Molecular adducts

Crystal engineering is a scientific area in constant flux, which helps explain why unambiguous definitions have not yet been developed and/or accepted. The term cocrystal is not well defined, and the existing literature contains terms such as molecular complexes, multicomponent solids, cocrystals, molecular adducts, molecular salts, clathrates, and inclusion compounds that frequently describe one and the same family or type of chemical compounds. We will not attempt to add to the ongoing discussion, and we limit our overview to structurally homogeneous crystalline materials containing two or more neutral building blocks that are present in definite stoichiometric amounts and that are made from reactants that are solids at ambient conditions [1] (therefore hydrates and other solvates are excluded from this overview). In addition, we do not discuss... 

Typical Mass Spectrum A cyclic-C Fg example shows the performance and response possible with this analytical instmment in an optimal case. Figure 5.6 shows a typical mass spectrum in the mass range up to m/z 210 [15]. Only the LF adduct molecular ion (no fragmentation) is produced for this test compound (Fig. 5.6, upper... 

Two distinct initiation pathways were observed in the presence of relatively large amounts of thermal initiator, as desaibed above. The smaller peaks at 16 amu higher than all of the main peaks are due to adducts as opposed to Na" adducts. Molecular structures 12 and 13 have predicted molecular masses of 1523.776 (C75Hi2of 3oh ) 2ind 1590.818 (C79Hi2503oh Na), respectively, as compared with 1523.774 and 1590.808 from MALDI-Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Table 1 lists the observed peaks along with their observed and predicted peak heights. 

In the above reaction one molecular proportion of sodium ethoxide is employed this is Michael s original method for conducting the reaction, which is reversible and particularly so under these conditions, and in certain circumstances may lead to apparently abnormal results. With smaller amounts of sodium alkoxide (1/5 mol or so the so-called catal3rtic method) or in the presence of secondary amines, the equilibrium is usually more on the side of the adduct, and good yields of adducts are frequently obtained. An example of the Michael addition of the latter type is to be found in the formation of ethyl propane-1 1 3 3 tetracarboxylate (II) from formaldehyde and ethyl malonate in the presence of diethylamine. Ethyl methylene-malonate (I) is formed intermediately by the simple Knoevenagel reaction and this Is followed by the Michael addition. Acid hydrolysis of (II) gives glutaric acid (III). 

The amino add analysis of all peptide chains on the resins indicated a ratio of Pro Val 6.6 6.0 (calcd. 6 6). The peptides were then cleaved from the resin with 30% HBr in acetic acid and chromatogra phed on sephadex LH-20 in 0.001 M HCl. 335 mg dodecapeptide was isolated. Hydrolysis followed by quantitative amino acid analysis gave a ratio of Pro Val - 6.0 5.6 (calcd. 6 6). Cycll2ation in DMF with Woodward s reagent K (see scheme below) yielded after purification 138 mg of needles of the desired cyc-lododecapeptide with one equiv of acetic add. The compound yielded a yellow adduct with potassium picrate, and here an analytically more acceptable ratio Pro Val of 1.03 1.00 (calcd. 1 1) was found. The mass spectrum contained a molecular ion peak. No other spectral measurements (lack of ORD, NMR) have been reported. For a thirty-six step synthesis in which each step may cause side-reaaions the characterization of the final product should, of course, be more elaborate. 

Two constitutional isomers of molecular formula CgHi20 are formed in the following reac tion Ignoring stereochemistry suggest reasonable structures for these Diels-Alder adducts... 

Typical Cl processes in which neutral sample molecules (M) react with NH to give either (a) a protonated ion [M + HJ or (b) an adduct ion [M + NHJ+ the quasi-molecular ions are respectively 1 and 18 mass units greater than the true mass (M). In process (c), reagent ions (CjHf) abstract hydrogen, giving a quasi-molecular ion that is 1 mass unit less than M. 

In Group 15 (V), nitrogen compounds readily form molecular compounds with BF. Phosphoms compounds also form adducts with BF. Inorganic or organic compounds containing oxygen form many adducts with boron trifluoride, whereas sulfur and selenium have been reported to form only a few (41—43). 

Donor Adduct name CAS Registry Number Molecular formula... 

Lubrication oil additives represent another important market segment for maleic anhydride derivatives. The molecular stmctures of importance are adducts of polyalkenyl succinic anhydrides (see Lubrication and lubricants). These materials act as dispersants and corrosion inhibitors (see Dispersants Corrosion and corrosion control). One particularly important polyalkenyl succinic anhydride molecule in this market is polyisobutylene succinic anhydride (PIBSA) where the polyisobutylene group has a molecular weight of 900 to 1500. Other polyalkenes are also used. Polyalkenyl succinic anhydride is further derivatized with various amines to produce both dispersants and corrosion inhibitors. Another type of dispersant is a polyester produced from a polyalkenyl succinic anhydride and pentaerythritol [115-77-5]. 

Peroxohydrates are crystalline adducts containing molecular hydrogen peroxide. These are commonly called perhydrates, but this name is better avoided because historically implied the maximum oxidation state and hjdrate implies the presence of water, neither of which apply to peroxohydrates. They have also been called hydroperoxidates (92). 

An excess of crotonaldehyde or aUphatic, ahcyhc, and aromatic hydrocarbons and their derivatives is used as a solvent to produce compounds of molecular weights of 1000—5000 (25—28). After removal of unreacted components and solvent, the adduct referred to as polyester is decomposed in acidic media or by pyrolysis (29—36). Proper operation of acidic decomposition can give high yields of pure /n j ,/n7 j -2,4-hexadienoic acid, whereas the pyrolysis gives a mixture of isomers that must be converted to the pure trans,trans form. The thermal decomposition is carried out in the presence of alkaU or amine catalysts. A simultaneous codistillation of the sorbic acid as it forms and the component used as the solvent can simplify the process scheme. The catalyst remains in the reaction batch. Suitable solvents and entraining agents include most inert Hquids that bod at 200—300°C, eg, aUphatic hydrocarbons. When the polyester is spHt thermally at 170—180°C and the sorbic acid is distilled direcdy with the solvent, production and purification can be combined in a single step. The solvent can be reused after removal of the sorbic acid (34). The isomeric mixture can be converted to the thermodynamically more stable trans,trans form in the presence of iodine, alkaU, or sulfuric or hydrochloric acid (37,38). 

N-protonation the absolute magnitude of the Ad values is larger than for Af-methylation <770MR(9)53>. Nuclear relaxation rates of and have been measured as a function of temperature for neat liquid pyridazine, and nuclear Overhauser enhancement has been used to separate the dipolar and spin rotational contributions to relaxation. Dipolar relaxation rates have been combined with quadrupole relaxation rates to determine rotational correlation times for motion about each principal molecular axis (78MI21200). NMR analysis has been used to determine the structure of phenyllithium-pyridazine adducts and of the corresponding dihydropyridazines obtained by hydrolysis of the adducts <78RTC116>. 

There is also evidence for stable 3,4-adducts from the X-ray analysis of 2-amino-4-ethoxy-3,4-dihydropteridinium bromide, the nucleophilic addition product of 2-aminopteridine hydrobromide and ethanol (69JCS(B)489). The pH values obtained by potentiometric titration of (16) with acid and back-titration with alkali produces a hysteresis loop, indicating an equilibrium between various molecular species such as the anhydrous neutral form and the predominantly hydrated cation. Table 1 illustrates more aspects of this anomaly. 2-Aminop-teridine, paradoxically, is a stronger base than any of its methyl derivatives each dimethyl derivative is a weaker base than either of its parent monomethyl derivatives. Thus the base strengths decrease in the order in which they are expected to increase, with only the 2-amino-4,6,7-trimethylpteridine out of order, being more basic than the 4,7-dimethyl derivative. 

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