Addition dipolar

A number of polar additions to unsaturated polymers are known. These include Michael additions, hydroboration, 1,3-dipolar additions, ene reaction, the Ritter reaction, Diels-Alder additions, and others. 

Among polar additions to unsaturated polymers are reactions of amines and ammonia with unsaturated polyesters in the form of a Michael condensation. Thus, for instance, additions to poly(l,6-hexanediol maleate) and poly(l,6-hexanediol fumarate) show a difference in the reactivity of the two isomers. The maleate polyester reacts with ammonia to yield a crosslinked product at room temperature, when stoichiometric quantities or an excess ammonia in alcohol is used. At the same reaction conditions, the fumarate isomer only adds a few percent of ammonia. In a 1 1 mixture of chloroform and ethanol, however, approximately half of the fumarate double bonds react. Also, the maleate polyester reacts differently with piperidine or cyclohexylamine. In butyl alcohol at 60 °C the polymer initially isomerizes and precipitates. After the isomerization is complete and the temperature is raised to 80 °C, the polymer redissolves. An exothermic reaction follows and Michael-type adducts form.  

Polymers and copolymers of butadiene or isoprene with styrene can react with diborane. A suitable solvent for this reaction is tetrahydrofuran. Subsequent hydrolyses result in introductions of hydroxyl groups into the polymer backbones. The reactions with diborane are very rapid. Some side reactions, however, also occur.  

Cyclic structures form on polymer backbones through 1,3-dipolar additions to caibon-to-caibon or carbon-to-nitrogen double bonds. Because many 1,3-dipoles are heteroatoms, such additions can lead to formations of five-membered heterocyclic rings. An example is addition of nitrilimine to an unsaturated polyesters  

iodine isocyanate adds to polyisoprene. The product can be converted to methyliodocar-bamate or to iodourea derivatives  

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A"-Octadienylatiori, rather than 0-octadienylation, of aldehyde oximes takes place to give the nitrone 37 as an intermediate, which undergoes 1.3-dipolar addition to butadiene, yielding the isoxazolidine 38[39],... 

The only example involving the 4-5 double bond in a 1-3 dipolar addition is given by the ozonolysis of the optically active 2-aminothiazOle (176) reported by Lardicci et al. (Scheme 112) (17). 

A general method for the preparation of 2JT-isoindol-4,7-diones, eg (97) [72726-02-4] involves 1,3-dipolar addition of oxa2ohum-5-oxides (sydnones) (98) to 2-meth5l-l,4-ben2oquinone (96). Yield of (97) is 37%. 

Pyridazinium and phthalazinium dicyanomethylides give indolizines as primary adducts with 1,2,3-triphenylcyclopropene, either by [4 + 2] cycloaddition or by 1,3-dipolar addition of the ylide to triphenylcyclopropene (81JCS(P1)73). 

Decomposition of the diazoacetic ester (548) to the keto carbene (549) is promoted by copper(II) trifluoromethanesulfonate. In the presence of nitriles, 1,3-dipolar addition to the nitrile occurred giving the oxazole (550) (75JOM(88)ll5) (see also Section 4.03.8.1). 

The interaction of diazomethane with 1-azirines was the first example of a 1,3-dipolar cycloaddition with this ring system (64JOC3049, 68JOC4316). 1,3-Dipolar addition produces the triazoline adduct (87). This material can exist in equilibrium with its valence tautomer (88), and allylic azides (89) and (90) can be produced from these triazolines by ring cleavage. 

A" -Isoxazolines, which are readily accessible by 1,3-dipolar addition of nitrones and nitronic esters to activated alkynes, undergo facile rearrangement upon warming (<110 °C)... 

R. Huisgen, Angew. Chem. Int. Ed. Engl. 2 565 (1963) R. Huisgen, R. Grashey, and J. Sauer, in The Chemistry of the Alkenes, S. Patai, ed.. Interscience Publishers, London, 1965, pp. 806-878 A. Padwa, 1,3-Dipolar Addition Chemistry, John Wiley Sons, New York, 1984. 

The types of cycloadditions discovered for enamines range through a regular sequence starting with divalent addition to form a cyclopropane ring, followed by 1,2 addition (i) of an alkene or an alkyne to form a cyclo-cyclobutane or a cyclobutene, then 1,3-dipolar addition with the enamine the dipolarophile 4), and finally a Diels-Alder type of reaction (5) with the enamine the dienophile. 

The reactions of enamines as 1,3-dipolarophiles provide the most extensive examples of applications to heterocyclic syntheses. Thus the addition of aryl azides to a large number of cyclic (596-598) and acyclic (599-602) enamines has led to aminotriazolines which could be converted to triazoles with acid. Particular attention has been given to the direction of azide addition (601,603). While the observed products suggest a transition state in which the development of charges gives greater directional control than steric factors, kinetic data and solvent effects (604-606) speak against zwitterionic intermediates and support the usual 1,3-dipolar addition mechanism. 

Extensions of 1,3-dipolar additions of aromatic azides (720,721) to other enamines (636), and particularly to the enamine tautomer of SchilTs bases, were explored (722,723). Further nitrone additions were reported (724,725) and a double nitrile oxide added to an endiamine (647). Cyanogen azide and enamines gave cyanoamidines through rearrangement (726). 

The only known representative of this type of compound, 91, was prepared by 1,3-dipolar addition of mesityl nitrile oxide to telluroketone 85 (93JA7019 94MI1). The reaction proceeds smoothly on heating equimolar amounts of the reactants at 80°C, giving rise to 91 in 70% yield. The heterocycle is a thermally unstable and light-sensitive compound. Thermolysis of a deuterochloroform solution of 91 at 60-90°C in a sealed ampule affords 1,1,3,3-tetramethylindanone and mesityl isonitrile (94MI1). 

Dipolar additions of diazomethane to acetylenes under mild conditions are restricted to monosubstituted acetylenes thus the formation of pyrazole derivatives 1 (1,3-dipolar addition, C=C isomerization, then methylation) confirms the existence of a terminal acetylene in caryoynencins (87TL3981) (Scheme 5). 

While Kakisawa et al. (87TL3981) reported formation of Wmethylpyrazole 1, Yamaguchi et al. obtained the NH derivative 2 by reaction of caryoynencins with diazomethane in ethyl acetate at 0°C (94BSJ1717 95JMC5015). The 1,3-dipolar addition was quite sensitive to the solvent employed, and a very low yield of pyrazole derivative 2 was obtained in ether or methanol (Scheme 5). 

Dipolar addition of 2-diazopropane to diacetylene in EtaO at -25°C to give 3,3-dimethyl-5-ethynylpyrazole (83) (42% yield) and at 0°C to give dipyrazole 84 (60% yield) has been described (83TL1775). 

Recently the synthetic method involving formation of the 1—5 and 3—4 bonds has been extended to the preparation of the completely hydrogenated system of A -substituted isoxazolidines (42). This interesting reaction results from 1,3-dipolar addition of nitrones (41) to olefins. " ... 

Friesner and coworkers investigated the 1,3-dipolar addition of phenyl azide 60 to carbon-carbon double bonds forming l-phenyl-4,5-dihydro-l//-l,2,3-triazoles (61 and 62) (Scheme 39) [99JPC(A)1276]. 

A rather unexpected discovery was made in connection to these investigations [49]. When the 1,3-dipolar cycloaddition reaction of la with 19b mediated by catalyst 20 (X=I) was performed in the absence of MS 4 A a remarkable reversal of enantioselectivity was observed as the opposite enantiomer of ench-21 was obtained (Table 6.1, entries 1 and 2). This had not been observed for enantioselective catalytic reactions before and the role of molecular sieves cannot simply be ascribed to the removal of water by the MS, since the application of MS 4 A that were presaturated with water, also induced the reversal of enantioselectivity (Table 6.1, entries 3 and 4). Recently, Desimoni et al. also found that in addition to the presence of MS in the MgX2-Ph-BOX-catalyzed 1,3-dipolar addition shown in Scheme 6.17, the counter-ion for the magnesium catalyst also strongly affect the absolute stereoselectivity of the reac-... 

Because of resonance stabilization of the anion, a tet-nazolyl moiety is often employed successfully as a bioisosteric replacement for a carboxy group. An example in this subclass is provided by azosemide (27). Benzonitrile analogue is prepared by phosphorus oxychloride dehydration of the corresponding benzamide. Next, a nucleophilic aromatic displacement reaction of the fluorine atom leads to The synthesis concludes with the 1,3-dipolar addition of azide to the nitrile liinction to produce the diuretic azosemi de (27). ... 

NITRILE OXIDES. Nitrile oxides are a well known class of compds represented by R.C N- 0, and are usually prepd by treating hydroxamic acid chlorides with a mild alkali, thus eliminating HQ (Ref 2). Wieland (Refs 1 3) was responsible for the first isolation of free nitrile oxides. These compds are somewhat unstable, showing a marked tendency to dimerize to (he corresponding furoxanes (1,3-dipolar addition) (Refs 2 3). The nitrile oxides add to a considerable number of carbenes, as benzonitrUe oxide (for example) to a large number of olefins in ether at 20° (Ref 3)... 

It has been shown that, on treatment with base, 1-aminopy-ridinium iodide undergoes 1,3-dipolar addition with ethyl propiolate or dimethyl acetylenedicarboxylate thus the N-aminoheterocycles may serve as convenient starting materials for the synthesis of a variety of unusual fused heterocycles.8... 

Carbon-carbon triple bonds can also undergo 1,3-dipolar addition." For example, azides give triazoles ... 

Perhaps the most characteristic property of the carbon-carbon double bond is its ability readily to undergo addition reactions with a wide range of reagent types. It will be useful to consider addition reactions in terms of several categories (a) electrophilic additions (b) nucleophilic additions (c) radical additions (d) carbene additions (e) Diels-Alder cycloadditions and (f) 1,3-dipolar additions. 

Pyridazine A-oxides undergo 1,3-dipolar addition with benzyne and a number of its analogues to form adducts which, with loss of nitrogen, form 1-benzoxepines and this work has now been extended to 1,2,4-triazine 1-oxides. In this case the product is 1,3-benzoxazepine <96H(43)2091>. 

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