Solvents, acidic dipolar aprotic

Kolthoff, I.M., Chantooni, M.K., Jr, Acid-base equilibria and titrations in nonaqueous solvents. A. General introduction to acid-base equilibria in nonaqueous organic solvents C. Dipolar aprotic solvents, in Ref. 1, pp. 239-302, 349-384. 

Dipolar aprotic solvents show little ability to donate protons to bases or hydrogen atoms to hydrogen bond acceptors. Dimethylsulphoxide, for example, has a pA"a value of about 32. Acetonitrile and nitromethane have such feeble acidic or basic properties that they are excellent differentiating solvents. All dipolar aprotic solvents are sufficiently basic to combine with and stabilise protons from acids. Going by the medium effects on the proton (Table 3.3.3), we expect dimethylsulphoxide to be more basic than water and acetonitrile to be much less basic. Dimethylformamide is between water and dimethylsulphoxide in basicity. Sulpholane and other sulphones are very weak bases. 

The two-step poly(amic acid) process is the most commonly practiced procedure. In this process, a dianhydride and a diamine react at ambient temperature in a dipolar aprotic solvent such as /V,/V-dimethy1 acetamide [127-19-5] (DMAc) or /V-methy1pyrro1idinone [872-50-4] (NMP) to form apoly(amic acid), which is then cycHzed into the polyimide product. The reaction of pyromeUitic dianhydride [26265-89-4] (PMDA) and 4,4 -oxydiani1ine [101-80-4] (ODA) proceeds rapidly at room temperature to form a viscous solution of poly(amic acid) (5), which is an ortho-carboxylated aromatic polyamide. 

Isoquinoline can be reduced quantitatively over platinum in acidic media to a mixture of i j -decahydroisoquinoline [2744-08-3] and /n j -decahydroisoquinoline [2744-09-4] (32). Hydrogenation with platinum oxide in strong acid, but under mild conditions, selectively reduces the benzene ring and leads to a 90% yield of 5,6,7,8-tetrahydroisoquinoline [36556-06-6] (32,33). Sodium hydride, in dipolar aprotic solvents like hexamethylphosphoric triamide, reduces isoquinoline in quantitative yield to the sodium adduct [81045-34-3] (25) (152). The adduct reacts with acid chlorides or anhydrides to give N-acyl derivatives which are converted to 4-substituted 1,2-dihydroisoquinolines. Sodium borohydride and carboxylic acids combine to provide a one-step reduction—alkylation (35). Sodium cyanoborohydride reduces isoquinoline under similar conditions without N-alkylation to give... 

With hydrogen sulfide at 500—600°C, monochlorotoluenes form the corresponding thiophenol derivatives (30). In the presence of palladium catalysts and carbon monoxide, monochlorotoluenes undergo carbonylation at 150—300°C and 0.1—20 MPa (1—200 atm) to give carboxyHc acids (31). Oxidative coupling of -chlorotoluene to form 4,4 -dimethylbiphenyl can be achieved in the presence of an organonickel catalyst, generated in situ, and zinc in dipolar aprotic solvents such as dimethyl acetamide (32,33). An example is shown in equation 4. 

Sn2 reactions with anionic nucleophiles fall into this class, and observations are generally in accord with the qualitative prediction. Unusual effects may be seen in solvents of low dielectric constant where ion pairing is extensive, and we have already commented on the enhanced nucleophilic reactivity of anionic nucleophiles in dipolar aprotic solvents owing to their relative desolvation in these solvents. Another important class of ion-molecule reaction is the hydroxide-catalyzed hydrolysis of neutral esters and amides. Because these reactions are carried out in hydroxy lie solvents, the general medium effect is confounded with the acid-base equilibria of the mixed solvent lyate species. (This same problem occurs with Sn2 reactions in hydroxylic solvents.) This equilibrium is established in alcohol-water mixtures ... 

Easy cyclization of 2, 6 -dinitrobiphenyl-2,6-dicarboxylic acids 290 during their heating in dipolar aprotic solvents providing high yields of tetracyclic... 

Solvent dependence of k, for di-r-alkyl peroxides is small when compared to most other peroxide initiators.128 212 For di-/-butyl peroxide,128 d is slightly greater (up to two-fold at 125 °C) in protic (/-butanol, acetic acid) or dipolar aprotic solvents than in other media (cyclohexane, triethylamine, tetrahydrofuran). 

It is obvious that the primary amines formed in this reaction will be uncontaminated by secondary or tertiary amines (unlike 10-44). The reaction is usually rather slow but can be conveniently speeded by the use of a dipolar aprotic solvent such as DMF or with a crown ether. Hydrolysis of the phthalimide, whether acid or base catalyzed (acid catalysis is used far more frequently), is also usually very slow, and better procedures are generally used. A common one is the Ing-Manske procedure,in which the phthalimide is heated with hydrazine in an exchange... 

Like the carbodiimide method, the mixed anhydride method results in an amide complex (Table 5, Figure 17). The acid-containing hapten is dissolved in a dry, inert, dipolar, aprotic solvent such as p-dioxane, and isobutyl chloroformate is added with an amine catalyst. The activated mixed anhydride is chemically stable and can be isolated and characterized. The aqueous protein solution is added to the activated acid and the pH is maintained at around 8.5. A low temperature (around 10 °C) is necessary during the reaction to minimize side reactions. 

The sulfonylated and acylated PPO presents solubility characteristics which are completely different from those of the parent PPO. Table V presents the solubility of some modified structures compared to those of unmodified PPO. It is very important to note that, after sulfonylation, most of the polymers become soluble in dipolar aprotic solvents like dimethyl sulfoxide (DMSO), N,N— dimethylformamide (DMF) and N,N-dimethylacetamide (DMAC). At the same time it is interesting to mention that, while PPO crystallizes from methylene chloride solution, all the sulfonylated polymers do not crystallize and form indefinitely stable solutions in methylene chloride. Only some of the acetylated polymers become soluble in DMF and DMAC, and none are soluble in DMSO. The polymers acetylated with aliphatic acid chlorides such as propionyl chloride are also soluble in acetone. 

The transesterification of sucrose has been performed with a fatty acid ester of a volatile alcohol in the presence of an alkaline catalyst in a dipolar, aprotic solvent.142 The reaction of sucrose (293 mmoles) with methyl dodecanoate (293 mmoles) in A/,N-dimethylformamide in the presence of sodium methoxide in a pressure bomb for 8 h at 130° gave, after solvent extraction and crystallization, sucrose mono(dodecanoate) (m.p. 72-80° [a]D+52°) in 50% yield.142 Commercialization of these sucrose esters has so far been limited, in part because of the use of expensive solvents, and, in part, because solvent remaining in the product makes it unsuitable for use as a food emulsifier. In view of this situation, methods have been developed in which the use of toxic and expensive solvents has been avoided. 

Starting materials which are only sparingly soluble in water may require solvents that are either partially or entirely organic. Diazotization can either be carried out as usual with an aqueous sodium nitrite solution, or alternatively with nitrosylsul-furic acid or an organic nitrite. Appropriate solvents must be stable to the reactants. Examples include aromatic hydrocarbons, chlorohydrocarbons, glycol ethers, nitriles, esters, and dipolar aprotic solvents, such as dimethyl formamide, dimethyl sulfone, tetramethylene sulfone, tetramethyl urea, and N-methylpyrroli-done. 

The dianhydride of perylene tetracarboxylic acid is converted into the pigment form by preparing the corresponding alkali salt and then reprecipitating the compound with an acid. The dianhydride is formed after separating the acid by thermal aftertreatment at 100 to 200°C, possibly under pressure, with an organic solvent. The list of suitable media includes alcohols, ketones, carboxylic acid esters, hydrocarbons, and dipolar aprotic solvents. 

Finer particle sizes are obtained if l,9-anthrapyrimidine-2-carboxylic acid chloride is condensed with 1-aminoanthraquinone in a dipolar aprotic solvent (such as N-methylpyrrolidone) at a temperature between 70 and 110°C. The reaction may be accelerated by using a proton acceptor such as triethylamine or tert-butanol,... 

Solvents can be classified into three categories according to their polarity namely, polar protic, dipolar aprotic and non-polar. Most of the common solvents fall under one of following chemical classes Aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, phenols, ethers, aldehydes, ketones, carboxylic acids, esters, halogen-substituted hydrocarbons, amines, nitriles, nitro-derivatives, amides and sulfur-containing solvents (Marcus, 1998). In certain cases a mixture of two or more solvents would perform better than a single solvent. 

Asymmetric transfer hydrogenation of imines catalyzed by chiral arene-Ru complexes achieves high enantioselectivity (Figure 1.34). Formic acid in aprotic dipolar solvent should be used as a hydride source. The reaction proceeds through the metal-ligand bifunctional mechanism as shown in the carbonyl reduction (Figure 1.24). 

P25 Each of these [previous methods] involves one or more of the following drawbacks uses expensive and toxic metals, demonstrates severe water sensitivity, or produces hydrazoic acid, which is highly toxic and explosive as well as volatile. The few methods that seek to avoid hydrazoic acid liberation during the reaction, by avoiding acidic conditions, require a very large excess of sodium azide. In addition, ah of the known methods use organic solvents, in particular, dipolar aprotic solvents such as DMF. This is one of the solvent classes that process chemists would rather not use. (Adapted from Demko and Sharpless, 2001)... 

Alkylation of saturated 5(4//)-oxazolones at C-4 is a well-known reaction that can be achieved under a wide variety of conditions. Numerous articles have described this reaction as a means to prepare 4,4-dialkyl-5(477)-oxazolones 147 that are valuable intermediates to prepare ot,ot-disubstituted a-amino acids. For instance,2-phenyl-5(4//)-oxazolone 146 readily obtained from hippuric acid and A,A -dicyclohexylcarbodiimide (DCC), is alkylated at C-4 with allyl, benzyl, or phenacyl halides if the reaction is conducted in dipolar aprotic solvents in the presence of weak bases. Hydrolysis of the resulting 5(477)-oxazolones leads to a,a-dialkylglycines 148 (Scheme 7.43). 

Izutzu, K. (1990). Acid-Base Dissociation Constants in Dipolar Aprotic Solvents, Chemical Data Series No. 35 Blackwell Scientific Publications, Oxford... 

Its solubility is poor in common organic solvents and water but readily soluble in dipolar aprotic solvents such as dimethyl formamide (DMF), dimethyl sulfoxide (DMSO) and N-Methyl pyrrolidinone (NMP). It is usually recrystallized from water containing acid. It may also be recrystallized from DMF or NMP [223, 224]. 

Water has high permittivity and moderate acidity and basicity. Thus, in water, many cations and anions are easily solvated (hydrated) and many electrolytes are highly soluble and dissociate into ions. Water has fairly wide pH and potential ranges and a convenient liquid temperature range. Of course, water is an excellent solvent. However, as in Table 1.7, the reaction environment can be expanded much wider than in water by use of a solvent of weak acidity and/or basicity. This is the reason why dipolar aprotic solvents, which are either protophilic or protophobic, are used in a variety of ways in modern chemistry. 

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