Dichloromethane, reaction with amines

The tetramethyl quinone methide 38f has been generated by cleavage of the chloride precursor in dichloromethane, and its reactions with amine bases studied.74... 

Chiral imines derived from 1-phenylethanone and (I. Sj-exo-l, 7,7-trimethyIbicyclo-[2.2.1]heptan-2-amine [(S)-isobornylamine], (.S>1-phenylethanamine or (R)-l-(1-naphthyl) ethanamine are transformed into the corresponding (vinylamino)dichloroboranes (e.g., 3) by treatment with trichloroborane and triethylamine in dichloromethane. Reaction of the chiral boron azaenolates with aromatic aldehydes at 25 "C, and subsequent acidic hydrolysis, furnishes aldol adducts with enantiomeric excesses in the range of 2.5 to 47.7%. Significantly lower asymmetric inductions are obtained from additions of the corresponding lithium and magnesium azaenolates. Best results arc achieved using (.S )-isobornylamine as the chiral auxiliary 3. 

This procedure, which is based on the work of Ishii and co-workers, affords a mild and general method for converting a wide variety of esters to primary, secondary, and tertiary amides (Table 1). While the preparation of the tertiary amide, N,N-dimethylcyclohexanecarboxamide, described here is carried out in benzene, aluminum amides derived from ammonia and a variety of primary amines have been prepared by reaction with trimethylaluminum in dichloromethane and utilized for aminolysis in this solvent. Although 1 equivalent of the dimethylaluminum amides from amines was generally sufficient for high conversion within 5-48 hours, best results were obtained when 2 equivalents of the aluminum reagent from ammonia was used. Diethyl-aluminum amides can also effect aminolysis, but with considerably slower rates. 

Dichloromethane was being distilled from its mixture with the amine at a bath temperature of 30°C when an exothermic reaction led to deflagration [1], Heat of reaction, AH = —343 kJ/mol (4.04 kJ/g) of dichloromethane [2], Reaction of amines with dichloromethane at ambient temperature is common, exothermic in cone, solutions, and involves formation of an IV-chloromethyl quaternary salt. Concentrating dichloromethane solutions of amines to low volumes should therefore be avoided [3],... 

A sensitive method for primary amines is shown in reaction 2, leading to the corresponding 7V-benzenesulfonyl-/V-trifluoroacetyl derivatives. These can be determined by GC-ECD using SE-30 columns LOD 1-5 pg, which is about 200 times more sensitive than GC-FID. The method was applied for determination of phenethylamine (33) in urine110. This analysis was performed also by LLE into n-pentane, derivatization to the benzenesulfonamide and GC-FPD using a capillary column recoveries of aliphatic primary amines in urine were 91-107%, RSD 0.2-4.5%111,112. Amines in environmental waters and sediments were determined after LLE with dichloromethane, derivatization with benzenesulfonyl chloride and GC-SIM-MS LOD 0.02-2 pg/L of water and 0.5-50 ng/g of sediment113. 

A kinetic smdy of the acylation of ethylenediamine with benzoyl chloride (110) in water-dioxane mixtures at pH 5-7 showed that the reaction involves mainly benzoylation of the monoprotonated form of ethylenediamine. Stopped-flow FT-IR spectroscopy has been used to study the amine-catalysed reactions of benzoyl chloride (110) with either butanol or phenol in dichloromethane at 0 °C. A large isotope effect was observed for butanol versus butanol-O-d, which is consistent with a general-base-catalysed mechanism. An overall reaction order of three and a negligible isotope effect for phenol versus phenol- /6 were observed and are consistent with either a base- or nucleophilic-catalysed mechanism. Mechanistic studies of the aminolysis of substituted phenylacetyl chlorides (111) in acetonitrile at —15 °C have revealed that reactions with anilines point to an associative iSN2 pathway. ... 

The treatment of 4-oxo-4Z/-pyrido[ 1,2-a]pyrimidine-3-carboxylic acid 429 with phosphorus pentachloride in dichloromethane at 0°C gave acid chloride 430, which reacted with amine 431 in tetrahydrofuran in the presence of /V-methyl-TV-trimethylsilyl trifluoroacetamide at room temperature overnight to give /-substituted 3-carboxamide 432 (88USP4777252). After catalytic debenzylation, the 3-substituent of 4//-pyrido[l, 2-a]py-rimidin-4-one 433 was involved in different reactions to give antibacterial derivative 434 (see Scheme 25). 

Extension of this proline-catalyzed a-amination to the use of aldehydes as starting materials has been described independently by the Jorgensen and List groups [6, 7]. The principle of the reaction and some representative examples are shown in Scheme 7.4. The practicability is high - comparable with that of the analogous reaction with ketones described above. For example, in the presence of 5 mol% L-proline as catalyst propanal reacts with azodicarboxylate 3a at room temperature in dichloromethane with formation of the a-aminated product 5a in 87% yield and with 91% ee [7]. Good yields and high enantioselectivity can be also obtained by use of other types of solvent, e.g. toluene and acetonitrile. The products of type 5 were isolated simply by addition of water, extraction with ether, and subsequent evaporation. 

Selective trifluoroacetylation of primary amines in the presence of secondary amines can be accomplished by reaction with a stoichiometric amount of ethyl trifluoroacetate (bp 60-62 °C) in THF, acetonitrile or dioxane at 0 °C. The product is simply isolated by evaporation of the solvent and liberated ethanol,45-47 Perhaps the most common method entails acylation of the amine with trifluoro-acetic anhydride in the presence of a suitable base such as trie thy lamine or pyridine in dichloromethane [Scheme 8.26],40 New reagents for the N-trifluoro-acetylation of amines include Af-ftrifluoroacetyOsuccinimide,48 a solid and storable reagent, W-(trifluoroacetoxy)succinimide,49 which must be stored in a frozen benzene matrix, and l-(trifluoroacetyl)-l,2,3-benzotriazole.50 The latter reagent is a stable, crystalline reagent (mp 89-91 °C) prepared in quantitative... 

Malsumoto, K., Synthesis under high pressure Mannich reaction of ketones and esters with dichloromethane and secondary amines, Angew. Chem. Int. Ed. Engl., 21, 922, 1982. 

Some examples of industrially important uses are the following reactions With alkyl halides or alcohols amines or imines can be manufactured. For example, inethanol forms mono- through trimethylamine dichloromethane yields ethylene imine in the presence of calcium oxide. Amines can also be produced by reacting ammonia with alkyl halides in multistage processes [1425]. 

These findings are understandable on the assumption that in the rate-determing step a zwitterionic intermediate is formed. A pronounced effect is also observed for the Mannich reaction of indoles with dichloromethane and secondary amines (Scheme 26 entry 6) indicating that polar intermediates are involved in this reaction. 

O-Benzoylhydroxamates. Primary amines are converted to RN(OBz)COR by reaction with BzOOBz in dichloromethane at pH 10.5 (buffer) and further A -acylation. 

---