Secondary with epoxides

Primary and secondary amines also react with epoxides (or in situ produced episulfides )r aziridines)to /J-hydroxyamines (or /J-mercaptoamines or 1,2-diamines). The Michael type iddition of amines to activated C—C double bonds is also a useful synthetic reaction. Rnally unines react readily with. carbonyl compounds to form imines and enamines and with carbo-tylic acid chlorides or esters to give amides which can be reduced to amines with LiAlH (p. Ilf.). All these reactions are often applied in synthesis to produce polycyclic alkaloids with itrogen bridgeheads (J.W. Huffman, 1967) G. Stork, 1963 S.S. Klioze, 1975). 

In some cases products of rearrangement are obtained either partially or exclusively on treatment of Grignard reagents with epoxides. Thus, reaction of the 2/ ,3/ -epoxide (14) with methyl Grignard reagent affords a mixture of two epimeric secondary A-nor alcohols (15) in 80% yield and the tertiary hydroxy compound, 2a-methyl-5a-cholestan-2/f-ol (16) in 15 % yield. ... 

Substitution of the free epoxide, which generally occurs under basic or neutral conditions, usually involves an Sn2 mechanism. Since primary substrates undergo Sn2 attack more readily than secondary, unsymmetrical epoxides are attacked in neutral or basic solution at the less highly substituted carbon, and stereospecifically, with inversion at that carbon. Under acidic conditions, it is the protonated epoxide that undergoes the reaction. Under these conditions the mechanism can be either SnI or Sn2. In S l mechanisms, which favor tertiary carbons, we might expect that attack would be at the more highly substituted carbon, and this is indeed the case. However, even when protonated epoxides react by the 8 2 mechanism, attack is... 

Many different pathways, mechanisms, and enzymes are associated with activation. These include dehalogenation, AT-nitrosation of secondary amines, epoxidation, conversion of phosphothionates to phosphate, metabolism of phen-oxyalkanoic acids, oxidation of thioethers, hydrolysis of esters and peroxides. The following is a summary. 

Reactions of organolithium species with epoxides, yielding secondary alcohols, are shown in equations 69 and 75 (Section VI.B.l). 

These compounds can initiate anionic polymerisation of epoxides, and when R, = H the secondary amine can react by addition to an epoxide group. Farkas and Strohm 64> have studied the reaction of 2-ethyl-4-methyl imidazole with phenyl glycidyl ether and BADGE resin using chemical analysis and proton NMR spectroscopy. They found that the imidazole readily forms adducts with epoxide of 1 1 and 1 2 molecular ratio ... 

The interpretation of the kinetics is based on the mechanisms proposed by Schechter et al.55) and Smith 57), for the reaction of secondary amines with epoxides, extended to include the primary amine reaction. The rate-determining step is assumed to be the reaction of amine, epoxide and hydroxyl or other proton-donor species, HX, to form a termolecular complex, Eq. (3-13). The proposed reaction scheme is ... 

The relative reactivity of secondary and primary amines with epoxide, k2/kt, can affect the overall kinetics. If k2/kj is not close to 0.5 the parameter f in Eqs. (4-7) and (4-13) becomes significant. In this respect there are differences between aliphatic and aromatic or alicyclic amines. For the aliphatic amines the ratio k2/kj is reported to be in the range 0.6-0.7 83 90), whereas for aromatic amines values in the range 0.2 to 0.5 have been observed 90 9S). For the reaction of BADGE with DDS, Dobas et al. 94) reported a value of 0.21 for k2/k, at 80 °C. This factor is likely to account for part of the observed non-linearity in reduced rate plots at higher levels of conversion. 

The carboxymethylation of sucrose can be achieved by reaction with sodium chloroacetate in water or water-2-propanol mixtures in basic medium. In this case, a similar regioselectivity is observed as for the reaction with epoxides or alkyl halides with major substitutions at secondary positions, notably at OH-2.80 Cyanoethylated sucrose derivatives and the corresponding carboxylated compounds were also prepared.81... 

For example, polymers having hydroxyl end groups can be prepared by reaction of polymer lithium with epoxides, aldehydes, and ketones III-113). Carboxylated polymers result when living polymers are treated with carbon dioxide (///) or anhydrides (114). When sulfur (115, 116), cyclic sulfides (117), or disulfides (118) are added to lithium macromolecules, thiol-substituted polymers are produced. Chlorine-terminus polymers have reportedly been prepared from polymer lithium and chlorine (1/9). Although lithium polymers react with primary and secondary amines to produce unsubstituted polymers (120), tertiary amines can be introduced by use of p-(dimethylamino)benzaldehyde (121). 

This synthesis involved the latter secondary amino-alcohols reacting with epoxides such as ... 

For curing at room temperature, systems based on primary and secondary amines and polyamides are used extensively. More reactive products are obtained with aliphatic chains rather than aromatic amines, which have lower basicity. Sulphur compounds like mercaptans react rapidly with epoxide systems and will provide a basis for rapid-curing—but the bonds resulting tend to be rather brittle and also to have the unpleasant odour of the mercaptan. 

The secondary electron-transfer processes, often used in mechanistic in estiga-tions and in preparative applications of electron-transfer photochemistry, enhance the quantum yields of product formation [167], In fact, as we have already pointed out in a previous section, the efficiency of separation of the geminate pair is strictly dependent on the redox potentials (see also indirect photooxygenation processes) [43, 50, 80-83, 135], Anyway, although in the present case the subsequent electron-transfer from epoxide to biphenyl radical cation BP is endothermic enough, in the absence of very fast competing reactions this primary radical cation may still undergo an endothermic electron-transfer process with epoxides. 

Unlike dialkylmagnesium compounds, normal dialkylzincs do not react with epoxides. However, the m situ reagents 2RMgX + ZnXa readily give secondary alcohols without primary alcohols (108). Since... 

Reaction with epoxides. The reagent (1) in the presence of ZnU as catalyst converts epoxides into /3-siloxyalkyl phenyl selenides in 70-90% yield (cf. cleavage of epoxides with NaSeQHs, 5, 272-273). The facility of C—O bond cleavage is tertiary > primary > secondary. The selectivity follows the reverse order if n-butyl-lithium is used as the eatalyst. 

Overman and Flippin utilized diethylaluminum amides for facile aminolysis of epoxides [71], The procedure involved treating a primary or secondary amine in CH2CI2 with EtsAl (1 equiv.) at room temperature for 30 min, then reaction with epoxide (1 equiv.) overnight. Hydrolysis of the resulting amino aluminate eventually afforded the /8-amino alcohol product in good yield. Aminolysis of cyclopentene oxide with diethylaluminum anilide is shown in Sch. 43 as a typical example. 

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