Acrylonitriles, substituted formation

The Michael-type addition of maleic hydrazide and other pyridazinones to activated alkenes, such as methyl acrylate, acrylonitrile, methyl vinyl ketone and other a,/3-unsatu-rated carbonyl compounds, results in the formation of mono-lV-substituted products. 

Thus the reactions of cyclic or acyclic enamines with acrylic esters or acrylonitrile can be directed to the exclusive formation of monoalkylated ketones (3,294-301). The corresponding enolate anion alkylations lead preferentially to di- or higher-alkylation products. However, by proper choice of reaction conditions, enamines can also be used for the preferential formation of higher alkylation products, if these are desired. Such reactions are valuable in the a substitution of aldehydes, which undergo self-condensation in base-catalyzed reactions (117,118). Monoalkylation products are favored in nonhydroxylic solvents such as benzene or dioxane, whereas dialkylation products can be obtained in hydroxylic solvents such as methanol. The difference in products can be ascribed to the differing fates of an initially formed zwitterionic intermediate. Collapse to a cyclobutane takes place in a nonprotonic solvent, whereas protonation on the newly introduced substitutent and deprotonation of the imonium salt, in alcohol, leads to a new enamine available for further substitution. 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

Other substituted olefins such as acrylonitrile, fumaronitrile, crotono-nitrile, cinnamonitrile, and diethylfumarate also formed adducts with Co (DMG)2 complexes containing py, H2O, or PBuj and, in one case, with [Co (DMG-BF2)2py]. Second-order rate constants were reported for the formation of several Tr-olefin-Co(I) complexes from organocobalt(III) complexes containing, for example, NCCH2CH2- with DMG, DPG, DMG-BF, py, H2O, and PBuj. 

Bromine was being added in portions to acrylonitrile with ice cooling, with intermediate warming to 20°C between portions. After half the bromine was added, the temperature increased to 70°C then the flask exploded. This was attributed either to an accumulation of unreacted bromine (which would be obvious) or to violent polymerisation [1], The latter seems more likely, catalysed by hydrogen bromide formed by substitutive bromination. Chlorine produces similar phenomena, even if the flask stays intact. The runaway is preceded by loss of yellow colouration and accompanied by formation of 3-chloroacrylonitrile and derivatives. It can be suppressed by presence of bases [2],... 

Formation of the ylide from the substituted pyrrolopyrazine 374 and subsequent [3+2] dipolar cycloaddition with a range of dipoloarophiles gives rise to the substituted 5 6 5 system 375 and the following examples are illustrative (Scheme 29) <1997T9341>. Reaction with acrylonitrile followed by oxidation with DDQ leads to the dihydroinda-cene 376. 

Formation of this ring system was also reported in the reaction of a,/3-unsaturated ketones with substituted pyrrol-5-ones, giving the tricyclic products in 41—46% yield <2004PS(179)61>. 4-Thienyl and 4-furyl derivatives of a dihydropyrano[2,3- 5,6-c]dipyrazole were also obtained via the heterocycle-substituted acrylonitrile in 77% and 74% yield, respectively <2005RJ0742>. 

In most of these nuclear substitution reactions, kojic acid did indeed react as a phenol. An exception was the reaction with acrylonitrile, as noted by Woods.97 Phenols usually form cyanoethy ethers under similar conditions, but the reaction of acrylonitrile with ketones leads to substitution of the a-hydrogen atom.100 This consideration points to a predominance of the diketo form of the kojate anion (LXIV) in these reactions. There are many good reasons for believing that, in the formation of all these derivatives, substitution actually takes place at C6 it should, however, be pointed out that this assumption still lacks confirmation by synthesis or by appropriate degradation studies. The nuclear mono-substitution products of kojic acid are listed in Table IV, and their functional derivatives in Tables V and VI. 

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. 

The kinetics and mechanism of the phosphorus-catalysed dimerization of acrylonitrile to give 1,4-dicyanobut-l-ene and 2,4-dicyanobut-l-ene have been studied.114 The reactions of aryhminodimagnesium (138) with //-substituted p-cyanobenzophenones, l-cyano-9-fluorenenone, o-, m-, and p-dicyanobcnzcnes, and o-, m-, and p-nitrobenzonitriles have been examined.115 The effect of pressure on the reaction of 3 -methyl- l-(4-tolyl)triazene (139) and benzoic acid in chloroform and acetonitrile has been studied.116 The effect of acids on the rate of urethane formation from alcohols and isocyanates in the presence of alkyltin carboxylates has been examined.117 A Hammett a value has been reported for the amidine group N=CHNMe2 and used for the prediction of the basicity of sites in bifunctional amidines.118... 

FMO calculations using PM3-C1 were used to investigate the regioselectivities obtained by the photochemical reactions between 2-pyridone and pcnta-2,4-dienoate.46 The hard and soft acid-base principle has been successfully used to predict product formation in Patemo-Buchi reactions.47 The 2 + 2-photo-cycloaddition of homobenz-valene with methyl phenylglyoxylate, benzyl, benzophenone, and 1,4-benzoquinone produced the corresponding Patemo-Buchi products.48 The photo-cycloaddition of acrylonitrile to 5-substituted adamantan-2-ones produces anti- and svn-oxetanes in similar ratios irrespective of the nature of the 5-substituent49... 

Nucleophilic addition reactions of para-substituted benzylamines (XC6H4CH2NH2) to a-phenyl-/9-thiophenylacrylonitriles [Y(C4SH2)CH=C(CN)C6H4Y/] have been studied in acetonitrile at 25.0, 30.0, and 35.0 °C. The reactions apparently take place in a single step in which the C/ -N bond formation and proton transfer to C of a-phenyl-/3-thiophenyl acrylonitriles occur concurrently with a four-membered cyclic transition structure. These mechanistic conclusions were deduced from the following ... 

Styrene and substituted styrenes react with tetramesityldisilene 1, tetra-tert-butyl-disilene 21, and tetrakis(tert-butyldimethylsilyl)disilene 22 to afford the corresponding disilacyclobutane derivatives.127,134 Similarly, [2 + 2] additions occur between the disilenes with a C = C double bond in an aromatic ring135 and acrylonitrile.136 Bains et al. have found that the reaction of disilene 1 with trans-styrene- provides a 7 3 diastereomeric mixture of [2 + 2] adducts, 201 and 202 [Eq. (95)] the ratio is changed, when czs-styrene-Ji is used.137 The formation of the two diastereomeric cyclic adducts is taken as the evidence for a stepwise mechanism via a diradical or dipolar intermediate for the addition, similar to the [2 + 2] cycloaddition of phenylacetylene to disilene ( )-3, which gives a 1 1 mixture of stereoiso-meric products.116,137... 

Ohashi et al. [136,139] have proposed a scheme describing the formation of ortho adducts and substitution products from anisole and the three dimethoxyben-zenes with acrylonitrile, methacrylonitrile, and crotonitrile (Scheme 39). Here, the ortho cycloadduct is supposed to be formed directly from an encounter complex or exciplex, whereas the substitution product arises via formation of an ion pair from the complex, followed by protonation of the radical anion and radical... 

Scheme 39 Formation of ortho photocycloadducts and substitution products from anisole and dimethoxybenzenes with acrylonitrile (R[ = R2 = H), methacrylonitrile f R, = Me R2 = H), and crotonitrile (R = H R2 = Me).

Ohashi et al. [128] found that the yields of ortho photoaddition of acrylonitrile and methacrylonitrile to benzene and that of acrylonitrile to toluene are considerable increased when zinc(II) chloride is present in the solution. This was ascribed to increased electron affinity of (meth)acrylonitrile by complex formation with ZnCl2 and it confirmed the occurrence of charge transfer during ortho photocycloaddition. This was further explored by investigating solvent effects on ortho additions of acceptor olefins and donor arenes [136,139], Irradiation of anisole and acrylonitrile in acetonitrile at 254 nm yielded a mixture of stereoisomers of l-methoxy-8-cyanobicyclo[4.2.0]octa-2,4-diene as a major product. A similar reaction occurred in ethyl acetate. However, irradiation of a mixture of anisole and acrylonitrile in methanol under similar conditions gave the substitution products 4-methoxy-a-methylbenzeneacetonitrile (49%) and 2-methoxy-a-methylbenzeneacetonitrile (10%) solely (Scheme 43). 

Trialkylammonium salts of the N-unsubstituted tetrazoles 231 are equally applicable as substrates in reactions both with haloalkyls and unsaturated compounds. These reactions, as already mentioned, lead mainly to formation of Nz-isomers. For instance, the reaction of 5-phenyltetrazole triethylammonium salt 231 (generated in situ from 5-phenyltetrazole and triethylamine) in acetonitrile with y-bromobutyronitrile (alkylation) or with acrylonitrile (Michael s method) afforded the corresponding Nz-substituted derivatives 254 and 255 in acceptable yields (Scheme 26) <2002CHE986>. 

The high electron density in the double bond system of ethylenes makes nucleophilic attack unfavorable unless the system is substituted with one or more electron withdrawing groups such as -N02, -CN, -COR. When these substituents are present, attack by alcohols or alkoxide ions occurs at the beta-carbon predominantly. For example, researchers have found (12) that sodium methoxide or sodium ethoxide added rapidly at room temperature to beta-nitrostyrene leads to the alkoxide formation of the derivative (Reaction VIII). This reaction is generally not only for arylnitroalkenes (13) but also for other activated double bonds (14). Another example of alcohol addition to an activated double bond includes the reaction of alcohols with acrylonitrile to produce a cyano-ethylated ether (14A). 

The formation of trans-products is observed to a lesser extent in the reaction of 3-alkoxycarbonyl-substituted cyclohexenones, in the reaction with electron-deficient alkenes and in the reaction with olefinic reaction partners, such as alkynes and allenes, in which the four-membered ring is highly strained (Scheme 6.11). The ester 26 reacted with cyclopentene upon irradiation in toluene to only two diastereomeric products 27 [36]. The exo-product 27a (cis-anti-cis) prevailed over the endo-product 27b (cis-syn-cis) the formation of trans-products was not observed. The well-known [2 + 2]-photocycloaddition of cyclohexenone (24) to acrylonitrile was recently reinvestigated in connection with a comprehensive study [37]. The product distribution, with the two major products 28a and 28b being isolated in 90% purity, nicely illustrates the preferential formation of HH (head-to-head) cyclobutanes with electron-acceptor substituted olefins. The low simple diastereoselectivity can be interpreted by the fact that the cyano group is relatively small and does not exhibit a significant preference for being positioned in an exo-fashion. 

In the preparative application of [2 + 2]-photocycloadditions of cyclic enones to (substituted) alkenes, two factors concerning product formation are of decisive relevance, namely the regioselectivity and the (overall) rate of conversion. Regarding the regioselectivity in the addition to mono- and 1,1-disubstituted alkenes, Corey had shown that the preferred addition mode of cyclohex-2-enone to isobutene or 1,1-dimethoxyethylene was the one leading to—both cis- and trans-fused—bicyclo[4.2.0]octan-2-ones with the substituents on C(7) [8]. In contrast, in the reaction with acrylonitrile, the alternate orientation was observed to occur preferentially. Similar results were also reported by Cantrell for the photocycloaddition of 3-methyl-cyclohex-2-enone to differently substituted alkenes [14]. No significant differences in the overall rates of product formation for the different alkenes were observed in these studies. In order to explain these observed... 

The radical polymerization behavior of captodative olefins such as acrylonitriles, acrylates, and acrylamides a-substituted by an electron-donating substituent is reviewed, including the initiated and spontaneous radical homo- and copolymerizations and the radical polymerizations in the presence of Lewis acids. The formation of low-molecular weight products under some experimental conditions is also reviewed. The reactivity of these olefins is analyzed in the context of the captodative theory. In spite of the unusual stabilization of the captodative radical, the reactivity pattern of these olefins in polymerization does not differ significantly from the pattern observed for other 1,1-disubstituted olefins. Classical explanations such as steric effects and aggregation of monomers are sufficient to rationalize the observations described in the literature. The spontaneous polymerization of acrylates a-substituted by an ether, a thioether, or an acylamido group can be rationalized by the Bond-Forming Initiation theory. 

Pyridylethyl derivatives of 2 are formed by reaction of a- or y-vinyl-pyridine with 2.107 Treatment of 1 or 2, as well as the 5-arylidene derivatives, with acrylonitrile in the presence of pyridine results in formation of 84 by cyanoethylation on the ring nitrogen (Scheme 2) however, cyanoethyla-tion of 5-aryl-2-iminothiazolidinones involves the exocyclic nitrogen.108 Aminoalkylation (Mannich reaction) of 2 or 2-aryl-4-thiazolidinones with formaldehyde and amines in warm alcoholic solvents affords the desired 3-alkylated product 85 (Scheme 2),109,110 whereas 3-aryl-2-iminothiazoli-dinones react with substituted anilines and aliphatic amines and formaldehyde to give the 2-arylaminomethyl derivatives 86 [Eq. (25)].111... 

Ruthenium(II) Treatment of [Ru(NH3)5(OH2)]2+ or [Ru(NH3)5(acetone)]2+ with L or [RuCl(NH3)5]2+ with zinc amalgam in the presence of L yields [RuL(NH3)5]2+ (L = acetonitrile, benzonitrile,358 substituted benzonitrile,196 358 359 acrylonitrile,360 hydrogen cyanide,36,37 ethyl cyano-formate,361 dicyanamide, malononitrile, substituted malononitrile, tricyanomethanide,362 4-cyano-l-methylpyridinium196). Reaction of a hundred-fold excess of RCHO (R = Ph, Me) with [Ru(NH3)6]2+ under alkaline conditions yields [Ru(NH3)sNCR]2+.363-365 The likely mechanism of this reaction is given in Scheme 12. An alternative route to nitrile complexes is by reaction of [Ru(NH3)sOH2]2+ with aldoximes, e.g. RMeC=NOH, to afford [Ru(NH3 )5 (NCMe)]2 + and... 

The sequence of steps presented assumes an electrofugal (from the point of view of the substituted atom Cl) opening of the cycle for elimination and it forces the hydride anion to leave the nitrogen atom. This concerns not only acrylonitrile formation 29, but also formation of beta-hydroxypropionitrile 28. 

Addition of anionic nucleophiles to alkenes and to heteronuclear double bond systems (C=0, C=S) also lies within the scope of this Section. Chloride and cyanide ions are effieient initiators of the polymerization and copolymerization of acrylonitrile in dipolar non-HBD solvents, as reported by Parker [6], Even some 1,3-dipolar cycloaddition reactions leading to heterocyclic compounds are often better carried out in dipolar non-HBD solvents in order to increase rates and yields [311], The rate of alkaline hydrolysis of ethyl and 4-nitrophenyl acetate in dimethyl sulfoxide/water mixtures increases with increasing dimethyl sulfoxide concentration due to the increased activity of the hydroxide ion. This is presumably caused by its reduced solvation in the dipolar non-HBD solvent [312, 313]. Dimethyl sulfoxide greatly accelerates the formation of oximes from carbonyl compounds and hydroxylamine, as shown for substituted 9-oxofluorenes [314]. Nucleophilic attack on carbon disulfide by cyanide ion is possible only in A,A-dimethylformamide [315]. The fluoride ion, dissolved as tetraalkylammo-nium fluoride in dipolar difluoromethane, even reacts with carbon dioxide to yield the fluorocarbonate ion, F-C02 [840]. 

The Michael-type addition of maleic hydrazide to activated olefins has been investigated. Maleic hydrazide when treated with methyl acrylate, acrylonitrile, methyl vinyl ketone, and other activated olefins forms monoaddition products - for which the structure as A-substituted derivatives has been determined. The exclusive formation of monoaddition products is in contrast to the saturated cyclic succinhydrazide which can form mono- and diaddition products. Additions of the foregoing type are valid also for pyrid-azinones. Low yields of addition products have been obtained when adding dihydropyran or its thio analog and dihydrofuran to pyrid-azinones or pyridazinethiones. ... 

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