Amine-Hydrogen Halide

Since H3N - HC1 exists only as a neutral pair and HF is less acidic than HCl, it is not surprising that HjN -HF, too, does not form an ion pair . Similarly for HjP -HCl and H3P—HF, as H3P is less basic than The latter set of calculations is particularly sig- 

The acidity was turned up one notch when NH3 was paired with HI ° . This smdy included the effects of electron correlation. In agreement with prior results, the surfaces of both H3N—HCl and HjN -HBr contain only a single neutral-pair minimum. H3N -HI, on the other hand, exists both as the neutral and ion pairs. Whereas the neutral is favored by 5 kcal/mol at the SCF level, the two types of complex are nearly equal in energy when correlation is added. On the other hand, zero-point vibrational contributions to the energy are quite distinct for the two minima. Whereas this effect destabilizes the neutral pair by 1.6 kcal/mol, the ion pair is raised in energy by 5.6 kcal/mol, leading to the near disappearance of the minimum in the potential. It is concluded unhkely that HjNH — would actually be observed. 

The calculations have demonstrated that the correlated potential energy surface of this sort of system typically contains a single minimum, and that the position of this minimum 

The progressive shift of the position of the single minimum was reaffirmed in a set of correlated calculations at the MP2/6-31+G(d,p) level . A single acid, HCl, was paired with a series of nitrogen bases, in this case 4-substituted pyridines. As the pyridine became more basic, the Cl—H bond was progressively elongated, until eventually the proton s equilibrium position was approximately equidistant between the Cl and the pyridine. Further enhancement of the basicity led to a full transfer of the proton, forming an ion pair, as may be seen in Fig. 6.19. 

None of the complexes pairing an amine with a hydrogen halide were computed to be of the pure ion pair variety with a minimal basis set ° . However, there were some that were close. More specifically, since the equilibrium position of the proton need not shift precipitously from one atom to the other, but rather can move gradually as the acidity and basicity increase, a proton-transfer parameter was devised to indicate the degree of transfer of the proton from the acid to the base. The quantity p was defined as 

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Primary amine Primary alkyl halide Ammonium halide salt Secondary amine Hydrogen halide ... 

A halogen atom directly attached to a benzene ring is usually unreactive, unless it is activated by the nature and position of certain other substituent groups. It has been show n by Ullmann, however, that halogen atoms normally of low reactivity will condense with aromatic amines in the presence of an alkali carbonate (to absorb the hydrogen halide formed) and a trace of copper powder or oxide to act as a catalyst. This reaction, known as the Ullmant Condensation, is frequently used to prepare substituted diphenylamines it is exemplified... 

Bromomethyl-5-methylthiophene gives normal displacement products with amines but it is isomerized on attempted reaction with copper(I) cyanide (Scheme 59) 48MI30200. Whereas 2-hydroxymethylthiophene reacts normally with hydrogen halides to give 2-halomethylthiophenes, reaction of 2-hydroxymethylfuran (2-furfuryl alcohol) with hydrochloric acid results in formation of laevulinic acid (151). 2-Furfuryl alcohol derivatives are... 

Therefore, in terms of acidity, alcohols will lie somewhere between amines and hydrogen halides ... 

Amine-phosphorus halide reactions involve hydrogen halide (or amine hydrohalide) formation. They can be complicated through acid catalysis or side reactions. Thus, the possible formation of skeletally stabilized products through transamination reactions in which no hydrohalide products are obtained is of interest. 

A simple and atom-economical synthesis of hydrogen halide salts of primary amines directly from the corresponding halides, which avoids the production of significant amounts of secondary amine side products, has been described by researchers from Bristol-Myers Squibb [227]. Microwave irradiation of a variety of alkyl halides or tosylates in a commercially available 7 m solution of ammonia in methanol at 100-130 °C for 15 min to 2.5 h followed by evaporation of the solvent provided the corre-... 

The use of a tertiary amine as an adjunct is not advised as it leads to increased formation of haloalkane the hydrogen halide generated is simply vented from the reaction system. Caution needs to be applied in handling the product alkyl (or aryl) phosphorodichloridites. They are extremely susceptible to moisture, and many are flammable upon contact with air. 

The nucleophilic addition of alcohols [130, 204-207], phenols [130], carboxylates [208], ammonia [130, 209], primary and secondary amines [41, 130, 205, 210, 211] and thiols [211-213] was used very early to convert several acceptor-substituted allenes 155 to products of type 158 and 159 (Scheme 7.25, Nu = OR, OAr, 02CR, NH2, NHR, NRR and SR). While the addition of alcohols, phenols and thiols is generally carried out in the presence of an auxiliary base, the reaction of allenyl ketones to give vinyl ethers of type 159 (Nu = OMe) is successful also by irradiation in pure methanol [214], Using widely varying reaction conditions, the addition of hydrogen halides (Nu= Cl, Br, I) to the allenes 155 leads to reaction products of type 158 [130, 215-220], Therefore, this transformation was also classified as a nucleophilic addition. Finally, the nucleophiles hydride (such as lithium aluminum hydride-aluminum trichloride) [211] and azide [221] could also be added to allenic esters to yield products of type 159. 

Compound CF3SNCO undergoes further reactions typical of organic isocyanates with hydrogen halides (41), amines (28), and other species (39, 69), as is shown in Table II. 

By far the most common method for preparation of amides is the reaction of ammonia or a primary or secondary amine with one of the reactive reagents described in Section 3.4.1. When acyl halides are used, some provision for neutralizing the hydrogen halide is necessary, because it will otherwise react with the reagent amine to form the corresponding salt. Acid anhydrides give rapid acylation of most amines and are convenient if available. The Schotten-Bauman conditions, which involve shaking an amine with excess anhydride or acyl chloride and an alkaline aqueous solution, provide a very satisfactory method for preparation of simple amides. 

Coupling of allylic or piopargylic halides and terminal acetylenes can also be realized under completely catalytic conditions [204,205]. The reactions are carried out in aqueous medium in the presence of catalytic amounts of cqpper(I)halide. The hydrogen halide liberated in the reaction is neutralized with ammonia, an amine or alkali hydroxide. In many cases both the 1,1- and the 1,3-coupling product is obtained ... 

Figure 11.4—The n — a transition in primary amines. This transition corresponds to an increase in the weight of the mesomeric form. Absorption corresponding to this transition disappears when a proton-containing hydrogen halide is added. This effect is due to the formation of a quaternary ammonium salt that mobilises the electron pair of the nitrogen atom, which is necessary for this transition (see formula in brackets).

AsH3, primary and secondary amines, and lower alcohols, BC13, BBr3, and BI3 react to liberate the corresponding hydrogen halide. Tertiary alcohols and the boron trihalides yield the alkyl halide and boric acid. The boron trihalides hydrolyze readily in water or moist air to produce boric acid and hydrogen halides. 

Compounds of the type L-BH2X can be prepared by the reaction of the appropriate amine borane and hydrogen halides or halogens. The synthesis of the trimethylamine iodoborane [25741-81-5] adduct (eq. 8) yields a precursor for the preparation of the trimethylamine isocyanoborane [60045-36-5] adduct as shown in equation 9 (15). 

Thiochrom-4-ones have also been prepared by the amine-promoted elimination of hydrogen halide from 3-haIothiochroman-4-ones,188 by the Puinmerer reaction on thiochroman-4-one S-oxides [Eq. (20)],98 from a ring expansion of activated benz[6]thiophenes [Eq. (21)],189 by the reaction of o-mercaptoaryl alkyl ketones with ethyl esters of... 

When an acyl group replaces the hydrogen of alcohols, carboxylic acids, hydrogen halides, ammonia or amines, we have the acyl compounds known as esters, anhydrides, halides, and amides, respectively. 

The mechanism of this type of reaction has been studied extensively, and much evidence has accumulated in support of a stepwise process, which proceeds first by base-catalyzed elimination of hydrogen halide (HX) from the aryl halide—as illustrated below for the amination of bromobenzene ... 

Another variation of the palladium-catalyzed carbonylation reaction occurs when hydrogen is added rather than an alcohol or a primary or secondary amine. This variation leads to aldehyde formation the hydrogen reduces the acylpalladium intermediate to aldehyde and metal hydride (76). A basic tertiary amine is also added as in the ester-forming reaction to neutralize the hydrogen halide formed in the dissociation of the hydride ... 

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