Group leaving

Multidentate Leaving Groups.—Rates of aquation of [Co(C03)(LL)2]+, where LL = en, pn, tn, or (NHa)2, are strongly acid-dependent, whereas those of the unidentate carbonate complex [Co(C03)(NH3)5]+ are not. The mechanism of aquation of the chelate complex is thought to involve rate-determining chelate ring opening assisted by water or protonated water molecules.  

Multidentate Leaving Groups. Further studies have appeared of the acid-induced and/or metal-ion-induced dissociation of biguanidine (LL) from [M(LL)s] + (M=CoHi or Cr ), from [Co(LL)2(en)] + and [Co(LL)(en)2] ions, and from// aw5-[Co(LL)2(CN)2] and m-[Co(LL)2(H20)2] + ions. For [M(LL)3] + ions (M=Co or Cr ), the catalytic effectiveness of bivalent metal ions parallels their ability to co-ordinate to bound LL Cu Ni Co Zn Mn. Studies of [Co(LL)2(en)] + and [Co(LL)(en)2] show that only the biguanidine molecules are lost between 55 and 90 °C. In the case of /rn j-[Co(LL)2(CN)2] ion, the product is aj-diaqua-/ra .y-dicyano-mono-biguanidinecobalt(m), and the activation parameters for loss of the first biguanidine are 15.6 kcal mol  

Values of AF, A/T, and IsS for the acid hydrolysis of [M(ox)3] ions (M = Co, Cr j or Rh ) are collected in Table 2. The pseudo-first-order rate constant varies with acidity as follows  

This is consistent with rapid [M(ox)2(OCa03)(OH2)] and [M(ox)2(OC203H)-(OHa)] formation in which one oxalato-ligand is unidentate  

Since the activation parameters in Table 2 are composite values associated with A obs, assumptions have to be made to dissect the observed values into those associated with kx, k, and A 3.It is concluded that A V ki) = A V k = 4- 3 3cm mol and AF (A 2)=AF (At3)= —18+3 cm mol for and Rh respectively. The cobalt complex is known to react with rate-determining bond breaking and the formation of radical intermediates. The Cr i and Rh complexes react with an /a mechanism (see Introduction, ref. 16). 

Multidentate Leaving Groups.— Rate data are reported for the acid-catalysed 

Multidentate Leaving Groups.—Very few reports have appeared for this class of reaction. Dicarboxylato-complexes of the type [Cofox) - or [Co(mal)3] (ox = oxalate ion, mal = malonate ion) continue to receive attention. Acid-catalysed decomposition of these complex ions is believed to occur concurrently with redox reactions involving the formation of organic radicals, e.g. [Co(ox)3] - Co +(aq) + ox + 2ox. Ignoring a previous study of [Co(mal)3] in which an analogous 

In this scheme acid-catalysed ring-opening is rapid, and the rate-determining steps are associated with hydrolysis (with or without acid catalysis) of an intermediate in which the protonated malonate ion is acting as a unidentate ligand. At 298.0 K and fi = 1.0moll = 6.30 X10 1 mol s and = 0.2451 mol s, and 

A study of micellar catalysis of the redox decomposition of the [Co(ox)3] ion has also appeared, but this will be discussed in the section dealing with catalysed aquation. 

Multidentate Leaving Groups.—The stepwise perchloric acid-catalysed dissociations of AA from [Co(AA)a(XX)] + ions (AA=biguanidine, XX=phenylbiguanidineor acetylacetonate ion) have been studied kinetically. Loss of the first biguanidine molecule is characterized for the acac complex by AH = 15.0 kcal mol, A5 = — 21 cal mol , and for the phenylbiguanidine complex by Afl = 15.4 kcal moL, AS = —20 cal K mol. Loss of the second biguanidine occurs at elevated tem- 

Multidentate Leaving Groups.—The hydrolysis of [Co(ox)a] - and of [Co(ox)2(OH2)2], which ultimately produces cobalt(n) and carbon dioxide, involves the formation of an intermediate containing a unidentate oxalate ligand previous to the rate-determining step. Free radical intermediates are thought unlikely in the decomposition of these oxalato-complexes, but malonate ion-radicals are thought to be intermediates both in the thermal and photochemical hydrolysis of the [Co(mal)3] anion. Kinetics are reported for a third example of these aquation-redox processes, [Co(acac)2] in acidic solution.  

The aquation of complexes of ethylenediamine and its derivatives is often thought to proceed through intermediates containing unidentate ethylenediamine. To support such hypotheses, several chromium(m) complexes containing unidentate ethylenediamine have been isolated, and their aquation kinetics studied. The preparation of the first cobalt(m) complex containing unidentate ethylenediamine has now been reported. There is kinetic evidence for the formation of an intermediate [Co(tren)(OH2)-(COsH)] +, containing unidentate — COsH , in the aquation of [Co(tren) (COs)]+ in strongly acidic solutions.  

Effects of Non-leaving Ligands.— The usual way of assessing the effect of a unidentate non-leaving ligand L on reactivity of cobalt(m -amine-halide complexes is to investigate aquation kinetics of compounds [Co(en)3-LC1] +. Recently described examples include complexes of cij-geometry, 

First-order rate constants and activation parameters for aquation of cobalt(jii) complexes in which non-leaving ligand effects are of primary interest 

One other type of complex wherein the effects of non-leaving ligands have been studied is that of the dioximato (6)-cobalt(in) series [Co(LLH)2-(S03H)C1] (Table 4), The complex with LLH2 = methylglyoxime (rngHj) 

Multidentate Leaving Groups.— The decomposition of dicarboxylate complexes of cobalt(in), particularly of [Co(ox)3] , has long been established to involve an internal redox step. Several papers published during the past couple of decades have concluded that the initial step is the charge-transfer or redox 

The kinetics of the closely related redox decomposition of [Co(mal)3] in aqueous solution, at pH 5.6, have been re-examined by radiochemical tracer techniques. An activation enthalpy of 86.5 kJ mol (20.7 kcal mol ) was deduced from series of experiments utilizing liquid scintillation monitoring and a value of 67.5 kJ mol (16.4 kcal mol ) by proportional counting. The former value is closer to previous estimates using spectrophotometry. 

Mechanisms available for the aquation of carboxylato-cobalt(in) complexes have been considered, with the discussion covering such topics as cobalt-oxygen versus oxygen-carbon bond breaking, dechelation of multidentate carboxylate ligands, and stereochemistry.  

The kinetic pattern and mechanism for the aquation of [Co(bipy)3] + have been elucidated as a by-product of investigating the vanadium(n) reduction of [Co(bipy)s] +. The aquation mechanism for [Co(bipy)s] + bears a considerable resemblance to that for the much studied [Fe(bipy)a] + cation. In particular there is the same need to invoke intermediates containing unidentate, and unidentate monoprotonated, bipy for both complexes. The activation parameters for dissociation are SH = 12.4 kcal mol and = —10 

The spontaneous reduction of cobalt(m)-ammine-water complexes has already been mentioned. Analogous cobaIt(in)-chelating amine-water complexes also undergo spontaneous redox reactions rather than ordinary aquation in acidic aqueous solution. The kinetics of several of these redox amine-loss processes have recently been described, for the complexes cis-[Co(en)a(OH2)2] +, i [Co(dien)(OH2)3] +, and [Co(dpt)(OH2)3] +. There were too many complications arising from side reactions for a study of the kinetics of redox aquation of the a-[Co(trenenXOH2)] + cation to be successful.  

To act as the substrate in a nucleophilic substitution reaction, a molecule must have a good leaving group. 

Note that the net charge is the same on each side of a properly written chemical equation. 

As we shall see later, the positive charge on a leaving group (like that above) usually results from protonation of the substrate by an acid. However, use of an add to protonale ihe substrate and make a positively charged leaving group is feasible only whai the nucleophile itself is not strongly basic, and when the nucleophile is present in abundance (such as in solvolysis). 

Let us now begin to consider the mechanisms of nucleophilic substitution reactions. How does the nucleophile replace the leaving group Does the reaction take place in one step or is more than one step involved If more than one step is involved, what kinds of intermediates are formed Which steps are fast and which are slow In order to answer these questions, we need to know something about the rates of chentical reactions. 

To understand how the rate of a reaction (kinetics) might be measured, let us consider an actual example the reaction that takes place between chloromethane and hydroxide ion in aqueous solution  

In this chapter, the concepts of organic bases and basicity were presented. These discussions were expanded to define nucleophiles and nucleophilicity. Trends associated with conjugate bases of acids and nucleophilicity were presented and translated to define the concept of leaving groups. As discussions continue, all of these concepts will play important roles in the various organic reaction mechanistic types presented in the following chapters. 

In each case, circle the better nucleophile. Explain your answers. 

Nucleophiles often participate in nucleophilic substitution reactions. The general form of these reactions may be represented by the following equation where Nuj and Nu2 are nucleophiles  

Arrange the following groups of molecules in order of increasing basicity. Explain your results using partial charges and inductive effects. 

Predict the order of protonation of the basic sites on the following molecules. Support your answers with pKa values. 

Show the products, including stereochemistry, of these SN1 reactions  

As can be seen from Table 8.3, the leaving ability of the halides increases as one goes down the column of the periodic table that is. Cl- is the slowest, Br- is faster, and 

I- is the fastest. This order parallels the decrease in basicity that occurs as one proceeds down a column of the periodic table. Fluoride ion (F ) is so slow that it is not commonly used as a leaving group. 

Explain whether these reactions would follow the SN1 or the SN2 mechanism and then explain which reaction is faster  

Click Alechon/sms in Motion to view this SNI Mechanism. 

We can now understand and predict why some nucleophihc substitution reactions are favoured and others are not. Thus, it is easy to convert methyl bromide into methanol by the use of hydroxide as nucleophile. On the other hand, it is not feasible to convert methanol into methyl bromide merely by using bromide as the nucleophile. 

Chemical modification of poor leaving groups into good leaving groups may also be considered 

Typically, these sulfonyl chlorides would be used Section 7.13.1), and this would then be the substrate 

The inversion process accompanying Sn2 reactions may have particular significance in cyclic compounds. Thus, if we consider the disubstituted cyclopentane derivative shown undergoing an Sn2 

A consequence of the low rate of reaction in Sn2 reactions is that side-reactions in cyclohexane derivatives, especially elimination reactions (see Section 6.4.1), may often dominate over substitution. 

The observed pseudo-first-order rate constants for the aquation of c/s-[Cr(mal)2(OH2)2] ion in acidic solution containing metal ion catalysts (M = Cu , Ni, Co, or Zn ) varies as shown in equation (17). 

Values of the second-order rate constants and the associated activation parameters are collected in Table 6.8. The metal ion catalysis arises from chelation by the coordinated malonate ion as shown in Structure 5, values 

An 5n2 mechanism is reported for the exchange of C-labeled ethane-1,2-diamine (en) with [Cr(en)3] ion in N-methyl formamide solution. Ligand exchange with [Cr(Et2NCS)3] proceeds in DMF solution with activation parameters A// = 15.9 kcal mol and A5 =-23.9 cal mor but in dioxane solution the reaction is very slow below 90°C.  

Rates and activation parameters have been measured for reaction (11) in the pH range 2-3 (L = histamine). Chelate-ring opening of the bidentate 

The metal-ion-catalyzed dissociation of oxalato complexes of the type [Cr(ox)(OH2)4] , [Cr(ox)2(OH2)2], and [Cr(ox)3] have been investi-gated/ The pseudo-first-order rate constant (fcobs) is given by fcobs = k + /cm[M ], and varies for different metal ions (M ) in the order Fe Cu Ni Zn Co Mn. This order reflects the ease of binding of to a chromium(III)-coordinated oxalato group. Protons also assist oxalate dissociation, with k between the values of k obtained for Co and Mn. The rate data are summarized in Table 6.4. A very similar study of the metal-ion-catalyzed aquation of [Cr(mal)3] ion (mal = malonate ion) has appeared. The data are presented in Table 6.5. 

In addition to studies of [Cr(ox)3] and [Cr(mal)3] (previous section), the acid-catalyzed loss of LL from [Cr(LL)3] [LL = (02CCR2C02)2, where R2 = Me,H Et,H Bz,H Me2 H2) has been investigated. In general fcobs = fco + fci[H ], with the acid-independent term only important for the cases where R2 = Me,H, and Me2. The data are summarized in Table 6.6.  

The acid hydrolysis of [Cr(LL)3] [LL = NH2CH2CH2OH, H0CH2CH(NH2)CH3, and NH2CH2CH(OH)CH3] was discussed previously (Reference 12). A study of the tris(ethanolamine) complex in aqueous/ acetone mixed solvents has also appeared. The acid hydrolysis of the low-spin tris(chelates) of chromium(II) with 2,2 -bipyridine and 

10-phenanthroline has been reexamined by stopped-flow spectrophotometry. The data for the loss of one bipy or phen molecule are given in Table Data for the thermal aquation of [Cr(phen)3] are 

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The reagent for the synthon RCO will be RCOX where X is a leaving group, such as OEt. So how would you make TM 94 ... 

The obvious ones are a carbonyl group next to the anion and an OH group (which can easily be converted into a leaving group) for the cation giving two possibilities ... 

As indicated in the general scheme below, butatrienes are the first products from base-induced 1,4-elinination of hydrogen and a suitable leaving group. The butatriene in general very readily undergoes isomerization into enynes, if sufficiently "acidic" protons are available (see Chapter 11 in Ref. 3a). In aprotic media cumulenic ethers are fixed as their lithio derivatives if an excess of alkyllithium is applied... 

Substutution can occur by a similar mechanism, if a leaving group (OR or Cl) is... 

The introduction of additional alkyl groups mostly involves the formation of a bond between a carbanion and a carbon attached to a suitable leaving group. S,.,2-reactions prevail, although radical mechanisms are also possible, especially if organometallic compounds are involved. Since many carbanions and radicals are easily oxidized by oxygen, working under inert gas is advised, until it has been shown for each specific reaction that air has no harmful effect on yields. 

Similar fragmentations to produce S-cyclodecen-l-ones and 1,6-cyclodecadienes have employed l-tosyloxy-4a-decalols and 5-mesyloxy-l-decalyl boranes as educts. The ringfusing carbon-carbon bond was smoothly cleaved and new n-bonds were thereby formed in the macrocycle (P.S. Wharton, 1965 J.A. Marshall, 1966). The mechanism of these reactions is probably E2, and the positions of the leaving groups determine the stereochemistry of the olefinic product. 

Allylic acetoxy groups can be substituted by amines in the presence of Pd(0) catalysts. At substituted cyclohexene derivatives the diastereoselectivity depends largely on the structure of the palladium catalyst. Polymer-bound palladium often leads to amination at the same face as the aoetoxy leaving group with regioselective attack at the sterically less hindered site of the intermediate ri -allyl complex (B.M. Trost, 1978). 

Unsymmetrically substituted dipyrromethanes are obtained from n-unsubstitued pyrroles and fl(-(bromomethyl)pyiToIes in hot acetic acid within a few minutes. These reaction conditions are relatively mild and the o-unsubstituted pyrrole may even bear an electron withdrawing carboxylic ester function. It is still sufficiently nucleophilic to substitute bromine or acetoxy groups on an a-pyrrolic methyl group. Hetero atoms in this position are extremely reactive leaving groups since the a-pyrrolylmethenium( = azafulvenium ) cation formed as an intermediate is highly resonance-stabilized. 

TosOH 4-methylbenzenesulfonic acid = p toluenesiilfonic acid, tosic acid X, Y leaving groups. e.g., halogen, RSOj, in substitution and elimination reactions... 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

Allylic amine is a less reactive leaving group[7], but the allylic ammonium salts 214 (quaternary ammonium salts) can be used for allylalion(l30,131]. Allylic sulfonium salts are also used for the allylation[130]. The allylic nitrile in the cyclic aminonitrile 215 can be displaced probably via x-allylic complex formation. The possibility of the formation of the dihydropyridinium salts 216 and subsequent conjugate addition are less likelyfl 32],... 

Imidazole can be A -allylated. The A -glycosylimidazole 299 is prepared by regiospecific amination at the anomeric center with retention of configuration. Phenoxy is a good leaving group in this reaction[181]. Heterocyclic amines such as the purine base 300 are easily allylatedfl 82]. 

Dienes and allylarcncs can be prepared by the Pd-catalyzcd coupling of allylic compounds with hard carbon nucleophiles derived from alkenyl and aryl compounds of main group metals. Allylic compounds with various leaving groups can be used. Some of them are unreactive with soft nucleophiles, but... 

This reactivity pattern underlies a group of important synthetic methods in which an a-substituent is displaced by a nucleophile by an elimination-addition mechanism. Even substituents which are normally poor leaving groups, such as alkoxy and dialkylamino, are readily displaced in the indole series. 

The photocyclization of iV-vinylanilines is an e.xarnple of a general class of photocyclizations[l]. If the vinyl substituent has a potential leaving group or the reaction is carried out so that oxidation occurs, the cyclization intermediate can aromatize to an indole. 

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

Dimethyl acetylenedicarboxylate (DMAD) has also been used to catalyse gramine alkylations (see Entry 7). It may function by both activating the dialkylamino leaving group and deprotonating the nucleophile[3]. 

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