One pot process

The Gassman indole synthesis involves an one-pot process in which hypohalite, a P-carbonyl sulfide derivative 2, and a base are added sequentially to an aniline or a substituted aniline 1 to provide 3-thioalkoxyindoles 3. Raney nickel-mediated desulfurization of 3 then produces the parent indole... 

In 1893 Pietro Biginelli reported the first synthesis of 4-aryl-3,4-dihydropyrimidin-2(l//)-ones (DHPMs) via an one-pot process using three components. Thus, DHPM 7 was synthesized by mixing benzaldehyde (5), ethyl acetoacetate (6), and urea (3a) in ethanol at reflux in the presence of a catalytic amount of HCl. 

The merits of this method are as follows technological feasibility, no-waste technology, one-pot process, high yield, and purity of thiophene. Probably, for... 

Transfer constants of the macromonomers arc typically low (-0.5, Section 6.2.3.4) and it is necessary to use starved feed conditions to achieve low dispersities and to make block copolymers. Best results have been achieved using emulsion polymerization380 395 where rates of termination are lowered by compartmentalization effects. A one-pot process where macromonomers were made by catalytic chain transfer was developed.380" 95 Molecular weights up to 28000 that increase linearly with conversion as predicted by eq. 16, dispersities that decrease with conversion down to MJM< 1.3 and block purities >90% can be achieved.311 1 395 Surfactant-frcc emulsion polymerizations were made possible by use of a MAA macromonomer as the initial RAFT agent to create self-stabilizing lattices . 

In the reaction of 88 with /(-phenethyl bromide, l-phenethyl-3-phenylpropyl methyl sulfoxide and bis-3-phenylpropyl sulfoxide, besides 3-phenylpropyl methyl sulfoxide are obtained118. Sulfoxides, bearing a /1-hydrogen to the sulfmyl function, give olefins upon thermolysis. Utilizing this reaction, Trost and Bridges120 alkylated benzyl phenyl sulfoxide, 3,4-methylenedioxybenzyl phenyl sulfoxide, phenylthiomethyl phenyl sulfoxide, phenylsulfinylmethyl phenyl sulfoxide and cyanomethyl phenyl sulfoxide with alkyl, allyl and benzyl halides and subjected these sulfoxides to thermolysis, obtaining olefins in one-pot processes. 

A domino Diels-Alder reaction (the term was chosen from the well-known game) is a one-pot process involving two or more Diels-Alder reactions carried out under the same reaction conditions without adding additional reagents or catalyst such that the second, third, etc., cycloaddition is the consequence of the functionality generated in the previous reaction. A historical example is illustrated in Equation 1.28 [60]. This type of transformation is sometimes named tandem or cascade, but these terms seem less appropriate for describing a time-resolved transformation. 

A consecutive or timed Diels Alder reaction is a one-pot process in which the first Diels-Alder does not promote the second, so it is necessary to change the experimental conditions or add reagents to allow the successive cycloadditions (Equations 1.31 [62] and 1.32 [63]). 

Sometimes it is difficult to classify a one-pot multi-step process. Thus for the sake of clarity, we think that the more general term multiple reaction is preferable to indicate a one-pot process in which several bonds are formed sequentially, regardless of whether the reaction conditions are changed or not, or whether new reagents are added during the process. 

In the case of the reaction of 2-vinylindole (83, R = Ri = H) with methyl propynoate, a diester is obtained by a multiple one-pot process involving two molecules of the dienophile and the extrusion of ethene (Equation 2.23). 

A similar strategy has been used to prepare pyrimidines, as well as pyra-zoles and isoxazoles by reacting the enamine intermediate with a variety of bidentate nucleophiles [78]. Microwave irradiation of a cyclic 1,3-diketone 49 and acetal 45 in water generated the corresponding enaminoketone 50 in situ which reacted with amidines, substituted hydrazines or hydroxylamine in only 2 min in a one-pot process to give 4-acylpyrimidines, pyrazoles or isoxazoles, respectively (Scheme 20). 

Besides furo[2,3-d]pyrimidines, 6-substituted 5H-pyrrolo[2,3-h]pyrazines have also been obtained in a microwave-promoted one-pot process starting from N-mesyl protected 2-amino-3-chloropyrazine (Scheme 60) [74]. The... 

The Pictet-Spengler reaction has mainly been investigated as a potential source of polycyclic heterocycles for combinatorial apphcations or in natural product synthesis [149]. Tryptophan or differently substituted tryptamines are the preferred substrates in a cyclocondensation that involves also aldehydes or activated ketones in the presence of an acid catalyst. Several versions of microwave-assisted Pictet-Spengler reactions have been reported in the hter-ature. Microwave irradiation allowed the use of mild Lewis acid catalysts such as Sc(OTf)3 in the reaction of tryptophan methyl esters 234 with different substituted aldehydes (aliphatic or aromatic) [150]. Under these conditions the reaction was carried out in a one-pot process without initial formation of the imine (Scheme 86). 

The stereoselective synthesis of hexacoordinated phosphate anions was also reported by the same group. A general one-pot process was developed for the preparation of C2-symmetric anions 15,16 and 17 containing enantiopure BINOL, hydrobenzoin, and tartrate-derived ligands respectively [38-40] Cpsymmetric anion 18 being prepared similarly in two steps from methyl-a-... 

It is concluded that zeoHte beta can be simultaneously detemplated and Fe-exchanged without FeO formation by treating the parent zeoHte with a Fenton reagent. The catalyst shows good performance on N2O decomposition. This one-pot process simplifies its preparation protocol and can be extended to other systems. Indeed, our approach was followed by Liu et al. [170], for preparing Fe-S BA-15 for benzylation of benzene with interesting results. 

Ecologically and economically valuable solvent-free Robinson annelation reactions, which proceed efficiently in a one-pot process at room temperature, have been reported [ 10]. For example, 2-methylcyclohexanone (59), methyl vinyl... 

In this section some examples of multistep, one-pot processes using NHC/Pd-based catalytic systems will be highlighted. One remarkable example, although the... 

Pioneering work on the desulphonylation of jS-ketosulphones was carried out by Corey and Chaykovsky - . This reaction was part of a sequence which could be used in the synthesis of ketones, as shown in equation (53). The main thrust of this work was in the use of sulphoxides, but Corey did stress the merits of both sulphones and sulphonamides for different applications of this type of reaction. The method soon found application by Stetter and Hesse for the synthesis of 3-methyl-2,4-dioxa-adamantane , and by House and Larson in an ingenious synthesis of intermediates directed towards the gibberellin skeleton, and also for more standard applications . Other applications of the method have also been madealthough it does suffer from certain limitations in that further alkylation of an a-alkyl- -ketosulphone is a very sluggish, inefficient process. Kurth and O Brien have proposed an alternative, one-pot sequence of reactions (equation 54), carried out at — 78 to — 50°, with yields better than 50%. The major difference between the two routes is that the one-pot process uses the desulphonylation step to generate the enolate anion, whereas in the Corey-House procedure, the desulphonylation with aluminium amalgam is a separate, non-productive step. 

The synthesis of unsymmetrical ketones can be carried out in a tandem one-pot process by successive addition of two different alkyllithium reagents.115... 

Identify an organometallic reagent that would permit formation of the product on the left of each equation from the specified starting material in a one-pot process. 

Indicate appropriate conditions and reagents for effecting the following transformations. Identify necessary co-reactants, reagents, and catalysts. One-pot processes are possible in all cases. 

Each of the following transformations was performed advantageously with a thexylborane derivative. Give appropriate reactants, reagents, and reaction conditions for effecting the following syntheses in a one-pot process. 

From a commercial viewpoint the most important compounds of this class are the 3,3-(bisindol-3-yl)phthalides. The first synthesis47 involved Route B as described in Scheme 7, in which a second indole derivative condenses with the indolylbenzoylbenzoic acid in acetic anhydride. However, for the preparation of symmetrical derivatives it has been shown61 that a one-pot process, avoiding isolation of the intermediate and use of aluminum chloride, is more convenient. 

Heating pyridine-2,3-dicarboxylic acid anhydride with l-ethyl-2-methylindole has been claimed to yield solely the pyridine-2-carboxylic acid, albeit in low yield. This then clearly reacts with Af,A/-diethyl-3-toluidine in acetic anhydride to give the 7-azaphthalide. This is surprising in view of a later report70 in which a one-pot process has been described. Heating pyridine-2,3-dicarboxylic anhydride, prepared in situ, with the indole and subsequent reaction with 3-/V,/V-diethylamino-phenetol under identical conditions to those used in Scheme 8 (but without intermediate isolations) produced a 20 1 mixture of the 4- and 7-azaisomers 16 and 17. It appears that in the previous report the major intermediate isomer, the pyridine-3-carboxylic acid, has not been isolated. 

Insertion of a C=0, C=S or S=0 group between an amino and a hydroxy function of a 1,2-aminoalcohol produces a five-membered heterocycle with O and N as ring heteroatoms linked by -CO-, -CS- and -SO-groups. Although the reaction proceeds in two steps, it can often be carried out as a one-pot process. 

The method can also be performed in an iterative manner [367],andthescopeofthe one-pot process can be broaden by replacing Bu3SnH by its allylic derivative Bu3SnAl-lyl, thus allowing tbe introduction of an allyl group instead of a hydrogen [365],... 

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