Methanol substitution reaction

The intervention of ion pairs, more important in t-butanol than in methanol, can increase the substitution reaction in such cases as the 4-and 5-halogenothiazoles, which are poorly activated by the aza substituent. 

Methanol substitution strategies do not appear to cause an increase in exposure to ambient formaldehyde even though the direct emissions of formaldehyde have been somewhat higher than those of comparable gasoline cars. Most ambient formaldehyde is in fact secondary formaldehyde formed by photochemical reactions of hydrocarbons emitted from gasoline vehicles and other sources. The effects of slightly higher direct formaldehyde emissions from methanol cars are offset by reduced hydrocarbon emissions (68). 

Methyl bromide slowly hydrolyzes in water, forming methanol and hydrobromic acid. The bromine atom of methyl bromide is an excellent leaving group in nucleophilic substitution reactions and is displaced by a variety of nucleophiles. Thus methyl bromide is useful in a variety of methylation reactions, such as the syntheses of ethers, sulfides, esters, and amines. Tertiary amines are methylated by methyl bromide to form quaternary ammonium bromides, some of which are active as microbicides. 

A more practical solution to this problem was reported by Larson, in which the amide substrate 20 was treated with oxalyl chloride to afford a 2-chlorooxazolidine-4,5-dione 23. Reaction of this substrate with FeCL affords a reactive A-acyl iminium ion intermediate 24, which undergoes an intramolecular electrophilic aromatic substitution reaction to provide 25. Deprotection of 25 with acidic methanol affords the desired dihydroisoquinoline products 22. This strategy avoids the problematic nitrilium ion intermediate, and provides generally good yields of 3-aryl dihydroisoquinolines. 

Nucleophilic displacement reactions One of the most common reactions in organic synthesis is the nucleophilic displacement reaction. The first attempt at a nucleophilic substitution reaction in a molten salt was carried out by Ford and co-workers [47, 48, 49]. FFere, the rates of reaction between halide ion (in the form of its tri-ethylammonium salt) and methyl tosylate in the molten salt triethylhexylammoni-um triethylhexylborate were studied (Scheme 5.1-20) and compared with similar reactions in dimethylformamide (DMF) and methanol. The reaction rates in the molten salt appeared to be intermediate in rate between methanol and DMF (a dipolar aprotic solvent loiown to accelerate Sn2 substitution reactions). 

The intermediate o-bromo acid bromide undergoes a nucleophilic acyl substitution reaction with methanol to give an a-bromo ester. 

Negative evidence for a common intermediate is just as important, for it can thereby eliminate a contending mechanism. The solvolysis of 2-halo-2,3,3-trimethylbutanes in methanol provides such an example.17 If it occurs by the elimination of a carbocation, the intermediate should undergo elimination and substitution reactions independent of the identity of the halide. These are shown as follows ... 

Rate constants for the substitution reactions of square-planar dithio-phosphates and dithiocarbonate complexes of Ni(II), Pd(II), and Pt(II), with ethylenediamine and cyanide ion as nucleophiles, have been measured in methanol. The results were compared with those obtained in previous investigations, and interpreted in terms of the stabilities of 5-coordinate species that are formed prior to substitution (377). 

The reaction of amides with half equiv. of BTMA Bf3 and one equiv. of DBU in dichloromethane-methanol at room temperature gave N-substituted acylureas in fairly good yields (Fig. 34). Furthermore, in the presence of a large excess of methanol, the reaction of amides with one equiv. of BTMA Bt3 and two equiv. of DBU in dichloromethane gave methyl carbamates as main products (Fig. 35). In these reactions, we assumed that in the presence of DBU, intermediary isocyanates react with excess of amides to afford acylureas, and react with excess of methanol to afford methyl carbamates (ref. 42). 

The reduction of pertechnetate with concentrated hydrochloric acid finally yields the tetravalent state, and no further reduction to the tervalent state takes place. Therefore, the tervalent technetium complex has usually been synthesized by the reduction of pertechnetate with an appropriate reductant in the presence of the desired ligand. Recently, the synthesis of tervalent technetium complexes with a new starting complex, hexakis(thiourea)technetium(III) chloride or chloropentakis(thiourea)technetium(III) chloride, has been developed. Thus, tris(P-diketonato)technetium(III) complexes (P-diketone acetylacetone, benzoyl-acetone, and 2-thenoyltrifluoroacetone) were synthesized by the ligand substitution reaction on refluxing [TcCl(tu)5]Cl2 with the desired P-diketone in methanol [28]. 

In addition to complexes of the type, trans-[Tc02(pyr)2]+ (pyr pyridine or imidazole), various species, such as Jrans-[TcO(RO)X2(pyr)2] (R CH3 or CH3CH2 X Cl or Br) were detected in alcohol. Further complicated mixed-valence species, [X2(pyr)3Tc-0-Tc(pyr)2X3] and [X(pyr)4TcO Tc(pyr)X4], appeared on long standing or heating in pyridine [44,45]. Rather peculiar features were found in the substitution reaction of trans-[Tc02(py)4] + with 4-aminopyridine (apy) in mixtures of methanol and toluene in the presence of excess pyridine ([py] — 0.14 M) [46]. Its rate was expressed as... 

Methanol-water and ethanol-water are commonmixed solvents for nucleophilic substitution reactions. 

The polymers used in this study were prepared by a nucleophilic activated aromatic substitution reaction of a bisphenate and dihalo diphenyl sulfone ( ). The reaction was carried out in an aprotic dipolar solvent (NMP) at 170°C in the presence of potassium carbonate (Scheme 1) (5,6). The polymers were purified by repeated precipitation into methanol/water, followed by drying to constant weight. The bisphenols used were bisphenol-A (Bis-A), hydroquinone (Hq) and biphenol (Bp). Thus, the aliphatic character of Bis-A could be removed while retaining a similar aromatic content and structure. The use of biphenol allows an investigation of the possible effect of extended conjugation on the radiation degradation. 

Consider the substitution reaction between a hydroxide, OH , ion and methyl bromide, BrCHs. Methanol, CH3OH, and a bromide, Br , ion are formed. 

On co-adsorbing phenol and methanol, the protonation of methanol occurs on the active acid sites as the labile protons released from the phenol reacted with methanol. Thus protonated methanol became electrophilic methyl species, which undergo electrophilic substitution. The ortho position of phenol, which is close to the catalyst surface, has eventually become the substitution reaction center to form the ortho methylated products (Figure 3). This mechanism was also supported by the competitive adsorption of reactants with acidity probe pyridine [79]. A sequential adsorption of phenol and pyridine has shown the formation of phenolate anion and pyridinium ion that indicated the protonation of pyridine. 

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. 

Related to catalytic methanol carbonylation reactions, substitution of iodide by CO in [M(CO)2l2r (M = Rh, Ir) has been studied by HP IR spectroscopy [103]. Under CO pressure, in CHCI3, both complexes were found to generate the corresponding neutral tricarbonyl, [M(CO)3l]. The Rh species had already been reported by Morris and Tinker in the reaction of [Rh(CO)2l]2 with CO [104] and the Ir species is observed under certain conditions during Ir-catalysed methanol carbonylation [39, 60]. While, for M = Ir, 35% conversion was attained at 150 bar CO, for Rh less than 4 % conversion occurred. 

The essential features of the mechanism for aliphatic nucleophilic substitution at tertiary carbon were established in studies by Hughes and Ingold." ° However, as chemists probed more deeply, the problems associated with the characterization of borderline reaction mechanisms were encountered, and controversy remains to this day about whether these problems have been entirely solved." What is generally accepted is that ferf-butyl derivatives undergo borderline solvolysis reactions through a ferf-butyl carbocation intermediate that is too unstable to diffuse freely through nucleophilic solvents such as methanol and water. The borderline nature of substitution reactions at tertiary carbon is exemplihed by the following observations. 

Our alternative approach has been to synthesize the solvento intermediate and then study its reactions in isolation. We thereby hope to show that its reactivity and steric course is inconsistent with the postulate stating that it is an intermediate in the substitution reactions. Complexes of the type cis- and trans-[Co en2 CH3OH q]+2 (7)f and cis-[Co en2 (CH3)2SO Cl]+2 32) have been prepared. We have shown in the first case that the lability of the coordinated methanol does not sufficiently explain the nonappearance of the solvento complex in the reactions of cis- and trans-[Co en2 Cb]"1" in methanol unless it is not an intermediate in the reaction. In dimethyl sulfoxide solution, cis- and trans-[Co en2 Cb] have been shown to isom-erize to an equilibrium mixture that also contains the solvento intermediate 32). 

In conclusion, this extreme importance of preassociation of reagents appears to be peculiar to the cobaltammine systems and may very well arise from some property of the N-H bond (27). Recent work on the substitution reactions of [Co diars2 Cl2]+ (diars = o-phenylenebis(dimethylarsine)) in methanol shows that, even in the case of the cis complex, there is absolutely no kinetic effect in isomerization, in... 

This is another of the very interesting contributions in Tobe s paper. Tobe has studied substitution reactions of the dichloro-bis(ethylenediamine)cobalt(III) ion in methanol, reported the preparation of the supposed solvo intermediate that would be required, and studied the rate of the chloride anion entry into this supposed solvo intermediate. He reports that the lability of methanol in this complex is insufficient to allow the complex to be an intermediate in a substitution process of the dichloro complex. Yet it is possible to obtain, in the case of the dichloro-chloride exchange, a term in the rate law for the free ion. This leads to the conclusion that, in fact, one has a genuinely unimolecular substitution process. 

Furthermore, it was recently shown, that enantiopure diaryl methanols can undergo stereospecific SN2-type substitution reactions with enolates at the (di)benzylic carbon affording 1,1-diarylalkyl derivatives (31 — 32 —> 33 Scheme 2.1.2.4). This discovery widened the preparative applicability of diaryl methanols significantly, and was used by Merck in the synthesis of selective PDE-IV inhibitors 34 and 35 [32]. 

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