2-Hydroxy- -dinitril

Diphenyl- -dinitril 508 -diphenylmethylimid 255 2-Fluor-3-oxo- -diathylester 2/7 2-Hydroxy- -dimethylester 204 2-Hydroxy- -propylimid 257 -imide 255... 

DiphenyI-athyI)- -dinitril 559 (1,2-Diphenyl-athyIiden)- -dinitril 559 Diphenylmethyl- -athylester-nitril 581 Diphenylmethylen- -athylester-nitril 206, 581 Dodecanoyl- -diathylester 195 Hexyliden-(2)- -dinitril 666 Hydroximino- -diathylester 6/3 Hydroxy- 314... 

The nitrilase from cyanobacterium Synechocystis sp. PCC6803 was found to effect the stereoselective hydrolysis of phenyl-substituted /3-hydroxy nitriles to (S)-enriched /3-hydroxy carboxylic acids. The enzyme also effected the conversion of y-hydroxynitrile, albeit with lesser enantioselectivity (Table 8.10). Interestingly, this enzyme was also was found to hydrolyze aliphatic dinitriles, such that for 1,2-dicyanoethane and 1,3-dicyanopropane the... 

The chemical transformation must not affect the stereogenic centers. Suitable acyclic candidates are compounds with easily convertible functional groups, such as diols, diamines, amino alcohols, dicarboxylic acids and so on. A number of procedures known before 1973 have been compiled, including conversion of diols and amino alcohols into sulfites or 1,3-dioxolanes by thionyl chloride, or acetalization with ketones31,1"319, as well as the conversions of dinitriles into imides320, dicarboxylic acids into cyclic anhydrides or imides321, and hydroxy acids into oxazolidones 322. 

An alternative approach, explored by Dowpharma, involved the desymmetrization of prochiral dinitrile (meso)-3-hydroxyglutaronitrile (3-HGN) with a nitrUase provided by Diversa (Figure 6.2b). The resulting (R)-3-hydroxy-4-cyanobutyrate can in several steps be converted into ethyl 6-cyano-3R,5R-dihydroxyhexanoate, an advanced intermediate to atorvastatin. 3-HGN could be easily prepared from... 

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. 

Malonsaure (1-Hydroxy-2,2,2-trifluor-1 -trifluormethyl-ethyl)- -dinitril E5, 1510 [Keton + H2C(CN)2]... 

Malonsanre [Amino-(2-hydroxy-ethoxy)-methylen]- -dinitril VII/4, 431 [2-(Dicyanmethylen)-... 

Malonsdure Hydroxy-phenthio- -dinitril E14a/1, 792 (Keton + Ar-SH)... 

Hydrazin 2-(Diniethylamino-met hy len)-1 -[1 -(2-hydroxy-phenyl)-ethyliden]- El4b, 671 (Hydrazonid-Bildung) Malonsaure (3-Diethylamino-3-methoxy-allyliden)- -dinitril E15/2, 1878 (Amin-Austausch)... 

Indol 3-(2-Dimethylamino-ethyl)-5-hydroxy- IV/lb, 803 Malonsaure (3-Oxo-3,4,4-trimethyl-cyclohexyl)- -dinitril E5, 1518 I(NC)2CH2 + 3-Oxo—1-en] Propan 2,2-Dimethyl-l-(2-methyl-phenyl)-l-nitrosimino- E14b, 746 (N-Nitrosier.)... 

SUCCINIC ACID DINITRILE see SNEOOO SUCCINIC ACID, HYDROXY- see MANOOO SUCCINIC ACID, O-ISOPROPYL-O -TRIBUTYLSTANNYL ESTER see TIE600 SUCCINIC ACID PEROXIDE (DOT) see SNC500 SUCCINIC ANHYDRIDE see SNCOOO SUCCINIC-1,1-DIMETHYL HYDRAZIDE see DQD400 SUCCINIC DINITRILE see SNEOOO SUCCINIC PEROXIDE see SNC500 SUCCINODINITRILE see SNEOOO... 

Malonsaure-dinitril kann mit Mercapto-essigsaure entweder 2-(Cyan-methyl)-4-hydroxy-1,3-thiazol oder Bis-[4-hydroxy-l,3-thiazol-2-yl]-methan bilden82. Letzteres entsteht, wenn ein mo-larer UberschuB an Mercapto-essigsaure verwendet wird. 

Analog wird bei der Umsetzung von Oxalsaure-dinitril mit 2-Mercapto-propansaure 4,4 -Di-hydroxy-5,5 -dimethyl-2,2 -bi-( 1,3-thiazol-2-yl) (87% Schmp. 242-243°) erhalten83. 

Cyclische Keten-0,0-acetale von Formyl-malonsaure-ester-nitril993 2444 und -dinitril [Herstel-lung von 3(5)-Amino-4-cyan-5(3)-(2-hydroxy-ethoxy)-lH-pyrazol s.Bd. VII/4, S.365 (1968)] reagieren wie offenkettige Keten-0,0-acetale (s. S.470) mit Hydrazinen. Sie ermoglichen die Einfuhrung der (2-Hydroxy-ethoxy)-Gruppe in die 3-Position. 

Brom-5-hydroxy-3-methyl-lH-pyrazol reagiert in Gegenwart von Piperidin mit C,H-aciden Verbindungen wie Malonsaure-dinitril und -ethylester-nitril unter Brom-Substitution und Ring-schluB2020. 

Amino-5(3)-hydrazino- -Bis-hydrochlorid aus Malonsaure-dinitril/llydrazin 449 l-Amino-5-hydroxy- 530... 

Dichlor-6-hydroxy-2-acctoxv- -dinitril 971 -[2-inethoxy-oxiranyl-(2)-imid] 1177... 

Coumarin ring formation presumably by way of an intermediate imide accompanied the demethylation of the dinitrile shown with aluminium chloride in chlorobenzene by refluxing for 3.5 hours to afford a 96% yield of 3-cyano-5-hydroxy-7-pentylcoumarin (ref. 148). 

For example, condensation of the 5-cyano ketone 146 with methyl [ C ]cyanoacetate gave (Figure 7.36) a-[ C]cyanobenzo[a]quinolizin-2-yUdeneacetate derivative 147 in 52% yield. Reduction of the double bond followed by selective de-methoxycarbonylation provided the dinitrile, a key intermediate in the synthesis of carbon-14-labeled 4a-hydroxy-allo-berbane (148) . Despite loss of half of the label during formation of the final ring by Thorpe-Ziegler condensation, this route was considered superior to the alternative longer route. 

---