Secondary reagents

Even though formic anhydride is not a stable compound (see p. 714), amines can be formylated with the mixed anhydride of acetic and formic acids (HCOO-COMe) °°° or with a mixture of formic acid and acetic anhydride. Acetamides are not formed with these reagents. Secondary amines can be acylated in the presence of a primary amine by conversion to their salts and addition of 18-crown-6. ° The crown ether complexes the primary ammonium salt, preventing its acylation, while the secondary ammonium salts, which do not fit easily into the cavity, are free to be acylated. 

The reagent composed of HC1 and ZnCl2 is called the Lucas reagent. Secondary and tertiary alcohols react with the Lucas reagent by the SnI mechanism. 

Primary alcohols are formed from formaldehyde + Grignard reagent. Secondary alcohols are formed from an aldehyde + Grignard reagent. Tertiary alcohols are formed from a ketone (or an ester) + Grignard reagent. 

Later work showed that such displacements can be effected with a BusSnCu reagent [83], With this reagent secondary mesylates afford allenylstannanes as the exclusive kinetic products (Eq. 68). The configuration of the allenic products was confirmed by an independent synthesis involving an orthoester Claisen rearrangement (Eq. 69). 

A primary or secondary dithizonate is obtained, depending on whether the dithizonate reacts as the anion of the monobasic acid (HDz ) or the dibasic acid (Dz ). Secondary dithizonates are formed by only a few metals. They are represented by such formulae as AgaDz and CuDz. Generally, acidic media and excess of dithizone favour the formation of primary dithizonates, whereas in alkaline media, and with insufficient amounts of the reagent, secondary dithizonates are formed. 

In two-layer methods, exemplified by the indirect and polymer-based labels, each of the separate immune reagents must be applied at optimal dilution. In addition, the dilutions of the primary and secondary antibodies (or labels) are interdependent in terms of contrast developed by the procedure as a whole. This fact necessitates comparison of the results obtained using several dilutions of the labeling reagent (secondary antibody) with several different dilutions of the primary antibody comparison is achieved by checkerboard titration (Table... 

Primary alcohols are cleanly oxidized to aldehydes (not to carboxylic acids as with Jones reagent), secondary alcohols yield ketones, and tertiary alcohols are again unre-active. Therefore, a Swem oxidation accomplishes the same transformations as PCC. Hence, in Example 10.11, the same products would be obtained with a Swern oxidation as with the application of PCC. 

Water, alcohols and hydroxy compounds generally, and also primary and secondary amines, give the hydrocarbon corresponding to the Grignard reagent,... 

To 5 ml. of water add 1-2 drops of the secondary amine if it does not dissolve, add a drop or two of concentrated hydrochloric acid. Place 1 ml. of the reagent in a test-tube, add 0 -5-1 ml. of concentrated ammonia solution, followed by 0-5-1 ml. of the above amine solution, A precipitate indicates a secondary amine. A shght turbidity points to the presence of a secondary amine as an impurity. 

Derivatives with 3-nitrophthalic anhydride. 3-Nitrophthalic anhydride reacts with primary and secondary amines to yield nitro-phthalamic acids it does not react with tertiary amines. The phthalamic acid derived from a primary amine undergoes dehydration when heated to 145° to give a neutral A -substituted 3-nitrophthalimide. The phthalamic acid from a secondary amine is stable to heat and is, of course, soluble in alkali. The reagent therefore provides a method for distinguishing and separating a mixture of primary and secondary amines. 

Acetone in conjunction with benzene as a solvent is widely employed. With cyclohexanone as the hydrogen acceptor, coupled with toluene or xylene as solvent, the use of higher reaction temperatures is possible and consequently the reaction time is considerably reduced furthermore, the excess of cyclohexanone can be easily separated from the reaction product by steam distillation. At least 0 25 mol of alkoxide per mol of alcohol is used however, since an excess of alkoxide has no detrimental effect 1 to 3 mols of aluminium alkoxide is recommended, particularly as water, either present in the reagents or formed during secondary reactions, will remove an equivalent quantity of the reagent. In the oxidation of steroids 50-200 mols of acetone or 10-20 mols of cyclohexanone are generally employed. 

The reason for this is that reaction (i) is usually much slower than (ii) and (iii) so that the main reaction appears to be (Iv) (compare the preparation of tertiary butyl chloride from tertiary butyl alcohol and concentrated hydrochloric acid, Section 111,33). If the reaction is carried out in the presence of P3rridine, the latter combines with the hydrogen chloride as it is formed, thus preventing reactions (ii) and (iii), and a good yield of the ester is generally obtained. The differentiation between primary, secondary and tertiary alcohols with the aid of the Lucas reagent is described in Section III,27,(vii). 

For this reason, acetic anhydride is generally preferred for the preparation of acetyl derivatives, but acetyl chloride, in view of its greater reactivity, is a better diagnostic reagent for primary and secondary amines. 

The condensation of aldehydes or ketones with secondary amines leads to "encunines via N-hemiacetals and immonium hydroxides, when the water is removed. In these conjugated systems electron density and nudeophilicity are largely transferred from the nitrogen to the a-carbon atom, and thus enamines are useful electroneutral d -reagents (G.A. Cook, 1969 S.F. Dyke, 1973). A bulky heterocyclic substituent supports regio- and stereoselective reactions. 

The widely used Moifatt-Pfltzner oxidation works with in situ formed adducts of dimethyl sulfoxide with dehydrating agents, e.g. DCC, AcjO, SO], P4O10, CCXTl] (K.E, Pfitzner, 1965 A.H. Fenselau, 1966 K.T. Joseph, 1967 J.G. Moffatt, 1971 D. Martin, 1971) or oxalyl dichloride (Swem oxidation M. Nakatsuka, 1990). A classical procedure is the Oppenauer oxidation with ketones and aluminum alkoxide catalysts (C. Djerassi, 1951 H. Lehmann, 1975). All of these reagents also oxidize secondary alcohols to ketones but do not attack C = C double bonds or activated C —H bonds. 

The Dess-Martin periodinane ( DMP ) reagent, U,l-tris(acetyloxy)-l,l-dihydro-l,2-benziodoxol-3(l//)-one, has also been used in several complex syntheses for the oxidation of primary or secondary alcohols to aldehydes or ketones, respectively (e.g., M. Nakatsuka, 1990). It is prepared from 2-iodobenzoic add by oxidation with bromic add and acetylation (D.a Dess, 1983). 

Selective oxidation of secondary alcohols to ketones is usually performed with CrOj/HjSO, I I in acetone (Jones reagent) or with CrOjPyj (Collin s reagent) in the presence of acid-sensitive groups (H.G. Bosche, 1975 C. Djerassi, 1956 W.S. Allen, 1954). As mentioned above, a,)S-unsaturated secondary alcohols are selectively oxidized by MnOj (D.G. Lee, 1969 D. Arndt, 1975) or by DDQ (D. Walker, 1967 H.H. Stechl, 1975). 

Amines are powerful nucleophiles which react under neutral or slightly basic conditions with several electron-accepting carbon reagents. The reaction of alkyl halides with amines is useful for the preparation of tertiary amines or quaternary ammonium salts. The conversion of primary amines into secondary amines is usually not feasible since the secondary amine tends towards further alkylation. 

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