Phthalimide imine

Is the second step of the overall reaction for R=Me (N-methylphthalimide + hydrazine —> phthalimide hydrazide + methylamine) exothermic or endothermic Will higher temperatures accelerate or inhibit the reaction Is the structure drawn above for phthalimide hydrazide its lowest-energy form or are either the imine or diimine tautomers preferred Compare energies for the hydrazide and imine and diimine tautomers. Examine the geometry of phthalimide hydrazide and any low energy tautomer, and draw the Lewis structure(s) that best describes it. Can your Lewis structures account for the energy differences Examine electrostatic potential maps for all three molecules. Which molecule(s) are stablized by favorable electrostatic interactions Which are destabilized Can this help explain the energy differences Elaborate. 

As mentioned in chapter 4.2.3, aliphatic imines are photochemically rather unreactive. When the C—N double bond is conjugated to an electron withdrawing group (e.g. carbonyl group), as in O-alkyl derivatives of succinimide and phthalimide, the reactivity increases and azetidines are obtained in cycloadditions to olefins486). A somehow similar example is the photoaddition of a 6-azauracil derivative to 2,3-dimethyl-2-butene... 

The activity and enantioselectivity of chiral Ir catalysts have been tested by using 2,3,3-trimethylindolenine as a model substrate. Hydrogenation of the cyclic imine with [Ir(bdpp)Hl2 2 gives the corresponding chiral amine with 80% ce (Scheme 1.99) [350]. The stereoselectivity is somewhat better than that with acyclic substrates (see Scheme 1.94). A neutral BCPM-Ir complex with Bil3 effects asymmetric hydrogenation in 91% optical yield [354], A complex of MCCPM shows similar enantioselection [354], These complexes are not applicable to the reaction of other acyclic and six-membered cyclic imines. An MOD-DIOP-Ir complex is also usable with the aid of ( -C4H9)4NI [355], An Ir complex of BICP with phthalimide effectively... 

Asymmetric hydrogenation of Scheme 1.101 provides a general route to isoquinoline alkaloids (see Section 1.3.1.1). An imine substrate is hydrogenated with the chiral titanocene (/ )-34 to give the S product with 98% ee [346a,b,352], A neutral BCPM-Ir complex with phthalimide in toluene also shows high enantioselection [358]. The choice of a weakly polar... 

Methyl-2-oxo- E21e, 5260 6-[n(Acyl) —SR] — en Cyclisier. 8-Aza-bicycIo]4.3.0]non-3-en 8-Hydroxy- E16a, 188 (N-OH —phthalimid-Red.) Azetidin 4-Ethenyl-3-isopropyl-2-oxo- E16b, 246 (Imin + R-C-COOR) Bicyclo 2.2.1]bept-2-en S-endo-(Hydroxyamino-methyl)- E16a, 26 (Oxim-Red.)... 

Methods of liberating simple 2-aminofurans from phthalimides (71CB681, 75AP713) and imines (84JA5753) by displacement using hydrazine and oxime, respectively, have been described but the products are not well-characterised. 

An imine-enamine annulation has been used in the synthesis of the indoloquinolizidine alkaloid ( )-deplancheine.52 The annulation of dialkyl (1-alkoxycarbonyl)vinylphosphonates via a Horner-Wadsworth-Emmons reaction has been developed in the synthesis of [3.3.0] fused pyrazolid-inones from monocyclic pyrazolidinones. - Treannent of diethyl l-(ethoxycarbonyl)vinylphos-phonate in excess (2 eq) with imide anions such as phthalimide, maleimide, and succinimide successfully produces the corresponding six-membered fused heterocycles. Similarly, synthesis of functionalized cyclohexenylphosphonates is achieved by condensation of diethyl l-(ethoxycar-bonyl)vinylphosphonate (2 eq) with cyclopentanone enolates (Scheme 8.29). - ... 

Aminals, compounds having two amino groups bound to the same carbon atom, are represented in many medicinal agents having versatile therapeutic action, such as proteinase inhibitors and neurotensins. Antilla and coworkers developed an en antioselective synthesis of protected aminals from the amidation reaction of N Boc imines with a series of sulfonamides catalyzed by chiral phosphoric acids (Scheme 3.54a) [111]. In this novel enantioselective transformation, phosphoric acid 9 exhibited excellent catalytic activity and enantioselectivity in addition to N Boc aromatic imines. The enantioenriched aminal products were stable upon storage neither decomposition nor racemization was observed in solution over several days. The same research group reported the enantioselective amidation reaction of N Boc aromatic imines with phthalimide or its derivatives (Scheme 3.54b) [112]. 

An interesting effect of imide and amine additives was observed for Ir-bcpm and Ir-binap catalysts. The catalyst performance for the hydrogenation of im-ines 7 was affected by the addition of phthalimide or perfluorophthalimide [26]. The highest enantioselectivity were obtained with the Ir-bcpm catalyst system 87% ee with F4-phthalimide and 86% with phthalimide. Primary or secondary amines were found to be useful co-catalysts for the asymmetric hydrogenation of N-benzyl-iV-(l-methylbenzylidene)amine and the cyclic imine 6 (R=Ph) with cationic Ir-binap (or Ir-tol-binap) catalysts [27]. For example, the addition of... 

Imines conjugated with electron-withdrawing carbonyl or aryl functions at nitrogen or carbon appear to more readily participate in cycloadditions. This was shown for 6-azauracil derivatives io2,103 ancj 3-ethoxyisoindole 9104-105, both reactions are thought to proceed via the triplet state of the electronically excited imines. The isoindole photochemistry, to some extent, resembles the reactions of phthalimides described in Section 1.6.1.4.3.8. For example, the azetidine 10 can be converted to the azepinedione derivative 11 using acid. 

A synthesis of 1-phenylisoindole represents a classical approach to the construction of a heterocycle a precursor is assembled in which there is an amino group (initially protected in the form of a phthalimide) five atoms away from a carbonyl group with which it must interact and form a cyclic imine. ... 

Isomannide (80) was the core for a hexahydrofurofuran library." Primary amines were loaded onto solid-support by reductive amination and acylated with bromoacetic acid to give bromides 79 (Scheme 7.16). Alkylation of bromides 79 on solid-support with isomannide (80) gave the solid-supported alcohols 81. A Mitsunobu reaction with phthalimide (82) proceeded to furnish amines 83 in excellent yield and purity after removal of the protecting group." " Support-bound primary amines 83 were converted to secondary amines by stepwise imine formation with aldehydes 84 and reduction with sodium borohydride." The hindered secondary amines 85 were acylated with acid chlorides, sulfonyl chlorides, isocyanates, and isothiocyanates to yield 87 after cleavage from solid-support. 

Additives can also be used to improve the hydrolytic stability of polyester polyurethanes. Glycol-cured materials are reported to be stabilized with cyclic imines. Substituted ureas or thioureas ethylene-diaminetetraacetic acid-derived chelating agents oxycarbonyl isocyanates epoxies carbodiimides, alone " or in combination with silica silanes " substituted phthalimides and an undisclosed combination of additives have all been cited as stabilizers for polyester polyurethanes. 

The last example presented in this section also involved a specialized hydrazone intermediate, a N-phlhalimide hydrazone. Once the amine group in 1,114 (prepared by literature methods) was blocked as the phthalimide, the acid moiety in 1.114 was subjected to the Amdt-Eistert sequence shown. This reaction sequence extended the carbon chain by one and this new acid was converted to its t-butyl ester (7.775).65 The N-phthalimido protecting group was removed, with reduction of the imine moiety, to give 5-methyl-7-aminooctanoic acid, 1.116. When another... 

Morimoto, T. Achiwa, K. An improved diphosphine-iridium(I) catalyst system for the asymmetric hydrogenation of cyclic imines Phthalimide as an efficient co-catalyst. Tetrahedron Asymmetry 1995, 6,2661-2664. 

In order to convert the substituent on the azetidinone into a functional group, which can be derivatized, several strategies were developed. Sheehan and Ryan reacted phthalimidylacetyl chloride 260 with imines in the presence of triethylamine. Acid-catalyzed removal of the phthalimide afforded an amino group for further functionalization. 

Among chemical methods for the separation of amines, those of Hinsberg (reaction with / -toluenesulfonyl chloride) and of Alexander (94) (reaction with 3-nitrophthalic anhydride) are most commonly used. Tertiary amines do not react with the reagents mentioned and they can be separated after the reaction — for example, by extraction. Derivatives of primary amines with p-toluenesulfonyl chloride are soluble in alkali hydroxide solutions, in contrast to sulfonamides of secondary amines this is utilized for their separation. When primary and secondary amines are separated by reacting them with 3-nitrophthalic anhydride, use is made of the fact that only phthal-imine acids derived from primary amines can be cyclized. Practical utilization of both procedures is demonstrated by the separated of a mixture of aniline, ethylaniline, and diethylaniline. However, it should be mentioned that in a number of cases the procedures fail or do not lead to a sufficiently sharp separation. Negatively substituted amines which do not react with / -toluenesulfonyl chloride can be separated with 3-nitrophthalic anhydride. Some p-toluenesulfonamides of primary amines are poorly soluble in alkali. The derivative of primary amine with 3-nitrophthalic anhydride is cyclized merely by boiling in benzene, and the phthalimide formed is soluble in benzene and can be isolated together with the tertiary amine. 

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