Secondary hahdes

There is also a problem with i-PrCl it is a secondary hahde and chloride is the worst leaving group among the halogens Cl, Br, I—it is prone to ehmination rather than substitution reactions. To make the required product, an aza-enolate (p. 593 in the textbook) or a silyl enol ether (p. 595 in the textbook) would be a better bet. 

Tertiary alkyl halides are better initiators than secondary hahdes, which, in turn, are better than primary alkyl halides. Sulfonyl chlorides also provide faster initiation than propagaion. 

The rearrangement of primary to secondary hahde in /3-haloamines has been postulated to involve a cyclic ethylene immonium ion intermediate A similar mechanism is also suggested for the... 

Secondary Substrate With secondary hahdes, however, a strong base favors elimination because steric hindrance in the substrate makes substitution more difficult ... 

The reaction of a secondary hahde with ammonia is almost always accompanied by some elimination. 

The primary and secondary alcohol functionahties have different reactivities, as exemplified by the slower reaction rate for secondary hydroxyls in the formation of esters from acids and alcohols (8). 1,2-Propylene glycol undergoes most of the typical alcohol reactions, such as reaction with a free acid, acyl hahde, or acid anhydride to form an ester reaction with alkaU metal hydroxide to form metal salts and reaction with aldehydes or ketones to form acetals and ketals (9,10). The most important commercial appHcation of propylene glycol is in the manufacture of polyesters by reaction with a dibasic or polybasic acid. 

Metal phosphides can be employed to direct the action of alkyl hahdes more toward primary and secondary phosphines. 

The majority of U(V1) coordination chemistry has been explored with the trans-ddo s.o uranyl cation, UO " 2- The simplest complexes are ammonia adducts, of importance because of the ease of their synthesis and their versatihty as starting materials for other complexes. In addition to ammonia, many of the ligand types mentioned ia the iatroduction have been complexed with U(V1) and usually have coordination numbers of either 6 or 8. As a result of these coordination environments a majority of the complexes have an octahedral or hexagonal bipyramidal coordination environment. Examples iuclude U02X2L (X = hahde, OR, NO3, RCO2, L = NH3, primary, secondary, and tertiary amines, py n = 2-4), U02(N03)2L (L = en, diamiaobenzene n = 1, 2). The use of thiocyanates has lead to the isolation of typically 6 or 8 coordinate neutral and anionic species, ie, [U02(NCS)J j)/H20 (x = 2-5). 

Where X is Br or Q, the free acids may be obtained by acidification of the alkaline solution, but where X is I, the acids must be isolated as salts to avoid reduction of the arsonic acids by HI. Rather than using alkyl haUdes, alkyl or dialkyl sulfates or alkyl arenesulfonates can be used. Primary alkyl haUdes react rapidly and smoothly, secondary haUdes react only slowly, whereas tertiary haUdes do not give arsonic acids. AHyl haUdes undergo the Meyer reaction, but vinyl hahdes do not. Substituted alkyl haUdes can be used eg, ethylene chlorohydrin gives 2-hydroxyethylarsonic acid [65423-87-2], C2H2ASO4. Arsinic acids, R2AsO(OH), are also readily prepared by substituting an alkaU metal arsonite, RAs(OM)2, for sodium arsenite ... 

AsH, primary and secondary amines, and lower alcohols, BCl, BBr, and BI react to hberate the corresponding hydrogen hahde. Tertiary alcohols and the boron tnhahdes yield the alkyl hahde and boric acid. The boron tnhahdes hydrolyze readily in water or moist air to produce boric acid and hydrogen hahdes. 

We discovered a complementary procedure for conversion of OMen to other functional groups. The ester P-OMen bond was shown to be cleaved in a stereoselective manner reductively [85,86]. The cleavage takes place with almost complete preservation of stereochemical integrity at phosphorus. The reducing agents are usually sodium or Hthium naphthalenide, lithium biphenyUde, and Hthium 4,4 -di-fert-butylbiphenyl (LDBB). The species produced is then quenched with an alkyl hahde or methanol to afford tertiary or secondary phosphines, respectively (Scheme 5b). Overall, the displacement reaction proceeds with retention of configuration. 

It is a reaction of wide scope both the phosphite 1 and the alkyl hahde 2 can be varied. Most often used are primary alkyl halides iodides react better than chlorides or bromides. With secondary alkyl halides side reactions such as elimination of HX can be observed. Aryl halides are unreactive. 

When stabilized (and consequently less reactive) anions are employed as the nucleophile, more reactive electrophiles are needed for successful carbon-carbon bond formation. Nitronate anions, which are highly resonance stabilized, fail to react widi simple alkyl hahde electrophiles. On the other hand, /3-dicarbonyl compounds react effectively with primary and some secondary alkyl bromides and iodides to give monoalkylated products. 

The cross-conpling of more hindered secondary and tertiary alkyl hahdes has also been studied. Thus, secondary alkyl halides can be cross-coupled with organozinc reagents in the presence of the so-called pybox hgands (eqnation 9). 

The reactivity of 02 - with alkyl halides in aprotic solvents occurs via nucleophilic substitution. Kinetic studies confirm that the reaction order is primary > secondary > tertiary and I > Br > Cl > F for alkyl hahdes, and that the attack by 02 - results in inversion of configuration (Sn2). Superoxide ion also reacts with CCI4, Br(CH2)2Br, CeCle, and esters in aprotic media. The reactions are via nucleophilic attack by 02 on carbon, or on chlorine with a concerted reductive displacement of chloride ion or alkoxide ion. As with all oxyanions, water suppresses the nucleophilicity of 02 (hydration energy, lOOkcalmoL ) and promotes its rapid hydrolysis and disproportionation. The reaction pathways for these compounds produce peroxy radical and peroxide ion intermediates (ROO and ROO ). 

Primary and secondary, but not tertiary, alkyl hahdes are easily converted to... 

The reaction between alkyl hahdes and ammonia or primary amines is not usually a feasible method for the preparation of primary or secondary amines, since they are stronger bases than ammonia and preferentially attack the substrate. However, the reaction is very useful for the preparation of tertiary amines and quaternary ammonium salts. If ammonia is the nucleophile, the three or four alkyl groups on the nitrogen of the product must be identical. If a primary, secondary, or tertiary amine is used, then different alkyl groups can be placed on the same nitrogen atom. The conversion of tertiary amines to quaternary salts is called the Menshutkin reaction It is sometimes possible to use this method for the preparation of a primary amine by the use of a large excess of ammonia or a secondary amine by the use of a large excess of primary amine. The use of ammonia in methanol with microwave irradiation has also been effective. Microwave irradiation has also been used in reactions of aniline with allyl iodides. A base other than the amine... 

A convenient way of obtaining secondary amines without contamination by primary or tertiary amines involves treatment of alkyl hahdes with the sodium or... 

The method is quite useful for particularly active alkyl hahdes, such as allylic, benzyhc, and propargyhc halides, and for a-halo ethers and esters. Other primary and secondary halides can show sluggish reactivity. The react of enamines with benzotriazole derivatives has been reported. Tertiary hahdes do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and ehmination predominates. The reaction can also be applied to activated aryl halides (e.g., 2,4-dinitrochlorobenzene see Chapter 13), to epoxides, and to activated alkenes, such as acrylonitrile. The latter is a Michael-type reaction (15-24) with respect to the alkene. 

Still another method for the conversion of halides to acid derivatives makes use of Na2pe(CO)4. As described in 10-76, primary and secondary alkyl hahdes and tosylates react with this reagent to give the ion RFe(CO)4 or, if CO is present, the ion RCOFe(CO)4. Treatment of RFe(CO)4 or RCOFe(CO)4 with oxygen or sodium hypochlorite gives, after hydrolysis, a carboxylic acid. " Alternatively, RFe(CO)4 or RCOFe(CO)4 reacts with a halogen (e.g., I2) in the presence of an... 

There are interesting transition metal-catalyzed-reactions that lead to aryl amides. The use of POCI3 and DMF, with a palladium catalyst, converts aryl iodides to benzamides. A palladium-catalyzed reaction of aryl hahdes and for-mamide leads to benzamide derivatives. Carbonylation is another method that generates amides. When an aryl iodide was treated with a secondary amine and Mo(CO)e, in the presence of 3 equivalents of DBU, 10% Pd(OAc)2, with micro-wave irradiation at 100°C, the corresponding benzamide was obtained. 

Primary, secondary, and tertiary aliphatic amines have been cleaved to give aldehydes, ketones, or carboxylic acids with aqueous bromine and with neutral permanganate. " The other product of this reaction is the amine with one less alkyl group. In a different type of procedure, primary alkyl primary amines can be converted to gem-dUialides [RCH2NH2 RCHX2 (X = Br or Cl)] by treatment with an alkyl nitrite and the anhydrous copper(I) hahde. ... 

The transition-metal catalyzed cross-coupling reaction of (hetero)aryl hahdes and triflates with primary and secondary amines or (hetero)aryl amines is know as the Buchwald-Hartwig reaction [144]. Mechanistically, this reaction is related to the crosscoupling reactions outlined thus far (Fig. 4.6). The modification arises at the point of transmetalation. This step in the process is substituted with the coordination of the amine reactant. Deprotonation of the amine nitrogen now precedes the reductive elimination step to generate the aryl amine product. This reaction has foimd utility in the academic setting, for use in natural product total synthesis, and in industry, for the preparation of materials up to the multi-hundred kilogram scale. 

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