Equivalents Of Triethylamine Research Articles

Iron(III) complexes of pyrrolidine and piperidine appended tridentate 3N donor ligands as models for catechol dioxygenase enzymes

Six new mononuclear iron(III) complexes [Fe(L1)Cl3]-[Fe(L6)Cl3] bearing tridentate all-nitrogen donor ligands (where L1 = N-(pyridin-2-ylmethyl)-2-(pyrrolidin-1-yl)ethanamine, L2 = 2-(piperidin-1-yl)-N-(pyridin-2-ylmethyl)ethanamine, L3 = 1-(piperidin-2-yl)-N-(pyridin-2-ylmethyl)methanamine, L4 = N-((1-methyl-1H-imidazol-2-yl)methyl)-2-(pyrrolidin-1-yl)ethan-1-amine, L5 = N-((1-methyl-1H-imidazol-2-yl)methyl)-2-(piperidin-1-yl)ethan-1-amine), L6 = 1-(1-methyl-1H-imidazol-2-yl)-N-(piperidin-2-ylmethyl)methanamine) have been prepared, characterized and evaluated as the functional models for the carbon–carbon bond-cleaving catechol dioxygenase enzymes. The molecular structure of complexes 1 and 3 revealed a distorted octahedral geometry around iron(III) center with facial coordination of ligands via three nitrogen atoms and three chloride ions occupy the remaining sites of the octahedron. Iron(III) catecholate adducts were generated in situ by adding one equivalent of various catechols pretreated with two equivalent of triethylamine. The 3,5-di-tert-butylcatecholate adduct of the complexes 1–6 show two intense bands in visible region (540–900 nm) as the result of DBC2--to-iron(III) ligand-to-metal charge-transfer transitions in acetonitrile. During electrochemical analysis, all the complexes display FeIII→FeII redox couple in the similar potential range (−0.260 to −0.336 V). The dioxygenase activity of present complexes produces major amount of extradiol cleavage products (75–92%) over the intradiol cleavage products (4–14%) at moderate rate (0.561–1.744 × 10−2 M−1 s−1). Interestingly, the iron(III) complexes 3 and 6 with facially coordinating tridentate ligands with heterocyclic piperidine amine (NH) nitrogen donor moiety produce major amounts of extradiol-cleavage products (3, 89%; 6, 75%) along with only minor amounts of other product (10–24%) without any intradiol-cleavage products.

Photochemical Synthesis of Solvatochromic Fluorophore from the C–C Coupling Reaction for Undergraduate Laboratory Experiment

Photochemical synthesis, in which light is used as an indispensable reagent, is recognized as a green technique for organic synthesis and has been paid extensive attention. In this laboratory experiment for chemistry classes, a photoinduced C–C coupling reaction is introduced, which can be conducted under mild conditions at room temperature. Generally, this reaction requires no photoredox catalyst and only 2 equiv of triethylamine with common LED light (400 nm) as the light source. Here, we report the photochemical synthesis of a favorable fluorophore (4MPB) with high yields (∼80%) using 4-iodobenzoate and N-methylpyrrole as the representative reagents in an undergraduate laboratory experiment. Importantly, all participating students were excited about the fluorophores that they synthesized and gained the basic principles of photoluminescence. This experiment is safe, easy to conduct, and cost-effective, and it received positive feedback from the students. The exercise reinforces their skills in photochemical synthesis and introduces students to the significance and importance of light in chemistry, which is a fascinating field in chemical research.

Benchtop NMR analysis of piperazine-based drugs hyperpolarised by SABRE.

Piperazine-based drugs, such as N-benzylpiperazine (BZP), became attractive in the 2000s due to possessing effects similar to amphetamines. Herein, BZP, in addition to its pyridyl analogues, 2-, 3-, and 4-pyridylmethylpiperidine (2-PMP, 3-PMP, and 4-PMP respectively) was subjected to the hyperpolarisation technique Signal Amplification By Reversible Exchange (SABRE) in order to demonstrate the use of this technique to detect these piperazine-based drugs. Although BZP was not hyperpolarised via SABRE, 2-PMP, 3-PMP, and 4-PMP were, with the ortho- and meta-pyridyl protons of 4-PMP showing the largest enhancement of 313-fold and 267-fold, respectively, in a 1.4-T detection field, following polarisation transfer at Earth's magnetic field. In addition to the freebase, 4-PMP.3HCl was also appraised by SABRE and was found not to polarise, however, the addition of increasing equivalents of triethylamine (TEA) produced the freebase, with a maximum enhancement observed upon the addition of 3 equivalents of TEA. Further addition of TEA led to a reduction in the observed enhancement. SABRE was also employed to polarise 4-PMP.3HCl (~20% w/w) in a simulated tablet to demonstrate the forensic application of the technique (138-fold enhancement for the ortho-pyridyl protons). The amount of 4-PMP.3HCl present in the simulated tablet was quantified via NMR using D2 O as a solvent and compared well to complimentary gas chromatography-mass spectrometry data. Exchanging D2 O for CD3 OD as the solvent utilised for analysis resulted in a significantly lower amount of 4-PMP.3HCl being determined, thus highlighting safeguarding issues linked to drug abuse in relation to determining the amount of active pharmaceutical ingredient present.

Synthesis and Crystallographic Characterization of the Tetravalent Actinide-DOTA Complexes [AnIV(κ8-DOTA)(DMSO)] (An = Th, U)

The reaction of UCl4 or ThCl4(DME)2 (DME = dimethoxyethane) with 1,4,7,10-tetrazacyclododecane-1,4,7,10-tetraacetic acid (H4DOTA), and 6 equiv of triethylamine, in dimethyl sulfoxide (DMSO) results in the formation of [AnIV(κ8-DOTA)(DMSO)] (1, An = U; 2, An = Th), which can be isolated in moderate yields after workup. Complexes 1 and 2 are the first structurally characterized actinide-DOTA complexes to feature the κ8 binding mode for the DOTA ligand. In addition, we isolated a few crystals of [U(κ4-H2DOTA)(DMSO)4][Cl]2 (3). Crystallographic characterization of this material reveals that the [H2DOTA]2- ligand in 3 is only coordinated to U4+ by its four carboxylate arms, generating an overall κ4 binding mode. Similar complexes have been previously proposed as intermediates along the H4DOTA complexation pathway, but this intermediate had not been structurally characterized until now.

Reaction of Methyl Vinyl Sulfone with Schiff Bases Derived from α-Alanine Methyl Ester and Aromatic Aldehydes

Schiff bases derived from α-alanine methyl ester and aromatic aldehydes reacted with methyl vinyl sulfone in toluene at 20°C in the presence of silver acetate and 1.5 equiv of triethylamine to give the corresponding 1,3-dipolar cycloaddition products, methyl (2S*,4S*,5S*)-5-aryl-4-methanesuffonylpyrrolidine-2-carboxylates containing a small impurity (8–25%) of diastereoisomeric (2S*,4R*,5S*)-5-aryl-4-methanesulfonylpyrrolidine-2-carboxylates. The same compounds were formed when the reaction was carried out in boiling toluene, but in this case the (4S*)-diastereoisomer was the minor product. The stereoselectivity of the cycloaddition reactions was interpreted by DFT/PBE calculations of the energies of the final products and transition states.

Gentisate-1,2-dioxygenase activity by an iron(II)-phenanthroline complex

In this work, we have synthesised and crystallographically characterized a mononuclear iron(II) complex, [ $$\hbox {Fe}(\hbox {phen})_{3}$$ ]( $$\hbox {NO}_{3})_{2}\cdot 2\hbox {H}_{2}\hbox {O}$$ (1) (phen = 1,10-phenanthroline). Single crystal X-ray diffraction (SXRD) analysis revealed that 1 crystallizes in monoclinic system with P $$1^{-}$$ space group. The lattice water molecules in 1 form a water-nitrate cluster, $$(\hbox {H}_{2}\hbox {O})_{2}^{\ldots }(\hbox {NO}_{3})_{2}$$ through strong H-bonding interaction mediated via iron(II) complex in a unique binding motif and provide additional stability to the compound in the solid state. This iron(II) complex is able to catalyze the cleavage of aromatic C-C linkage of 2,5-dihydroxybenzoic acid (Gentisic acid, GA) in oxygen environment. The iron(II) complex in the presence of two equivalent of triethylamine $$(\hbox {Et}_{3}\hbox {N})$$ binds with GA stoichiometrically in acetonitrile medium at $$25\,{^{\circ }}\hbox {C}$$ . Observation of GA-to-iron LMCT optical bands at 521 and 609 nm supports in situ generated iron-GA adduct in solution. This in situ generated iron-GA adduct reacts with molecular oxygen at the rate, $$k_{\mathrm{obs}} = 6.58 \times 10^{-3}\,\mathrm{min}^{-1}$$ in acetonitrile and affords exclusively 2-oxo-4-hydroxy-hepta-3,5-dienedioic acid. The incorporation of both the oxygen atoms of molecular oxygen in the bio-mimicking activity of gentisate-1,2-dioxygenase by this iron(II)-phenanthroline complex remain a rare example in scientific literature. A mononuclear iron(II) phenanthroline complex exhibits significant catalytic activity towards oxidative cleavage of 2,5-dihydroxy benzoic acid at a rate, $$\hbox {k}_{\mathrm{obs}}(\mathrm{min}^{-1}) = 6.58\times 10^{-3}$$ which predominantly produced 2-oxo-4-hydroxy-hepta-3,5-dienedioic acid upon addition of 2,5-dihydroxybenzoic acid in the presence of molecular oxygen.

One‐Pot Reaction of Amidrazones, Phthaloyl Chloride, and Triethyl Amine: Synthesis of 1‐(1′,2′,4′‐Triazole)‐2‐Benzoic Acid

One‐pot reaction of equimolar amounts of phthaloyl chloride and N‐aryl‐benzamidrazones in the presence of two equivalents of triethylamine (Et3N), gave at r.t. 4‐aryl‐3‐(o‐carboxyphenyl)‐5‐phenyl‐1,2,4‐triazoles in good yields. The structure of the obtained products was proved by IR, mass, NMR spectra, and elemental analyses. The mechanism of product formation is discussed.

An Oxido‐Bridged Diiron(II) Complex as Functional Model of Catechol Dioxygenase

AbstractAn oxido‐bridged diiron(II)‐phenanthroline complex, [Fe2O(phen)2Cl2] (1) [phen =1,10‐phenanthroline] has been synthesized from an oxido‐bridged diiron(III) precursor in presence of sodium azide and structurally characterized by different spectroscopic tools including single crystal X‐ray diffraction study.From X‐ray crystal structure of 1, it is revealed that each of the Fe(II) centre is in distorted octahedral geometry with FeN4OCl core and the molecule crystallizes in Pnc2 space group. Bond valence sum (BVS) calculation confirms the existence of iron ions in +2 oxidation state in 1. The diiron(II) complex has been evaluated as model system for the catechol dioxygenase enzyme by using 3,5‐di‐tert‐butylcatechol (DTBC) as the substrate in acetonitrile medium, revealing that 1 efficiently mimics the catalytic cycle of catechol dioxygenase. Upon stoichiometric addition of DTBC pretreated with two equivalents of triethylamine (Et3N) to the diiron complex, two catecholate‐to‐iron(III) LMCT bands (515 nm and 734 nm) are observed. The in situgenerated catecholate adduct from 1in acetonitrile solution react with dioxygen to afford exclusively extradiol cleavage products along with a small amount of benzoquinone, which is also discerned from the appearance and decrease in intensity of the electronic spectral bands around (708 nm; 507 nm) nm. Nucleophilic attack by molecular oxygen on catecholate adduct in solution provides substantial evidence for the regioselective extradiol cleavage products.

Regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of 5,6-isopropylidene-l-ascorbic acid

An efficient regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of vitamin C 5,6-acetonide has been developed which does not involve tedious column chromatographic separation of the desired products from contaminants exhibiting very similar Rf values. Vitamin C 5,6-acetonide is first acylated with one equivalent of acyl halide in the presence of two equivalents of pyridine. The crude 2-O-acylated product is then alkylated with one equivalent of 1-acyloxyalkyl-1-iodide in the presence of one equivalent of triethylamine. The 2-O-acyl-3-O-(1-acyloxyalkyl) vitamin C 5,6-acetonides are obtained in moderate yields.

Amide and thioamide of cyanoacetic acid in Аd N E type reactions with 2-halopyridinium salts

A mixture of pyridine-2-thiones and 2-amino-1-cyanoindolizines was obtained by condensation of N-[(alkoxycarbonyl)methyl]- or N-[(aroyl)-methyl]-2-chloro(bromo)pyridinium halides in the presence of 2 equivalents of triethylamine. Furthermore, reacting cyanoacetamide with N-[(alkoxycarbonyl)methyl]-2-chloro(bromo)pyridinium salts afforded a mixture of 2-amino-1-carbamoylindolizine-3-carboxylates and a novel heterocyclic system, 2,4-dioxo-2,3,4,5-tetrahydropyrido[1,2-d][1,4]diazepine-1-carbonitrile.

Reaction of ω-nitrostyrene with diethyl malonate in the presence of chiral nickel(II) complexes

Single-ligand complexes of nickel(II) with chiral diamines based on L-proline and (S)-camphor efficiently catalyze addition of diethyl malonate to ω-nitrostyrene in the presence of 1 equiv of triethylamine as co-catalyst. The reaction enantioselectivity depends on the chiral ligand structure.

A Novel Synthesis of Carboxylic Esters from 2-Methyl-4,6-pyrimidyl Dicarbonates and Grignard Reagents

The carboxylic esters are mostly prepared by the reaction of carboxylic acids or their derivatives with alcohols and a large number of methods have been known. However, a few methods have been reported on the derivation of carboxylic esters from the alkoxycarbonylation of organometallics via σ bond formation between α-carbon and carbonyl carbon. Among them, the reaction of alkynyllithiums with methyl chloroformate or 2,2,2-trichloroethyl chloroformate affords the corresponding α,β-alkynoic esters at low temperature, but it requires an excess of chloroformate reagents to avoid competing side reactions. Although the treatment of ethyl chloroformate with organomanganates or organocopper reagents associated with magnesium salt under Pd catalysis produces the corresponding ethyl esters, these organometallics are prepared by an additional step and the scope is limited to primary and alkenyl group, respectively. The direct alkoxycarbonylation of Grignard reagents with dialkyl carbonates or alkyl chloroformates affords the corresponding esters, but the former requires 2 equiv of dialkyl carbonates and the latter is limited to the preparation of α-diazo esters at −78 C. Instead, the alkoxycarbonylation of Grignard reagents proceeds well with 1 equiv of 2-pyridyl carbonates, but the yield of 2,2,2-trichloroethyl ester depends on reaction temperature. Recently, alkyl cyanoformates have been utilized for the alkoxycarbonylation of organometallics. Thus, the alkoxycarbonylation of alkynyllithiums or allenyllithiums with 2 equiv of methyl or ethyl cyanoformate provides methyl akynoates or ethyl allenates, respectively. The reaction of heteroaromatic magnesium halides with an excess of alkyl cyanoformates also affords carboxylic esters in moderate to high yields. Furthermore, the treatment of methyl cyanoformate with magnesium metalated nitriles, derived from αbromonitriles and isopropylmagnesium chloride, at −78 C affords methyl α-cyanoates in moderate to high yields. Thus, the success of carboxylic esters synthesis by the alkoxycarbonylation of organometallics depends largely on the nature/amount of alkoxycarbonylating reagents and metals employed. However, there are no reports of alkoxycarbonylating reagents that can produce 2 equiv of carboxylic esters with organometallics. Inspired by our previous reports on ketones synthesis using pyrimidyl diesters, we investigated the synthesis of carboxylic esters from 2-methyl-4,6pyrimidyl dicarbonates and Grignard reagents. In choosing 2-methyl-4,6-pyrimidyl group as active moiety, we considered i) chelation effect between nitrogen atom and magnesium atom ii) thermal stability and storage of 2-methyl-4,6-pyrimidyl dicarbonates rather than other pyrimidyl dicarbonates. 2-Methyl-4,6-pyrimidyl dicarbonates 3 were newly prepared by the addition of 2 equiv of alkyl chloroformates 2 to a suspended solution of 4,6-dihydroxy-2-methylpyrimidine 1 and 2 equiv of triethylamine in THF at room temperature (Scheme 1). The nucleophilic acyl substitution of 2 with 1 was completed in 2-10 h at room temperature because 1 was slightly soluble in THF. After completion of the reaction, the resulting triethylamine hydrochloride precipitate was filtered off. After usual workup, the residue was subjected to silica gel (Davisil, pH = 7) or recystallized to afford 3 in 67-89% yields. During the synthesis of 2-methyl-4,6-pyrimidyl diisobutyl dicarbonate 3a, a small amount (~10%) of N,Ndiethyl isobutyl carbamate was produced by the nucleophilic acyl substitution of isobutyl chloroformate with triethylamine, which was distilled out under vacuum. However, 2-

ChemInform Abstract: Novel Type Elimination Reactions of Sulfoxides Bearing Several Heteroaromatics: Trapping of Sulfines with 2,3-Dimethyl-1,3-butadiene.

Previously we reported the novel thioaldehydes generation via thermolyses of phenacyl sulfoxides bearing some heteroaromatics. Thermolysis of sulfoxides (1a,b and 2a-4a) bearing other heterocycles such as thiadiazole, triazole, and tetrazole in the presence of 2,3-dimethyl-1,3-butadiene in dioxane at 100 degrees C led to the unexpected products 6-substituted-5,6-dihydro-3,4-dimethyl-2H-thiapyran 1-oxide (5a,b). These products were considered to be formed by the Diels-Alder reaction of the diene with the sulfines formed initially by the thermal decomposition of the sulfoxides. The rate acceleration and the improvement of the yield by addition of 1.5 equiv of triethylamine, especially in the case of ethoxycabonylmethyl sulfoxide 1c, was observed. The cis-trans selectivity for sulfine cycloadducts was also studied by NMR spectrometry. The reactions of alpha-substituted phenacyl sulfoxides 1d-f bearing a phenyl-substituted tetrazolyl group in the presence of the same diene were also studied.

Platinum–triethylamine-catalyzed hydrogenation of aldehydes and cyclohexanones

The first hydrogenation of aldehydes and chemoselective hydrogenation of cyclohexanones catalyzed by PtO 2–Et 3N are presented. An additionally attractive feature of this hydrogenation is being applicable to the complicated molecules. Three equivalent of triethylamine and 0.05 equiv of PtO 2 in 95% ethanol are found to be the optimal condition.

Trivalent Iron and Ruthenium Complexes with a Redox Noninnocent (2-Mercaptophenylimino)-methyl-4,6-di-tert-butylphenolate(2-) Ligand

The 3,5-di-tert-butyl substituted N-(salicylidene)-o-mercaptoaniline (H(2)L) ligand reacted with equimolar amounts of FeBr(2) and 2 equiv of triethylamine in air affords [Fe(III)(L-L)Br](0) (1), where (L-L)(2-) is a pentacoordinate ligand formed from the oxidative dimerization of L(2-) via disulfide bridge formation. Reaction of H(2)L with RuCl(3) x H(2)O and NEt(3) gives a dark green-brown dinuclear complex, [Ru(III)(2)(L)(2)Cl(2)(NCCH(3))(2)](0) (2). Both complexes have been characterized by X-ray crystallography. A Ru-Ru single bond is evident in 2. Complex 1 has also been characterized by electron paramagnetic resonance and Mossbauer spectroscopies and magnetic susceptibility measurements that identify a high-spin Fe(III) (S = (5)/(2)) center. Diamagnetic 2 is successively twice reversibly one-electron oxidized to produce [Ru(III)(2)(L(*))(L)Cl(2)(NCCH(3))(2)](+), [2](+) (S = (1)/(2)), and [Ru(III)(2)(L(*))(2)Cl(2)(NCCH(3))(2)](2+), [2](2+) (S = 0). Spectroelectrochemical and electron paramagnetic resonance measurements identify these as ligand-based oxidations affording o-coordinated phenoxyl radicals. DFT calculations on the electron transfer series corroborate this result and that the Ru-Ru single bond is retained throughout this series.

Catalytic alkynone generation by Sonogashira reaction and its application in three-component pyrimidine synthesis

The Sonogashira alkynylation of acid chlorides can be efficiently conducted in less than an hour by performing the reaction in tetrahydrofuran as a solvent and in the presence of one stoichiometrically necessary equivalent of triethylamine as a base. This approach also opens new avenues for consecutive one-pot multicomponent reactions. As an example, the one-pot three-component pyrimidine synthesis illustrates the versatility of this modified Sonogashira protocol as an entry to diversity-oriented heterocycle synthesis in a one-pot fashion. The protocol can be completed within a few hours.

3-acyl-1,2,3,4-tetrahydropyridine-2,4-diones: Synthesis and chemical properties

N-Substituted 6-methyl-1,2,3,4-tetrahydropyridine-2,4-diones reacted with aliphatic carboxylic acid chlorides in the presence of pyridine or triethylamine to give the corresponding 4-O-acyl derivatives which underwent O,C-migration of the acyl group by the action of 2 equiv of triethylamine and a catalytic amount of 2-hydroxy-2-methylpropanenitrile. Reactions of 3-acyl-6-methyl-1,2,3,4-tetrahydropyridine-2,4-diones thus formed with aliphatic and aromatic amines gave the corresponding enamino derivatives at the side acyl group. Enamino derivatives at the C4 =O group were obtained by transformation of 3-acyl-1,2,3,4-tetrahydropyridine-2,4-diones into 3-acyl-4-methoxy-6-methyl-1,2-dihydropyridin-2-ones via alkylation with dimethyl sulfate and subsequent treatment with amines.

Microwave-Assisted Synthesis of N-2-Benzyl-3-(4-ethoxycarbonylphenyl)indazole Derivatives

- The microwave-assisted synthesis for promoting N-2 substituted indazoles as the major products were successfully developed by treating 3-(4-ethoxycarbonylphenyl)indazoles with various substituted benzyl chloride (benzyl, o-chlorobenzyl, m-chlorobenzyl, and p-chlorobenzyl chloride) in the presence of two equivalents of triethylamine. The result was better than two trandional methods including the directly substitution with benzyl chloride and Mitsunobu reaction with benzyl alcohol.

Molecular and electronic structure of square planar complexes [PdII(tbpy)(LIPN,O)]0, [PdII(tbpy)(LISQN,O)](PF6), and [PdII(tbpy)(LIBQN,O)](PF6)(BF4)·2CH2Cl2: an o-iminophenolato based ligand centered, three-membered redox series

Three Pd(II) complexes which are members of the same electron-transfer series have been synthesized. Refluxing of the reaction mixture containing equimolar amounts of PdCl(2), 2-(2-trifluoromethyl)anilino-4,6-di-tert-butylphenol (H(2)L(N,O)), 4,4'-di-tert-butyl-2,2'-dipyridyl ((t)bpy), and 3 equiv of triethylamine in MeOH under an argon atmosphere followed by exposure to air and addition of KPF(6) after cooling to room temperature yields reddish brown crystals of paramagnetic (S = 1/2) [Pd(L(N,O)(ISQ))((t)bpy)](PF6) (2). Reaction of 2 with one equiv of [CoCp2] in dry and degassed CH(2)Cl(2) using anaerobic conditions gives diamagnetic [Pd(L(N,O)(IP))((t)bpy)] (1), which is the one-electron reduced form of 2. One-electron oxidation of 2 in CH(2)Cl(2) under argon with one equiv of NOBF4 affords diamagnetic [Pd(L(N,O)(IBQ))((t)bpy)](PF6)(BF4).2CH(2)Cl(2) (3). Complexes 1, 2, and 3 constitute three members of the same electron-transfer series. They are ideally suited to distinctly distinguish the geometrical and spectroscopic features of the N,O-coordinated, closed-shell, diamagnetic o-iminophenolate (L(N,O)(IP))2-, the corresponding open-shell pi-radical o-iminobenzosemiquinonate (L(N,O)(ISQ))1-.(S(rad) = 1/2), and the closed-shell o-iminobenzoquinone (L(N,O)(IBQ))0 forms. All complexes were characterized by X-ray crystallography (100 K), cyclic voltammetry, EPR, and UV-vis spectroscopy. Complex 2 exhibits three reversible electron transfer waves in the cyclic voltammogram. Structural characterization of complex 3 reveals an interesting strong ion pairing between the BF4 anion and the complex dication with a short C-F distance of 2.7 A.

Highly flexible and efficient synthesis of the GABA B enhancer 4-(2-hexylsulfanyl-6-methyl-pyrimidin-4-ylmethyl)-morpholine

In the course of establishing a flexible synthesis of 2,4,6-substituted pyrimidines, we discovered that 2-hexyl-isothiourea hydrobromide reacts at ambient temperature and in a mildly exothermic fashion with 5,5-diethoxy-pent-3-yn-2-one upon treatment with 2 equiv of triethylamine in tetrahydrofuran to afford 4-diethoxymethyl-2-hexylsulfanyl-6-methyl-pyrimidine in 80% isolated yield. The methodology was developed in the search for an improved synthesis of the GABA B enhancer 4-(2-hexylsulfanyl-6-methyl-pyrimidin-4-ylmethyl)-morpholine.