N- - dimethylamid

The second problem involves the measurement of pKa values for carbonyl and thiocarbonyl derivatives. Grieg and Johnson (157) have pointed out that the measurement of pKa values for very weak bases (11) is an inaccurate and arbitrary process. Of particular difficulty for our purposes is the fact that different carbonyl derivatives may require different acidity functions. As a result of this situation, no attempt was made to make correlations of pKa data for carbonyl and thiocarbonyl derivatives with eq. (2). Because accurate pKa values can be measured for imines, these values were correlated with eq. (2), although the conformational problem remains. The imine sets were first studied by Charton and Charton (73), who correlated them with eq. (2). No correlations of data for carbonyl or thiocarbonyl derivatives with eq. (2) are extant in the literature. Bhaskar, Gosavi, and Rao (158) have reported that AG values for complex formation of substituted thioureas with iodine are a linear function of the Taft a values. Drago, Wenz, and Carlson (159) have reported similar results for complex formation between iodine and substituted amides. Oloffson (160) has reported a linear relationship between -AH for the complex of substituted N,N-dimethylamides with SbCls and the ffj constants. 

N,N-dimethylamides methyl carboxylates propionyl derivatives acetyl ... 

The structurally related 1-amino-substituted azabicyclo[3.1.0]hexanes 132 were prepared by intramolecular cyclopropanation of N -allylaminoacetic acid N,N-dimethylamides 131 as diastereomeric mixtures (Scheme 11.34) [127]. 

Acylpyrroles can also be prepared by using the Vilsmeier reaction with various amides. Excellent yields of 2-aroylpyrroles were obtained using morpholides instead of the more common N,N- dimethylamides (equation 178) (77JOC4248). Similarly, a variety of 3-acylin-doles have been prepared using the Vilsmeier-Haack reaction (79HC(25-3)357). 

The free energy of activation for the breakdown (AGcleav does not vary con siderably with the amide structure, while that for the conformational change at the nitrogen (aG onf) changes appreciably from the formamide to the acetamide (or propionamide). This confirms that the conformational step is influenced appreciably by the steric interaction of the R group in these N,N-dimethylamides. 

To a suspension of IOB (5.72 g, 26 mmol) in dichloromethane (50 ml) was added the catalyst RuCl2(Ph3P)3 (96 mg in 25 ml of dichloromethane). The substrate (10 mmol) in dichloromethane (25 ml) was then added at once. After stirring for 90 min, excess IOB was filtered out, the solvent was evaporated and the residue purified by column chromatography (silica gel, dichloromethane, then ether) to give the N,N-dimethylamides in 44-84% yield. 

Figure 6.12 shows that carboxylic acids can also be converted into carboxylic chlorides without releasing HC1. This is possible when carboxylic acids are treated with the chloro-enamine A. First the carboxylic acid adds to the C=C double bond of this reagent electrophilically (mechanism Figure 3.40, see also Figure 3.42). Then, the addition product B dissociates completely to give the ion pair C it constitutes the isopropyl analog of the Vilsmeier-Haack intermediate B of the DMF-catalyzed carboxylic chloride synthesis of Figure 6.11. The new Vilsmeier-Haack intermediate reacts exactly like the old one (cf. previous discussion) The chloride ion undertakes an SN reaction at the carboxyl carbon. This produces the desired acid chloride and isobutyric N,N-dimethylamide.

This is an example of the Vilsmeier reaction. It can also be performed with other N,N-dimethylamide derivatives using POCI3, POBr3, COCI2, or SOCI2. Experimental conditions and illustrations are provided (2). 

P-HYDROXY amides (S)-(—)-Menthyl p-tolu-cnesulfinate. (R)-(a-p-Tolylsulfinyl)-N,N-dimethylamide. 

N-dimethylamide and the imidazolinyl ring seemed to be good alternatives for the second amidine. 

Acetal esters such as diethoxyacetic ester and /3,/S-diethoxypropionic ester are readily converted to amides with concentrated ammonium hydroxide. The former ester gives an N,N-dimethylamide by reaction with dimethylamine. ... 

Reaction with aUyhc alcohols (1, 271 272). The reaction of rran.v-3-penten-2-ol (1) with N, N-dimethylacetamide dimethyl acetal and/or its synthetic equivalent 1 -methoxy-l-dimcthylaminoethylene in refluxing xylene for 17 hr. gives the N,N-dimethylamide of 3-mcthyl-4-trani-hexenoic acid (2) in 80% yield. When the reaction was carried out... 

T-ij problem is analysed in detail at the end of the chapter (pp. 299-301) where the alternatives -girited include using the acid chloride with Me2CuLi, using the free acid or the N,N-dimethylamide T--.. MeLi, using Weinreb amides, and using nitriles. 

Some reactions can be controlled to give good yields of monosubstituted products. One is the Vilsmeier reaction in which a combination of an N,N-dimethylamide and POCI3 is used to make a carbon electrophile in the absence of strong acid or Lewis acid. It is a substitute for the Friedel-Crafts acylation, and works with aromatic compoimds at the more reactive end of the scale (where pyrrole is). 

BMB reduces only specific functional groups. In tetrahydrofiirane at 0° it reduces aldehydes and ketones to alcohols, -y-valerolactone (11) to y-hydroxyvaleraldehyde (12), and N,N-dimethylamides to aldehydes. Under the same conditions it does not reduce carboxylic acids, sulfonic acids, amides, esters, acid chlorides, anhydrides, or sulfones. The failure of the carboxyl group to react makes possible the conversion... 

Reactions (see also DMF-POCI3, DMF-SOCI,). In the conversion of an acid chloride into the corresponding N,N-dimethylamide, use of the somewhat objectionable dimethylamine (b.p. 7.4°) can be avoided by substitution of DMF. This permits elimination of any solvent other than the reactants. When an anhydride is used, a catalytic amount of sulfuric acid is added. 

N-Dimethylamides react with EtOTf to give iminium salts, which can be selectively reduced to aldehydes by Li(s-Bu)3BH in THF at —78°C [TR2]. This method can be applied to a,p-unsaturated amides and is compatible with isolated double bonds, nitriles, and esters. 

Dimethylallylidenecyclopropane, 337 N,N-Dimethylamides, 209 />-Dimethylaminobenzaldehyde, 146 p-(Dimethylamino)bromobenzene, 205 N-(4-DimethyIamino-3,5-dinitrophenyl>... 

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