Phthalimide, addition

Tributylvinylphosphonium bromide forms the betaine 213 with sodium phthalimide. Addition of aldehydes RCHO (ketones are inert) gives almost exclusively the ( )-allylphthalimides 214, which form the corresponding allylamines by cleavage with hydrazine210. 

Scheme 4-180. Phthalimide addition to cyclopropanyl annulated T -cycloheptadienyliumiron complexes.

Phthalide. In a 1 litre bolt-head flask stir 90 g. of a high quality zinc powder to a thick paste with a solution of 0 5 g. of crystallised copper sulphate in 20 ml. of water (this serves to activate the zinc), and then add 165 ml. of 20 per cent, sodium hydroxide solution. Cool the flask in an ice bath to 5°, stir the contents mechanically, and add 73-5 g. of phthalimide in small portions at such a rate that the temperature does not rise above 8° (about 30 minutes are required for the addition). Continue the stirring for half an hour, dilute with 200 ml. of water, warm on a water bath imtil the evolution of ammonia ceases (about 3 hours), and concentrate to a volume of about 200 ml. by distillation vmder reduced pressure (tig. 11,37, 1). Filter, and render the flltrate acid to Congo red paper with concentrated hydrochloric acid (about 75 ml. are required). Much of the phthalide separates as an oil, but, in order to complete the lactonisation of the hydroxymethylbenzoic acid, boil for an hour transfer while hot to a beaker. The oil solidifles on cooling to a hard red-brown cake. Leave overnight in an ice chest or refrigerator, and than filter at the pump. The crude phthalide contains much sodium chloride. RecrystaUise it in 10 g. portions from 750 ml. of water use the mother liquor from the first crop for the recrystaUisation of the subsequent portion. Filter each portion while hot, cool in ice below 5°, filter and wash with small quantities of ice-cold water. Dry in the air upon filter paper. The yield of phthalide (transparent plates), m.p. 72-73°, is 47 g. 

I itro-DisplacementPolymerization. The facile nucleophilic displacement of a nitro group on a phthalimide by an oxyanion has been used to prepare polyetherimides by heating bisphenoxides with bisnitrophthalimides (91). For example with 4,4 -dinitro monomers, a polymer with the Ultem backbone is prepared as follows (92). Because of the high reactivity of the nitro phthalimides, the polymerkation can be carried out at temperatures below 75°C. Relative reactivities are nitro compounds over halogens, Ai-aryl imides over A/-alkyl imides, and 3-substituents over 4-substituents. Solvents are usually dipolar aprotic Hquids such as dimethyl sulfoxide, and sometimes an aromatic Hquid is used, in addition. 

Bromoethylamine hydrobromide has been prepared by the reaction of potassium phthalimide with ethylene bromide, followed by hydrolysis,1 by the addition of hydrogen bromide to ethyleneimine,2 and by the present method.3... 

The complex tra s-[AuBr2(ptm)(PEt3)] (ptm = phthalimide) was prepared by oxidative addition... 

Method of Preparation Add 1.8 mL of liquid Br2, with continuous stirring, to a solution of 6.5 g of NaOH dissolved in 25 mL of ice cooled water. Cool the contents to 0°C and add 5 g of phthalimide, followed by the addition of a solution of 5 g of NaOH, dissolved in 20 mL of water. Heat the mixture to about 80°C, for 3 1 min and filter hot. Cool the filtrate in ice and add cone. HC1 slowly to neutralize the solution. Add about 5 mL of glacial acetic acid to precipitate anthranilic acid completely. Filter the product, wash with little cold water and recrystallise in boiling water. 

However, not all nucleophiles show the same bias as shown in Scheme 4.5 on addition to the nitroalkene. The product of the addition of potassium phthalimide has 5 (R) stereochemistry (Eq. 4.38).47 This stereoselective addition is applied for the synthesis of other related antibiotics, such as nikkomycine B.48... 

The mechanism presumably involves initial oxidative addition of the alkenyl halide to the Cu(I) species and ensuing cyclization analogy for this type of process is provided by the Cu(I)-mediated reaction of phthalimide anions with alkenyl and aryl halides.40 The -isomer of 15 reacts in a different fashion to give an isothiazolidinone derivative, albeit in low yield. 

Asymmetric hydrogenation of 3,4-hydroisoquinolines with Ir-chiral phosphorus ligand complexes has been studied. Although the highest enantioselectivity to date is obtained with a chiral titanocene catalyst,308,308a 308c chiral BCPM-Ir or BINAP-Ir complexes with additive phthalimide or F4-phthalimide have shown some good selectivity. Some examples are listed in Table 24. 

Usually, the diastereoselectivity in Michael additions is the one predicted by the Felkin-Anh model.57 However, it was discovered that in the case of the addition of highly hindered nucleophiles, as potassium phthalimide and succinimide, the major product has the opposite configuration to the one predicted by this model, because of the presence of steric hindrance interactions.58... 

The reactions of dimethyl phenylphosphonite with acid chlorides, a-halogeno-ketones, and iV-(bromomethyl)phthalimide have been used to prepare acyl phos-phinates, /3-keto-alkylphosphinates, and phthalimidomethylphosphinates as intermediates in the synthesis of a-diazophosphinic esters.39 a-Amino-phosphonates have also been prepared by the addition of secondary phosphites to nitriles40 and to isocyanides.41... 

Finally, it must be mentioned that phenylselenation of some diolefins may provide a suitable method for the construction of heterocycles containing two phenylseleno groups. For instance, 3 reacts142 with lV-(phenylseleno)phthalimide (NPSP) in the presence of cyanamide (FENCN) to give the regioisomeric 9-azabicyclo[3.3.1]- and 9-azabicyclo [4.2.1]-nonanes, 173 and 174, as the result of a combined process of inter- and intramolecular nucleophilic addition of cyanamide (equation 140). 

In addition, desulfonation generally has to be taken into account with benzamides and phthalimides that are sulfonated at the amine subunit. The sulfonamide linkage proved to be stable with sulfonated and nonsul-fonated sulfonamides. Compounds with electron-withdrawing substituents at the sulfonic acid-bearing ring were more stable with respect to the hydrolysis of sulfonic acid groups. 

Diastereoselective tandem conjugate addition of both oxygen- and nitrogen-centred nucleophiles (potassium phthalimide, TsNHK, MeONa, and MesSiOK) to the novel (IN)-lO-camphorsulfonic acid-derived nitroalkenes (139 R = Me, Pr, and... 

An intermolecular addition on phthalimides employing heteroatom-substituted carboxylates was reported by the same group. In that study, a-thioalkyl-and a-oxoalkyl-substituted carboxylates were decarboxylated in the presence of... 

The discovery of the imidazolinotte herbicides had its beginnings in a random screening test some 12 years ago. The phthalimide 1 prepared originally as an anticonvulsant at Cyanamid s Lederle Laboratories had sufficient herbicidal activity to warrant the synthesis of additional members of this series. One of these, the chloro analog was essentially devoid of herbicidal activity but had instead a pronounced... 

The additions of ammonia equivalents, i.e. nitrogen nucleophiles like dibenzylamine (Scheme 27) which are essentially a protected primary amino group, are of special synthetic interest with respect to their possible subsequent chemical transformations. Poorly nucleophilic ammonia equivalents like acetamide or the classical phthalimide, did not add or originally gave low yields of 92a (Scheme 28) [9],but later phthalimide was found to add to 1-Me very well under mild conditions [53]. However, the a-chlorine in 92a could neither be substituted nor could the phthalimido group be cleaved without destroying the cyclopropane ring. The potassium bis(alkoxycarbonyl)amides (Boc)2NK and (Moc)(Boc)NK add to 1-Me in satisfactory yields, but the a-chlorine atom in... 

In addition to the preceding chemotypes, a limited number of patent specifications include PDKI as a target for the inhibitors exemplified in the cases. Thus, 5-aminocarbonylindazoles, pyrazolopyrimidines, triazolo[l,5-a]-pyrimidines, pyrazolopyrroles and phthalimides have been claimed to be active against PDKI [1], but further biological data are awaited. 

The UV spectrum [7max 238, 256 (sh), 293 (sh), 314, 362 (sh), and 390 (sh) nm] of rebeccamycin (337) indicated the presence of an indolo[2,3-fl]pyrrolo[3,4-c]carbazole-5,7(6H)-dione framework. This was also discernible from its IR spectrum. The H-NMR spectrum indicated the presence of an amide NH at 8 11.37 and an indole NH at 6 10.30, in addition to signals for aromatic protons and a sugar moiety. Unlike (+)-staurosporine (295) (see Scheme 2.74), where the lactam function deshielded only the ortho C-4 proton, the C-4 and C-8 aromatic protons in rebeccamycin are both deshielded due to the anisotropic deshielding effect of the phthalimide function. 

Simple amides are satisfactory protective groups only if the rest of the molecule can resist the vigorous acidic or alkaline hydrolysis necessary for their removal. For this reason, only amides that can be removed under mild conditions have been found useful as amino-protecting groups. Phthalimides are used to protect primary amino groups. The phthalimides can be cleaved by treatment with hydrazine. This reaction proceeds by initial nucleophilic addition at an imide carbonyl, followed by an intramolecular acyl transfer. 

Figure 6.27 Representative (R,R)-l,2-diaminocyclohexane-derived thiourea derivatives incorporating a phthalimide (Phthal) and tetraphenylphthalimide (TPhP) moiety catalyst screening was performed in the Michael addition of acetophenone-derived morpholine enamine to trans-()-nitrostyrene in toluene as the solvent.

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