Schotten-Baumann conditions, amine

Picolinamide 22 could be isolated in 87% yield by crystallization from aqueous i-PrOH, which also resulted in an ee upgrade from 92% to 99.3%. Deprotection of the N-Boc group was performed by dissolving 22 in 5 M aqueous HC1. It was found that the subsequent N-acetylation of the revealed amine could be performed in the same pot under Schotten-Baumann conditions by simply adding 10M aqueous NaOH and Ac20. After extraction with CH2C12, the organic phase was concentrated and used in the nitration step without any further purification. 

Because the reaction of an amine with an acyl chloride is much faster than the hydrolysis of the acyl chloride, the reaction can usually be carried out in an aqueous alkali solution. This is well known as the Schotten-Baumann procedure.6 For example, a number of N-acyl taxol analogs have been prepared under Schotten-Baumann conditions by the reaction of A-debenzoyltaxol with various acid chlorides (Eq. 9.4).7 Highly purified /V-long-chain-acyl neutral amino acids such as potassium AMauroyTy-aminobutyrate, useful as surfactants for detergent... 

Wordy Over the past few years, we have encountered numerous examples of water as the perfect solvent. We observed this first in osmium-catalyzed dihydroxylation reactions and also in nucleophilic ring-opening reactions of epoxides. We also observed this in cycloaddition reactions and in most oxime ether, hydrazone, and aromatic heterocycle condensation processes.Finally, we observed it in formation reactions of an amide from a primary amine and an acid chloride using aqueous Schotten-Baumann conditions. ... 

Carbamates are by far the most common type of amine protection used in solid-phase synthesis. Various types of carbamate have been developed that can be cleaved under mild reaction conditions on solid phase. Less well developed, however, are techniques that enable the protection of support-bound amines as carbamates. Protection of amino acids as carbamates (Boc or Fmoc) is usually performed in solution using aqueous base (Schotten-Baumann conditions). These conditions enable the selective protection of amines without simultaneous formation of imides or acylation of hydroxyl groups. Unfortunately, however, Schotten-Baumann conditions are not compatible with insoluble, hydrophobic supports. Other bases and solvents have to be used in order to prepare carbamates on, for example, cross-linked polystyrene, and more side reactions are generally observed than in aqueous solution. 

Deamination of primary amines. The conversion of primary amines into N-sulfonamides under Schotten-Baumann conditions is the basis for the classical Hinsberg test. Baumgarten et aO have found that N-sulfonamides can be converted into N,N-disulfonimides, usually in high yield, by conversion into the sodium salt (NaH) and subsequent reaction with a sulfonyl chloride in DMF as solvent ... 

In an effort to more clearly understand the mechanism by which bleomycin degrades DNA, three new bleomycin analogues were synthesized, 2-4. All three analogues were formed by the condensation of the primary amine function of BLM-A2 with either benzoyl chloride (2) or a sulfonyl chloride (3,4) using Schotten-Baumann conditions (l ). The compounds were purified via chromatographic means were characterized using H and nmr and po-tentiometric titration methods. Particularly noteworthy in the titration curves of the derivatives is the absence of inflections at pH values of 2.9 and 7.4. For BLM-Az, inflections at these pH values correspond to the loss of a proton from the protonated, but hydrogen bonded, secondary amine function (Eq. 1) and a loss of a proton from the protonated primary amine function respectively (Eq. 2). 

Although water hydrolyses acetic anhydride, amino groups and phenolic hydroxyls react much faster, and can therefore be acetylated in aqueous solution. This is the basis of the Schotten-Baumann conditions the reaction is driven by addition of sodium bicarbonate to remove the acid formed. The stirred aqueous solution of amines (or amine extract from tissues or biological fluids), totalling 4 ml, is treated with acetic anhydride (0.3 ml). A slight molar excess of sodium bicarbonate is added in small portions, letting effervescence subside each time. At the end of the reaction the products are extracted with dichloromethane (2x5 ml), and the combined extracts are blown down in a stream of nitrogen [25-27]. Similar procedures have been described for phenols [28, 29]. 

Benzoyl and benzenesulphonyl derivatives have not been widely applied for chromatographic analyses, but because they can be detected in the ultraviolet they have found some use in HPLC. They are also used to make derivatives from volatile compounds as a means avoiding evaporative losses. They are readily made under Schotten-Baumann conditions. Thus, an amine solution (3 ml) is made alkaline with an equal volume of 7.5 M NaOH, and 50 fi of benzoyl choride is vigorously shaken with this solution until consumed. The product is extracted twice with 2 ml of diisopropyl ether, and the ether extracts are blown dry with nitrogen before being taken up in the ether for analysis [142]. A similar procedure was used for amines by Terashi et at. but using benzenesulphonyl chloride [143]. 

Acyl chlorides react readily with amino groups to form amides. The reactions (Figure 1) are carried out in an alkaline medium (Schotten-Baumann conditions). The use of amide derivatives for the HPLC analysis of amines has been widely studied. Clark and Wells [9] described several acyl chlorides such as p-nitrobenzoyl, p-methoxy-benzoyL p-methylbenzoyl and p-chlorobenzoyl chlorides. The spectrophotometric properties of their benzamides were investigated. The methoxybenzamides showed the most intense absorption at 252 nm, and therefore most fixed-wavelength (254 nm) UV detectors can conveniently be used for detection. The reaction of p-methoxybenzoyl chloride with some amines and the molar absorptivities of the derivatives are shown in Table I. 

PAS) uses an excess of chlorosulfonic acid, which also serves as the solvent. Sulfonation of heterocyclic amine TM 7.2b is performed in an organic solvent in the presence of amine as acid scavenger. The industrial method for the sulfonation of amines prefers Schotten-Baumann conditions, where the reaction is completed in aqueous medium, an acetone-water or methanol-water solvent mixmre, with continuous addition of one mole of hydroxide. 

In the first steps, ester condensation to diketo acid, preparadon of oxime and cyclization are completed under standard conditions. Ester ammonolysis is followed by Hofmann rearrangement of amide to heterocyclic amine. Sulfonation of amine under Schotten-Baumann conditions, in a water-organic solvent mixmre, is based on an interesting trick hydroxide is added at a controlled rate to scavenge the hydrochloric acid formed in sulfonation and to maintain the neutral pH of the aqueous solution of heterocyclic amine as a stronger nucleophile than water, avoiding the hydrolysis of sulfonyl chloride ... 

Al-Acetylation. Primary and secondary amines can be N-acetylated to form acetamides by treatment with AcCl under Schotten-Baumann conditions (aq NaOH), but hydrolysis of AcCl is a significant competing side reaction. Use of AC2O (2.5 equiv A, 10-15 min) is therefore recommended. ... 

Aminopyrroles can usually be acetylated e and benzoylated a, 199, 200 (Schotten-Baumann conditions have been used), and have given benzal derivatives 200, 201 and ureas . In some cases these reactions fail the amines (81, = Me or C02Et) could not be acetylated, benzoylated,... 

The HCl salt of A-butyl-iV-(cyclohexylethyl)amine (2 HC1) was synfiiesized firom commercially available cyclohexylacetic acid (11). Acid chloride formation using thionyl chloride in toluene with catalytic DMF was followed by amine acylation under Schotten-Baumann conditions to give the amide (8). After workup, the resulting toluene solution was azeotropically dried and the amide was reduced with BH3 SMe2. The crude reaction mixture was quenched with HCl in MeOH and the resulting salt was crystallized from toluene/MTBE. The salt was isolated in 80% yield for the 3 steps. 

Benzoyl derivatives. Both primary and secondary amines form benzoyl derivatives under the conditions of the Schotten-Baumann reaction (see Section IV,52 and preceding discussion). 

Schotten-Baumann alkaline conditions from primary and secondary amines using acid chlorides ben2amides from ben2oyl chloride distinguish 1 ° and 2°... 

The Bts derivative is formed from the sulfonyl chloride, either using apro-tic conditions for simple amines or by the Schotten-Baumann protocol for amino acids (87-97% yield). The primary drawback of this reagent is that its stability depends on its quality. It can on occasion rapidly and exothermically lose SO2 to give 2-chlorobenzothiazole. ... 

The first enantioselective total synthesis of (-)-tejedine was completed by P.E. Georghiou using a chiral auxiliary-assisted diastereoselective Bischler-Napieralsid cycHzation as one of the key steps.The chiral auxiliary was the commercially available (S)-a-methylbenzylamine, which was coupled to the substrate using the original Schotten-Baumann acylation conditions. The acid chloride was reacted with the chiral amine in a solvent mixture containing aqueous sodium hydroxide and dichloromethane and the desired amide was isolated in excellent yield. 

A simultaneous way of determining ammonia including aliphatic amines, aromatic amines, and phenols in environmental samples by GC-MS method using a single derivatization reagent has been reported recently by Mishra et al. The method consisted in precolumn formation of benzoate esters and benzamides under the conditions of the Schotten-Baumann procedure with benzoyl chloride and SPE of the derivatives. The limit of detection of ammonia was 20 /rg/l when 80 ml of sample was preconcentrated, after derivatization, on a styrene divinyl benzene copolymer sorbent. 

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