Ethanol reactivity

The Mannich Reaction involves the condensation of formaldehyde with ammonia or a primary or secondary amine and with a third compound containing a reactive methylene group these compounds are most frequently those in which the methylene group is activated by a neighbouring keto group. Thus when acetophenone is boiled in ethanolic solution with paraformaldehyde and dimethylamine hydrochloride, condensation occurs readily with the formation of... 

Some less reactive tertiary amines can be mixed with an excess of methyl toluene-/)-sulphonate, m.p. 28 , and the mixture (without a solvent) heated to a much higher temperature. The mixture is allowed to cool, but before solidification occurs, it is thoroughly stirred with ether to extract unused sulphonate, and the insoluble quaternary metho-toluene-/)-sulphonate may then crystallise. If ciystallisation does not occur, dissolve this residue in ethanol and treat one portion with ethanolic picric acid (to precipitate the methopicrate) and another portion with cold concentrated ethanolic sodium iodide (to precipitate the methiodide). (M.ps. of the siilphon.ates, pp. 553 -554.)... 

Treatment of 7r-allylpalladium chloride with CO in EtOH affords ethyl 3-butenoate (321)[284]., 3, y-Unsaturated esters, obtained by the carbonylation of TT-allylpalladium complexes, are reactive compounds for 7r-allyl complex formation and undergo further facile transformation via 7r-allylpalladium complex formation. For example, ethyl 3-butenoate (321) is easily converted into 1-carboethoxy-TT-allylpalladium chloride (322) by the treatment with Na PdCL in ethanol. Then the repeated carbonylation of the complex 322 gives ethyl 2-... 

Alkylation can also be accomplished with electrophilic alkenes. There is a dichotomy between basic and acidic conditions. Under basic conditions, where the indole anion is the reactive nucleophile, A-alkylation occurs. Under acidic conditions C-alkylation is observed. The reaction of indole with 4-vinylpyri-dine is an interesting illustration. Good yields of the 3-alkylation product are obtained in refluxing acetic acid[18] whereas if the reaction is done in ethanol containing sodium ethoxide 1-alkylation occurs[19]. Table 11.2 gives some examples of 3-alkylation using electrophilic alkenes. 

The rearrangement discovered by Kolosova et al. probably involves such reactivit (159). This reaction provides a good preparative method for various 5-amino-methylthiazoles (Scheme 43). No mechanism is proposed in the report, and it is not easy to understand how the C-5 enamine-like position competes with the very nucleophilic thiocarbonyl group of the formed A-4-thiazoline-2-thione. An alternative mechanism could start with ethanol addition at C-2. leading to the A-4-thiazoline (90) (Scheme 44). In this intermediate, C-5 nucleophilic reactivity would be favored bv the true enaminic structure. After alkylation on C-5,... 

Two moles of /3-alkoxyaicene can condense on each other by means of their a- and /3-carbon atoms. The resulting intermediate reacts on the anhydrobase by elimination of a molecule of ethanol resulting in a neocyanine formation (Schemes 59 and 60). Both monoanilino and bis-anilino derivatives resulting from the condensation of dimethylform-amide have been isolated. They are capable of furnishing various condensations on either ketomethylene or another reactive nucleus (Scheme 61). 

The high reactivity of the 5-position in 1.3-selenazoles toward electrophilic substitution was also observed on azocoupling. By reacting molar quantities of an aqueous solution of a diazonium salt with an ethanolic solution of a 2-arylamino selenazole. for example, the corresponding 2-arylamino-5 azoselenazoles are formed in a smooth reaction (100). They deposit from the deeply colored solution and form intenselv red-colored compounds after their recrystallization from a suitable solvent (Scheme 36l. 

A more quantitative approach to the influence of the thiazole ring on the reactivity of a lateral functional chain was made in a recent study by Noyce and Fike (383), already discussed in Section 10.4. The first-order rates of solvolysis for three isomeric 1-thiazolylethyl chlorides were determined in 80% ethanol. The order of relative reactivity observed. 

The more reactive bromacetone gives not only 2-mercapto-4-methylthiazole but also its substitution products. The higher homologs, as far as C15. are obtained in reasonably good yield in absolute ethanol (150, 156. 234. 316, 530). The best result (85%) was obtained by working in aqueous solution with the 3-bromobutan-2-one (597). 

Ethylene oxide is a very reactive substance It reacts rapidly and exothermically with anionic nucleophiles to yield 2 substituted derivatives of ethanol by cleaving the car bon-oxygen bond of the nng... 

Once m the organic phase cyanide ion is only weakly solvated and is far more reactive than It IS m water or ethanol where it is strongly solvated by hydrogen bonding Nude ophilic substitution takes place rapidly... 

The diacid-diamine amidation described in reaction 2 in Table 5.4 has been widely studied in the melt, in solution, and in the solid state. When equal amounts of two functional groups are present, both the rate laws and the molecular weight distributions are given by the treatment of the preceding sections. The stoichiometric balance between reactive groups is readily obtained by precipitating the 1 1 ammonium salt from ethanol ... 

Suitable catalysts include the hydroxides of sodium (119), potassium (76,120), calcium (121—125), and barium (126—130). Many of these catalysts are susceptible to alkali dissolution by both acetone and DAA and yield a cmde product that contains acetone, DAA, and traces of catalyst. To stabilize DAA the solution is first neutralized with phosphoric acid (131) or dibasic acid (132). Recycled acetone can then be stripped overhead under vacuum conditions, and DAA further purified by vacuum topping and tailing. Commercial catalysts generally have a life of about one year and can be reactivated by washing with hot water and acetone (133). It is reported (134) that the addition of 0.2—2 wt % methanol, ethanol, or 2-propanol to a calcium hydroxide catalyst helps prevent catalyst aging. Research has reported the use of more mechanically stable anion-exchange resins as catalysts (135—137). The addition of trace methanol to the acetone feed is beneficial for the reaction over anion-exchange resins (138). 

In the presence of the organic siHcate, the heavy-metal salts trigger the chain extension and cross-linking reactions that lead to siHcone mbber and volatile ethanol as a byproduct. Useful metal soaps iaclude stannous octanoate [1912-83-0], ziac octanoate [557-09-5], dibutyltin dilaurate [77-58-7], and dibutyltin diacetate [1067-33-0]. The reactivity of the different salts varies considerably. Stannous octanoate effects a cure ia 0.5—2 min ziac octanoate may require 24—96 h the dibutyltin dilaurate, 10—20 min. Heat and moisture accelerate the curing rate, but to a lesser degree than ia the case of the polysulfide mbbers. 

These effects can be attributed mainly to the inductive nature of the chlorine atoms, which reduces the electron density at position 4 and increases polarization of the 3,4-double bond. The dual reactivity of the chloropteridines has been further confirmed by the preparation of new adducts and substitution products. The addition reaction competes successfully, in a preparative sense, with the substitution reaction, if the latter is slowed down by a low temperature and a non-polar solvent. Compounds (12) and (13) react with dry ammonia in benzene at 5 °C to yield the 3,4-adducts (IS), which were shown by IR spectroscopy to contain little or none of the corresponding substitution product. The adducts decompose slowly in air and almost instantaneously in water or ethanol to give the original chloropteridine and ammonia. Certain other amines behave similarly, forming adducts which can be stored for a few days at -20 °C. Treatment of (12) and (13) in acetone with hydrogen sulfide or toluene-a-thiol gives adducts of the same type. 

Rate data are also available for the solvolysis of l-(2-heteroaryl)ethyl acetates in aqueous ethanol. Side-chain reactions such as this, in which a delocalizable positive charge is developed in the transition state, are frequently regarded as analogous to electrophilic aromatic substitution reactions. In solvolysis the relative order of reactivity is tellurienyl> furyl > selenienyl > thienyl whereas in electrophilic substitutions the reactivity sequence is furan > tellurophene > selenophene > thiophene. This discrepancy has been explained in terms of different charge distributions in the transition states of these two classes of reaction (77AHC(21)119>. 

Alcohols — (ROH) are not very reactive. The lower molecular weight alcohols (methanol, ethanol, propanol) are completely miscible with water, but the heavier alcohols tend to be less soluble. Most common alcohols are flammable. Aromatic... 

Because the pK s of the aldehyde and water are similar, the solution contains significant quantities of both the aldehyde and its enolate. Moreover, their reactivities are complementary. The aldehyde is capable of undergoing nucleophilic addition to its carbonyl group, and the enolate is a nucleophile capable of adding to a carbonyl group. And as shown in Figure 18.4, this is exactly what happens. The product of this step is an alkoxide, which abstracts a proton from the solvent (usually water or ethanol) to yield a (3-hydroxy aldehyde. A compound of this type is known as an aldol because it contains both an aldehyde function and a hydroxyl group (aid + ol = aldol). The reaction is called aldol addition. 

Hydrolysis of an enamine yields a carbonyl compound and a secondary amine. Only a few rate constants are mentioned in the literature. The rate of hydrolysis of l-(jS-styryl)piperidine and l-(l-hexenyl)piperidine have been determined in 95% ethanol at 20°C 13). The values for the first-order rate constants are 4 x 10 sec and approximately 10 sec , respectively. Apart from steric effects the difference in rate may be interpreted in terms of resonance stabilization by the phenyl group on the vinyl amine structure, thus lowering the nucleophilic reactivity of the /3-carbon atom of that enamine. 

Experimental pKa data suggests that simple alkyl groups all affeet acid-base reactivity in roughly the same way. What is more, this universal alkyl effect is roughly equivalent to the effect of a hydrogen atom. For example, the difference in pKa between water and ethanol is approximately the same as that between formic acid and propanoic acid (see table at right). 

The thenyl chlorides appear to be more reactive in nucleophilic aliphatic substitution than the benzyl analogs. Thus, 2-thenyh chloride gives, in the reaction with sodium cyanide in ethanol, a mixture of ethyl 2-thenyl ether (25% yield) and 2-thenyl cyanide (32% yield), whereas benzyl chloride gives a high 3deld of benzyl cyanide uncontaminated with benzyl ether. When 2-thenyl chloride and benzyl chloride were allowed to compete for a deficiency of sodium amyloxide, 2-thenyl chloride reacted three times faster. In acetone solution 2-thenyl cyanide is obtained smoothl. ... 

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