Isoindoles dihydro

Reduction of isoindoles with dissolving metals or catalytically occurs in the pyrrole ring. Reduction of indolizine with hydrogen and a platinum catalyst gives an octahydro derivative. With a palladium catalyst in neutral solution, reduction occurs in the pyridine ring but in the presence of acid, reduction occurs in the five-membered ring (Scheme 38). Reductive metallation of 1,3-diphenylisobenzofuran results in stereoselective formation of the cw-1,3-dihydro derivative (Scheme 39) (80JOC3982). 

Benz-7-azabicyclo[2.2.1]heptenes in isoindole synthesis, 4, 351 Benz[e][l, 2]azaborine, 2-chloro-1,2-dihydro-synthesis, 1, 647... 

A useful and possibly more general alternative to the Lwowski synthesis- of 1,3-diphenylisoindoles involves condensation of a l,2-dibenzoyl-l,4-cyclohexadiene (e.g., 55) with ammonia or a primary amine. Cyclohexadiene derivatives of this type are easily prepared by Riels-Alder addition of a 1,3-diene to dibenzoylacetylene, and these adducts lead directly, and in high yield, to the corresponding isoindoles (56). The reaction is closely related to the well-known synthesis of pyrroles by condensation of 1,4-diketones with ammonia. 4,7-Dihydro- and 4,5,6,7-tetrahydroisoindoles (57 and 58) have been... 

Mendoza and Torres and later Torres alone carried out systematic studies of the consequences of replacing an isoindole ring by a 1,2,4-triazole one. A first attempt to introduce two triazole subunits gave the dihydro 20-77 ring 86 instead of the I8-77 system 87 [89JCS(P2)797]. All attempts to oxidize 86 into 87 failed. Compound 87 was calculated to be less stable than... 

An interesting extrapolation of this synthesis deals with the preparation of the bispyridinium salt 62 from 1,2-phthalic dicarboxaldehyde and its subsequent reaction with primary amines (92BSB509).Tlie expected diimines 63 readily cyclize so that 2-aryl-l-arylimino-2,3-dihydro-l//-isoindoles 64 can be isolated in excellent yields (90-95%). Contrary to the reactions performed by employing the dialdehyde and amines directly, the syntheses involving the azinium salts do not produce those typical dark-colored complex mixtures of products (77JOC4217 85JHC449) (Scheme 20). 

Chemical Name 6-Chloro-2-cyclohexyl-2,3-dihydro-3-oxo-1H-isoindole-5-sulfonamide Common Name —... 

Chemical Name 2-Ethyl-2,3-dihydro-3-[ [4-[2-(1 -piperidinyDethoxy ] phenyl] -amino] -1 H-isoindol-1-one... 

Chemical Name 4-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)-a-methylbenzeneacetic acid Common Name —... 

Chemical Name 5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo[2,1-a] isoindol-5-ol Common Name —... 

Step 2 5-(p-Chlorophenyll-5-Hydroxy-2,3-Dihydro-5H-lmidazo[2,1 -a]Isoindole 1-(p-Chlorophenyl)-3-ethoxy-1 H-isoindole (1 g), 2 g of ethyleneimine hydrotetrafluoroborate moistened with methylene chloride (containing approximately 0.66 g of dry salt) is refluxed in 25 ml of absolute toluene for 2 hours in an atmosphere of nitrogen. The result-... 

Phth-Gly-Gly-OEttGlycme, V-[(l,3-dihydro-l,3-dioxo-2/f-isoindol-2-yl)aeetyl]-, ethyl ester] B 88%... 

Phthalimide, potassium [ 1H Isomdole-l,3(2//)-dione, potassium salt], 96 Phth-Gly.Gly-OEt [Glycine, N [(1,3-dihydro-1,3-dioxo-2//-isoindol-2-yl)acelyl], ethyl ester], 93 a-Pinene [Bicyclo 3.1.1]hept 2-ene,... 

Hydroxy-l-oxo-2,3-dihydro-lH-(isoindol)Zu einer Suspension von 147 g (1 Mol) Phthalimid in 1 / 90%igem Methanol wird unter Riihren bci 25-30° innerhalb 30 Min. eine Losung von 76 g (2 Mol) Natriumbo-ranat in 1,5/ Methanol getropft. Man riihrt 10 Stdn. bei 25-30 nach, laBt 12 Stdn. bei 20° stchcn, sauert mit Es-sigsaure an, engt i.Vak. ein, verdiinnt mit Wasser und filtriert. Das Rohprodukt wird aus Wasser umkristallisicrt Ausbeute 98 g (66% d.Th.) F 179°. 

Als Beispiel fur die Reduktion eines tertiaren Carbonsaure-amids mit Lithiumalanat sei die Herstellung von 2-Athyl-2,3-dihydro-1H-isoindol erwahnts s a 6 ... 

Einige 4-substituierte 1-Phenyl-phthalazine werden in 1 n Salzsaure (mit 30—40% Athanol) unter Abspaltung der 4-standigen Substituenten und Ringverengung zu 1-Phenyl-2,3-dihydro-isoindol (70-95% d.Th.) reduziert1 ... 

Phthalazin selbst kann bei — 1,95 V zum /,2,3,4-Tetrahydro-phthalazin reduziert werden2. In 8 n Salzsaure entsteht bei —0,85 V1,2-Bis-[aminomethyl]-benzol (72% d.Th.) in 0,2 n Salzsaure bei -1 V hingegen 2,3-Dihydro-isoindol (85% d.Th.). Auch dimere Pro-dukte konnen auftreten2. 

Auf analoge Weise erhalt man aus N-Anilino-phthalimid in schwach saurer Losung2-Anilino-3-hydroxy-1-oxo-2,3-dihydro-isoindol (79% d.Th. F 1480)1 ... 

N- [(1,3-dihydro-l, 3-dioxo-2ff-isoindol-2-yl)acetyl] -, ethyl ester [2641-02-3],... 

Added in Proof Isoindole and ethylene are similarly obtained by vacuum pyrolysis of 124 see J. Bomstein, D. E. Remy, and J. E. Shields, Chem. Commun., 1149 (1972). Tlie 2,3-dihydro derivative of adduct (107) also gives the corresponding isoindole at only 120° see H. Heaney, S. V. Ley, A. P. Price, and R. P. Sharma, Tetrahedron Lett., 3067 (1972). 

Phosphonic acid, [(1,3-dihydro-l,3-dioxo-2H-isoindol-2-yl)methyl]-, diethyl ester, 65, 119... 

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