Acid Methyl Amides

Assignee BASF Aktiengesellschaft Utility Fungicide Intermediate 

1- Pentanol (0.2 mol) was added to 1.8 ml water dissolved in toluene (80 g) and hydrogen chloride gas (0.4 mol) introduced. The temperature was lowered to 0°C, 2-(chloromethyl)-benzoyl cyanide (0.09 mol) added dropwise, and the mixture stirred 2 hours at ambient temperature. Thereafter, the mixture was heated to 60 °C 8 hours then cooled. It was extracted once with 50 ml of 15% strength HCl, 3 times with 50 ml water, dried, concentrated, and isolated in 95% yield but containing 4.99% of the impurity, pentyl 

2- (chloromethyl)benzoate. The product mixture was further purified by flash chromatography on silica gel 60 using cyclohexane/toluene, 2 1. H-NMR data supplied. 

O-Methylhydroxylamine hydrochloride (0.4mol) and lOg 3A molecular sieves were added to a solution of the product from Step 1 (0.1 mol) dissolved in 50 ml methyl alcohol and the mixture stood at ambient temperature 16 hours. The solution was concentrated, the residue partitioned between methyl t-butyl ether and water, the organic phase washed, dried, concentrated and the product isolated in 100% yield as 1 1 E/Z isomer mixture. H-NMR data supplied. (Note 3) 

The product mixture from Step 2 (0.1 mol) was dissolved in 500 ml diethyl ether saturated with hydrogen chloride gas while cooling in ice and then stood 16 hours at ambient room temperature. Thereafter, it was concentrated, purified by chromatography on silica gel using methyl t-butyl ether/n-hexane, and the product isolated in 81% yield as a colorless oil. HNMR data supplied. 

---

Selected physical properties of various methacrylate esters, amides, and derivatives are given in Tables 1—4. Tables 3 and 4 describe more commercially available methacrylic acid derivatives. A2eotrope data for MMA are shown in Table 5 (8). The solubiUty of MMA in water at 25°C is 1.5%. Water solubiUty of longer alkyl methacrylates ranges from slight to insoluble. Some functionalized esters such as 2-dimethylaniinoethyl methacrylate are miscible and/or hydrolyze. The solubiUty of 2-hydroxypropyl methacrylate in water at 25°C is 13%. Vapor—Hquid equiUbrium (VLE) data have been pubHshed on methanol, methyl methacrylate, and methacrylic acid pairs (9), as have solubiUty data for this ternary system (10). VLE data are also available for methyl methacrylate, methacrylic acid, methyl a-hydroxyisobutyrate, methanol, and water, which are the critical components obtained in the commercially important acetone cyanohydrin route to methyl methacrylate (11). 

Amides can be produced from fatty acid methyl esters by reaction with ammonia at 220 °C at 12.4 MPa (1800 psi) pressure. Reaction times are reduced to 1 h by this route however, the fatty acid feedstocks must fkst be converted to methyl esters (21). 

Esters are named by replacing the ending -ic acid with the suffix -ate. The alcohol portion of the ester is named by replacing the -ane ending of the parent hydrocarbon name with the suffix -yl. The alkyl radical name of an ester is separated from the carboxylate name, eg, methyl formate for HCOOCH. Amides are named by changing the ending -oic acid to -amide for either systematic or common names, eg, hexanamide and acetamide. 

A-methoxy-A-methyl amides.87 LiAlH4 and DiBAlH have both been used as the hydride donor. The partial reduction is again the result of the stability of the initial reduction product. The A-methoxy substituent leads to a chelated structure that is stable until acid hydrolysis occurs during workup. 

Lewis, P. N., F. A. Momany, and H. A. Scheraga. 1973a. Energy Parameters For Polypeptides Conformational Energy Analysis Of The N-Acetyl N -Methyl Amides of The Twenty Naturally Occurring Amino Acids. Isr. J. Chem. 11, 121-152. 

Reaction of iV-[(benzotriazol-l-yl)methyl]amide 707 with PCI5 gives chloroimine 708, which upon treatment with Bu OK is converted to nitrile ylide 709. Benzyl esters of ot,(3-unsaturated acids used as dipolarophiles trap species 709 to generate pyrroles 712 (Scheme 110) <2002JHC759>. When no trapping agent is added, the N-2 atom of benzotriazole act as a nucleophile, and tricyclic system 711 is formed <2001TL9109>. Addition of benzyl bromide... 

Various nucleophiles other than methanol can be introduced onto the carbonyl carbon. Anodic oxidation of acylsilanes in the presence of allyl alcohol, 2-methyl-2-propanol, water, and methyl /V-methylcarbamate in dichlorometh-ane affords the corresponding esters, carboxylic acid, and amide derivatives (Scheme 24) [16]. Therefore, anodic oxidation provides a useful method for the synthesis of esters and amides under neutral conditions. 

It is noteworthy that the l.d. 50 by intravenous injection for fluoroacetic acid, methyl fluoroacetate and the amide are almost identical (0-25 mg./kg. for rabbits). 

The last group of aliphatic amides to be discussed are the tertiary amides, which, by definition, carry two alkyl substituents on the N-atom. Investigations of their chemical stability have disclosed a surprising difference between tertiary and secondary amides, since the rate of acid-catalyzed hydrolysis of N,N-dimethyl amides is higher than that of A-methyl amides. If steric fac-... 

Banisteriopsis caapi The primary hallucinogenic constituents of B. caapi are the jS-carbolines. These include harmaline, tetrahydroharmine, harmol, harmic acid methyl ester, harmic amide, acetyl norharmine, harmine A/-oxide, harmalinic acid, and ketotetrahydronorharmine (figure 9.8). B. rusbyana also contains DMT, as well as A/-methyltryptamine, 5-methoxy-N,/V-dimethyltryptamine, and 5-hydroxy-N,/V-dimethyltryptamine (bufotenin). /V-methyltetrahydro-jS-carboline is found in trace amounts. 

Propenoic acid amide, see Acrylamide 2-Propenoic acid, ethyl ester, see Ethyl acrylate Propenoic acid, methyl ester, see Methyl acrylate 2-Propenoic acid, methyl ester, see Methyl acrylate 2-Propenoic acid, 2-methyl methyl ester, see Methyl methacrylate... 

More practical from the point of view of starting material availability is the use of the A-f-butyl-A-methyl amides 30, whose f-butyl group may be removed with acid (Scheme 17) . De-f-butylation of amides can be capricious however, though it seems much more successful with acyclic than cyclic amides. 

Among the a-acidic isocyanides, isocyano esters (1) (for the first isolated example of a-acidic isocyano ester see [24]), isocyano amides (2) (for the first isolated example of a-acidic isocyano amide see [25]), and arylsulfonyl methyl isocyanides (3) (for the first report of TosMlC see [26]) have been studied predominantly, and therefore this mini review will mainly focus on the MCRs involving these species. 

The conversion of sterically hindered carboxylic acids to A-methoxy-A-methyl amides can be efficiently carried out with methanesulfonyl chloride, 3 equivalents of triethy-lamine and A-methoxy-A-methylamine. Yields for this process range from 59% to... 

---