Solvents, aprotic

CH3)2N]3P0. M.p. 4°C, b.p. 232"C, dielectric constant 30 at 25 C. Can be prepared from dimethylamine and phosphorus oxychloride. Used as an aprotic solvent, similar to liquid ammonia in solvent power but easier to handle. Solvent for organolithium compounds, Grignard reagents and the metals lithium, sodium and potassium (the latter metals give blue solutions). 

Esters are alkylated in the presence of strong bases in aprotic solvents. A common combination is LDA in tetrabydrofuran at low temperatures. Equimolar amounts of base are sufficient and only the mono-carbanion Js formed. After addition of one mole of alkyl halide the products form rapidly, and no dialkylation, which is a problem in the presence of excess base, is possible. Addition of one more mole of LDA and of another alkyl halide leads to asymmetric dialkylation of one or-carbon atom in high yield (R.J. Cregge, 1973). 

An interesting case are the a,/i-unsaturated ketones, which form carbanions, in which the negative charge is delocalized in a 5-centre-6-electron system. Alkylation, however, only occurs at the central, most nucleophilic position. This regioselectivity has been utilized by Woodward (R.B. Woodward, 1957 B.F. Mundy, 1972) in the synthesis of 4-dialkylated steroids. This reaction has been carried out at high temperature in a protic solvent. Therefore it yields the product, which is formed from the most stable anion (thermodynamic control). In conjugated enones a proton adjacent to the carbonyl group, however, is removed much faster than a y-proton. If the same alkylation, therefore, is carried out in an aprotic solvent, which does not catalyze tautomerizations, and if the temperature is kept low, the steroid is mono- or dimethylated at C-2 in comparable yield (L. Nedelec, 1974). 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

In contrast to oxidation in water, it has been found that 1-alkenes are directly oxidized with molecular oxygen in anhydrous, aprotic solvents, when a catalyst system of PdCl2(MeCN)2 and CuCl is used together with HMPA. In the absence of HMPA, no reaction takes place(100]. In the oxidation of 1-decene, the Oj uptake correlates with the amount of 2-decanone formed, and up to 0.5 mol of O2 is consumed for the production of 1 mol of the ketone. This result shows that both O atoms of molecular oxygen are incorporated into the product, and a bimetallic Pd(II) hydroperoxide coupled with a Cu salt is involved in oxidation of this type, and that the well known redox catalysis of PdXi and CuX is not always operalive[10 ]. The oxidation under anhydrous conditions is unique in terms of the regioselective formation of aldehyde 59 from X-allyl-A -methylbenzamide (58), whereas the use of aqueous DME results in the predominant formation of the methyl ketone 60. Similar results are obtained with allylic acetates and allylic carbonates[102]. The complete reversal of the regioselectivity in PdCli-catalyzed oxidation of alkenes is remarkable. 

Nevertheless, they are stable to standard work-up and purification methods. The benzenesulfonyl group can be introduced using base and an aprotic solvent[3] or under phase transfer conditions[4], Table 9.2 gives some representative examples of acylation and sulfonylations. 

Use of aprotic solvents increases the quantity of exocyclic N-alkylation the potassium salt of A -(2-thiazolyDcaTbamate heated in DMF with 2-phthalimidoethyl bromide gives predominantly exocyclic N-alkylation (70% 47a, 30% 47b) (Scheme 34) (131). 

The large rate enhancements observed for bimolecular nucleophilic substitutions m polai aprotic solvents are used to advantage m synthetic applications An example can be seen m the preparation of alkyl cyanides (mtiiles) by the reaction of sodium cyanide with alkyl halides... 

Rate increases with increasing po larity of solvent as measured by its dielectric constant e (Section 8 12) Polar aprotic solvents give fastest rates of substitution solvation of Nu IS minimal and nucleophilicity IS greatest (Section 8 12)... 

HCN(CH3)2 DMF IS a polar aprotic solvent (Section 8 12) and an excellent medium for Sm2 reactions... 

This IS an example of an Sn2 reaction in a polar aprotic solvent... 

Aprotic solvent (Section 8 12) A solvent that does not have easily exchangeable protons such as those bonded to oxy gen of hydroxyl groups... 

The equation above suggests that one approach would be to use a pore Hquid that has a low surface tension. Indeed, two-step acid—base or acid—acid catalyzed sHica gels have been made, aged in ethanol or water, washed with various aprotic solvents, and finally evaporatively dried at 323 K for 48 hours and then at 383 K for 48 hours (43). The aprotic solvents used and their corresponding surface tension in N/m at room temperature (shown in... 

A brief review has appeared covering the use of metal-free initiators in living anionic polymerizations of acrylates and a comparison with Du Font s group-transfer polymerization method (149). Tetrabutylammonium thiolates mn room temperature polymerizations to quantitative conversions yielding polymers of narrow molecular weight distributions in dipolar aprotic solvents. Block copolymers are accessible through sequential monomer additions (149—151) and interfacial polymerizations (152,153). 

Keta.Is, Trimethylpentanediol reportedly forms a cycHc ketal by heating it with benzophenone ia the presence of sulfonic acid catalysts at reflux temperatures ia toluene (64). These are said to be useful as aprotic solvents for ink-jet printing and as inflammation inhibitors for cosmetic preparations... 

Synthesis and Properties. Several methods have been suggested to synthesize polyimides. The predominant one involves a two-step condensation reaction between aromatic diamines and aromatic dianhydrides in polar aprotic solvents (2,3). In the first step, a soluble, linear poly(amic acid) results, which in the second step undergoes cyclodehydration, leading to an insoluble and infusible PL Overall yields are generally only 70—80%. 

New heat-resistant polymers containing -iiitrophenyl-substituted quinoxaline units and imide rings as well as flexible amide groups have been synthesi2ed by polycondensation reaction of a dianainoquinoxaline derivative with diacid dichlorides (80). These polymers are easily soluble in polar aprotic solvents with inherent viscosities in the range of 0.3—0.9 dL/g in NMP at 20°C. AH polymers begin to decompose above 370°C. 

Aromatic Radical Anions. Many aromatic hydrocarbons react with alkaU metals in polar aprotic solvents to form stable solutions of the corresponding radical anions as shown in equation 8 (3,20). These solutions can be analyzed by uv-visible spectroscopy and stored for further use. The unpaired electron is added to the lowest unoccupied molecular orbital of the aromatic hydrocarbon and a... 

More recently, a commercial process has been introduced for the manufacture of methyl isocyanate (MIC) which involves the dehydrogenation of /V-m ethyl form am i de [123-39-7] in the presence of palladium, platinum [7440-06-4], or mthenium [7440-18-8], at temperatures between 50—300°C (31). Aprotic solvents, such as ben2ene [71-43-2], xylenes, or toluene [108-88-3], may optionally be used. A variation of this synthesis employs stoichiometric amounts of palladium chloride [7647-10-1], PdCl2. 

Many organic syntheses requHe the use of stericaHy hindered and less nucleophilic bases than //-butyUithium. Lithium diisopropylamide (LDA) and lithium hexamethyldisilazide (LHS) are often used (140—142). Both compounds are soluble in a wide variety of aprotic solvents. Presence of a Lewis base, most commonly tetrahydrofuran, is requHed for LDA solubdity in hydrocarbons. A 30% solution of LHS can be prepared in hexane. Although these compounds may be prepared by reaction of the amine with //-butyUithium in the approprite medium just prior to use, they are also available commercially in hydrocarbon or mixed hydrocarbon—THF solvents as 1.0—2.0 M solutions. 

Reaction takes place ia aqueous solution with hydrogen peroxide and catalysts such as Cu(II), Cr(III), Co(II), ferricyanide, hernia, or peroxidase. Chemiluminescent reaction also takes place with oxygen and a strong base ia a dipolar aprotic solvent such as dimethyl sulfoxide. Under both conditions Qcis about 1% (light emission, 375—500 am) (105,107). 

Condensation ofDianhydrides with Diamines. The preparation of polyetherknides by the reaction of a diamine with a dianhydride has advantages over nitro-displacement polymerization sodium nitrite is not a by-product and thus does not have to be removed from the polymer, and a dipolar aprotic solvent is not required, which makes solvent-free melt polymerization a possibiUty. Aromatic dianhydride monomers (8) can be prepared from A/-substituted rutrophthalimides by a three-step sequence that utilizes the nitro-displacement reaction in the first step, followed by hydrolysis and then ring closure. For the 4-nitro compounds, the procedure is as follows. 

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. 

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