Schotten-Baumann conditions

Examples of benzoylation under Schotten-Baumann conditions are —... 

By the Schotten-Baumann reaction. Under the usual Schotten-Baumann conditions (compare discussion preceding Section IV,52, also Section IV,100,2and Section IV,114,2), esters are readily formed, forexample ... 

Arninobenzoyl-L-glutarnic acid (12) is obtained by condensation of -nitrobenzoyl chloride [122-04-3] (18) with L-glutamic acid [56-86-0] (19) under Schotten-Baumann conditions. This is followed by reduction of the nitro group with either sodium hydrogen sulfide (29) or by electrochemical methods (30). 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

Acylation of j8-carboline under Schotten-Baumann conditions yields the ind-N-, cy derivative. An intramolecular acylation of the cis-isomer of 278 to yield 279 has been carried out (see Section V). On the other hand, intramolecular acylation at the pyr-N of a j8-carboline, in the instance of the spontaneous cyclization of 281 to the pentacyclic compound 282, has been reported. 

Efficient synthetic methodologies for N-acylation of 6-APA have been developed. Ampiciilin, for instance, can be prepared conveniently by acylation with phenylglycyl chloride hydrochloride under Schotten-Baumann conditions in an aqueous medium. As circumstances require, either ampiciilin anhydrate, ampiciilin trihydrate or ampidllin sodium can easily be produced on an industrial scale. 

Acyl chlorides 304 led to the corresponding ketenes 308 while the allylamines were deactivated as ammonium salts 309 (Schotten-Baumann conditions). 

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... 

In the development of the protein-fatty acid condensates it was possible to combine the renewable resources fatty acids (from vegetable oil) and protein, which can be obtained from both animal waste (leather) as well as from many plants, to construct a surfactant structure with a hydrophobic (fatty acid) and a hydrophilic (protein) part (Fig. 4.12). This was carried out by reacting protein hydrolysate with fatty acid chloride under Schotten-Baumann conditions using water as solvent. Products are obtained that have an excellent skin compatibility and, additionally, a good cleaning effect (particularly on the skin) and, in combination with other surfactants, lead to an increase in performance. For instance, even small additions of the acylated protein hydrolysate improve the skin compatibility. An... 

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. ... 

No resolvable separation of the signals of the diastereomers formed from reaction of the amino acid with (5)-2-bromopropionyl chloride or Mosher s acid chloride are observed. However, with common amino acids, the latter reagent can be successfully used under similar Schotten -Baumann conditions for the detection of differences in 19F spectra57. The a-alkylated amino acids are particularly challenging. However, by proper choice of solvent and signal, sufficient peak separation can be obtained. No measurable amount of kinetic resolution occurs during acylation of the acids. 

Examples of benzoylation under Schotten-Baumann conditions are — C6H6NH2 + C4HsCOC1 + NaOH — C HtNHCOC H6 + NaCl + H,0... 

Azoles containing a free NH group react comparatively readily with acyl halides. yV-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (75) — (76) or type (79)—>(80) or (81). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. 

Acylation with acetic anhydride or under Schotten-Baumann conditions generally occurs on the 1-amino group and, as with the reactions of the bifunctional aldehydes and ketones,... 

The 2H-and 3//-pyrroles and -indoles are considerably more basic than the corresponding H-isomers and they readily undergo alkylation to give the quaternary salts, which are then highly susceptible to nucleophilic attack. Thus, for example, methylation of the trialkyl-3//-indole (507), followed by reaction with aqueous base, yields the indolin-2-ol (508). A similar reaction sequence results from the acylation of (507) under Schotten-Baumann conditions to give (509 X = OH). When the benzoylation is conducted in benzene in the absence of the base, the 2-chloroindoline (509 X = C1) is formed and acylation of (507) with a carboxylic acid anhydride produces the ester (509 X = OCOR) (79HC(25-3)l). 

H-o-APha-OH (3.8 g, 25 mmol) was reacted with Z-Cl under Schotten-Baumann conditions. After acidification with coned HC1, the product was obtained as a crystalline solid yield 3.5g (49%) mp 111-112 °C after recrystallization (MeOH). 

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. 

Esterification of aromatic carboxylic acids with phenols, however, cannot be accomplished by a direct esterification procedure and resort must be made to the greater reactivity exhibited by the acid chlorides. Reaction is usually carried out in dilute aqueous alkali (Schotten-Baumann conditions, Section 6.6.2, pp. 916 and 1248). The preparation of 2-naphthyl benzoate is a typical example of this procedure (Expt 6.166). 

In general, the use of biphasic aqueous basic conditions is often named Schotten-Baumann conditions . 

The hydrolysis of an IV-acylated amino acid by an enzyme provides a resolution method to amino acids. Because the starting materials are readily available in the racemic series by the Schotten-Baumann reaction, the method can be cost effective (Scheme 2.21).68-71 The L-amino acid product can be separated by crystallization, whereas the D-amino acid, which is still /V-acylated, can be recycled by being resubjected to the Schotten-Baumann conditions used for the next batch. Tanabe has developed a process with an immobilized enzyme,72 73 whereas Degussa uses the method in a membrane reactor.69 74 The process is used to make L-methionine. 

The Sepracor group demonstrated that (l/ ,2S)-indene oxide 26 could be prepared from readily available indene 25 in the presence of 1.5 mol% of (R,R)-MnLCl and 13% NaOCl in dichlo-romethane in 83% yield and 84% ee (Scheme 24.2). Chiral indene oxide 26 was then subjected to nucleophilic opening with ammonia to provide /ram-aminoindanol, which was transformed without isolation to its benzamide under the Schotten-Baumann condition (83% ee, >99.5% ee after recrystallization). The optically pure trans-benzamidoindane was then converted to the optically pure benzaoxazoline 27 by exposure to 80% H2S04, followed by addition of water to give cis-1-amino-2-indanol.53 54 The sequence was demonstrated on multi-kilogram scale to prepare optically pure (IR, 2.S )-1 in 40% yield from indene. 

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