Reaction of alcohols with urea

CONDENSATION REACTIONS A. Reactions of Alcohols with Urea... 

The direct carboxylation of alcohols (6.6) and the reaction of alcohols with urea (used as an active form of CO2) (6.7) represent appealing alternatives. The former has some kinetic and thermodynamic barriers, the latter raises NH3 recovery issues and product separation problems. 

A. Reactions of Alcohols with Urea 30-1. Preparation of Ethyl Carbamate 30-2. Preparation of n-Butyl Carbamate... 

Alkyl carbamates (urethanes) ate formed from reaction of alcohols with isocyanic acid or urea (see Urettpane polymers). 

Reaction of / fZ-amyl alcohol with urea in the presence of sulfuric acid gives a monoalkylated urea (61,62). Monoalkyl ureas are used to prepare uracil derivatives which are useful as herbicides, fungicides, and plant growth regulators (61). 

CP can also be prepared by the reaction of cellulose with phosphoms oxychloride in pyridine (37) or ether in the presence of sodium hydroxide (38). For the most part these methods yield insoluble, cross-linked, CP with a low DS. A newer method based on reaction of cellulose with molten urea—H PO is claimed to give water soluble CP (39). The action of H PO and P2 5 cellulose in an alcohol diluent gives a stable, water-soluble CP with a high DS (>5% P) (40). These esters are dame resistant and have viscosities up to 6000 mPa-s(=cP) in 5 wt % solution. Cellulose dissolved in mixtures of DMF—N2O4 can be treated with PCl to give cellulose phosphite [37264-91-8] (41) containing 11.5% P and only 0.8% Cl. Cellulose phosphinate [67357-37-5] and cellulose phosphonate [37264-91 -8] h.a.ve been prepared (42). 

Commercial 70 % nitric acid can be used for the 6>-nitration of low molecular weight alcohols like ethanol and 2-propanol. The nitrate ester products are isolated from the cautious distillation of a mixture of the alcohol and excess 70 % nitric acid. The presence of urea in these reactions is very important for the destruction of nitrous acid and its omission can lead to very violent fume-off. However, this method is not recommended on safety grounds. Using temperatures above ambient for the O-nitration of alcohols, with either nitric acid or mixed acid, is dangerous and greatly increases the risk of explosion. 

The replacement of both -OH groups with chlorine produces Ccirbonyl dichloride, also known as phosgene, a useful reactant. For example, phosgene reacts with two moles of alcohol to form a dialkyl carbonate. The reaction of phosgene with one mole of alcohol produces an alkyl chloroformate, which is a useful intermediate in organic syntheses. The reaction of phosgene with four moles of ammonia yields urea and two moles of ammonium chloride, NH Cl. Figure 12-40 shows the structures of some of these compounds. 

Ricci and co-workers introduced a new class of amino- alcohol- based thiourea derivatives, which were easily accessible in a one-step coupling reaction in nearly quanitative yield from the commercially available chiral amino alcohols and 3,5-bis(trifluoromethyl)phenyl isothiocyanate or isocyanate, respectively (Figure 6.45) [307]. The screening of (thio)urea derivatives 137-140 in the enantioselective Friedel-Crafts reaction of indole with trans-P-nitrostyrene at 20 °C in toluene demonstrated (lR,2S)-cis-l-amino-2-indanol-derived thiourea 139 to be the most active catalyst regarding conversion (95% conv./60h) as well as stereoinduction (35% ee), while the canditates 137, 138, and the urea derivative 140 displayed a lower accelerating effect and poorer asymmetric induction (Figure 6.45). The uncatalyzed reference reaction performed under otherwise identical conditions showed 17% conversion in 65 h reaction time. 

For the most part, the preparation of monomeric and polymeric carbamates (urethanes), semicarbazides, and ureas consists of condensation reactions of isocyanates with alcohols, hydrazines, or amines. The synthesis of ureas and semicarbazides are described in Chapters 6 and 8, respectively. 

The reaction of primary alcohols with urea gives carbamates when the reaction is carried out at 115°-l 50°C [7-10] (Eqs. 2, 3). Since 150°C is the temperature for the optimum dissociation of urea to cyanic acid and ammonia, lower-boiling alcohols (methyl, ethyl, and propyl) must be heated under pressure. Refluxing urea and n-butanol at 115°-120°C requires a 40-hr reaction time to... 

Reaction of polyvinyl alcohol with urea to give polyvinyl carbamates [11,47, 48]. 

Several metal oxides (either acidic or alkaline) have also been investigated for urea alcoholysis [228, 229], with PG finding PC product yields in excess of 90% for ZnO, PbO, and MgO. In such studies, the results obtained coupled with the results of thermal programmed desorption (TPD) and Fourier transform infrared (FTIR) analyses, indicated that catalysts with appropriate acid and base properties were required for the synthesis of CCs. These results confirmed the reports of Aresta et al. [94] and Ball et al. [39], who previously had investigated the reaction of primary and secondary alcohols with urea to form carbonate. These authors found the reaction to proceed in two steps, with a combination of a weak Lewis acid and a Lewis base improving the carbonate formation. 

Nagasawa and co-workers reported the use of a chiral bis-thiourea catalyst (108) for the asymmetric MBH reactions of cyclohexenone with aldehydes [95]. Since others had already shown that thioureas form hydrogen bonds with both aldehydes and enones, it was hypothesized that the inclusion of two thiourea moieties in close proximity on a chiral scaffold would organize the two partners of the MBH reaction and lead to enantiofacial selectivity. Initial studies showed that the achiral 3,5-bis-(trifluoromethyl)phenyl-substituted urea increased the rate of MBH reaction between benzaldehyde and cyclohexenone. These authors then showed that chiral 1,2-cyclohexyldiamine-linked bis-thiourea catalyst 108, used at 40 mol% loading in the presence of 40 mol% DMAP, promoted the MBH reactions of cyclohexenone with various aliphatic and aromatic aldehydes (40) to produce allylic alcohols in moderate to high yields (33-99%) and variable enantio-selectivities (19-90% ee Table 6.33). 

O-alkylisoureas, formed in the reaction of carbodiimides with alcohols, are excellent alkylation reagents. For example, reaction of O-alkylisoureas 442 with anions of alcohols or phenols form the corresponding ethers 443 with formation of NJSl -disubstituted ureas." ... 

Oxidation. Epoxidation of chiral allylic alcohols with urea-H Oj catalyzed by ZSM-5 zeolite (titanium silicate-1) and ene-type hydroperoxidation of alkenes photosensitized by thiazine dye cation-exchanged zeolites have been reported. In the latter reaction, only one product is formed. 

Ureas and Carbonates. Reagent (1) may be used as a direct replacement for the highly toxic Phosgene in reactions with alcohols and amines. Reaction of (1) with two equivalents of a primary aliphatic or aromatic amine at room temperature rapidly yields a symmetrical urea (eq 9). If only one equivalent of a primary amine is added to (1), then the imidazole-Al-carboxamide (4) is formed (eq 10). These compounds can dissociate into isocyanates and imidazole, even at room temperature, and distillation from the reaction mixture provides a useful synthesis of isocyanates (eq 10).7 Secondary amines react only at one side of (1) at room temperature, again giving the imidazole-Al-carboxamide of type... 

Figure 5 Log of reaction rate constant versus jT T in kelvins) for the reaction of ortho and para hydroxybenzyl alcohol with urea, detailing the relative rates of condensation with urea of ortho and... 

High yields of 2-substituted chromans are readily attained from the asymmetric intramolecular oxa-Michael addition reaction of phenols bearing an (f -a,P-unsaturated ketone or thioester moiety mediated by a cinchona-alkaloid-urea-based bifunctional organocatalyst (140BC119). Molecular iodine-catalyzed reaction of phenols with a,P-unsaturated alcohols affords a wide range of 2,2-disubstituted chromans (14T5221). Chiral derivatives result from the intramolecular allylic alkylation of phenols bearing an... 

This reaction is slow compared to the catalyzed reaction of lEM with primary alcohols but it can be accelerated with triethylene diamine. Moisture must be kept away from lEM monomer and lEM-containing polymers to avoid gel formation due to this urea cross-linker. The presence of water will slow the tin catalyzed reactions with alcohols. Presumably, this inhibition results from hydrolysis of the catalyst. 

Isocyanates react with alcohols and phenols to form urethanes. In general, rates of urethane formation decrease in the following order primary alcohols > secondary alcohols > 2-alkoxyethanols > l-alkoxy-2-propanols. Isocyanates can react with urethanes to form allophanates. This reaction is much slower than the reaction of isocyanate with alcohol. Isocyanates react rapidly with primary and secondary amines to form ureas. The reaction is much faster than the reaction of isocyanates with alcohols. Isocyanates can react with ureas to form biurets. Biuret formation is slower than urethane formation, but faster than allophanate formation. Isocyanates react with water to form imstable carbamic acids, which dissociate into carbon dioxide and an amine. The amine is so much more reactive that it reacts with another isocyanate (in preference to water) to form mea. The reactivity of water with isocyanates is somewhat slower than that of secondary alcohols, but much more rapid than that of imcatalyzed reaction with methanes or ureas. 

---