Step addition/condensation

Two closely related indoles fused to an additional saturated ring have been described as CNS agents. The first of these is obtained in straightforward manner by Fischer indole condensation of functionalized cyclohexanone 0 with phenyl hydrazine (19). The product, cyclindole (21) shows antidepressant activity. The fluorinated analogue flucindole (26) can be prepared by the same scheme. An alternate route starting from a somewhat more readily available intermediate involves as the first step Fischer condensation of substituted phenyl hydrazine with 4-hydroxycyclohexanone (23). The resulting alcohol (24) is then converted to its tosylate (25). Displacement by means of dimethyl amine leads to the antipsychotic agent flucindole (26). ... 

Reactions with dialdehydes allow the introduction of two additional rings in one step. Thus, condensation of 1 -(2-aminoethyl)pyrrole with glutaraldehyde and benzotriazole gives tricyclic intermediate 627 in which the benzotriazolyl moiety can be readily substituted with nucleophiles to give products 628 (Scheme 97) <2002JOC8220>. Condensation of ethyl ester of L-tryptophan with 2,5-dimethoxytetrahydrofuran and benzotriazole in acetic acid gives tetracyclic intermediate 629 which upon treatment with nucleophiles (silyl derivatives) is converted to products 630 <1999T3489>. 

This section introduces simple polymer reaction chemistry used to produce many commodity polymers. Understanding this simplified approach to the chemistry of polymer production Is Important In troubleshooting many extrusion processes, especially those that are producing unwanted degradation products that contaminate the discharge resin. There are two general types of polymer production processes 1) step or condensation reactions, and 2) addition or vinyl polymerization reactions. An overview of the reaction mechanisms wifi be presented in the next sections. 

First, let us treat in more detail the different types of chain or addition polymerizations and then later discuss as a unit the step or condensation polymerizations. 

LaMer, Monomer Addition Growth Model. Most of the recent publications (13,18,37,43-45) concerning the Stober silica precipitation describe a first-order hydrolysis of TEOS as the rate-limiting process in the silica particle precipitation. The second reaction step, the condensation reaction, was found to be faster by at least a... 

Isoniazide, the hydrazide of pyridine-4-carboxylic acid, is still, well over half a century after its discovery, one of the mainstays for the treatment of tuberculosis. Widespread use led to the serendipitous discovery of its antidepressant activity. This latter activity is retained when pyridine is replaced by isoxazole. The requisite ester (45-4) is obtained in a single step by condensation of the diketo ester (45-1), obtained by aldol condensation of acetone with diethyl oxalate, with hydroxylamine. One explanation of the outcome of the reaction assumes the hrst step to consist of conjugate addition-elimination of hydroxylamine to the enolized diketone to afford (45-2) an intermediate probably in equilibrium with the enol form (45-3). An ester-amide interchange of the product with hydrazine then affords the corresponding hydrazide (45-5) reductive alkylation with benzaldehyde completes the synthesis of isocarboxazid (45-6) [47]. 

Step, aldol condensation to form the benzylidene derivative (12-3). Conjugate addition of a second mole of acetoacetate would then afford the 1,5-diketone (12-4). Reaction of the carbonyl groups with ammonia will lead to the formation of the dihydropyridine ring. Alternatively, acetoacetate may go on to form the imine (12-5) reaction of this with the aldol product (13-3) will give the same dihydropyridine. The product, nifedipine (12-6) [13], has been used extensively for the treatment of angina and hypertension. 

Know the meaning of and illustrate the difference between chain-growth (addition) and step-growth (condensation) polymerization. 

In Stork s synthesis (148), 5 - methyl - 6 - methoxy - 1 - tetralone (CLXXXIV) was converted into the tricyclic intermediate CLXX XVII in several steps involving condensation with dimethyl carbonate, addition of methyl isopropenylketone, and cyclization to the a, -unsaturated ketone CLXXXVI, followed by catalytic hydrogenation, replacement of the hydroxyl group in the resulting dihydro alcohol by a chlorine atom on treatment with phosphorus oxychloride in pyridine solution, and elimination of hydrogen chloride by methanolic sodium methoxide. 

Synthetic polymers are used in a number of areas of life and range from the nylon used in various articles of clothing to the polyvinyl chloride (PVC) used in plumbing and other applications. Synthetic polymerization of organic monomers can take place by addition polymerization or by step-growth (condensation) polymerization. Polystyrene is a common product of addition polymerization, and nylon is a common product of step-growth polymerization. 

A one-pot three-component reaction of 2-aminobenzimidazoles, aldehydes 71 and P-ketoesters 72 has been developed for the synthesis of 4//-pyrimido[2,l-6]benzothiazoles 75 <05BMCL5553>. The reaction presumably proceeds in two steps Knoevenagel condensation of 71 with 72 produces 3-benzylidene-2,4-pentanedione 73 Michael addition of 73 with 2-aminobenzothiazole then generates 74, which cyclizes to 75. 

Table 5.1 Comparison of Step-Growth and Chain-Growth Polymerizations Step-growth/condensation polymerization Chain-growth/addition polymerization...

Step-growth/condensation polymerization Chain-growth/addition polymerization... 

This conclusion is supported by low-temperature 29Si NMR work of Boonstra and co-workers (21) on a two-step TEOS-ethanol sol-gel system. The results indicate that formamide acts as a base to reduce H+ concentration and the hydrolysis rate, but more importantly it also reduces the dimerization rate. In a two-step process, less than stoichiometric acidic water is added for hydrolysis, and condensation remains relatively slow. Dimerization is retarded, and so the number of free silanols available for condensation in the second step (addition of basic water) is enhanced. Thus, addition of formamide decreases the gel time by increasing the number of silanols for condensation. Gels with larger particle sizes and larger mean pore size are produced, and drying stresses are reduced. 

This type of condensation occurs readily at C4 of 2,4-dihydropyrazol-3-ones. It takes place in two steps addition of pyrazol-3-one C4 onto an electrophile and then elimination of a neutral molecule to form a double bond. A second elimination of a neutral molecule may occur to form an exocyclic alkene at C4 of the pyrazol-3-one. 

More specifically, the metathesis polymerization of acyclic alkenes is defined as an equilibrium step propagation, condensation-type polymerization, where the term condensation-type arises from the liberation of a by-product that advances the reaction. The other possibility for step polymerization is addition-type, where the resulting polymer linkage is an adduct of the two monomers, and no atoms are lost (e.g. polyurethanes). 

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