Reactivity of Substituents Attached to Ring Carbon Atoms

Reactivity of Substituents Attached to Ring Carbon Atoms 

Parallel liquid synthesis has been applied to the preparation of a variety of N,N -disubstituted 3-aminoazepin-2-ones 54 (e.g., R1 = m-BrC6H4) starting from 1-substituted 3-aminoazepin-2-ones 2003BMC3193 . 

The tetrahydroazepine diphenylphosphates 62 (R = OPO(OPh)2, R1 = C02Ph) underwent a Stille coupling and carbonylation to form 62 (R Cl I—Cl I,. R1 = C02Ph) and 62 (R = C02Me, R1 C02Ph), respectively 1998CC1757 . 

The synthesis of the reduced 27/-azepin-2-imine 64 (as its hydrochloride salt) via 63 with ammonia in EtOH followed by treatment with hydrochloric acid in dioxane has also been described 2003BMC689 64 is notably an inhibitor of inducible nitric oxide synthase. 

Enzymatic reactions now have a sound place in contemporary synthetic methodology. Illustrative of this, lipase-catalyzed transesterification of the racemic alcohol 65 has been used effectively to produce (6)-(+)-66 (LipaseQL, 0-5 °C, 4 h 47% yield 99% ee), plus the (R)-(—)-acetoxy derivative 67 (Equation 8). The 1-benzazepine derivative 66 was then converted to a chiral precursor required for the synthesis of the nonpeptide vasopressin V2 receptor agonist, OPC-51803 2002H(58)635 . The synthesis of a 1-benzazepine-based antagonist (OPC-41061) at this receptor has also been reported 2002H(56)123 . 

Much attention was paid in CHEC-II(1996) to nucleophilic substitution in chlorinated cyclopenta- and cyclohepta-1,2,3-dithiazoles 1996CHEC-II(4)409 . 

Bifunctional 1,2,3-dithiazole 13 bridged by an azine spacer has been prepared from Appel salt 20 and hydrazine, with a goal to determine the extent of communication between the two dithiazole rings as a function of the electronic and steric demands of the bridge (Equation 29) (see Section 6.01.2) 2001IC2709 . 

The thermolysis of the 1,2,3-dithiazole 138, containing an azide group in the ortho-position relative to the diazo group, produced in high yield the previously unknown benzotriazole 139 containing the 1,2,3-dithiazole fragment (Equation 30) 2004JHC37 . 

Herz salts bearing chlorine at the 6-position 140 react with malononitrile to afford highly colored ylidenes 141 in low to moderate yields (Equation 31) 2002J(P1)315 . The reaction is general but complex few by-products were isolated. 

7 REACTIVITY OF SUBSTITUENTS ATTACHED TO RING CARBON ATOMS 

Decarboxylation of the carboxylic acid (74) gives very little of the parent compound (3) instead (75) is produced when the anionic intermediate, formed on decarboxylation, adds in a Michael manner to the pyrroUzinone 82CB706 . 

A number of transformations of the carbonyl group of pyrrolizin-3-ones have been reported. Wittig alkenation of 3H-pyrrolizin-3-one (2) gave the azafulvenes (76) 71CB2170, 73CB1993). 

The dimethyliminopyrrolizinium salt (77a) has been hydrolyzed to (77b) and converted into a mixture of E- and Z-imines (77c) by primary amines 74LA2i io . On the other hand, the immonium salt (78) was reported to give the adduct (79) on hydrolysis 82CB714 . 

The diketopyrrolizine (80a) can be converted into a number of derivatives of the C-2 carbonyl group (i.e. (80b)). 

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Reactivity of Substituents Attached to Ring Carbon Atoms. 192... 

Reactivity of substituents attached to ring carbon atoms 87... 

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