1.1- Dinitriles malononitriles

The Knoevenagel reaction (Scheme 6.20) involves the reaction of aromatic aldehydes with a variety of molecules CH2XY. The groups X and Y may be the same or different, but are invariably electron withdrawing, so creating an activated methylene group from which the carbanion CHXY is produced. The reaction is usually carried out in pyridine solution, with piperidine as the basic catalyst. The reactions of benzaldehyde with propane-1,3-dinitrile [malononitrile, CH2(CN)2] and diethyl propane-1,3-dioate [diethyl malonate, CH.,(CO,Et)2] are illustrative. In both cases, manipulation of the CH=CX2 group in the product allows the synthesis of other compounds. 

Biphenyl, perchloro 8.8 Malonic acid dinitrile (malononitrile) 15.1... 

The NHase and amidase from Rhodococcus rhodochrous IFO 15 564 was studied using a series of a,a-disubstituted malononitriles. This amidase preferentially hydrolyzes the pro (R) amide of the prochiral di-amide, which is an intermediate resulting from the nonenantiotopic NHase activity on the dinitrile substrate. This transformation was combined with a Hofmann rearrangement to generate a key precursor of (A)-methyldopa in 98.2% ee and 95% yield (Figure 8.5) [41],... 

A nitrilase from the hyperthermophile Pyrococcus abyssi, which exhibits optimal growth at 100 °C, was cloned and overexpressed. Characterization of this nitrilase revealed that it is operational as a dimer (rather than the more common multimeric structure for nitrilases), with optimal pH at 7.4 and optimal apparent activity at 80 °C with Tm (DSC) at 112.7 °C. The substrate specificity of the nitrilase is narrow and it does not accept aromatic nitriles. The nitrilase converts the dinitriles fumaronitrile and malononitrile to their corresponding mononitriles [58],... 

Dicyanomethane or Malononitrile (called Malonsaure-dinitril, Malonitril or Methylen-cyanid in Ger), NC.CH2.CN mw 66.06, N 42.41% col crysts, mp 31.6-32.4°, bp 108-09° at 17mm press, cryst d 1.191 at 20°, liq d 1.0494 at 35°, nfi 1.4139 at 34.2° prepd by esterification of cyanoacecic acid, and treatment of the ester with NH3 which leads to cyanoacetamide which, on reaction with phosphorous oxychloride or pentachloride, gives Dicyanomethane (Ref 1)... 

CS. A US CWS code designation for o-ckloro-benzylidene malononitrile (called 2-Chlor -benzylidenmalonsaure-dinitril in Ger), Cl-C6H4.CH C(CN)2 col crysts (from ale,... 

Okamoto et a/.156 cyclized the dinitriles (86 R = CN, R2 = H) by heating in 15° hydrochloric acid to obtain pyrido[l,2-a]pyrimidine-3-carboxylic acids (89 R2 = H). 2-Aminopyridinium chloride and ethoxymethylene-malononitrile at 110CC yielded 3-cyano-4-imino-4H-pyrido[l,2-a]pyrimi-dine (87 R1 = R2 = H, X = NH) and compound 91. Under similar conditions, 2-amino-3-methylpyridine gave a noncyclized product of type 91. 

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. 

For the cyclocondensation of 5-bromo-2-(cis-2,6-dimethylmorpholin-4-yl)benzaldehyde with malononitrile in DMSO at 23 °C for 1 h, at 130 °C for 20 h furnished l,2,4,4a,5,6-hexahydro[1,4Joxazino[4,3-a]quinoline-5,5-dinitrile 168 in 54% yield (09JA3991). Similar cyclocondenzation of dideut-erated 428 provided a 3 1 mixture of spiro derivatives 429 and 430, which were separated by using preparative HPLC. 

In the presence of morpholine and malononitrile, the initial reaction of cyclohex-3-enal with cyanothioacetamide is followed by a condensation with the dinitrile. Cyclization follows through attack of the thiol on a nitrile function and a penta-substituted 477-thiopyran is formed (Scheme 126) <1998RJ0557, 2005RJC1537>. 

The preparation of amide hydrazones is quite simple, by mixing corresponding nitriles (or dinitriles) and hydrazine (1 1.5 molar ratio) in ethanol at room temperature and then allowing the mixture to stand overnight. This is called the direct method. The yield by this method is normally good (>90%). If this method does not work, the so-called indirect method can be used, in which a nitrile, e.g., malononitrile, is converted into its imidate then reacted with hydrazine. In early references (e.g., Case, 1965150), anhydrous or 95% hydrazine was employed. We have found that 85% hydrazine hydrate still works without any difference in yield. Common recrystallization solvents are benzene or toluene. The amide hydrazones are stable to moisture, and so some amide hydrazones can be recrystallized from water, but they are sensitive to light and heat. As an example, we observed that picolinamide hydrazone (white crystals) partially turns into an orange compound, which has been identified as 3,6-picolin-(2H)-tetrazine. 

Q The nitroso group exhibits similar behaviour to a carbonyl group. Predict the products from the reaction of nitrosobenzene with (a) malononitrile (propane-1,3-dinitrile), (b) hydroxylamine and (c) aniline. Suggest a mechanism for the last reaction. 

Aminoprop-l-ene-l,l,3-tricarbonitrile ( malononitrile dimer ) condenses with mesoxalo-dinitrile arylhydrazones to give 2,4-diamioo-6-aryl-5-imino-5,6-dihydropyrido[2,3-(/]pyridazine-3,8-dicarbonitriles l.29... 

Solvated electrons generated electrochemically in HMPA were used to reduce several nitriles to amines. Under these conditions acetonitrile and acrylonitrile gave ethylamine and propylamine, respectively, but with dinitriles (adiponitrile and malononitrile) mixtures of diamines and cyanoamines were obtained and their ratios depended upon the excess of solvated electrons produced. 

The acute toxicity of adiponitrile is somewhat lower than that of malononitrile. It is toxic by inhalation and oral routes. Inhalation of its vapors can cause nausea, vomiting, respiratory tract irritation, and dizziness. The symptoms are similar to those of other aliphatic mono- and dinitriles. Similar poisoning effects may be manifested from ingestion of this compound. However, its toxicity is very low from skin absorption. 

Malonic acid dinitrile Malonic dinitrile. See Malononitrile... 

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