Microwave-promoted synthesis of cyclic imides

Cyclic imides have been extensively investigated because of the wide range of biological activities they exert, as well as due to their importance as synthetic intermediates. Nowadays, focus has been placed on this important class of compounds for their potential new applications, especially in the area of pharmaceutical chemistry. Consequently, the strategies applied for the synthesis of these compounds have attracted considerable attention. Several innovative methodologies have been developed to obtain and functionalize this class of compounds. The use of microwave heating, which is an environmentally harmless strategy, has been making successful inroads in many chemistry areas, such as organic synthesis. Herein we present an update of the microwave-promoted methods for the synthesis of cyclic imides.


Figure 1
The capacity of imides to cross biological membranes in-vivo conferred by their hydrophobicity is well known. 1 Due to their pharmacokinetic properties, derivatives of cyclic imides exhibit a wide range of biological properties.Cyclic imides have also a great number of applications in polymer and synthetic chemistry.
11][12][13] The phthaloyl group is well known for its protective capacity of the primary amines of many compound families, particularly aminoacids, peptides, aminoglycosides and β-lactam antibiotics.14 In addition, phthalimides have also been used as key components in materials and polymers, 15,16 as catalysts 17 and fluorescent probes.18,19 Maleimides (2) are a prominent class of substrates suitable for biological, pharmacological and chemical applications.The activity of maleimides as antifungal, antimicrobial and insecticide compounds has been reported.2,[20][21][22][23][24] These compounds have also proved to have analgesic and antispasmodic activities. 2 They can also form conjugates with peptides and antibodies and act as enzyme inhibitors.1][32][33] A recent review shows the importance of maleimides as building blocks for the synthesis of polymers.34 Substituted succinimides (3) such as ethosuximide, methosuximide or phensuximide, among others (Figure 2), have strong anticonvulsant activity.2,35,36 This type of imides, also have a variety of biological and pharmaceutical uses such as CNS depressant, analgesic, antitumor, cytostatic, anorexigenic, nerve conduction blocking, antispasmodic, bacteriostatic, muscle relaxant, hypotensive, antibacterial, antifungal and antitubercular.2,37,38 Chiral succinimides with antifungal activity have shown higher activity than the corresponding racemic mixtures, thus opening new avenues for the development of highly active drugs containing 3-and 3,4substituted chiral succinimides.39

N
Glutarimide derivatives ( 4) have a hydrophobic nature, which accounts for their antibacterial and antifungal potencies. 2,40The antitumoral and analgesic effects, as well as the effect on the CNS have been reported. 2The glutarimide moiety is present in alkaloids, such as filantimide, julocrotine and streptimidone, among others. 41These alkaloids exhibit interesting biological activities, mainly antimicrobial.
Thalidomide (Figure 3), which presents a glutarimide moiety, was first synthesized as an antihistaminic drug and introduced as a sedative drug in 1956.It was widely used to treat nausea during pregnancy; however, the drug was withdrawn from the market because of its high teratogenicity.Due to its immunomodulatory properties, thalidomide was then employed for the treatment of leprosy and multiple myeloma.3][44][45] It has also been used in AIDS therapy. 46

N
The development of environmentally harmless and efficient synthetic protocols is still a central goal in chemistry research.8][59][60][61] Under MW irradiation conditions, organic reactions can be accelerated and product selectivities can be achieved by choosing appropriate MW parameters, thus offering several advantages over conventional heating, such as rapid and deep internal heating, high temperature homogeneity, and selective heating.Some of the novel areas in which MAOS has been applied are solid-phase synthesis, biopolymer synthesis, proteomics, parallel processing in microwave reactors and automated library generation by means of sequential microwave irradiation methods. 62ince the first reports in 1986, 63,64 the use of the MW heating technique has become an essential tool in all areas of organic synthesis.The use of MW-assisted reactions in organic chemistry has reduced the cost, and time and energy requirements.Employment of this novel strategy has given rise to the so -called "Green Chemistry", and the application of such strategy is now fostered to minimize the use of nonrenewable resources as well as polluting solvents, which are known to generate secondary toxic products, and to reduce the emission of harmful gases. 62In the context of the Green Chemistry, 65,66 solvent-free 67,68 and water-mediated [69][70][71] MW-assisted reactions acquire a relevant role.
Initially, household MW devices were used in organic synthesis at the laboratory scale.Some modifications of domestic MW ovens, such as the introduction of condensers, have been developed.These ovens (with limited power 800-1000 W) are characterized by a non-homogeneous distribution of the electric field caused by reflections from the metallic walls of the oven.Currently, two types of MW reactors are used in the laboratory: multimode MW reactors, (with a heterogeneous distribution of electric field inside the cavity) and monomode microwave reactors (with a homogeneous distribution).Nowadays, reactors have a built-in external reaction vessel with compressed air for the simultaneous cooling while being irradiated with MW.Thus, more energy can be directly applied to the reaction mixture (Enhanced Microwave Synthesis, EMS).The use of single mode MW reactors in continuous flow reactions, capable of operating at elevated temperatures and pressures, are gaining popularity. 72,73The MW-induced flow chemistry has also been adapted to the use of microreactors. 74W-induced chemistry has been used in combination with ultrasound (US), either in a sequential or a simultaneous fashion.][77] MW-assisted organic reactions are classified into two categories: MW-assisted reactions in which solvents are used and those that proceed under solvent-free conditions.In the case of the MW-assisted reactions in which solvents are employed, the reactants are usually dissolved in the solvent, which often couples effectively with MW, thus acting as the energy transfer medium (Solution Phase Chemistry, SPC).On the other hand, reactions occurring under solid state conditions using polymeric supports (Solid Phase Organic Synthesis, SPOS) 57,78 have gained increasing attention in combinatorial chemistry. 57,79W-assisted solvent-free organic synthesis (MASFOS) can be carried out under three different conditions, i.e., reactions using neat reactants, reactions using solid-liquid phase transfer catalysis (PTC) and reactions using solid mineral supports.When neat reactants are used, at least one of the reactants should normally be liquid at the reaction temperature.Under such conditions, either the solid is partially soluble in the liquid phase or the liquid is adsorbed onto the surface of the solid with the reaction occurring at the interface.Alternatively, both reactants can be solids.Usually, these reactants melt before the reaction takes place.The use of PTC is specific for anionic reactions, as it involves an "anionic activation" step, as is the case of reactions involving tetra-alkylammonium salts.Free-solvent reactions can also be carried out by adsorbing the reactants onto solid supports like silica and alumina, which are essentially inorganic oxides.
Taking into account the biological importance of imides and the great deal of attention that the use of green synthetic methods has attracted over the last years, we present an update of the methods that use MW as an alternative energy source for the synthesis of these compounds.

From anhydrides or diacids
The most common method for the preparation of N-unsubstituted imides involves the condensation of either the anhydride or the dicarboxylic acid with an aminating agent.The reaction proceeds through the generation of amic acid intermediates which then undergo cyclization to form the imide (Scheme 1).

Scheme 1
Conventional synthetic techniques employing ammonium salts, urea, amides and other agents have been adapted to MAOS.The synthesis strategies described below have better performance, are less timeconsuming and are simple to work-up when compared with conventional heating.2.1.1Employing ammonia or ammonium salts.Aqueous solutions of ammonia have proved suitable for the synthesis of phthalimide 80 and quinolinimide. 81For instance, Perillo et al. have studied the reaction of quinolinic acid or its anhydride with aqueous ammonia or with a reagent capable of generating ammonia in situ, such as urea, acetamide or ammonium carbonate, under MW irradiation in a modified domestic oven.The highest yields were obtained with 28% aqueous ammonia (Scheme 2).

Scheme 2
Hijji et al. have synthesized a variety of cyclic imides using ammonium chloride (NH 4 Cl), and 4-N,Ndimethylaminopyridine (DMAP) or ammonium acetate (NH 4 OAc) under MW irradiation in both monomode and conventional microwave ovens. 82Several substituted succinic anhydrides used as reactants were synthesized efficiently through Diels-Alder addition reactions of maleic anhydride with 1,3-cyclohexadienes (Scheme 3).When maleic anhydride was employed, polymeric by-products were obtained instead of maleimide.
2.1.2Employing amides and thioamides.Amides serve both as aminating reagents and solvents.Their polar nature makes them suitable for the use with MW.Peng and Kacprzak have reported the simple high-yielding and rapid MW-assisted synthesis of a wide array of aromatic mono-and bis-imides using formamide. 83,84In these reactions, small quantities of formamide are required.Reactions were performed in a domestic oven operating at 600-700 W for 2.5-5 min.Examples of the synthesized bis-imides are shown below (Figure 5).Attempts to obtain maleimide from formamide have been unsuccessful, since in all cases polymeric byproducts were obtained instead of the desired imide. 83However, maleimide was obtained through a one-pot conversion of anhydrides in solid phase (NaCl) by using thioacetamide. 85.1.3Employing urea and thiourea.Urea and thiourea are the most widely used reagents for imidation reactions (Scheme 4).As a rule, thiourea has proved to be more efficient than urea for the synthesis of Nunsubstituted imides.

Scheme 4
Several conditions have been described for the imidation reactions using these reagents.The results are evidently influenced by the nature of the reagents and the equipment used.Thus, in some cases the presence of solvents such as DMF is essential, 84 though in some cases, only a few drops of DMF are required. 86Solventfree reactions have also been reported. 87In particular, Seijas 88 has reported the direct synthesis of thalidomide in high yield through the MW irradiation (domestic oven) of N-phthaloyl-L-glutamic acid in the presence of either urea or thiourea (Scheme 5).
Taherpour et al. 89 have described the solvent free one-pot MW-assisted synthesis of phthalimides and maleimides from cyclic anhydrides using KBr as solid phase and urea or thiourea as reagents.

Employing other reagents.
Potassium cyanate or sodium thiocyanate have been used in neutral media (DMF) to obtain a variety of unsubstituted imides in good to excellent yields. 90The reaction did not proceed under solvent-free conditions.The cyanate proved to give higher yields than the thiocyanate, probably due to the stronger nucleophilicity of the nitrogen atom present in the former reagent.The proposed reaction mechanism is shown in Scheme 6.

Scheme 6
A number of unsubstituted cyclic imides have been synthesized from a mixture of cyclic anhydrides, hydroxylamine hydrochloride and 4-N,N-dimethylaminopyridine (DMAP) as base catalyst in sealed vials under MW irradiation. 91This synthesis rendered the unsubstituted cyclic imides in high yields instead of the predicted N-hydroxy derivatives which were found to be the minor products.The production of unsubstituted cyclic imides appeared to be enhanced by higher temperatures and longer reaction times.Good yields were obtained in both multimode and monomode MW ovens (Scheme 7).

Scheme 7 2.2 Other methods
Taherpour et al. have reported the conversion of N-unsubstituted lactams to cyclic imides by oxidation, with an oxidative agent such as peracetic acid or tert-butylhydroperoxide and a transition metal salt (manganic II or III) under MW irradiation. 92,93Thus, 2-pyrrolidinone, δ-valerolactam and γ-caprolactam were converted in good yields into succinimide, glutarimide and adipimide, respectively (Scheme 8).

Condensation of anhydrides with amines without isolation of the amic acid intermediate
It is generally accepted that imidation involves two steps: aminolysis of the anhydride giving amic acids and subsequent dehydration.This method is limited to the use with amines which are stable under dehydration conditions (Scheme 10).This reaction has been performed by different methodologies compatible with MW.

Reactions employing solvents.
The first antecedent of this type of MW-promoted reaction is that reported by Bose et al. 95 who have developed a technology known as MORE (Microwave-Assisted Organic Reaction Enhancement).An Erlenmeyer flask covered with a watch glass or funnel is used as the reaction vessel.For the reaction medium, a polar solvent with a boiling point that is 20-30 o C higher than that of the desired reaction temperature is selected.The reaction mixture is then rapidly heated under MW irradiation.Thus, using a domestic MW oven, the authors prepared phthalimidoacetic acid from phthalic anhydride and glycine in DMF in the presence of triethylamine (TEA) as catalyst (Scheme 11).

Scheme 11
A substantial difference between the reaction with MW in DMF (5-8 min) and the classical one carried out in toluene (1.5 hr) was found. 95The higher rate of the MW-promoted reaction was attributed to a specific activation of the molecules by the MW (non-thermal effect).This reaction was re-examined by Westaway and Gedye, 96 who have found that the reaction rate was actually the same when either conventional or MW heating were applied, using DMF at the same temperature.Hence, the authors concluded that the rate increase observed by Bose et al. could be attributed to the change of solvent from toluene to DMF, which allowed working at higher temperatures.Based on the simplicity of the methodology developed by Bose et al., the reaction of phthalic anhydride with glycine was selected to test the suitability of MW acceleration in an undergraduate teaching laboratory setting. 97he tetrachlorophthaloyl (TCP) group has been used as an aminoacid protecting group in the MORE methodology.Bose et al. 98 have described the synthesis of tetrachlorophthalimidoacetic acid as an intermediate in the synthesis of α-amino-β-lactams.More recently, Bardaji et al. 99 have tested the stability of the TCP function in comparison with the standard Fmoc and Boc removal conditions as well as to TFA cleavage treatments, demonstrating that the method is suitable for solid phase synthesis of peptides.
In some cases, the amount of solvent can be reduced to a few drops, necessary only to moisten the reaction mixture, thereby obtaining high quantities of pure cyclic imides in a matter of hours. 80,86,100,101lthough one advantage of DMF as solvent is its capability to retain water formed during the course of the reaction, hence avoiding the need for a water separator, 102 the employment of molecular sieves can improve the results as is the case of the synthesis of quinolinimides from quinolinic anhydride. 81ther neutral, acid or basic solvents with different polarity, have proved useful.Chorell has synthesized Nsubstituted phthalimides from phthalic acids and amines in one step employing acetonitrile, acetic acid or pyridine. 103The method is general and good yields were obtained even when anilines with electron acceptor groups and sterically hindered amines were employed.
Recently, a series of bispyromellitimides, 104 which is an important class of substrates in polymer chemistry, were synthesized through the condensation of pyromellitic dianhydride (PMD) with anilines in glacial acetic acid and few drops of pyridine and using MW irradiation in a modified domestic oven (Scheme 12).

Scheme 12
The use of water as a green solvent has been successful.In 2001, Ondrus et al. described a new route for the synthesis of novel chiral maleimides.A cheap and readily available exo-Diels-Alder adduct of furan and maleic anhydride reacted with α-amino acids in water under MW irradiation conditions, with the release of furan to give maleimides in good to excellent yields (Scheme 13). 105© ARKAT USA, Inc

Scheme 13
Kočevar et al. 106 have described the transformation of fused succinic anhydride derivatives of the bicyclo[2.2.2]oct-2-ene system with various amines under MW irradiation conditions.In aqueous suspensions, the reaction of an acetyl-containing derivative yielded chemoselectively succinimide derivatives with the acetyl group remaining unchanged.Conversely, the application of neat reaction conditions with a small amount of a liquid additive (toluene) yielded succinimide derivatives with the acetyl moiety transformed into an imine group (Scheme 14).

Scheme 14
MW-promoted imidation reactions have been extended to the synthesis of polyimides.Thus, polysuccinimide (PSI) has been prepared by MW-enhanced polycondensation of L-aspartic acid in the presence of a high boiling point solvent (Scheme 15). 107,108

Scheme 15
In some cases, the use of catalysts has allowed improving the results of MW-promoted reactions in solution.Thus, the synthesis of N-alkyl and N-arylphthalimides has been achieved by eco-friendly MW irradiation methods, using Montmorillonite-KSF as a reusable clay catalyst in AcOH as solvent. 9Martínez-Palou et al. have explored the use of ionic liquids (ILs) as catalysts in these reactions. 109These authors synthesized bis-imides from dianhydrides or diamines with high melting points in AcOH as solvent.All ILs tested increased the reaction rates and yields.The best conversions were obtained with 1-butyl-4-methylpyridinium tetrafluoroborate ([BMPy]BF 4 ) and 1-propyl-2,3-dimethylimidazolium iodide ([PMIM]I).An example is given in Scheme 16.

Scheme 16
3.1.2Solvent-free reactions.Solvent-free MW-mediated reactions are advantageous since they reduce the occurrence of hazardous explosions and eliminate the need to remove high boiling point aprotic solvents from the reaction mixture.In 1998, Sandhu et al. 110 and Srivastava et al. 111 described the one-pot synthesis of Nsubstituted maleimides and phthalimides by reaction of the corresponding anhydrides with aminoacids and alkyl amines using MW-promoted free-solvent reactions.Subsequently, Loupy and Gedye et al. 112 re-evaluated some of those reactions using a monomode reactor with focused MW.That study demonstrated that solventfree MW-assisted reactions need at least one liquid phase.This is possible if a liquid reactant or a solid with low melting point able to melt rapidly is used, giving a polar liquid which is more prone to MW absorption. 113If these conditions are not met, i.e. in reactions between two solids, the reaction does not proceed and requires the use of high boiling point solvents.These results were later corroborated by other researchers.

Scheme 17 ARKAT USA, Inc
As indicated above (Section 2.1.3),Seijas et al. 88 have described the synthesis of thalidomide by cyclization of the N-phthaloylglutamic acid with urea or thiourea.In the same work, thalidomide was also obtained in a one-pot MW-promoted procedure from equimolar amounts of glutamic acid, phthalic anhydride and thiourea, yielding 60% without obtaining significant amounts of pyroglutamic acid (Scheme 18).Thalidomide was obtained (44%) by conventional heating techniques.

Scheme 18
Recently Benjamin and Hijji 115 have reported the synthesis of thalidomide and thalidomide analogs (Scheme 19) under MW irradiation conditions through a one-pot reaction of glutamic acid with the corresponding anhydride and ammonium chloride, using DMAP as a basic catalyst (150 o C, 10 min).Considerable quantities of the N-unsubstituted cyclic imide are also produced during the reaction.
Although these are one-pot reactions, they require a multistep mechanism in which the glutamic acid has to form an amide-acid (amic acid) with the cyclic anhydride.If these open intermediates are not formed, then the reaction proceeds towards by-product formation with the N-unsubstituted cyclic imide as major product.Thus, the reaction of phthalic anhydride and glutamic acid with reagents that readily generate ammonia (such as ammonium acetate), is efficient at forming phthalimide (90%) but not thalidomide (7%).On the other hand, higher yields of thalidomide were obtained when DMAP/NH 4 Cl were used.

Scheme 20 Scheme 21
9][120][121] A parallel synthesis of a representative 28-member library of phthalimides, has also been reported. 122n some cases, solvent-free MW-assisted reactions require the use of catalysts or promoting agents.For example, Baldwin has described the first solventless preparation of imides from sterically hindered acids (such as Kemp's triacid) in the presence of imidazole in unsealed reaction vessels (Scheme 22). 123The activity of the imidazole as promoting agent was attributed to the ability to form polar carboxylic acid salts for efficient MW energy absorption, and to the formation of anhydride species, generally considered fast reacting intermediates in condensation reactions.

Scheme 22
Inorganic solid supports are useful media for the rapid and efficient synthesis of different imides under "dry" conditions.5][126] Montmorillonite clays were also used as support and catalyst for a variety of organic reactions, offering several advantages over other supports.For example, the strong acidity, noncorrosive properties, cheapness, the requirement of mild reaction conditions, high yields and selectivity, and the easy working up.Mortoni et al. have synthesized a library of N-substituted quinoline-3,4-dicarboximides with different moieties from the reaction of the corresponding anhydride and several primary amines (Scheme 23).They tested different supports, such as silica, neutral, acid and basic alumina, and Montmorillonite K-10. 127The authors found that wet Montmorillonite (commercial Montmorillonite) proved to be the best medium for the condensation, leading to a complete conversion of reactants.This result was not obtained when vacuum-dried Montmorillonite was used.This effect was attributed to the presence of an unquantified amount of water, in the commercial product, that interacts with MW and increases the medium capacity to absorb the MW energy.

Scheme 23
Habibi et al. have used Montmorillonite KSF and K-10 as efficient catalysts for the solventless synthesis of bis-maleimides and bis-phthalimides from the appropriate anhydride and aliphatic and aromatic diamines using MW irradiation. 128Good yields, short reaction times and the easy recovery and reuse of the natural clay are the advantages of this method.
Chandrasekhar has described the first Lewis acid-catalyzed and solvent-free procedure for the preparation of a variety of imides from the corresponding anhydrides and different amines employing silica-gel as support and TaCl 5 -SiO 2 as catalyst under MW irradiation (Scheme 24). 129The good results achieved are due to the high oxophilicity of TaCl 5 , the affinity of activated silica gel as water scavenger and the rapid heating capacity of the MW oven.

24
Chandrasekhar et al. have modified the previous methodology by transforming it into a synthesis on a polymeric support (SPOS). 130The authors employed, for the first time, two insoluble supports, namely Merrifield's resin and silica gel.The polymeric resin was esterified with an amino acid such as γ-aminobutyric acid or alanine.The subsequent MW-promoted reaction with an anhydride (phthalic, succinic or maleic) in the presence of the catalyst led to the generation of the polymer-bound imide which is cleaved by treatment with trifluoroacetic acid to furnish N-carboxyalkyl imides (Scheme 25).

Amic acid cyclizations
Cyclization of amic acids in the presence of acidic reagents is a typical method for obtaining imides.However, literature data describing the use of MW for cyclization are scarce.Perillo et al. 81 have developed methods for the synthesis of N-substituted 2,3-pyridinedicarboximides (quinolinimides) by aminolysis of the anhydride.The authors observed that when the amine could be used directly as free base, it was convenient to isolate the amic acid intermediates and then proceed to their cyclization (Scheme 26).

Scheme 26
Thus, in the first step the amic acids from quinolinic anhydride were generated employing a low polarity solvent.Subsequently, the MW-promoted cyclization in acetic anhydride led, in short times, to imides as the major products, with good yields and high purity.Amounts of nicotinamide as secondary product did not exceed 5% and in some cases only traces of such by-product were obtained.

Scheme 28
The use of MW to promote cyclization of amic acids was extended to other techniques, such as solid phase synthesis.Chassaing et al. have developed a traceless solid-phase synthesis of N-substituted phthalimide libraries. 132The synthetic route involves the use of the Wang resin loaded with phthalic acid employing the Mitsunobu protocol.Subsequent reaction with alkyl or aralkyl amines under standard amide coupling conditions led to the generation of resin-bound N-alkyl or benzylphthalamic acids.Finally, the isolated resin suspended in DMF was irradiated in a single monomode MW reactor (170 o C for 20 min) affording N-substituted phthalimides in good yields and excellent purity (Scheme 28).The authors emphasized the fact that the reaction proceeds well with fluoro-substituted phthalimides.Previous attempts to synthesize these compounds in solution were unsuccessful due to aromatic nucleophilic substitution of the fluorine by the amines as a side reaction.

N-Alkylation of imides with halogenated compounds
The method involves the alkylation of an unsubstituted imide, easily obtained from the dicarboxylic acid or its corresponding anhydride (see 2.1 and 2.2).The reaction proceeds in basic medium to generate the strongly nucleophilic imide anion.The most common procedure makes use of alkyl halides, either in a reaction with the preformed imide salt or generating the stabilized imide anion in situ (Scheme 29).Taking into account that the reaction takes place through an S N 2 mechanism, its application is limited by the nature of the alkylating agent.Therefore, it is not useful to obtain N-aryl or N-tert-alkyl derivatives.

Scheme 29
This methodology is perfectly compatible with the use of MW, and is versatile, since allows the reactions to be conducted with or without solvent; the use of PTC, supported reagents, different type of bases, the salt of the imide or its in situ generation.

Reactions in solution.
N-Alkylation of quinolinimides has easily been achieved by MW irradiation of a mixture of quinolinimide, triethylamine and the corresponding alkyl halide in dry DMF. 81The method represents a typical example of the MORE chemistry developed by Bose 95 and gives good results for the substitution of the quinolinimide hydrogen by alkyl (even secondary), aralkyl and functionalized alkyl groups.Blanco et al. have reported an efficient and simple method for the N-alkylation of aromatic cyclic imides employing Cs 2 CO 3 as base in anhydrous DMF at low temperatures (20-70 o C). 133 The MW irradiation presented noteworthy advantages over the conventional heating.Thus, phthalimide, naphthalimide and heteroaromatic imides were synthesized.Reactions proceeded efficiently with various functionalized primary alkyl halides, including 3-bromopropionic acid derivatives.The method is especially suitable for pyridine and pyrazinedicarboximides having a labile base nucleus due to the presence of the pyridine nitrogen.][136] 3.3.2Solvent-free reactions.In general, free-solvent reactions require the use of PTC and/or reagents adsorbed on inorganic supports.In 1996, Bogdal described, for the first time, the N-alkylation of an imide (phthalimide) in dry media under PTC. 137The synthesis was carried out by simple mixing of phthalimide with 25% excess of an alkyl halide and a catalytic amount of TBAB.The mixtures were adsorbed on K 2 CO 3 and irradiated in an open Erlenmeyer flask in a domestic microwave oven.
Asadolah et al. have reported the synthesis of N-alkylphthalimides and succinimides through alkylation of potassium phthalimide and succinimide in dry media catalyzed by PTC under MW irradiation. 138The reactions