways towards polypeptides (see Sect. 3.3.7). CAAs can also be synthesized by reaction of free amino acids with cyanic acid/cyanate (a likely prebiotic compound [50]). In the presence of a steady-state concentration of either cyanate or urea in aqueous medium, CAAs are at equilibrium with A A [51]. 

This last example shows the addition of two alkyl groups to a dinitrile (pKa =11). Because the alkyl groups to be added are identical, they do not have to be added in sequence. Instead, the reaction is conducted by adding two equivalents of base and two equivalents of the alkylating agent, benzyl chloride, simultaneously ... 

Amin +NaNOz) (Alkylamino-methylen)- -dinitrile E6a, 600 (CH-CHO -C=CH —NHR) N-Alkyl(Aryl)-N-ethoxycarbo-nyl- -diamide E4, 232 (Umamidier.)... 

This is a new reaction for the preparation of N-alkyl amides. Nitriles and various substituted cyano compounds are treated with active olefins in the presence of sulfuric acid. Reaction occurs at room temperature in glacial acetic acid or dibutyl ether solution. The use of hydrogen cyanide in the reaction leads to the formation of N-alkylformamides. /-Butyl alcohol and sodium cyanide are used in place of the olefin and hydrogen cyanide in the preparation of N-/-butylfotmamide (50%). The reaction has been extended to the synthesis of N-alkyl diamides from dinitriles and olefins or alcohols. ... 

The bisoxindole (19) is built up as followsoxidative coupling of N-methyl-oxindole gives iV( )iV(o.)-dimethyl-3,3 -bisoxindole which can be alkylated, using chloroacetonitrile, at the 3 and 3 positions. Reduction of the resulting dinitrile... 

More recently, Yamamoto and coworkers [36] have developed a new acyl anion equivalent based upon the ethoxyethyl-protected a-hydroxymalonodini-trile derivative shown in Scheme 13 and have applied it in the area of N-sulfonyl imine chemistry. Thus, the carbanion derived from the dinitrile was added to imine 60 to afford adduct 61 which was rather unstable. However, N-alkylation of 61 with chloromethyl methyl ether yielded the stable product 62. Removal of... 

Einige substituierte Malonsaure-dinitrile (R2 = Alkyl, Aryl) reagieren mit Hydrazinen auch di-rekt zu 4-substituierten 3,5-Diamino-lH-pyrazolen422,440-442,2243. 

Dichlor-fumarsaure-dinitril kann mit Natriumsulfinaten und Aminoearbonyl-hydrazinen nach einer Eintopf-Methode direkt zu4-Alkyl(Aryl)-sulfonyl-5-amino-1 -aminocarbonyl-3-cyan-1 H-pyrazolen umgesetzt werden570. 

The addition of primary, secondary or tertiary alkyl radicals to an oc./l-unsaturated dinitrile, bearing a chiral substituent at the attacked carbon atom, affords the two isomeric nitriles with modest selectivity2. The radicals are generated via photolysis of the corresponding alkyl thiohydroxamates or from alkyl iodides using sonication. 

Nitriles and dinitriles are also valuable intermediates, and their preparation by phosphite deoxygenation of furoxans (Section V,D,3) opens further routes via these compounds. It has been suggested512 that methyl groups may be modified, by alkylation, condensation, etc., before deoxygenation ... 

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